Chapters 29 and 30, Immunology

7/31/2019 Chapters 29 and 30, Immunology

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ImmunologyChapters 29 and 30

ImmunityA. Innate immunity

1. Physical and chemical barriers (previous chapter)2. Phagocytes-nonspecific but activate specific immunity

B. Specific immunity-specific recognition ofantigens1. Cell mediated immunity (CMI): Lymphocytes-

recognize specific antigens and divide very rapidly

forming clones. Some of these clones destroy the

antigen directly. 2. Humoral immunity (antibody mediated immunity):

Other clones make solubleproteins called antibodies

that specifically recognize the antigen that triggered the

response.

Table 29-1


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Lymph system

Lymph vessels are closely associated with the circulatory system vessels and resemble the

veins of the circulatory system.

Contraction of skeletal muscles forces the lymph through valves in the lymph vessels.

Lymph organs include thebone marrow, lymph nodes, spleen, and thymus.

Bone marrow produces stem cells that eventually mature into several types of different cells.

Lymphocytes mature intoB-cells in thebone marrow and into T-cells in the thymus gland.

Lymph nodes and spleenLymph nodes are areas in the lymphatic veins where leukocytes (lymphocytesandmacrophages) are found in high concentration. The arrangement of these cells in

the nodes allows them to filter out any microorganisms or other antigens that passthrough the lymph system. This is why lymph glands get infected and swollen

during some types of infections.

The spleen performs a similar function and filters or purifies the blