Cell Quiz Review - Dr Magranndrmagrann.com/MLT/Immuno PPT Flashcards Unit 1.docx · Web viewThe study of the reactions of a host when foreign substances are introduced into the body

Immuno PPT Flashcards Unit 1

Too many leukocytes is called leukophiliaToo few leukocytes is called leukopeniaAbout how many percent of all leukocytes are basophils?

0.5%

What color dye does the cytoplasm of basofils absorb?

The basic pH dye, which is blue, so they are called basophils (“basic dye lovers”).

These granules of the basophils secrete histaminesWhat is the role of histamines? Causing vasodilation; more WBCs can get to

the infection siteWhat interfere with the function of basophils? AntihistaminesWhat is a Mast Cell? A type of basophil that is in the tissues.About how many percent of all leukocytes are eosinohils?

1-4%

What color dye does the cytoplasm of eosinofils absorb?

Granules in cytoplasm absorb the pink dye called eosin, so they are called eosinophils (“eosin dye lovers”).

Eosinophils cells play roles in: Ending allergic reactions, parasitic infectionsThe most numerous WBCs are the NeutrophilsWhat color dye does the cytoplasm of neutrofils absorb?

Granules in cytoplasm do not absorb either the basic or the eosin dye, so they are called neutrophils.

Which WBCs respond first to infection? NeutrophilsWhat is the main role of the netrophils? Phagocytize and destroy bacteria;

Also destroy bacterial toxins in body fluidsThe nucleus of the neutrophils has how many lobes?

2-6

How do neutrophils contribute to immunity? mainly by engulfing bacteria and foreign bodies (thorns, dirt, etc)

How is a process of engulfing bacteria and foreign bodies called?

phagocytosis

What do the lysosomes do to the invaders? They release the contents of their lysosomes onto the invader, dissolving it.

When a bacterium has a capsule, it makes it hard to phagocytize, so the neutrophil requires what?

opsonization by antibodies

What do some bacteria have evolved as a defense against phagocytosis?

a slippery capsule around them

Can the neutrophil or macrophage engulf bacterias with a capsule around them?

No

How can neutrophil phagocytize encapsulated bacteria?

When an antibody attaches to this type of bacteria, the neutrophil can now grab onto the antibody like a handle, enabling it to phagocytize the bacteria

The process of facilitation of phagocytosis is called

opsonization

When an invading bacteria has the antibody antigen-antibody complex

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attached to its cell membrane, the entire structure is calledIf a bacterium does not have a capsule, how can the neutrophil destroy it?

without opsonization

How can the antibody destroy the bacterium by itself?

by popping the cell membrane

The neutrophil and antibody work best together when

a capsule is present

About how many percent of all leukocytes are monocytes?

about 5%

What are the monocytes do? Like neutrophils, they phagocytize (eat) bacteria, old cells, and foreign bodies.

What is the difference between monocytes and neutrophils?

Monocytes have more types of lysosome enzymes than neutrophils so they are better at killing difficult pathogens.

Monocytes use what for opsonization? antibodiesWhen monocytes leave the bloodstream and enter the tissues, they are called

Macrophages

What characterize the dendritic cells? Dendritic cells save a piece of the bacterium to present to a T-Cell.

What is the purpose of saving a piece of the bacterium to present to a T-Cell?

To activate a humoral response.

Why are the basophils, eosinophils, neutrophils, and dendritic cells classified as granulocytes?

They have granules in their cytoplasm.

Why are the monocytes not granulocytes? The monocytes do not have granules in their cytoplasm

Except for dendritic cells, they are all descendants from the same precursor cell called

a myeloid cell

All of these WBCs are called myeloid cellsThe lymphocytes and dendritic cells are descended from a different precursor, so they are called

lymphoid cells

How are the lymphoid cells classified? T-Cells (three types; Helpers, Killers, and Suppressers)B-cells (three age groups; virgins, plasma cells, memory cells)Dendritic Cells (these are also granulocytes)

Which WBCs are the most numerous in the bloodstream?

There are 10x more neutrophils in the bloodstream than monocytes/Macrophages

Which WBCs are the most numerous in the tissues?

There are more macrophages in the tissues of the body. They are everywhere!

How long do neutrophils live? only a few daysHow long do Monocytes/Macrophages live? few monthsHow long do lymphocytes live? Lymphocytes live for yearsWhat’s the Difference between Neutrophils and Monocytes/Macrophages?

Monocytes/Macrophages are larger and slower than neutrophils, but they can phagocytize

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larger organisms and more of themWhat’s the Difference between Neutrophils and Monocytes/Macrophages and Dendritic cells?

Neutrophils and macrophages just phagocytize bacteria until they die. Dendritic cells phagocytize and then take pieces of the dead bacteria and present them to lymphocytes so a larger immune response can occur

Neutrophils , macrophages, and dendritic cells mainly function by

phagocytizing bacteria (not viruses)

Lymphocytes are mostly needed to kill off what?

body cells infected by viruses

All WBC’s secrete chemicals to do what? To recruit more white blood cells to the site.Unlike neutrophils, macrophages have what? surface receptorsWhat are the surface receptors? "recognize" the surface of the pathogen’s cell

membraneHow do the macrophages kill the bacteria? Macrophages phagocytize the bacteria, pop

their lysosomes onto it, and dissolve itWhat are the dendritic cells do? Dendritic cells also do phagocytize the bacteria,

pop their lysosomes onto it, and dissolve it, except they save some pieces of the bacteria’s cell membrane

What are the dendritic cells do with the pieces of the bacteria’s cell membrane?

They places these pieces of bacteria on its own cell membrane, and finds a lymphocyte to present it to

Dendritic cells present these pieces to T cell lymphocytesT cell will present these pieces to B cell lymphocytesWhen the B lymphocyte feels the shape of the bacteria pieces is called

“antigen presentation”

About how many percent of all leukocytes are lymphocytes?

20–45%

The most important cells of the immune system are

Lymphocytes

How many types of lymphocytes are there? 2What is the function of the two types of lymphocytes?

one makes antibodies and the other engages in direct combat with viruses and can also kill our body cells infected with viruses

Both types of lymphocytes can only act against a specific foreign molecule (antigen)What are two main classes of lymphocyte? B cells and T cellsB cells originate in the bone marrowWhen it has not been presented to, it is called a virgin B cellAfter presentation, it will mature into plasma cellsWhat is a mature plasma cell do? fights infection by producing antibodiesAfter the war is over, the plasma cell will mature into a

“queen” , called a Memory Cell

T cells originate in the thymus glandWhat are the T-cells do? They attack foreign cells directly (including

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organ transplants!). They can also kill viruses by killing the infected host cell.

B cells – start as virgin cellsPlasma cells secrete antibodiesWhat kills the attacking cell? the plasma cell’s antibodiesIn which three ways antibodies attack? -They attach to bacteria and pop the cell

membrane-They attach to encapsulated bacteria to help neutrophils and macrophages to phagocytize them.-They agglutinate (clump all over the bacteria, binding their receptor sites so they cannot cause harm)

When Epstein Barr virus attacks B lymphocytes, the disease is called

Mononucleosis

How is mononucleosis characterized? inflammation of lymph vessels (lymphangitis)In mononucleosis, how do infected lymphocytes appear under the microscope?

Infected lymphocytes have a characteristic scallopededge where they touch RBC’s

T cells – coordinate the immune response by recruiting other white blood cellsHow can T-cells destroy bacteria? They can directly destroy bacteria by popping

their cell membraneT cells can also directly destroy foreign cells by popping the cell membrane, so who are at risk?

organ transplants

T-cells can also kill a host body cell that has become infected with viruses

Do the T-cells need to phagocytize the invading cell?

No, they do not

After the T-cells kill the cell, what will happen with the debris?

the macrophages dissolve the debris

Do the T-cells need the assistance of antibodies?

No, they do not

Which cells attack organ transplants? T cellsImmunosuppression drugs are designed to inhibit the action of T cellsT cells are attacked by the HIV (AIDS) virusThe thymus gland secrets certain hormonesThe hormones secreted by the thymus gland cause

T cells to become immunocompetent (makes the cells mature and start to work)

What are the main types of T cells? Natural Killer cells, Helper T cells, Suppressor T cells

What is the role of the Natural Killer cells? Go out and directly kill bacteria or infected host cells

What is the role of the Helper T cells? Release chemicals called “cytokines” to call in

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more white blood cells of all types to join in the war. They also present the macrophage’s antigen to a B cell, which causes it to produce antibodies against that particular bacteria.

What is the role of the Suppressor T cells? Stop the immune process when it is over, and also "tell" some plasma cells to "remember" how to destroy that specific pathogen.

They can react to the same pathogen faster, the next time it invades because

Memory B-cells already have the proper antibodies stored up for that pathogen.

The study of the reactions of a host when foreign substances are introduced into the body is defined as

Immunology

A foreign substance that induces such an immune response in a host is

An antigen

The condition in a host of being resistant to infection is defined as

Immunity

Edward Jenner found what? that milkmaids who were exposed to cowpox had immunity to smallpox

The procedure of injecting powdered scabs from someone with cowpox lesions was known as

vaccination

What is the Latin terminology for “vacca” ? “cow”.The phenomenon in which closure to one agent produces protection against another agent is known as

cross-immunity

Who was Louis Pasture? He worked with the bacteria that cause chicken cholera. He accidentally found that old cultures would not cause disease in chickens. Subsequent injections of more virulent organisms had no of effect on the chickens that had been previously exposed to older cultures. In this manner, the first attenuated vaccine was discovered.

What is attenuation? Change; may occur through heat, aging, or chemicals

An attenuated substance is one that has been weakened, and it does not cause disease.

Louis Pasteur applied this same principle of attenuation to the prevention of

Rabies

Metchnikoff, a Russian scientist, observed that foreign objects introduced into transparent starfish larvae became surrounded by white blood cells that attempted to destroy the foreign objects by eating them.

The process where white blood cells attempt to destroy foreign objects by eating them is

phagocytosis

Cellular immunity involves direct cell-to-cell interaction

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(This includes monocytes/macrophages, neutrophils, and Killer T-lymphocytes. It can include eosinophils and basophils as well)

Humoral (“blood”) immunity involves Antibodies(This refers to the action of B-lymphocytes)

Who linked the two theories by showing that the immune response involved both cellular and humoral elements?

An English physician named Wright

What did Wright observe? that certain humoral, or circulating, factors acted to coat bacteria so that they became more susceptible to ingestion by phagocytic cells

The humoral, or circulating, factors are called opsoninsThese serum factors include specific proteins known as

antibodies

These serum factors included also non-specific factors called

acute-phase reactants

The ability of the host to resist infection by means of normally present body functions is called

Innate immunity

Is prior exposure required for innate immunity? No, they are nonspecific and are the same for all pathogens or foreign substances to which one is exposed.

Does the response change with subsequent exposures?

The response does not change; the phagocytes and Killer T cells are just doing their jobs by identifying and eliminating pathogens that might cause infection.

Innate immunity is the same as calling it cellular immunityCharacterized by specificity for each individual pathogen, or microbial agent, and the ability to remember a prior exposure, which results in an increased immune response is

Adaptive immunity

This refers to the action of the B-lymphocytesAdaptive immunity is the same as calling it humoral immunityWhich immune responses are required for a healthy host?

Both innate and adaptive

The two types of Adaptive Immunity are Active and Passive Immunity

Both types of immunities are acquired how? Naturally and artificiallyThe natural defense system can be considered as being composed of which two parts?

the external defense system and the internal defense system

Which system attempts to prevent entry of pathogens?

External system

What are the structural barriers that prevent most infectious agents from entering the body?

unbroken skin and the mucosal membrane surfaces

Other external defenses include Lactic acid in sweat and fatty acids from sebaceous glands to keep skin acidic and inhibit

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bacteria from growing.What clear away 90% of the deposited material in the respiratory tract?

mucous secretions and cilia

What helps to remove many pathogens in the renal system?

The flushing action of the urine, plus its slight acidity

What plays role in preventing invasion of pathogens in the female genital tract?

Lactic acid keeps the vagina acidic, preventing invasion of pathogens

What halts bacterial growth in the digestive tract?

acidity of the stomach

Lysozyme is an enzyme found in tears and saliva and it attacks the cell walls of bacteria, especially Gram…?

-positive

Why is normal flora present on the body? to keep pathogens from establishing themselves

Which defense system deals with pathogens that gain entry?

The Internal defense system

What play essential parts in the internal defense system?

Both cells and soluble factors

The internal defense system is designed to recognize molecules that are unique to infectious organisms.

This typically involves recognizing what? a carbohydrate such as mannose that is found in bacteria and not on human cells

In internal defense system WBSs seek out and destroy the invading cellsPhagocytosis is enhanced by soluble factors called

acute-face reactants

Both internal and external defense systems promote what?

phagocytosis

Acute phase reactants are produced primarily by hepatocytes (liver cells) within 12-24 hours in response to cytokines

Chemicals that call other white blood cells to the area of infection are called

Cytokines

Cytokines are produced by monocytes and macrophages during the inflammatory response

Cytokines are released, not only from infection, but also by

injury to the tissues

The main cytokines are: Interleukin 1 beta (IL-1b), Interleukin -6 (IL-6) andTumor necrosis Factor – alpha (TNF-a)

Acute phase reactants include C-reactive proteinSerum amyloid AThe complement systemMannose-binding proteinAlpha-1 antitrypsinHaptoglobinFibrinogen

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CeruloplasminA substance found in small amounts in the serum, thought to be an antibody to the polysaccharide capsule of pneumococcal bacteria is

C-reactive protein (CRP)

When is CRP increases rapidly? after infection, surgery, or traumaWithin 48 hours after infection, the levels of CRP can increase with how much?

Levels can rise to 1000 fold

How will the levels decline? The levels decline rapidly when the stimulus stops

Elevated CRP levels are found in bacterial infections, rheumatic fever, viral infections, malignant diseases, tuberculosis, and after a heart attack

CRP acts like an antibody and is capable of optimization, agglutination, precipitation, and activation of complement

CRP binds to specific receptors on monocytes, macrophages and neutrophils, which promotes phagocytosis

Because the levels of CRP rise and then decline so rapidly, it is the most widely used indicator of

acute inflammation

CRP is a nonspecific indicator of disease or trauma, but it can be used to

follow a disease process and observe the response to treatment of inflammation and infection

CRP is also used to monitor what? malignancy and organ transplantation rejectionHow can CRP used to monitor malignancy and organ transplantation rejection?

A rise in its level may mean a return of malignancy, or beginning of organ rejection

An increased level of CRP is also a significant risk factor for

myocardial infarction and ischemic stroke in people who have no previous history of cardiovascular disease

Another major protein whose concentration can rise 1000 fold is

Serum amyloid A

Where can Serum amyloid A found? It is made in the liver and circulates in the plasma

What is the role of Serum amyloid A? it is associated with HDL cholesterol, and is thought to play a role in metabolism of cholesterol

By removing cholesterol from macrophages at the site tissue injury, serum amyloid A contributes to the

cleaning up of the area

Serum amyloid A levels increases in what types of infections?

more in bacterial infection than in viral infections

A series of serum proteins that are normally present and whose function is mediation of inflammation refers to

Complement

How many complement proteins are there? 9Complements are activated by antibodies

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When are the complement proteins activated by antibodies?

in an event called classical complement cascade

Several additional proteins are involved in the alternate pathwayThe alternate pathway is triggered by microorganismsThe major functions of complement are opsinization, chemotaxis, and lysis of cellsWhich protein is able to recognize foreign carbohydrates such as mannose which are found on bacteria, yeast, viruses, and parasites?

Mannose-binding protein (MBP)

How does MBP acts? MBP acts as an opsoninWhere can MBP found? MBP is widely distributed on mucosal surfaces

throughout the bodyWhat happens when MBP binds to the sugar? It activates the complement cascade and helps

to promote phagocytosisLack of MBP is associated with recurrent yeast infectionsA general Plasma inhibitor of proteases released from leukocytes, especially elastase, which is an enzyme that degrades elastin and collagen is called

Alpha-1 antitrypsin (AAT)

Because of its activity in chronic pulmonary disease, what is damaged?

Lung tissue

During an inflammatory response, what does AAT do?

It counteracts the effects of neutrophil invasion

AAT also regulates what? Expression of cytokines such as TNF-a, IL-b, and IL-6.

AAT deficiency can result in premature emphysema in smokers since uninhibited proteases remain in the lower respiratory tract, leading to destruction of cells in the lungs

AAT can also react with any serine protease, such as those generated by the complement cascade

Once bound to AAT, what happens to the protease?

the protease is completely inactivated

Haptoglobin’s job it to bind to what that is released when RBCs are lysed i

free hemoglobin

Once haptoglobin is bound, the complex is ingested rapidly by

Kupffer cells in the liver

Why are the Kupffer cells ingest the complex? Once bound, the complex is ingested rapidly by Kupffer cells in the liver so the kidneys are not damaged by trying to filter out that large protein

What do the Kupfer cells prevent? the loss of ironWhere is the complex sent? it can be sent to the bone marrow to be recycledHaptoglobin also protects against oxidative damage that the free hemoglobin

would causeThe rise of haptoglobin in the plasma is due to the

liver making too much

What does the rise of haptoglobin indicates? inflammation, stress, or tissue necrosis

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Early on in the inflammatory response, haptoglobin levels may drop because of

intravascular hemolysis; consequently masking the protein’s behaviour as an acute phase reactant

What levels must be evaluated along with the other acute phase reactants?

Plasma levels

Which one is the most abundant of the coagulation factors in plasma?

Fibrinogen

What does fibrinogen do? it forms the fibrin blood clotWhy is the formation of fibrin blood clot important?

A clot stops bleeding and also creates a barrier that helps prevent the spread of microorganisms further into the body

Fibrinogen also serves to promote aggregation of RBCsIncreased levels of the fibrinogen contribute to an increased risk for developing coronary artery

disease, especially in womenThe main copper-transporting protein in human plasma is

Ceruloplasmin

How is Ceruloplasmin oxidizes iron? from Fe2+ to Fe3+, which releases iron from ferritin

Fe3+ releases iron from ferritin, so it can bind to what?

transferrin

What happen to RBC’s that are old? their cell membranes become irregular and they become trapped in the reticular fibers in the spleen

After the RBC’s are trapped, what happen to them?

A macrophage engulfs it, and breaks down the hemoglobin

Hemoglobin is made from heme (a porphyrrin ring with iron in the center), and globin chains

These three segments of hemoglobin are detached from each other and liberatedThe globin chains (proteins) are broken down into

amino acids (the building blocks of proteins)

Amino acids are used for synthesis of any other proteins wherever they are needed

In the hemoglobin what are the globins? The alpha and beta chainsThe heme units are the the porphyrin ringsWhat is essential to nearly all cells but also is quite toxic?

Iron

Iron is essential for its role in oxidation-reduction reactions needed for metabolism

Where is iron’s toxicity comes from? from its propensity to form oxygen radicals that damage cells.

What happen when hemoglobin is broken down?

the iron (Fe+2) is released into plasma (ceruloplasmin is needed for that).

Which protein binds to iron? apoferrinAfter apoferrin binds to the iron, the apoferrin is called

transferrin

What does transferring do? takes the iron into cells that can use or store it

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The iron is stored in most body cells as ferritin (Fe+3) or as hemosiderin in white blood cells.

A depletion of ceruloplasmin is found in what disease?

Wilson’s disease

Wilson’s disease, which is characterized by massive increase of copper in the tissuesCopper accumulates where in the body? in the brain, cornea, kidneys, and bonesNormally, the circulating copper is found where?

It is absorbed by the liver and combined with ceruloplasmin and returned to the plasma

Cellular defense mechanisms include which 6 main types of WBCs?

Basophils (in blood vessels) and Mast Cells (in tissues)EosinophilsNeutrophilsDendritic CellsMonocytesNatural Killer Cells

About how many percent of all WBCs are basophils?

Less than 1%

How big are the basophils when comparing them to the other granulocytes?

They are the smallest of the granulocytes

The granules of the basophils contain histamine, heparin, and eosinophilic chemotactic factor-A

What are histamine, heparin, and eosinophilic chemotactic factor-A do?

induce immediate hypersensitivity reactions

Histamine causes what? vasodilation of the blood vesselsVasodilation of the blood vessels allows white blood cells to migrate to the tissues faster,

but also allows the plasma to leak out, which causes stuffiness and discomfort

What is Heparin? an anticoagulantWhich immunoglobin is formed in allergic reactions?

IgE

What is the role of IgE? IgE binds to basophil cell membranesWhat happens when IgE binds to basophil cell membranes?

causing the granules to release when they contact an antigen

What is a Mast Cell? A mast cell is similar to a basophil, but exists in the tissues

What is the difference between the mast cells and basophils?

The mast cells are larger and have more granules than basophils

Mast cells live how long comparing to basophils?

They live 9-18 months, whereas basophils only live a few days.

The enzyme of the Mast cells’ granules contain acid phosphatase, alkaline phosphatase, and protease

What is the function of mast cells? It functions the same as a basophil, by playing a role in hypersensitivity reactions by binding IgE

About how many percent of all WBCs are eosinophils?

1-3%

When is the number of eosinophils increased? during an allergic reaction or in response to a

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parasitic infectionThe eosinophil’s granules contain acid phosphataseThe eosinophil-specific granules contain several different proteins including peroxidase

and neurotoxinWhat are the eosinophils capable of? They are capable of phagocytosisHow efficient the eosinophils are? not efficient because they lack digestive

enzymesThe most important role of the eosinophils is neutralizing basophil and mast cell products and

killing certain parasitesAnother name for Neutrophils are also called? Polymorphonuclear Neutrophils (PMN’s)Why are neutrophils sometime called “segs”? Because of their segmented nucleusHow many granules does a neutrophils contain? 3 types of granules

-Primary granules-Secondary granules-Tertiary granules

What color is primary granules contain? BlueWhat defensive properties does primary granules contain?

Antibacterial proteins

What does secondary granules have? -collagenase, lactoferrin, lysozyme, NADPH, and protein found in cell membranes.

What does tertiary granules contain? Gelatinase and plasminogen activatorAcid hydrolases are called what, which are found in separate compartments?

Lysosomes

About what percentage of neutrophils are found in the blood vessels?

About 50%

Neutrophil circulate in the blood for how long? About 6-10 hoursWhen WBC enter blood vessel tissue by a process called what?

Diapedesis

What the name of the receptor that make neutrophils become stick y like Velcro against the inside wall of the blood vessel?

Selectins

Diapedesis occurs when neutrophil sense a what?

Cytokine

When neutrophils move toward or away from a chemical is called what?

Chemotaxis

What the chemical messengers that cause cells to migrate in a particular direction?

Chemotaxins

Some of the factor that effect chemotactic for neurtophils included?

-complement components-proteins from coagulation-product of virus and bacteria-platlet activating factor-secretion from mask cells

What the life span of a neutrophil once in the tissue?

5 days

Named because they care covered with long membranous extensions that make them

Dendritic cells

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resemble nerve cell?What the main function of dentritic cells? Phagocytose antigen and present it to helper T

LymphocytesDendritic cells are classified according to their tissue location, true or false?

True

Dendritic cells found on the skin and mucous membranes are called what?

Langerhans cells

Dendritic cells found in the heart, lungs, liver, kidney, GI tracts are called what?

Interstitial dendritic cells

In the secondary lymphoid tissue and thymus they are also called what?

Interdigitating dentrici cells

After dendritic cells capture an antigen by phagocytosis or endocytosis, where do they migrate?

To the blood and lymph organs where they present antigen to T-lymphocytes to initiate the adaptive (humoral) immune response of making antibodies

Dendritic cells are the most potent phagocytic cell in the tissue, true or false?

True

What the name for monocytes when found in the tissue

macrophages

What he larges blood cells? MonocytesWhat the shape of the monocyte? “horseshoe”shapedWhat the appearance of the monocytes? Grayish blue and has a ground glass appearance

due to presence of fine dust-like granulesOne type of monocyte contain similar property to neutrophils such as?

Peroxidase, acid phosphatase, and arylsulfatase

Other type of monocyte granules contains what? Glucuronidase, lysozyme, and lipse, but no alkaline phosphatase.

What percentage does monocyte make up of circulating WBCs?

About 5-10%

How long do monocyte stay in circulation? About 3 daysAfter circulation for 3 days where they migrate to?

To the tissue, where they are now called macrophages

Once monocytes enter the tissue, it is now called what?

Macrophage, becomes larger and lose its peroxidase

Lung macrophages are called what? Alveolar macrophagesIn the liver they are called what? Kupffer cellsIn the brain they are called what? Microglial cellsIn the connective tissue they are called what? histiocytesWhen compare to neutrophil, are monocytes faster or slower?

Slower, they are not as efficient as neutrophil in phagocytosis

When compare to neutrophil do monocytes live longer or shorter?

Longer, can live for months instead of days

What role do monocyte perform? Help initiating and regulating the immune response, microbial killing, turmoricidal activity, intracellular parasite eradication, secretion of cell mediators, and antigen

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presentation.Killing activity is enhanced when they become activated by what?

Contact with microorganism or cytokines which are release by T-lymphocytes

What cell are the only lymphocytes that participate in cellular (innate) immunity?

Natural killer cells

What can natural killer cells do? They are able to recognize self from non-self materials

What the mechanism of natural killer cells? They will pop cell membrane of microorganisDoes Natural killer cell participate in phagocytosis?

No

Additional set of mechanism on certain cells are what?

Toll-like receptors

What exactly is Toll? It is a protein originally discovered in the frut fly Drosophila, where it plays an important role in antifungal immunity in adult

Similarity of toll-like receptors are also found where?

Similar molecules are found on human leukocytes and some non-leukocyte cell types

Higher concentration of toll-like receptors occurs on what WBCs?

Monocytes, macrophages, and neutrophils

Each of toll-like receptors recognizes a different microbial product, true or false?

True

How does toll-like receptors function? Once a receptor binds to its particular substance, or ligand, phagocytosis may be stimulated, or the cell produces cytokins that enhance inflammation and eventual destruction of the microorganism.

What kind of immunity does toll-like receptors enhance?

Innate immunity

How many steps occurs in phagocytosis? 4 main stepsWhat are the 4 main steps? 1. Physical contact between the white cell

and the foreign particle2. Formation of a phagosome3. Fusion with cytoplasmic granules to

form a phagolysosome4. Digestion and release of debris to the

outsideNeutrophils and macrophages migrate by what mechanism?

Chemotaxis from chemicals such as bacterial factors, complement components, or CRP

Receptors on the phagocyte come in contact with foreign particle surface and activates what?

Enhanced by opsonins

What are opsonins? They are serum proteins that attach to the foreign substance, such as antibodies, CRP, and complement components.

How does phagocytosis work? Phagocyte has receptors that attach to the opsonin, and grab it like a handle so it can ingest the foreign object or bacterium

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How does opsonin help in phagocytosis? Opsonin may act by neutralizing the surface charge on the foreign particle, making it easier for the cells to approach one another

What is opsonization? Is the process whereby a substance binds to the foreign object to enhance phagocytosis

Opsonization are perform by opsonin serum protein, true or false?

True

What the process of phagocytosis? Once attachment occurs, the phagocytes’ cytoplasm forms pseudopods and engulfs the particle. This cause an increase in oxygen consumption.

An increase in oxygen consumption in phagocytosis is termed

Respiratory burst or oxidative burst

Once the particle is inside the phagocyte the vacuole is called what?

Phagosome

When the cytoplasmic granule fuse to the phagosome, and the entire complex is now called what?

Phagolysosomes

The granules release their contents, and digestion occurs, true or false?

True

Any undigested material is excreted by what? ExocytosisThe duration of the whole process of phagocytosis take how long?

About 20 seconds

During the respiratory burst or oxidative burst, the bacterial activates what?

The cell membrane of the phagocytic cell, and a radical known superoxide is formed

Superoxide is highly toxic but can be rapidly converted to more lethal products, true or false?

True

By adding hydrogen ions, the enzyme superoxide disumatase converts superoxide to what?

To hydrogen peroxide or the hydroxyl racial OH

Hypochlorite ions help potentiated the effect, true or false?

True

How is this accomplished? Action of the enzyme myeloperoxidase in the presence of chloride ions. Hypochlorite ions are powerful oxidizing agents.

New evidence indicates that an enzyme known as what, will depolarize the bacterial cell membrane, allowing hydrogen potassium ions to enter the vacuole?

Enzyme from Electron transport system called NAPDH

When hydrogen combines with the superoxide, what happen to the pH? Increase or decrease?

Increase pH

What does increase in pH activates? Activates protease (protein digesting enzymes) which contribute to microbe killing

The dysfunction of the NADPH oxidase system causes what disease?

Chronic granulomatous disease

What the out come of chronic granulomatous Patients suffer from recurring, severe bacterial

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disease? infectionsWhat is termed inflammation? Overall reaction of the body to injury or

invasion by an infectious agent.What immunity are involved? Both cellular and humoral mechanism are

involvedWhat are the four clinical symptoms of inflammations?

• Redness (rubor)• Swelling (tumor)• Heat (calor)• Pain (dolor)

What are some examples of major events that associated with process of inflammation?

• Increased blood supply to the infected area

• Increased capillary permeability• Migration of white blood cells, mainly

neutrophils to the injured area• Migration of macrophages to the injured

areaWhen inflammation occurs what chemical mediator are release?

Histamine

What the purpose of histamine? Released from injured mast cells which causes dilation of blood vessels and bring additional blood flow to the affected area, resulting in redness and heat

Vasodilation allows what to leaked into the tissues?

Plasma

When vasodilation causes plasma to leaked in to the tissue causes what to happen?

Produce swelling, and pain from the fluid pressing on nerves

What soluble mediators initiate and control the response?

Acute-phaase reactants

Amplification occurs through what formation? Formation of clots by the coagulation system and then the triggering of the fibrinolytic system

As the endothelial cells contract, which WBCs move out of circulation and into the tissue?

Neutrophils

Neutrophils are attracted by what substance? ChemotaxisNeutrophils are mobilized within how many minutes after the injury?

30-60 minutes

How long does neutrophil emigration last? 24-48 hoursMigratin of macrophates from surrounding tissue and from blood monocytes occurs when?

Several hours later and peaked at 16 to 48 hours

Macrophages attempt to clear the area through what process?

Phagocytosis

When the inflammation process becomes proglonged it is said to be what?

Chronic, and tissue damage and loss of function may result

What may contribute to the damage? Specific immunity with infiltration of lymphocytes

Failure to remove microorganism or injured Continued tissue damage

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tissue may results in what?What is the most widely monitored of the acute phase reactants and is the best indicator of acute inflammation?

C-reactive protein (CRP)

What are of primary importance in the lymphoid system’s immune response?

Lymphocytes

Lymphocytes represent between what percent of the circulating white blood cell?

About 20-40%

The size of small lymphocyte is typically between what in diameter?

between 7 and 10 μm

Does a lymphocyte have a nucleus? YesWhat color does the nucleus stain? Deep blueWhat does the lympocyte’s cytoplasm container?

Contains a few organelles with no specific granules, and stains a lighter blue

What is lymphocytes rise from? Hematopoietic stem cell in the bone marrowWhere is hematopoietic stem cell further differentiate in?

Primary lymphoid organs

Where is the primary lymphoid organs in human located?

Bone marrow and the thymus

The lymphocytes that go from the bone marrow to the thymus glad differentiate into what?

T-cells (T for thymus)

Those that stay in the bone marrow to differentiate are called what?

B-cell (bone marrow)

The secondary organs in the lymphoid system includes what?

Spleen, lymph nodes, appendix,tonsils, and other mucosal-associated lymphoid tissue

The main contanct with foreign antigens take place in secondary or primary organ?

Secondary organs

The spleen is part of what lymphoid system? Secondary organThe spleen serve what purpose? Serves as a filtering mechanism for antigens in

the bloodstreamWhat does the lymph nodes do? Help filter fluid from the tissueMucosal surface are equip with what? Backed with lymphoid tissue as an additional

means of contacting foreign antigens as they enter the body

The circulation of lymphatic fluid are controlled by what?

cytokines

T lymphocytes are also known as what type of cell that serve a regulatory role?

Effector cells

What the main purpose of B lymphocytes Produce antibodiesWhich lymphocytes recirculate continuously from the bloodstream to the secondary lymphoid organs and back, to increase contact with foreign antigens?

Both T and B lymphocytes

A third type of lymphocyte, with large granules, plays a role in both the innate and adaptive immune response?

NK cells (Natural Killer cell)

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T,B, and NK cell arise from what common precursor?

Common lymphoid precursor (CLP)

In the peripheral blood, what percent of all lymphocyte make up B cells?

About 10-20%

In the peripheral blood, what percent of all lymphocyte make up T cells?

About 61-89%

In the peripheral blood, what percent of all lymphocyte make up NK cells?

Up to 22%

What are the two primary lymphoid organs? Bone marrow and ThymusAll lymphocytes arise from what stem cell? Pluripotential hematopoietic stem cellWhere does pluripotential hematopoietic stem cells found in?

Yolk sac of developing embryo and are later found in the fetal liver

The bone marrow assumes this role when the infant is born, true or false?

True

What organ can be considered the largest tissue of the body?

Bone marrow

Where are bone marrow found? In the epiphyses of long bones and is also found in flat bones of the body, especially the iliac crest, the vertebral bodies, and the sternum

Which bone marrow is the source of the hematopoietic stem cells?

Red bone marrow

What can red bone marrow give rise to? Erythrocytes, granulocytes, monocytes, platelets, and lymphocytes

The bone marrow functions as what? The center for antigen-independent lymphopoiesis

T, B, and NK cells arise from what precursor? Common lymphoid precursor (CLP)Lymphocyte leave what organ and migrate to the primary lymphoid organs where they differentiate further?

Red bone marrow

Some of these cells will go to the thymus and develop into what cell?

T cells

While the other remain in the bone marrow and mature into what?

B cells

T cells develop their identity characteristic in what organ?

Thymus

Where is the thymus organ located? Sits on top of the heartThe thymus gradually atrophies at what age? After pubertyMost of the virgin T cells are produce during when?

First three years of life

The thymus are capable of producing new T cells until what age?

Fifth or sixth decade of life

Progenitors of T cells appear in the fetus as early as?

Eight weeks in utero

By the time the infant is born the differentiation of lymphocytes take place during when?

Early in fetal development

There are two different layer of the thymus Cortex (outer edge)

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called? Medulla (inner area)Mature T lymphocytes are released from what area of the thymus?

Medulla (inner area)

Once differentiation occurs, mature T lymphocytes are released from what organ?

Thymus

Once differentiation occurs, mature B lymphocytes are released from what organ?

Bone marrow

After differentiation is complete where do lymphocytes migrate to?

Secondary lymphoid organs and become part of the the recirculating pool

Secondary lymphoid organs consist of what tissue?

Spleen,lymph nodes, tonsils, appendix, peyer’s patches in the intestines, and other mucosal-associated lymphoid tissue

The lymphocytes travel through the tissue and return to the bloodstream by what body part?

Thoracic duct

Each lymphocytes spend most of its life in what kind of tissue?

Solid tissue

Lymphocytes go from one secondary organ to another via what route?

Circulation

Recirculation increase the likelihood of a lymphocyte to come in contact with what?

Specific antigen

Lymphopoiesis occurs in what tissue? Secondary tissueThe reproduction of lymphocytes is termed what?

Lymphopoiesis

Most naïve or resting lymphocytes die with in how many days?

Within a few days

Within a few days most lymphocyte will die if they are not activated by the presence of what?

Foreign antigen

It is this second process that gives rise to the long-lived?

Memory cells

What is the largest secondary lymphoid organ? SpleenWhere is the spleen located? Upper left quadrant of the abdomen just below

the diaphragm and surround by a connective tissue capsule

What the purpose of the spleen? Act like a sponge to help remove old and damaged cells and foreign antigens from the blood

The spllen has two type of tissue known as what?

Red pulp and white pulp

What percentage does the red pulp make up? More than one-half of the spleenWhat is the function of red pulp? Function to destroy old red blood cellsBlood flow into the red pulp via what? ArteriolesBlood flow from the arterioles into the red pulp but exits through what vein?

Splenic vein

What percentage does the white pulp make up? About 20% of the spleenThe sheath within the white pulp contain what cells?

T cells

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Attached to this sheath are primary follicles, which also contain what cell that are not yet stimulated by antigen?

B cells

Surrouding the PALS (periarteriolar lymphoid sheath) containing what cells?

Dendritic cells that trap antigen

Lymphocytes enter and leave the spleen by mean of many what?

Capillary branches that connect to the arterioles

Each day blood volume passes through the spleen approximately how many times?

Approximately 4 times

At the same time allow what WBCs to constantly survey for infectious agents and other foreign matter?

Lymphocytes and macrophages

The white pulp composes of approximately what percentage of the total weight of the spleen?

20%

White pulp contains what kind of tissue? Lymphoid tissueWhere are lymph nodes located? Along lymphatic ductsWhat is the purpose of lymph nodes? Serve as central collecting points for lymph

fluid from adjacent tissueLymph fluid arises from what? Passage of fluids and low-molecular-weight

solutes out of the blood vessel walls and into the interstitial spaces between cells

Some of the interstitial fluid returns to the bloodstream via what?

Venules

Lymph nodes are especially numerous near what body part?

Joints and where the arm and legs join the body

Filtration is a main function of what tissue? Lymph nodesThe lymph nodes contains what, which are lined with macrophages?

Sinuses

The lymph node is organized into how many parts?

Outer cortexParacortexMedulla

The lymph fluid flows slowly through spaces called what?

Sinuses

Sinuses are line with what? MacrophagesMacrophages allow what process to take place? PhagocytosisForeign antigens enter the lymph nodes through what vessels?

Afferent lymphatic vessel

Numerous lymphocytes also enter the nodes from what?

Bloodstream by mean of specialized venules called high endothelial venules

The outermost layer of the lymph node is called what ?

The cortex

The cortex of the lymph nodes contains what? Macrophages and aggregations of B cells in primary follicles

Specialized cells called what are also located in the primary follicles?

Follicular dendritic cells

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Follicular dendritic cells are found only in what?

Lymphoid follicles and have long cytoplasmic processes that radiate out like tenticles

Follicular dendritic cells exhibit large number of what?

Receptors for antibody and complement and help to capture antigen to present it to T cells and B cells

The secondary follicles consist of what? Antigen-stimulated proliferating B cellsThe interior of a secondary follicle is known as what?

Germinal center

What so important about germinal center? It is where blast transformation of B cells take place

What does plasma cell secrete? Secrete antibody and memory cellsB-cell memory is a primary function of? Lymph nodesWhere does T lymphocytes mainly localized? ParacortexParacortex is located where? Region between the follicles and the medullaThe medulla is more or less dense? Less denseMedulla contains what cells? T cells in addition to B cells, macrophages, and

numerous plasma cellsParticulate antigens are removed as the fluid travel across what?

Lymph node from cortex to medulla

The transit time through a lymph node is about how many hours?

18 hours

Fluid and lymphocytes exit by way of what? Efferent lymph vesselsLymph nodes eventually connect with the thoracic duct and the venous system to recirculate what?

Between lymph nodes and blood

Additional areas of lymphoid tissues includes? MALT, tonsils, appendix, and cutaneous-associated lymphoid tissue

MALT is found where? In the gastrointestinal, respirator, and urogenital tracts

What does Peyer’s patches represent? Represent a specialized type of MALT and are located at the lower ileum of the intestinal tract

Another area of lymphoid tissue found in the mucus membrane lining of the oral and pharyngeal cavities

tonsils

Additional location of lymphoid tissue is the what?

Appendix

All of these secondary organ function as what? Potential sites for contact with foreign antigen, and they increase the probability of an immune response.

The cutaneous-associated lymphoid tissue with the epidermis contains what?

Intraepidermal lymphocytes, where most of these are T cells

Within each of these secondary organs, which cells are segregated and perform specialized functions?

T and B cells

B cells differentiate into what? Plasma cells and memory cellsPlasma cell and memory cells are responsible Humoral immunity or antibody formation

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for what immunity?T cells play a role in what immunity? Cell-mediated immunity and produce sensitized

lymphocytes that secrete cytokinesB cells are derived from what precursor? Common lymphoid precursor (CLP)Common lymphoid precursor differentiate into what?

B cell progenitor cell

Early lymphocyte progenitors can becomes what?

T-cell, B-cell NK cells, or dendritic cells

What are some example of differentiation of B cell?

• Pro- B cells• Pre-B cells• Immature B cells• Mature B cells• Activated B cells• Plasma cells• Memory cells

The earliest B-cell precursor can be recognized by the presence of a surface molecule called?

CD45R

What so important about antigen-independent phase?

Process that prepares them for their role in antibody production and restricts the types of antigen to which the cell can respond.

How does influence of growth factors and cytokines effect the differentiation of B cells?

This causes rearrangement of genes to occur and codes for the heavy and light chains of an antibody molecule.

After the rearrangement of genes occurs what is the outcome?

B lymphocyte programmed to produce a unique antibody molecule, consisting of two identical light chains and two identical heavy chains.

When B lymphocytes produce two identical light chains and two identical heavy chains, what is this process called?

Pro-B cell

What are some example of markers that exist on surface of pro-B cells?

CD19, CD45R, CD43, CD24, and c-Kit

In order for pro-B cells to differentiate into pre-B cell successfully what must occur?

Successful rearrangement of heavy-chains genes.

What cell interact with pro-B cells to secrete cytokines, hormones, chemokines, and adhesion molecules?

Stromal cells

What does the pre-B stage begins? When synthesis of the heavy chain part of the antibody molecule occurs

After pre-B cells is complete which marker surface marker does it lose?

CD43 marker as well as c-Kit and TdT

Where does Mu chains accumulate? In the cytoplasmWhich combination of chain forms the pre-B cell receptors?

Combination of two heavy chains and two surrogate light chains plus two very short (Ig-α and Ig-β)

The pre-B cell receptor adheres to what part of Bone marrow stromal cell membranes and

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the body? transmits a signal to prevent rearrangement of any heavy-chains genes

Which cell only express heavy chains in association with surrogate light chain?

Pre-B cells

The next stage after pre-B cells is known as what?

Immature B cell

Immature B cells have what molecules on the cell surface?

IgM molecules

Its specificity is determine by what? Variable regions, which occur on both the light and heavy chains of the antibody molecules

What other surface protein appears on the immature B cell?

CD21, CD40, and MHC class II molecules

The receptor that help breakdown product of the complement component C3, and C3d?

CD21

Antigen coated with complement fragments during the immune response help trigger what?

Enhances the likelihood of contact between B cells and antigen

CD40 and MHC class II are important for which interaction?

B cells with T cells

Many B cells are deleted form the marrow by the process of programmed cell death, termed?

Apoptosis

Which organs doe immature B cells leave and proceed to?

Leave bone marrow and proceed to seed the spleen and other secondary lymphoid organs

In the spleen, what does immature B cells develop into?

Mature B- cells

Mature B –cells in the spleen is also called what?

Marginal zone B cells

B cells remain in the spleen to do what? Respond quickly to any bloodborne pathogens they may come in contact with

Other immature B cells differentiate into what and where are they found?

Become follicular B cells, which are found in the lymph nodes and other secondary organs

Besides IgM antibody, which class of antibody are exhibit?

All mature B cells exhibit IgD on the surface

How does IgD affect the life span of mature B cells in the periphery

Prolong it

Unless contact with antigen occurs, the life span of a mature B cell is typically how many days?

Few days

What occurs when B cell is stimulated by antigen?

It undergoes transformation to a blast stage, which eventually forms memory cells and antibody-secreting plasma cells

The transformation process is known as what? Antigen-dependent phase of B cell developmentWhat the half-life of B cells? More than 6 weeksWhere does antigen-dependent activation of B cells take place in?

The primary follicles of peripheral lymphoid tissue

Activated B cells exhibit identify markers including?

CD25, which is found on both activated T and B cells and acts as a receptor for Interleukin 2.

What is Interleukin- 2? A growth factor produced by T cells

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When B cells are activated in this manner, they transform into what?

Blast cells that will give rise to both plasma cells and so-called memory cells

What are the size of plasma cells? 10-20umDoes a plasma cell have abundant cytoplasmic immunoglobulin or abundant surface immunoglobulin

Abundant cytoplasmic immunoglobulin

Where are plasma cells located? In the germinal centers of peripheral lymphoid organs

Do plasma cells divide? NoPlasma cells can differentiate into what type of cells?

Memory B cells

Where are memory B cells located? Germinal centersHow long due memory cells remain activated? Months or yearsWhat percentage of circulating lymphocytes are T cells?

60-80%

What are lymphocyte precursors called? ThymocytesWhere do thymocytes enter and migrate? They enter the thymus and migrate to the cortexWhat is T cell differentiation driven by? ChemokinesWhat are the early surface markers of T cells? CD44 and CD25Are distinct surface markers created during specific stages of development

Yes

How long does T cell differentiation take? 3 weeksWhat are the thymic stromal cells? Epithelial cells, macrophages, fibroblasts and

dendritic cellsWhat percentage of the cortical cells die intrathymically before maturing completely?

97%

Early thymocytes lack which CD markers? CD4 and CD8Double negative thymocytes proliferate under the influence of which IL?

IL-7

How many chains does CD3 have? 8The alpha and beta chains have variable regions. What does that mean?

It means that those regions recognize specific antigens

When a functional beta chain is seen on the cell surface, what happens?

A signal is sent to suppress further beta chain gene rearrangements

Signaling by the beta chain triggers what response in the thymocyte?

Allows thymocyte to become CD4 and CD8 positive

Do thymocytesexpress gamma and delta chains? YesThymocytes with gamma and delta chains are + or – for CD4 and CD8?

Negative

Where are negative CD4 and negative CD8 cells located?

Intestinal epithelium and pulmonary epithelium

Cells that are negative for CD4 and negative for CD8 may behave like what other type of cell?

Natural Killer cell

When cells express both CD4 and CD8 antigens, what are the cells called?

Double positive cells

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Thymocytes that are unable to recognize self antigens die where?

In the thymus

Approximately how many double positive thymocytes survive T cell differentiation?

1-3%

Thymocytes that express both CD4 and CD8 antigens are called what?

Double positive

True/False: Survivors of selection exhibit only 1 type of marker, either CD4 or CD8.

True

CD4+ cells are also known by what name? T-helper or inducer cellsCD8+ cells are also known by what name? T-cytotoxic cellsWhat MHC class do CD8+ cells recognize? MHC class IWhat lymphoid organ are mature T cells released from?

Thymus

In peripheral organs, how long can resting T cells live?

Several years

What do TH1 cells produce? IFN-B and INF-YWhich interleukins do the Th2 cells produce? IL-4, IL05, IL-10, and IL-13What is the main role of the TH 2 cell? To help B cells produce antibodiesWhich antigens do T-regs possess? CD4 and CD25What is the main function of T regs? To suppress the immune response to self-

antigensHow do T regs suppress the immune response? They produce interleukins such as IL-10 and

transforming growth factor BWhat are the 3 types of T cells? Helper T cells, Natural killer cells, and

suppressor T cellsWhat CD markers do NK cells have? CD8What CD markers do helper T cells have? CD4Single positive T cells spend how many days in the thymic medulla?

12 days

What do T regulatory cells prevent? They prevent autoimmune reactions with any surviving T cells that can react with self antigens

After leaving the thymus, where do T cells migrate?

Secondary lymphoid organ

Where must antigens be transported for activation?

T cell zones of the secondary lymphoid tissue

T lymphocytes transform into what cells when antigen recognition occurs?

Large activated cells

Activated T lymphocytes express receptors for what IL?

IL-2

What do T lymphoblasts differentiate into? Functionally active small lymphocytesDo memory T cells express a broader or limited array of cytokines?

Broader

All activities of T cells make up what? Cell mediated immunityDo natural killer cells express the markers of T No/Neither

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or B cells?What percentage of the circulating lymphoid pool do natural killer cells make up?

5-10%

What is a unique ability of the natural killer cell?

To kill target cells without prior exposure to them

True/False: Natural killer cells lack specificity in their response?

True

What cell line do NK cells arise from? Common lymphocyte precursorNK cells in the bone marrow respond to which IL to become NK cells?

IL-15

NK cells present in the thymus become what cell?

T cells

What are the 2 CD markers present on NK cells?

CD 16 and CD 56

NK cells high in CD56 and with little CD16 have what function?

Produce cytokines to support antibody production

NK cells high in CD16 but low in CD56 provide what function?

Produce cytokines to support cytotoxic activity

Name the 3 cytokines that stimulate NK cells. Il-12, interferon gamma, and interferon betaHealthy self cells have which MHC class proteins on their membrane?

MHC I

What substances do NK cells release to kill cells?

Perforins and granzymes

What is the function of granzymes? To lyse the cellWhat laboratory method is used to identify T and B lymphocytes?

Flow cytometry

What are the 5 CD markers recognized on T cells?

CD2, 3, 4, 7, and 8

What are the 3 CD markers recognized on B cells?

CD19, 20, and 22

What is an antigen? A substance that reacts with an antibody or sensitized T cell, but may not invoke an immune response

What 3 factors cause a lack of immune response?

Nature of the immunogen, genetic coding of MHC molecules, immunogen processing and presentation

Name the 5 factors that influence the nature of the immune response.

Age, overall health, dose, route of transmission, and genetic capacity

What 3 populations have decreased immune responses?

Older people, newborns, and people in poor health

True/False: The larger the dose of an immunogen one is exposed = greater the immune response

True

What happens if a person receives large doses of an immunogen?

T and B cell tolerance

Does the amount of immunogen needed to Yes

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generate an immune response differ with route of inoculation?Name the 4 routes for an immunogen IV, intradermal, subcutaneous, and oralDoes genetic predisposition play a role in individual’s response to a particular immunogen?

Yes

Name the 4 characteristics that influence the ability of an immunogen to stimulate a host

Macromolecular size, chemical composition and molecular complexity, foreignness, ability to be processed and presented with MHC molecules

What is the minimum molecular weight of an immunogen to be recognized by the immune system?

At least 10,000 daltons

The _______ the molecular weight, the more potent the molecule is an immunogen

Greater

What are the 2 best immunogens? Proteins and polysaccharidesWhat are the proteins composed of? Amino acidsIf a string of amino acids are in a helix, is that primary, secondary, or tertiary structure?

Secondary

What do proteins contain that stimulate T cells? EpitopesAre synthetic polymers immunogenic? NoSince synthetic polymers lack immunogenicity, what are they used to make?

Heart valves, elbow replacements and other medical appliances

Why are carbohydrates less immunogenic than proteins?

The units of sugars are more limited than the number of amino acids in proteins

As immunogens, carbohydrates occur most often in what form?

Glycolipids and glycoproteins

Are the A and B blood antigens glycolipids or glycoproteins?

Glycolipids

Are the Rh antigens glycolipids or glycoproteins?

Glycoproteins

Substances recognized by the immune system as non-self are immunogenic or non-immunogenic?

Immunogenic

What happens to lymphocytes that are capable of reacting with self antigens?

They are eliminated

What is a better immunogen, a plant or animal protein?

Plant protein

True/False: Pure nucleic acids and lipids are immunogenic by themselves

False

Is foreignness a characteristic that all immunogens share?

Yes

What is antigen processing? Enzymatic digestion to create small peptides that are complexed to MHC molecules to present to responsive lymphocytes

For a substance to elicit an immune response, Yes

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does it have to undergo antigen processing?True/False: If an antigen cannot be joined with an MHC molecule, it would be a poor immunogen

True

What is the determinant site? Part of the immunogen that is actually recognized in the immune response

What cells recognize epitopes? T or B lymphocytesTrue/False: Large molecules have few epitopes FalseAre epitopes sequential in nature? YesWhat is the molecular weight of an immunogen?

At least 10,000 Daltons

What portion of the immunogen is recognized in the immune response?

Determinate site or epitope

What cells recognize epitopes? B or T cellsWhat are the shapes of epitopes? Linear and conformationalThe folding of 1 chain or multiple chains bringing certain AAs so they ca be recognize together is which epitope?

Conformational

True/False: Epitopes recognized by B cells may differ from those recognized by T cells

True

Surface antibodies on B cells react with what epitopes?

Both linear and conformational

What will trigger B cell activation? Anything that will cross-link to immunoglobulin

If an immunogen is a protein, B cells will recognize which structure?

The primary, secondary, tertiary, or quaternary structure

In polysaccharides, do the branch points contribute to recognition?

Yes

Are T cells able to recognize an epitope without MHC proteins on the surface?

No

What must an antigen presenting call do to process an immunogen?

It must degrade the immunogen

Are T cell epitopes linear or conformational? LinearIf some substances are too small for recognition, what can they do?

Bind to larger molecules to stimulate a response

What are haptens? Nonimmunogenic materials that, when combined with a carrier, create new antigenic determinants

Can a hapten react with antibody when the hapten is not complexed to a carrier molecule?

Yes, when antibody production is initiated

What reaction can occur when haptens cross-link with more than 1 antibody molecule?

Precipitation or agglutination reactions

What hapten does poison ivy contain? CatecholWhat does poison ivy cause on the skin? Contact dermatitisTrue/False: Therapeutic drugs and hormones True

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can function as haptensHow are antigens categorized? Based on relationship to hostWhat are autoantigens? Antigens that belong to the hostDo autoantigens evoke immune responses under normal circumstances?

No

What are alloantigens? Antigens from other members of the host’s species

What are heteroantigens? Antigens from other species, such as other animals, plants, or microorganisms

What are heterophile antigens? Heteroantigens that exist in unrelated plants or animals that are either identical to or closely related in structure so that antibody will cross-react with antigen of the other

What is an adjuvant? A substance administered with an immunogen that increases the immune response

How does an adjuvant function? It acts by producing a local inflammatory response that attracts a large number of immune system cells to the injection site

What is the only adjuvant approved for clinical use in the US?

Aluminum salts

True/False: The hepatitis B vaccine uses an adjuvant

True

What antigens determine organ histocompatibility?

MCH molecules

Where are MHC molecules found? In all nucleated cellsWhat is the main function of the MHC molecules?

To bring antigen to the cell surface for recognition by T cells

Why are MHC molecules clinically relevant? They are involved in transfusion reactions, graft rejection, and autoimmune diseases

Genes that control expression of molecules are known as?

Major histocompatibility complex

True/False: The MHC system is polymorphic TrueOn what chromosome is the coding for the MHC molecules located?

Chromosome 6

How many classes of the MHC molecule are there?

3

How many locations are class I molecules coded for?

3

Where are class II genes situated? In the D regionWhat do class III genes code for? Complement proteins and cytokinesWhat are class I and II gene products involved in?

Antigen recognition

True/False: Class III proteins are secreted proteins expressed on cell surfaces

False

How many copies of chromosome 6 does a person inherit?

2 copies

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True/False: MHC genes are codominant TrueWhat is a haplotype? MHC genes that are closely linked and inherited

together as a packageWhat are in each haplotype? A, B, C, DR, DP, DQPolymorphism of MHC has implications in what?

Organ donation and paternity testing

True/False: Class I MHC molecules are expressed on all nucleated cells

True

What cells contain the most class I MHC molecules?

Lymphocytes

In what type of organ transplants is HLA testing not completed?

Liver transplants

True/False: HLA-C antigens have the lowest expression of HLA antigens

True

What cells have class II MHC molecules? B lymphocytes, monocytes, macrophages, and dendritic cells

What are the 3 major class II molecules? DP, DQ, and DRWhich class II molecule is expressed at the highest level?

DR

What are the 3 other class II genes? DM, DN, and DOProducts of the nonclassical class II genes do what?

Play a regulatory role in antigen processing

What is the main role of class I and class II MHC molecules?

Bind peptides within cells and transport them to the plasma membrane, where T cells can recognize them in the phenomenon known as antigen processing

True/False: T cells can respond to antigens without being combined with MHC molecules

False

What molecules do class I molecules present? PeptidesTrue/False: Class I molecules act as watchdogs for viral antigens

True

What cells do class II molecules present? They present antigens to CD 4 cellsWhen do class II molecules stimulate CD4 cells?

In bacterial infections

Where are class I and class II molecules synthesized?

Rough endoplasmic reticulum

Where do class I molecules bind peptides? In the rough endoplasmic reticulumPeptides that associate with class I molecules are how many amino acids in length?

8-10 amino acids

What are TAP 1 and TAP 2 proteins responsible for?

Responsible for the ATP- dependent transport from the cytoplasm to the lumen of the endoplasmic reticulum

What chain must bind the peptide, MHC-1 peptide complex to transport to the cell surface?

Alpha chain

How do class I molecules determine which antigens an individual will respond?

Binding affinities

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Class I molecules complexed to antigens allow CD 8 positive T cells to continuously do what?

Check cell surfaces for the presence of non-self antigens

Before class II molecules can bind peptides, where must they be transported?

To the endosomal compartment

Which cells are the most potent activators of T cells?

Dendritic cells

What helps to unfold molecules and uncover functional sites?

Antigen processing

What enzyme degrades an invariant chain? ProteaseWhen the invariant chain is degraded, what fragment is left?

Class II invariant chain peptide

What molecule helps to remove the CLIP fragment?

HLA-DM

Do class I or class II molecules have a closed end?

Class I molecules

Does hydrogen bonding take place along the length of the peptide in class II molecules?

Yes

Can class II proteins accommodate amino acid side chains?

Yes

Once class II protein – peptide complex is stabilized where is it transported?

To the cell surface

What makes up a trimolecular complex? Class II molecules are responsible for forming the trimolecular complex that occurs between antigen, the class II molecule, and an appropriate T-cell receptor

What results when binding occurs with a T-cell receptor on a CD4-positive T cell and then T helper cell recruits and triggers a B-cell response?

Antibody formation

Why is testing for MHC antigens typically done?

Both class I and class II molecules can induce a response that leads to graft rejection

Which test method for MHC antigens is more accurate?

Molecular method

What is the major role of MHC molecules? They determine the types of peptides to which an individual can mount an immune response

What role do MHC antigens play? Development of autoimmune diseaseTrue or False: MHC molecules typically have a broad binding capacity and small biochemical differences in these proteins are responsible for differences seen in the ability to react to a specific antigen.

True

True or False: MHC molecules to a particular vaccine such as hepatitis B do not have the genetic capacity to respond.

True

What is an example of the presence of a particular MHC protein conferring additional

HLA B8 and the increased resistance to HIV infection

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protection?What is made when B cells are stimulated by antigen?

Antibodies

What are antibodies also known as? ImmunoglobulinsWhat does “globin” refer to? Globular shape of proteinWhere are immunoglobulins found? Serum portion of bloodImmunoglobulins are composed of about ____ polypeptide and about ____ carbohydrate.

85%; 10%

What are the 5 classes of immunoglobulins? IgG, IgM, IgA, IgD, IgEImmunoglobulins are considered to be the humoral branch of the ____ _____.

Immune response

What is the essential role of immunoglobulins? Antigen recognition and biological activities related to immune response

Are opsonization and complement activation roles of immunoglobulins?

Yes

(T or F) All immunoglobulin molecules share many common features.

True

What kind of unit are all immunoglobulin molecules made up of?

Four-chain polypeptide unit

What does the basic four-chain polypeptide unit consist of?

2 heavy (H) chains and 2 light (L) chains

How are the H chains and L chains held together?

Non-covalent forces and disulfide interchain bridges

When subjected to electrophoresis at 8.6, immunoglobulins appear primarily in the ___ band.

Gamma

When was the structure of antibodies first discovered?

1960’s

What was used to cleave IgG into 3 pieces of about equal size, each having a sedimentation coefficient of 3.5 Svedberg units (S) and representing a molecular weight of approximately 45,000 to 50,000 Daltons (d)?

Proteolytic enzyme papain

What separated the material into two types of fragments, on which spontaneously crystallized a 4°C?

Carboxymethyl cellulose ion exchange chromatography

What fragment had no antigen-binding ability and is known to represent the carboxy-terminal halves of two H chains that are held together by S-S bonding?

FC fragment (“fragment crystallizable)

What do antibodies consist of? Light and heavy chains that form an FC fragment, Fab fragment, and a hyervariable region

What is important in effector functions of immunoglobulin molecules, which include opsonization and complement fixation?

FC fragment

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What are the remaining 2 identical fragments called?

Fab fragments (fragment antigen-binding)

Because precipitation would not occur if Fab fragments were allowed to react with antigen, what was gu100,essed that each fragment represented?

One antigen-binding site and that 2 such fragments were present in an intact antibody molecule

What does each Fab fragment consist of? One L chain and one-half of a H chainHow is each Fab fragment held together? Disulfide bondingWhat was found to cleave IgG at the carboxy-terminal side of the interchain disulfide bonds, yielding one single fragment with molecular weight of 100,000 d and all the antigen-binding ability, known as F(ab)2?

Proteolytic enzyme pepsin

What additional fragment was similar to FC except that it disintegrated into several smaller pieces?

FC’

What is found in the urine of patients with multiple myeloma?

Bence Jones porteins

What type of chains were being secreted by malignant cells in patients with multiple myeloma?

L chains

Who discovered Bence Jones proteins in 1845? Dr. Henry Bence JonesWhen heated to 60°C, Bence Jones proteins ____ from urine, but on further heating to 80°C, they ____.

precipitated; redissolved

What were the two main types of L chains in Bence Jones proteins?

Kappa (κ) and lambda (λ)

How much amino acid is contained in each L chain?

Between 200-220 amino acids

What was the region called from positions number 111 and one where each type had essentially the same sequence?

Constant region

What was the amino-terminal end called? Variable regionWhat is the difference between the κ and λ chains?

Amino acid substitutions at a few locations along the chain

(T or F) Both κ and λ L chains are found in all 5 classes of immunoglobulins, but only one type is present in a given molecule.

True

What demonstrated the presence of domains similar to those in the L chains- that is, variable and constant regions?

H chain sequencing

What is the first approximately 110 amino acids at the amino-terminal end?

Variable domain

What are the remaining amino acids typically divided up into?

3 or more constant regions with similar sequences (CH1. CH2, CH3)

Constant regions of the _____ are unique to H chain

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each class and give each immunoglobulin type its name.What chain does IgG have? γH chainWhat chain does IgM have? μ chainWhat chain does IgA have? α chainWhat chain does IgD have? δ chainWhat chain does IgE have? ε chainWhat is an unique amino acid sequence that is common to all immunoglobulin molecules of a given class in a given species?

Isotype

What are minor variations of amino acid sequences that are present in some individuals but not others?

Allotypes

What do the variable portions of each chain that are unique to a specific antibody molecule constitute?

Idiotype

What is essential to the formation of the antigen-binding site?

The aminoterminal ends of both L and H chains contain these variable regions

What is the segment of H chain located between the CH1 and CH2 regions?

Hinge region

What does the hinge region have a high content of?

Proline and hydrophobic residues

What does the high proline content allow for? FlexibilityWhat does the ability to bend in the hinge region allow for?

Two antigen-binding sites to operate independently

What is an example of an effector function? Initiation of the complement cascadeWhat chains have a hinge region? Gamma, delta, alphaWhat chains do not have a hinge region? Mu and epsilon(T or F) The CH2 domains of the latter two chains are paired in such a way as to confer flexibility to the Fab arms.

True

What do all types of immunoglobulins contain? Four polypeptide chains and a carbohydrate portion

Where is the carbohydrate portion located? Between the CH2 domains of the two H chainsWhat are the functions of the carbohydrate portion?

Increasing the solubility of Ig, providing protection against degradation, and enhancing functional activity of the FC domains.

(T or F) The basic four-chain structure of all immunoglobulin molecules does not exist as a straight “Y” shape.

True

Is the basic four-chain structure of the Ig folded into compact globular subunits?

Yes

What is the basic four-chain structure of Ig based on?

The formation of balloon-shaped loops at each of the domains

What type of bonds stabilize the globular regions?

Intrachain disulfide bonds

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Within each of the regions or domains, what is formed when the polypeptide chain is folded back and forth on itself?

Beta-pleated sheet

What cylindrical structure is produced when the folded domains of the H chains line up with those of the L chains?

Immunoglobulin fold or barrel

What is captured within the barrel by binding to a small number of amino acids at strategic locations on each chain (hypervariable regions)?

Antigen

What is the predominant immunoglobulin in humans?

IgG

What is the percentage of total IgG in humans? 75-80%(T or F) IgG has the longest half-life of any Ig class?

True

How long is the IgG half-life? 23-25 daysWhat are the four major subclasses of IgG? IgG1 (67%), IgG2 (22%), IgG3 (7%), IgG4

(40%)How do the four major subclasses of IgG differ? In the number and position of the disulfide

bridges between the chainsWhich type of immunoglobulin has the largest hinge region and the largest number of interchain disulfide bonds, and is the most efficient at binding complement?

IgG3

Which type of immunoglobulins have shorter hinge segments and tend to make poor mediators of complement activation?

IgG2 and IgG4

What are the major functions of IgG? Providing immunity for the newborns because IgG can cross the placenta, fixing complement coating antigen for enhanced phagocytosis (opsonization), neutralizing toxins and viruses, and participating in agglutination and precipitation reactions

(T or F) All subclasses of IgG appear to be able to cross the placenta.

True

What is the least efficient IgG? IgG2What has FC receptors on their surfaces that are specific for the FC region of IgG?

Macrophages, monocytes, and neutrophils

What is the function of FC receptors? Enhances contact between antigen and phagocytic cells and increases the efficiency of phagocytosis

What does IgG have that allows it to enter extravascular spaces more readily than other Ig types?

High diffusion coefficient

(T or F) IgG plays a major role in neutralizing toxins and viruses.

True

IgG is better at ____ reactions than at ____. Precipitation; agglutination

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What does precipitation involve that are more easily brought together by relatively small IgG molecules?

Small soluble particles

What is defined as the clumping together of larger particles?

Agglutination

Which Ig is much more efficient at agglutination than IgG?

IgM

What is known as a macroglobulin? IgMWhat has a sedimentation rate of 19S, which represents a molecular weight of approximately 970,000d?

Macroglobulin

IgM accounts for ____% of all serum. 5-10What is the half-life og IgM? 10 days(T or F) IgM has a shorter half-life than IgG. TrueWhat can IgM exist as? Monomer or pentamerWhat is the difference between the pentamer and monomer form?

Pentamer form is found in secretions; monomer form occurs on the surface of B cells

When a pentamer forms, what holds the five monomeric units together?

J (joining) chain

What is a glycoprotein with several cysteine residues?

J chain

What do the cysteine residues serve as? Linkage points for disulfide bonds between two adjacent monomers

What is the shape of a IgM configured as a pentamer?

Starlike

How many functional binding sites are on a IgM?

10

How many functionl binding sites are used on a IgM?

5

The ____ valency of IgM antibodies contravenes the fact that they tend to have ____ affinity for antigen.

High; low

Where is IgM mainly found? In the intravascular pool and not in other body fluids or tissues

Which Ig cannot cross the placenta? IgMWhat is the primary response antibody? IgMWhat is the first Ig to appear after antigenic stimulation and the first to appear in the maturing infant?

IgM

(T or F) IgM is synthesized only as long as antigen remains present.

True

Are there memory cells for IgM? NoWhich Ig is known as the secondary response? IgGWhat is the primary response characterized by? Long lag phase

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What is the secondary response characterized by?

Shortened lag period and much more rapid increase in antibody titer

What are the functions of IgM? Complement fixation, agglutination, opsonization, and toxin neutralization

What is the most efficient of all immunoglobulins at triggering the classical complement pathway?

IgM

(T or F) IgM has multiple binding sites. TrueThe larger number of binding sites makes IgM more efficient at ____ reactions, especially with multivalent antigens.

Agglutination

What does IgM form a potent defense against? Many bacterial diseasesBecause IgM has a J chain, what can it occasionally acquire like IgA does?

Secretory component

What does the IgM’s secretory component allow for?

To traverse epithelial cells and patrol mucous membranes

What does IgM serve as? Surface receptor for antigenWhat does the presence of membrane IgM classify lymphocytes as?

Mature B cells

What percentage of all circulation immunoglobulin is IgA?

10-15%

What is the molecular weight of the H chain? Between 55,000-60,000How much amino acids does the H chain consist of?

472

What does IgA appear as? MonomerWhat is the approximate molecular weight of IgA?

160,000

What are the two subclasses of IgA? IgA1 and IgA2How do IgA1 and IgA2 differ? In content by 22 amino acidsHow many amino acids are located in the hinge region and are deleted in IgA2?

13

What makes IgA more resistant to? Some bacterial proteinases that are able to cleave IgA1

Where is IgA2 predominately found? In secretions at mucosal surfacesWhere is IgA1 mainly found? In serumIgA2 is found as a ____ along the respiratory, urogenital, and intestinal mucosa.

Dimer

What does IgA2 appear in? Milk, saliva, tears, and sweatSince mucosal surfaces are a major point of entry for pathogens, what does IgA2 serve?

To keep antigen from penetrating further into the body

What does the dimer consist of? 2 monomersHow are the 2 monomers of the dimer held together?

J chain

What is the molecular weight of the dimer? 15,000

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Where is secretory IgA synthesized? In plasma cells found mainly in mucosal-associated lymphoid tissue

What form is secretory IgA released in? DimericWhat is the molecular weight of a secretory component?

About 70,000

What is later attached to the FC region around the hinge portion of the alpha chain?

Secretory component

How many immunoglobulin-like domains, does the secretory component consist of?

Five

Where is the secretory component derived from?

Epithelial cells found in close proximity to the plasma cells

What is the molecular weight of the SC precursor?

100,000

Where is the SC precursor found? On the surface of epithelial cellsWhat does the SC precursor serve as? A specific receptor for IgAPlasma cells that secrete IgA actually home to ____ ____, where IgA ca bind as soon as it is released from the plasma cells.

Subeithelial tissue

How are epithelial cells traversed? By transcytosisWhat occurs after trancytosis? A small fragment of SC sttached to IgA is

cleaved to liberate the IgA dimer with the remaining portion of the SC

What can the secretory component act to facilitate transport of?

IgA to mucosal surfaces

What does the secretory component make the dimer more resistant to?

Enzymatic digestion by masking sites that would be susceptible to protease cleavage

What is the main function of secretory IgA? To patrol mucosal surfaces and act as a first line of defense

How does secretory IgA act as first line defense?

Neutralizes toxins produced by microorganisms and helping to prevent bacterial adherence to mucosal surfaces

What is easily trapped in mucus and then eliminated by the ciliated epithelial cells of the respiratory and intestinal tracts?

Complexes of IgA and antigen

What does IgA appear not to be capable of? Fixing complement by the classical pathwayWhat may trigger the alternate complement pathway?

Aggregation of IgA immune complexes

What possess specific receptors for serum and secretory IgA?

Neutrophils, monocytes, and macrophages

What triggers a respiratory burst and degranulation of the cell involved?

Binding to the sites of IgA

What can both forms of IgA act as? OpsoninsWhat are opsonins? Promoters of phagocytosisWhen was IgD discovered? 1965

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IgD was found in a patient with what disease? Multiple myelomaWhat is the percentage of IgD in the total serum?

Less than 0.001%

What is the molecular weight of IgD? 180,000What is the molecular weight of the H chain? 62,000What appears to have an extended hinge region consisting of 58 amino acids?

H chain

Because of the unusually long hinge region, what is IgD more susceptible to?

Proteolysis

What is the half-life of IgD? 2-3 daysWhere are most of the IgD found? On the surface of immunocompetent but

unstimulated B lymphocytesWhat is the second type of immunoglobulin to appear?

IgD

What may IgD play a role in? B-cell activationWhat makes IgD an ideal early responder to antigen?

High level of surface expression and its intrinsic flexibility

What do B lymphocytes bearing only IgM receptors appear incapable of?

IgG response

What are those with both IgM and IgD receptors capable of?

Responding to T-cell help and switching to synthesis of IgG, IgA, or IgE

(T or F) IgD may play a role in regulationg B-cell maturation and differentiation.

True

In the secreted form in the serum, why doesn’t IgD appear to serve a protection function?

It does not bind complement, it does not bind neutrophils, or macrophages, and it does not cross the placenta

Which immunoglobulin is the least abundant in the serum?

IgE

What is the percentage of IgE in the total serum?

0.0005%

What is composed of around 550 amino acids that are distributed over one variable and four constant domains?

The H chain

What cells produce IgE and are located primarily in the lungs and skin?

Plasma cells

Does IgE participate in typical immunoglobulin reactions such as complement fixation, agglutination, or opsonization?

No

Is IgE incapable of crossing the placenta? YesWhat happens to IgE shortly after synthesis? IgE attaches to basophils and tissue mast cells

by means of specific surface proteinsWhat are the specific surface proteins called? High- affinity FC RI receptorsWhere are the high-affinity FC RI receptors found?

Basophils and tissue mast cells

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Where does the IgE molecule bind at? CH3 domain on the FC regionAre the antigen-binding sites free to interact with specific antigen?

Yes

Where are mast cells mainly found? In the skin and in the lining of the respiratory and alimentary tracts

How many receptors are on each mast cell? Several hundred thousandWhat happens when two adjacent IgE molecules on a mast cell bind specific antigen?

A cascade of cellular events is initiated that results in degranulation of the mast cells with release of vasoactive amines (histamine and heparin)

What is induced when vasoactive amines are released?

Type 1 immediate hypersensitivity

What is an allergic reaction called? Type 1 immediate hypersensitivityWhat are examples of typical allergic reactions? Hay fever, asthma, vomiting and diarrhea,

hives, and life-threatening anaphylactic shockWhat immunoglobulin serves a protective role by triggering an acute inflammatory reaction that recruits neutrophils and eosinophils to the area to help destroy invading antigens that have penetrated IgA defenses?

IgE

What cells play a major role in the destruction of large antigens, such as parasitic worms, that cannot be easily phagocytized?

Eosinophils

What is the term for one of the first theories to be formulated in an attempt to explain antibody diversity in the early 1900s by Paul Ehrlich?

Side-chain theory

(T or F) Paul Ehrlich postulated that certain cells had specific surface receptors for antigen that were present before contact with antigen occurred.

True

What happened after an antigen was introduced and it would select the cell with the proper receptors?

Combination would take place and then receptors would break off and enter the circulation as antibody molecules

(T or F) Ehrlich’s side-chain theory laid the foundation for further hypotheses.

True

In the 1950s, what idea did Niels Jerne and Macfarlane Burnet independently support?

A clonal selection process for antibody formation

What is occurring when individual lymphocytes are genetically preprogrammed to produce one type of immunoglobulin and that a specific finds or selects those particular cells capable of responding to it, causing them to proliferate?

Clonal selection

Where are the surface immunoglobulins IgM and IgD found?

On immune-competent but unstimulated B lymphocytes

What would repeated contact with antigen continually increase?

A specific lymphocyte pool

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What explains the kinetics of the immune response?

Clonal selection

Who proposed a solution to the tissue of the large number of genes required by the clonal selection theory?

Dryer and Bennett

What did Dryer and Bennett suggest? The constant and variable portions of immunoglobulin chains are actually coded by separate genes

There could be a small number coding for the ____ region and a larger number coding for the ____ region.

Constant; variable

What happens within lymphocytes? Genetic rearrangementsWhat controls synthesis of a particular immunoglobulin, and through a random selection process these individual segments are joined to commit that lymphocyte to making antibody of a single specificity?

More than one gene

(T or F) B cells are genetically preprogrammed to synthesize very specific antibody.

True

What antibodies are used for diagnostic testing and for therapeutic purposes?

Monoclonal antibodies

Why is the normal response to antigen heterogeneous?

A purified antigen has multiple epitopes that stimulate a variety of B-cell clones

In 1975, what did Georges Kohler and Cesar Milstein discover?

A technique to produce antibody arising from a single B cell

In Kohler and Milstein’s technique, what is fused with an activated B cell?

A myeloma cell

What is a myeloma cell? A cancerous plasma cell(T or F) Plasma cells normally produce antibody.

True

What kind of cell line is chosen for the Kohler and Milstein’s technique?

A particular cell line that is not capable of producing antibody

What enzyme is deficient in the cell line that is not capable of producing antibody?

Hypoxanthine guanine phosphoribosyl transferase (HGPRT)

What enzyme is incapable of synthesizing nucleotides from hypoxanthine and thymidine, which are needed for DNA synthesis?

Hypoxanthine guanine phosphoribosyl transferase (HGPRT)

What cells are harvested after a mouse is immunized with a certain antigen?

Spleen cells

What cells are combined in the presence of polyethylene glycol (PEG), a surfactant?

Spleen and myeloma cells

What is produced when the PEG brings about fusion of plasma cells with myeloma cells?

Hybridoma

(T or F) In hybridoma production, only a small percentage of cells actually fuse and some of

True

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these are two meloma cells or two spleen cells.After fusion and cells are placed in culture, what is contained in the selective medium used?

Hypoxanthine, aminopterin, and thymidine (HAT)

What is the culture in the HAT medium used to separate?

Hybridoma cells by allowing them to grow selectively

What can hybridoma cells synthesize? Nucleotides in the HAT medium

Why is one pathway, which builds DNA from degradation of old nucleic acids, blocked?

The myeloma cell line employed is deficient in the required enzymes HGPRT and thymidine kinase

The other pathway, which makes DNA from new nucleotides, is blocked by what?

Presence of aminopterin in the medium

In hybridoma production, what cells normally die out?

Myeloma cells and normal B cells

What cells have the ability (acquired from the myeloma cell) to reproduce indefinitely in culture and the ability (acquired from the B cell) to synthesize nucleotides by the HGPRT and thymidine kinase pathway?

Fused hybridoma cells

What antibodies were initially used for in vitro diagnostic testing and in delivering therapeutic agents in a variety of diseases?

Monoclonal antibodies

Define cytokines in two parts. Cytokines are small soluble proteins that regulate the immune system’s innate immunity.

They are the adaptive response to infection.Cytokines are chemical messengers. several different cell types produce them.True or False?

True

Cytokines have activity modulating effects. They affect ___________ and___________ systems. They act through through activation of cell-bound receptor proteins.

Hematopoietic and immune systems

Induce means__________________. to bring about, produce, or causeto stimulate the synthesis of (a protein,especially an enzyme) by increasing gene transcription.

Cytokines are induced in response to specific stimuli.Clarify some example stimuli.Be Specific.

bacterial lipopolysaccharides (Lipid A), flagellin, and other bacterial products.

Cytokines can scale to effect: regulation of growth, differentiation gene expression many different cell types including leukocytes are effected

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Define autocrine stimulation. affecting the same cell that secreted itDefine paracrine stimulation. affecting a target cell in close proximityDo cytokines exert systemic or endocrine activities always? True or False?

False, only occasionally do they do so

Elaborate the stages of basic cytokine production by host lymphocytes

the ligation of cell adhesion moleculesthe recognition of foreign antigens

Cytokines act individually and separately. True or False?

False; they do not act alone, but in concert with many others that are induced during the process of immune activation.

What is the result of cytokine expression. Clarify.

A network is formed regulating leukocyte activity.

What is a cytokine cascade The cytokine cascade produces a spectrum of activities that lead to the rapid generation of innate and adaptive immune responses.

What often determines the outcome and the clinical course of infection?

the ability or inability to generate certain cytokine patterns

Massive overproduction plus deregulation in the immune system creates a cytokine storm. What terminal effects can be expected?

shock, multi-organ failure, or even death.

The cytokines include major families. What are some major families available for study today.

tumor necrosis factors (TNF), interferons (IFN), chemokines, transforming growth factors (TGF), and colony-stimulating factors (CSF), interleukins(IL)

An Interleukin is a _________ cytokine. unrelatedFor the cytokines to be classified as interleukins. What are the three criteria they must satisfy?

They must have had their genes cloned. They must be inducible in leukocytes. Their biological activities in inflammatory processes must be cataloged.

Interleukins are numbered… IL-1 to IL-32 IL-1 to IL-32Cytokines were originally thought to act solely on cells of the immune system. What new discovery was made about them?

They may also act on cells outside the immune system.

Pleiotropic means… Having many effects ieThe nature of cytokine activity relates to: the widespread distribution of cytokine receptors on many cell types, and the ability of cytokines to alter expression of numerous genes.

Can many different cytokines share their properties?

Yes, they activate some of the same pathways and genes.

Many cytokines share receptors. Illustrate some of the effects or activities.

Some may have overlapping effects.Some may alter the activity of many of the same genes.

Name two clinical uses of cytokines. cytokine antagonists cytokine receptor antagonists

What conditions could the two variants of rheumatoid arthritis, psoriasis, asthma, Crohn's

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cytokines be usable for? disease, transplantation, and cancer treatmentsWill there be future demands placed on the labs for cytokine assays.

Defenitely

The patterns of cytokine expression can determine…

whether the host will be able to mount an effective defense against and survive certain infections.

A patient has presented defects in the cytokines or their receptors/signal transduction circuits. What possible illnesses could be a play in the patient’s body?

Numerous immunodeficiency syndromes and leukemias are theoretically possible.

What sort of analyses are recommended for the patient above?

Genetic and Proteomics.Assess treatment modalities, effectiveness, and potential gene replacement therapies

Inflammation due to the body’s innate immune response has several criteria. Name four.

fever, swelling, pain, and cellular infiltrates into damaged tissues.

The innate immune response is___________ but occurs within hours of first contact with microorganisms .

nonspecific

What is the main function of the innate immune response?

To recruit effector cells to area.

Choose several cytokines involved in innate immune response.

interleukin-1, tumor necrosis factor-α, interleukin-6 chemokines, transforming growth factor-β, and interferons, both α and β.

IL-1 has 2 subtypes plus 1 antagonist. IL-1α, IL-1β, and IL-1RA (IL-1 receptor antagonist)

IL-1α facts Proinflammatorymonocytes and macrophagesrequires the presence of microbial pathogens, bacterial lipopolysaccharide's, or other cytokines.Intracellularcan be released after cell deathcan help attract inflammatory cells to areas where cells and tissues are being killed or damaged.

IL-1β facts is responsible for most of the systemic activityfeveractivation of phagocytesproduction of acute phase proteinsis secreted by monocytes

IL-1 facts endogenous pyrogeninduces fever(acute phase response)acts on the hypothalamus(thermostat)hypothalamus resets body temp to higher levelbacterial and viral growth is inhibited

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lymphocyte activity is increasedIL-1 facts part 2

Define diapedesis

induces the production of vascular cell-adhesion moleculeschemokines and IL-6 production are increasedAlso induces the production of colony stimulating factors in the bone marrow, thereby increasing the available number of phagocytic cells that can respond to the damaged tissues

a process,Chemokines and cell-adhesion molecules attract and assist leukocytes to enter the inflamed area.

IL-1RA facts produced by monocytes and macrophagesacts as an antagonist to IL-1blocks the IL-1 receptorlimits the availability of the receptor for IL-1turns off the response to IL-1 when no longer needed

Tumor necrosis factor-α (TNF-α) fact sheet first isolated from tumor cellsinduce lysis in tumor cellsthe most prominent member of the TNF superfamilyat least 19 different peptides that have diverse biological functions.both membrane-bound and soluble formscauses vasodilationincreased vasopermeabilitylipopolysaccharide is the main trigger from gram-negative bacteria

Tumor necrosis factor-α (TNF-α) fact sheet II secreted by activated monocytes and macrophagesactivate T cells through its ability to induce expression of MHC class II moleculesenhances antigen presentationactivates T cells

Tumor necrosis factor-α (TNF-α) fact sheet III major drawbacks

secreted at high levels, TNF can have deleterious systemic effectsseptic shock can resultlarge amounts of TNF secreted in response to gram-negative bacterial infections, causing a decrease in blood pressure, reduced tissue perfusion, and disseminated intravascular

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coagulation.uncontrolled bleeding

Where can TNF-α be found? present in rheumatoid synovial fluids and synovial membranes

TNF-α has a major role in inflammatory illnesses. Name 2.

Crohn’s disease, with rheumatoid arthritis (RA)

IL-6 fact sheet a single proteintriggered by lipopolysaccharidea pleiotropic cytokineAffects the inflammation, acute phase reactions, immunoglobulin synthesis, and the activation states of B cells and T cells.Stimulates B cells to proliferate and differentiate into plasma cells.Induces CD4+ T cells to produce greater quantities of both pro- and anti-inflammatory cytokines.Chemokines facilitate the extravasation of leukocytes into the tissues in areas of inflammation.facilitate the migration of leukocytes into the tissuesactivate integrinsAllow for the co--localization of multiple cell typesto the damaged tissueHelp to broaden the response to tissue damage.Enable the leukocytes to migrate between the endothelial cells.The gradient of concentration is important to leukocytesthat chemokines can make.abnormal receptors have some protection from the HIV virus

Where is IL-6 produced? lymphoid and nonlymphoid cells, including a variety of normal and transformed cells: T cells, B cells, monocytes and macrophages, fibroblasts, hepatocytes, keratinocytes, astrocytes, vascular endothelial cells, and various tumor cells.

Chemokines fact sheet family of cytokines that enhance motilityAre classified into four families based on the position of N-terminal cysteine residues.40 known chemokines

46


Define chemotaxis? A process that promotes migration of many types of white blood cells toward the source of the chemokine.

Chemokines regulate leukocyte activities include the response to infectious diseases, autoimmune inflammation, cancer, and the homing of lymphocytes to all the lymphoid tissues.

Identify the four chemokine groups and state the differences.

alpha, or CXC, chemokines—contains a single amino acid between the first and second cysteines.

beta, or CC, chemokines—has adjacent cysteine residues.C chemokines—lacks one of the cysteines.

CX3C—has three amino acids between the cysteines.

What are chemokines’ key roles in numerous disease processes?

Initiation, development of inflammatory processes.

Chemokine drawbacks. Chemokine receptors are utilized by the HIV virus to gain access to the cell.

Transforming growth factor beta (TGF-β) fact sheet

composed of three isoforms: TGF-β1, β2, and β3Induced growth arrest in tumor cells in early studies.Induces antiproliferative activityinhibits the activation of macrophagesanti-inflammatory factor for mature T cells.production by helper T cellsimportant factor in the establishment of oral tolerance to bacteria normally found in the mouth.autocrine regulator to limit the expansion of activated cells

When active TGF-β regulates…. cell growth differentiation apoptosis, migration, the inflammatory response

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helps down-regulate the inflammatory response when no longer needed

Type I interferons can interfere with___________. Especially IFN-α and IFN-β.

viral replication

What cells produce interferons? dendritic cellsInterferons induce…. The production of proteins and pathways that

directly interfere with viral replication and cell division.

Type I IFN can activate__________. natural killer cellsType I IFN enhances ____________. The expression of MHC class I proteins, thus

increasing the recognition and killing of virus-infected cells.

Type I IFN works against… certain malignancies and other inflammatory processes

Cytokines involved in the _____________are mainly secreted by T cells, especially T helper (Th) cells, and affect T- and B-cell function more directly than was the case with cytokines in the innate immune response.

adaptive immune response

There are three main subclasses of Th cells. Identify them.

Th1, Th2, and Treg (T regulatory cells).

What is the function of the T-cell receptor? Captures antigens and is a target of clonal expansion of CD4+ T helper cells.

Th1 cell factsheet induce high-level expression of IFN-γ.Th1 cells also secrete IL-2.IL-2

a. T-cell growth factorb. drives the growth and differentiation of

both T and B cellsc. and induces lytic activity in NK cellsd. can activate proliferation of Th2 cellse. helps to generate IgG1- and IgE-

producing cells

IL12 fact sheet produced by macrophages and B cellsmultiple effects on both T cells and natural killer (NK) cellsresponds to certain stimuli, such as mycobacteria, intracellular bacteria, and virusesincreases the cytolytic ability of natural killer (NK) cells.

IFN-γ fact sheet the principal molecule produced by Th1 cellsIt affects the RNA expression levels of more than 200 genes.

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stimulates antigen presentation by MHC I and MHC II moleculesregulates theactivation of CD4+ Th1 cells, CD8+ cytotoxic lymphocytes, NK cells, bactericidal activities, IL-12R, and IL-18R

Th2 cell factsheet primarily responsible for antibody-mediated immunityproduced by monocytes, macrophages, CD8+ T cells, and Th2 CD4+ T cellsIt inhibits antigen presentation by macrophagesstimulates CD8+ T cellsallergies, autoimmune diseases, fighting off parasites

IL-10 fact sheet anti-inflammatory and suppressive effects onTh1an antagonist to IFN-γdown-regulator of the immune response.

Tregs fact sheet CD4+ CD25+ T cellsThymus is their home.Play a key role in establishing peripheral tolerance to a wide variety of self-antigens, allergens, tumor antigens, transplant antigens, and infectious agents.

Effected by Foxp3 a transcription factor that causes Treg cells to suppress the activity of other T cells.

Responsible for inducing IL-10 and TGF-β expression in adaptive T regulatory 1 (Tr1) cells in the peripheral circulation.prevent chronic inflammation.

Name the colony stimulating factors(CSF). IL-3EPO erythropoietinG-CSF granulocyeM-CSF macrophageGM-CSF granulocyte

colony stimulating factors(CSF) fact sheet act on bone marrow cells and promote specific colony formation for the various cell lineages.

Erythropoietin (EPO) fact sheet regulates RBC production in the bone marrowprimarily produced in the kidneys

Erythropoietin can improve __________. oxygenation of the tissuesWhich one is not a symptom of endotoxic Dypsia is not a mechanism of Endotoxic Shock.

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shock?A. DICB. Multi-organ failureC. NuetropeniaD. Dypsia

D is the answer

What is the Complement immune system? • Complement is a complex series of more than 30 soluble and cell-bound proteins that interact in a very specific way to enhance host defense mechanisms against foreign cells.

• It was named by Paul Ehrlich because it complements the action of antibody in destroying microorganisms.

• While complement promotes opsonization and lysis of foreign cells and immune complexes, chronic activation can lead to inflammation and tissue damage. It is the latter that occurs in autoimmune diseases; therefore, complement activation needs to be carefully regulated in order to minimize tissue damage. In addition to the major proteins involved in activation, there are numerous proteins that act as controls or regulators of the system. The three pathways for activation of complement will be discussed along with major system controls.

Where does the compliment protein synthesis?

• Most plasma complement proteins are synthesized in the liver, with the exception of C1 components, which are mainly produced by intestinal epithelial cells, and factor D, which is made in adipose tissue.

• Other cells, such as monocytes and macrophages, are additional sources of early complement components, including C1, C2, C3, and C4.

• Most of these proteins are inactive precursors, or zymogens, which are converted to active enzymes in a very precise order (see Table 6-1).

How does the complement system get activated?

The complement system can be activated in three different ways

• The first is the classical pathway, which involves nine proteins that are triggered

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by antigen–antibody combination.• The second pathway, the alternative

pathway, is an antibody-independent means of activation of complement.

• The third pathway, the lectin pathway, is another antibody-independent means of activating complement proteins.

• Its major constituent, mannose- (or mannan-) binding lectin (MBL), adheres to mannose found mainly in the cell walls or outer coating of bacteria, viruses, yeast, and protozoa.

• Complement activation seldom involves only one pathway.

What are the roles of the complement in the immune defense system?

• The complement system plays a major part in the inflammatory response directed against foreign antigens.

• Although the end product of complement activation is lysis of the invading cell, many other important events take place along the way.

• Complement fragments act as opsonins, for which specific receptors are present on phagocytic cells, thus enhancing the metabolism and clearance of immune complexes.

• In fact, uptake of immune complexes in the spleen appears to be complement-dependent.

• Complement components are also able to increase vascular permeability, recruit monocytes and neutrophils to the area of antigen concentration, and trigger secretion of immunoregulatory molecules that amplify the immune response.

• Any deficiencies in the complement system can result in an increased susceptibility to infection or in the accumulation of immune complexes with possible autoimmune manifestations.

What is the immune classic pathway? • The classical pathway, or cascade, is the

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main antibody-directed mechanism for triggering complement activation.

• IgM, IgG1, IgG2, and IgG3 are capable of activation through the classical pathway.

• IgM is the most efficient, because it has multiple binding sites; thus, it takes only one IgM molecule attached to two adjacent antigenic determinants to initiate the cascade.

How does the IgG play a role in the classic pathway?

• Two IgG molecules must attach to antigen within 30 to 40 nm of each other before complement can bind, and it may take at least 1,000 IgG molecules to ensure that two are close enough to initiate such binding.

• Within the IgG group, IgG3 is the most effective, followed by IgG1 and then IgG2.

What are the other substances that can bind complement directly to initiate the classical cascade?

• Some epitopes, notably the Rh group, are too far apart on the cell for this to occur, so they are unable to fix, or activate, complement.

• In addition to antibody, there are a few substances that can bind complement directly to initiate the classical cascade.

• These include C-reactive protein, several viruses, mycoplasmas, some protozoa, and certain gram-negative bacteria, such as E. coli.

• However, most infectious agents can directly activate only the alternative pathway.

How many stages can the complement activation can be divided and what are they?

• Complement activation can be divided into three main stages, each of which is dependent on the grouping of certain reactants as a unit.

• The first stage involves C1, which is known as the recognition unit.

• Once C1 is fixed, the next components activated are C4, C2, and C3, known collectively as the activation unit.

• C5–C9 comprise the membrane attack complex, and it is this last unit that completes lysis of the foreign particle.

• Figure 6-1 depicts a simplified scheme of

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the entire pathway.

What is the first recognition unit in the complement complex?

• The Recognition Unit: C1qrs• The first complement component to bind

to the cell membrane of the bacterium or other cell to be destroyed is C1, which consists of three subunits: Clq, Clr, and Cls, which are stabilized by calcium.

• The complex is made up of one Clq subunit and two each of the Clr and Cls subunits.

What is the shape and the function of the Clq in the complement complex?

• The (Clr, Cls)2 complex is an S-shaped structure with several domains of unequal size.

• It is hypothesized that this structure assumes the shape of a distorted figure eight, and it wraps itself around the arms of Clq (see Fig . 6-2).

• Clq has a molecular weight of 410,000 and is composed of six strands that form six globular heads with a collagen-like tail portion.

• This structure has been likened to a bouquet with six blossoms extending outward (see Fig. 6-2).

• Each of the six “stalks” is composed of three homologous polypeptide chains—A, B, and C—that form a triple helix.

What is the function of the Clq in recognizing antibodies?

• Clq “recognizes” the fragment crystallizable (FC) region of two adjacent antibody molecules, and at least two of the globular heads of Clq must be bound to initiate the classical pathway.

What are the Clr and the Cls and how are they activated?

• Clr and Cls are both serine protease proenzymes or zymogens; as binding of Clq occurs, both are converted into active enzymes.

• Autoactivation of Clr results from a conformational change that takes place as Clq is bound.

• Mechanical stress transmitted from the stems as binding occurs opens up the active site on Clr.

• Once activated, Clr cleaves a thioester

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bond on Cls, which activates it.• Activated Clr is extremely specific,

because its only known substrate is Cls.• Cls has a limited specificity, with its only

substrates being C4 and C2.• Once Cls is activated, the recognition

stage ends.

What is phase 2 of the activation unit and what does it produce?

• Phase 2, the formation of the activation unit, results in the production of an enzyme known as C5 convertase.

• Cls cleaves C4 to split off a 77-amino acid fragment called C4a.

• In the process, it opens a thioester-containing active site on the remaining part, C4b.

• C4b must bind to protein or carbohydrate within a few seconds, or it will react with water molecules to form iC4b, which is rapidly degraded.

• Thus, C4b binds mainly to antigen in clusters that are within a 40 nm radius of C1.

• This represents the first amplification step in the cascade, because for every one C1 attached, approximately 30 molecules of C4 are split and attached.

• C2 is the next component to be activated.

How is C2 cleaved and form C2a? • When combined with C4b in the presence of magnesium ions, C2 is cleaved by Cls to form C2a (which has a molecular weight of 70,000) and C2b (which has a molecular weight of 34,000) (see Fig. 6-3A).

• This is the only case for the designation “a” to be given to the cleavage piece with enzyme activity (see Fig. 6-1).

How is C2 converted to C4b and how will they form the C3 convertase?

• Binding of C2 to C4b can occur in the fluid phase, but C4b attached to antigen is much more efficient in accepting C2. This serves to keep the reaction localized.

• The combination of C4b and C2a is

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known as C3 convertase (see Fig. 6-3B).• This is written as C4b2a to indicate that

the complex is an active enzyme.• The half-life is estimated to be between 15

seconds and 3 minutes, so C3 must be bound quickly.

• If binding does occur, C3 is cleaved into two parts, C3a and C3b.

How does C3 important in the activation pathway and what is it's structure?

• C3 serves as the pivotal point for all three pathways, and cleavage of C3 to C3b represents the most significant step in the entire process of complement activation.

• C3 consists of two polypeptide chains, alpha and beta.

• The alpha chain contains a highly reactive thioester group, and when C3a is removed by cleavage of a single bond in the α chain, the thioester is exposed.

• The remaining piece, C3b, is then capable of binding to hydroxyl groups on carbohydrates and proteins in the immediate vicinity.

After the cleavage of C3, what are the amplification processes?

• The cleavage of C3 represents a second and major amplification process, because about 200 molecules are split for every molecule of C4b2a.

• In addition to being required for the formation of the membrane attack complex, C3b also serves as a powerful opsonin.

• Macrophages have specific receptors for C3b.

• However, a large number of molecules are needed for this to occur; hence the need for amplification.

• If C3b is bound within 40 nm of the C4b2a, then this creates a new enzyme known as C5 convertase.

• Figure 6-3C depicts this last step in the formation of the activation unit.

The membrane attack complex is which phase Phase 3

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of the complement cascade?The cleaving of C5 with deposition of C5b at another site on the cell membrane constitutes the beginning of the?

membrane attack complex (MAC)

What consists of two polypeptide chains, α and β, which are linked by disulfide bonds?

C5

C5 convertase consists of what? C4b2b3bC5 convertase splits into what? C5a and C5bC5b attaches to what, forming the beginning of the MAC?

the cell membrane

What is extremely labile, and it is rapidly inactivated unless binding to C6 occurs?

C5b

C6, C7, C8, and C9 do not have what? enzymatic activityMembrane damage is caused by what two different mechanisms?

channel formation and the binding of phospholipids

What causes a reordering and reorientation of molecules that results in leaky patches?

the binding of phospholipids

When complement proteins are bound, membrane phospholipids rearrange themselves into domains surrounding the C5b6789 complex causing what?

the integrity of the membrane to be destroyed

What is able to pass freely out of the cell? IonsThe membrane attack unit begins when? C6 binds to C5bC6 does what when it binds to C5b? It stabilizes itWhat attaches to the cell surface? The C5bC6 complexWhat binds to C5b6 forming a trimolecular complex that has a high affinity for lipid constituents of the cell membrane?

C7

What allows for insertion of the C7 part of the C5b67 complex into the membrane of the target cell?

The binding of C7

What binds to C7 and exposes a hydrophobic region that interacts with the cell membrane to form a small hole in the membrane?

C8

Which protein is inserted into the lipid bilayer? C8Lysis can be observed after which protein binds?

C8

Which protein accelerates the lysis process? C9Binding of C8 causes a loss of what from the cell?

potassium

What follows the leakage of potassium from the cell?

The leakage of amino acids and ribonucleotides

What polymerizes only when bound, and it is believed that the C5–C8 complex acts as a catalyst to enhance the rate of reaction?

C9

What forms a hollow, thin-walled cylinder, Polymerized C9

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which constitutes the transmembrane channel?Pathogens can be destroyed in the absence of antibody in which pathway?

the alternative pathway

Which pathway acts as part of innate or natural immunity?


Which pathway was originally named for the protein properdin?


What does not initiate this pathway but rather stabilizes the C3 convertase formed from activation of other factors?

Properdin

The alternative pathway does not involve which proteins?

C2 and C4

Which pathway has to get to C3 without going through C2 and no C4 and without antibodies?


Some Ag’s, like LPS, directly trigger a little of which protein to be cleaved?

C3

Which protein is unstable, and is the pivotal molecule to activate?

C3

What protein acts on factor B? C3bWhat acts on Bb to create C3Bb? Factor DWhat binds to host cells to prevent lysis and inhibits C3 activation?

Factor H

What •is a FACTOR that becomes a SUBSTRATE, which acts as an ENZYME on C3, as part of a complex?

Properdin (Factor P)

What are the proteins that are unique to the alternative pathway?

Properdin, factor B and factor D

Bacterial cell walls, especially those containing lipopolysaccharide, fungal cell walls, yeast, viruses, virally infected cells, tumor cell lines, and some parasites, especially trypanosomes are substances that trigger which pathway?

The alternative pathway

Bacterial cell walls, especially those containing lipopolysaccharide, fungal cell walls, yeast, viruses, virally infected cells, tumor cell lines, and some parasites, especially trypanosomes can serve as sites for binding what?

C3bBb

What is the first step in the alternative pathway? The conversion of C3In plasma, which protein is not stable? native C3Water is able to hydrolyze a thioester bond and thus spontaneously activate a small number of which molecules?

C3

Once activated, C3 can bind to what in the alternative pathway?

factor B

Binding of C3b to B causes a conformational change that makes B more susceptible to

serine proteases

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cleavage by what?Bound factor B can be cleaved by which factor? factor DFactor D is a plasma protein that goes through a conformational change when it binds to what factor?

factor B

Factor D’s only substrate is bound to which factor?

factor B

What protein cleaves factor B into two pieces: Ba and Bb?

factor D

What complex forms the initial C3 convertase of the alternative pathway?

C3Bb

C3bBb is then capable of cleaving what protein?

C3

C3Bb creates an amplification loop that feeds C3b into which pathway(s)?

the classical and alternative pathways

The enzyme C3bBb is extremely unstable unless what binds to the complex?

properdin

C3bBb can also cleave what protein, but it is much more efficient at cleaving C3.?

C5

Which enzyme has a high affinity for C5 and exhibits C5 convertase activity?

C3bBb3bP

What is the first part of the membrane attack unit?

C5b

Both the alternative and classical pathways are identical from the cleavage of which protein?

C5 to make C5b

Which pathway provides link between the innate and acquired immune response?

lectin pathway

Which pathway involves nonspecific recognition of carbohydrates that are common constituents of microbial cell walls and that are, importantly, distinct from those found on human cell surfaces?

lectin pathway

What proteins bind to carbohydrates? LectinsWhat binds to mannose or related sugars in a calcium-dependent manner to initiate the lectin pathway?

mannose-binding, or mannan-binding, lectin (MBL)

What are found in glycoproteins or carbohydrates of a wide variety of microorganisms, such as bacteria, yeasts, viruses, and some parasites?

sugar

What is a component of many fungi (those which contain chitin, which is composed of mannose), protozoa, and some bacteria (those which have unusual LPS, OPS, or capsules with mannose)?

Mannose

What is considered an acute phase protein, mannan-binding lectin (MBL)

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because it is produced in the liver and is normally present in the serum but increases during an initial inflammatory response?Deficiencies of MBL have been associated with what serious infections?

neonatal pneumonia and sepsis

The structure of what is similar to that of C1q? mannan-binding lectin (MBL)MBL is associated with which proteases? three MBL-serine proteases (MASPs): MASP-

1, MASP-2, and MASP-3MBL binds to what cellular surface structure? MASP-2What is homologous to C1s and causes auto activity?

MASP-2

What takes the active role in cleaving C4 and C2?

MASP-2

The functions of which MASPs are unclear at this time.

MASP-1 and MASP-3

Once C4 and C2 are cleaved, the rest of the lectin pathway is identical to which pathway?

Classical pathway

All complement pathways produce which proteins?

C3a and C5a

Which proteins are released in a gradient that increases as it gets closer to the source?

C3a and C5a

What is also an anaphylaxis protein, constricts blood vessels to prevent spread?

C5a

What cells in the area have receptors (C3aR and C5aR) on their surface?

Phagocytes

What signals the nucleus that they have been activated?

receptors

What happens after the receptors signal the nucleus that they have been activated?

Cytoskeletal Reorganization

What is intentional direction movement by chemonavigation UP the gradient called?

vector motility

On the way to the bacteria, the phagocyte will begin to express what?

Adhesion molecule receptors

What causes the neutrophils to stick weakly to the host epithelium so they can creep along the surface of the epithelium, seeking its target?

Selectons

What causes the neutrophils to squeeze through the blood vessel wall (DIAPEDESIS) to get to the bacteria?

Integrins

What ensures that infectious agents and not self-antigens are destroyed and that the reaction remains localized?

plasma proteins

Why are the majority of the control proteins acts to halt accumulation of C3b?

Because activation of C3 is the pivotal step in all pathways

Which is a glycoprotein that inhibits activation at the first stages of both the classical and lectin

C1 inhibitor, or C1INH

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pathways?What glycoprotein’s main role is to inactivate C1 by binding to the active sites of C1r and C1s?


What remains bound to the antibody, but all enzymatic activity ceases when C1 inhibitor, or C1INH binds?

C1q

What inactivates MASP-2 binding to the MBL-MASP complex, thus halting the lectin pathway?


Soluble C4b-binding protein (C4BP) and three cell-bound receptors, complement receptor type 1 (CR1), membrane cofactor protein (MCP), and decay accelerating factor (DAF) all inhibit what?

formation of C3 convertase in the classical and lectin pathways

What is a serine protease that inactivates C3b and C4b when bound to one of these regulators?

factor I

Once bound to CR1, both C4b and C3b can then be degraded by?

factor I

What also acts as a receptor on platelets and red blood cells and to mediate transport of C3b-coated immune complexes to the liver and spleen?

CR1

What is the most efficient cofactor for factor I–mediated cleavage of C3b?

MCP

How does MCP also help to control the alternative pathway?

Since binding of factor B to C3b is inhibited

What is capable of dissociating both classical and alternative pathway C3 convertases?

DAF

What portion of DAF is covalently attached to a glycophospholipid anchor that is inserted into the outer layer of the membrane lipid bilayer?

The carboxy-terminal

What is the reason that DAF can reach C3 convertase sites that are not immediately adjacent to it?

arrangement of DAF in the lipid bilayer allows DAF mobility within the membrane

What is the reason that the presence of DAF on host cells protects them from bystander lysis and is one of the main mechanisms used in discrimination of self from nonself?

because foreign cells do not possess DAF

What is the principal soluble regulator of the alternative pathway?

factor H

Which factor acts by binding to C3b, thus preventing the binding of factor B?

factor H

C3b in the fluid phase has a hundredfold greater affinity for which factor than for factor B?

factor H

On cell surfaces, C3b preferentially binds which Factor B

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factor?Which factor accelerates the dissociation of the C3bBb complex on cell surfaces?

Factor H

Which factor acts as a cofactor that allows factor I to break down C3b

Factor H

Which protein is also known as vitronectin? S proteinWhich protein interacts with the C5b67 complex as it forms in the fluid phase and prevents it from binding to cell membranes?

S protein

What causes binding of C8 and C9 to still proceed, but polymerization of C9 does not occur, and the complex is unable to insert itself into the cell membrane or to produce lysis?

S protein

What also acts to block formation of the membrane attack complex besides S protein?

Membrane inhibitor of reactive lysis (MIRL), or CD59

What protein’s main function is to bind to C8 and prevent insertion of C9 into host cell membranes?

Membrane inhibitor of reactive lysis (MIRL), or CD59

What protein plays an important role as part of the B-cell coreceptor for antigen?

CR2

What acts with CD19, and binds complement-coated antigen and cross-links it to membrane immunoglobulin to activate B cells?

CR2

What are more effective at enhancing B-cell differentiation and production of memory cells than is antigen by itself?

Immune complexes

What cell surface molecule is found on monocytes, macrophages, neutrophils, and natural killer cells, specifically binds particles opsonized with iC3b, a C3b degradation product?

CR3 (CD11b/CD18)

What receptor plays a key role in mediating phagocytosis of particles coated with these complement fragments?

CR3

Patients whose white blood cells lack CR3 receptors fail to exhibit functions such as:

chemotaxis, surface adherence, and aggregation

What proteins are found on neutrophils, monocytes, tissue macrophages, activated T cells, dendritic cells, NK cells, and activated B cells?

CR4

What proteins’ function appears to be similar to that of CR3, and they may assist neutrophil adhesion to the endothelium during inflammation?

CR4

What proteins also serve as a means of linking innate and natural immunity?

Complement proteins

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What is a small peptide that causes increased vascular permeability, contraction of smooth muscle, and release of histamine from basophils and mast cells?

anaphylatoxin

C3a, C4a, and C5a are classified as? anaphylatoxinWhat also serves as a chemotaxin for neutrophils, basophils, eosinophils, mast cells, monocytes, and dendritic cells

C5a

What type of molecules direct neutrophils, basophils, eosinophils, mast cells, monocytes, and dendritic cells to the source of antigen concentration?

chemotaxin

Which molecules facilitate phagocytosis and clearance of foreign substances?

C4b, C3b, and iC3b

What can be harmful if (1) activated systemically on a large scale, as in gram-negative septicemia, (2) it is activated by tissue necrosis such as myocardial infarction, or (3) lysis of red cells occurs?

Complement

Lysis may be another end result of complement activation, such as in what?

cold autoimmune hemolytic anemia

What usually manifests itself in increased susceptibility to infection and delayed clearance of immune complexes?

Hereditary deficiency of any complement protein

Most of these complement protein conditions are inherited on an autosomal recessive gene, and they are quite rare, occurring in what percent of the general population?

0.03%

A second deficiency that occurs with some frequency is that of mannose-binding lectin, found in what percent of the population?

3 – 5%

Lack of what has been associated with pneumonia, sepsis, and meningococcal disease in infants?

MBL

The most serious deficiency is of what, because it is the key mediator in all pathways?

C3

Individuals with paroxysmal nocturnal hemoglobinuria (PNH) have red blood cells that are deficient in what?

DAF

Some studies indicate that a DAF deficiency is associated with a lack of what?

CD59 (MIRL)

A deficiency in the what of the DAF molecule prevents its insertion into the cell membrane?

glycophospholipid anchor

What prevents insertion of C9 into the cell membrane by binding to the C5b678 complex, thus inhibiting formation of transmembrane

CD59

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channels?Recurrent attacks of angioedema that affect the extremities, skin, gastrointestinal tract, and other mucosal surfaces are characteristic of?

hereditary angioedema

What results in excess cleavage of C4 and C2, keeping the classical pathway going and creating kinin-related proteins that increase vascular permeability?

deficiency or lack of C1INH

What are the methods most frequently used to assay individual complement components?

radial immunodiffusion (RID) and nephelometry

Assays are available for Clq, C4, C3, C5, factor B, factor H, factor I, C1 inhibitor, and C3a, C4a, and C5a, but what can they not tell about the factors?

whether the molecules are functionally active

What is most commonly used to measure lysis, the end point of complement activation, as a functional test of complement activity?

The hemolytic titration (CH50) assay

What test measures the amount of patient serum required to lyse 50 percent of a standardized concentration of antibody-sensitized sheep erythrocytes?

The hemolytic titration (CH50) assay

The CH50 titer is expressed in what kind of units, which is the reciprocal of the dilution that is able to lyse 50 percent of the sensitized cells?

CH50 units

What is defined as when the change in lytic activity per unit change in complement is at a maximum?

The 50 percent point

What has been designed as another means of measuring activation of the classical pathway?

ELISA assays

In ELISA assays, what attaches to solid-phase IgM attached to the walls of microtiter plates?

Patient complement

Antihuman antibody to C9 conjugated to alkaline phosphatase is the indicator of what?

complement activation

Alternative pathway activation by means of what assay?

AH50 assay

In the AH50 assay what results from the buffer system that chelates calcium?

The blocking of classical pathway activation

What can detect C3bBbP or C3bP complexes? ELISA assays(1) Decreased production, (2) increased in vivo consumption, or (3) in vitro consumption can lead to what levels of complement components or activity?

Decreased levels of complement components or activity

A typical screening test for complement abnormalities includes testing for which protein/factor levels?

C3, C4, and factor B levels

What occurs after the binding of antigen and Complement fixation

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antibody, with uptake of complement, can be used as an indicator of the presence of either specific antigen or antibody?What technique has been used in the detection of viral, fungal, and rickettsial antibodies?

Complement fixation testing

What test involves a two-stage process: (1) a test system with antigen and antibody, one of which is unknown, and (2) an indicator system consisting of sheep red blood cells coated with hemolysin, which will cause lysis of the indicator cells in the presence of complement


If patient antibody is present, it will combine with the reagent antigen, and what will bind?

complement

If hemolysis is present in the complement fixation test, this means that no patient antibody was present, and the test is?

negative

Lack of hemolysis in the complement fixation test then the test result is?

positive

Which testing results are expressed as the highest dilution showing no hemolysis?


Why is the use of controls is extremely important?

to ensure the accuracy of test results

What test uses the following controls for testing: running known positive and negative sera, an antigen control, a patient serum control, a cell control, and a complement control?


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Cell Quiz Review - Dr Magranndrmagrann.com/MLT/Immuno PPT Flashcards Unit 1.docx · Web viewThe study of the reactions of a host when foreign substances are introduced into the body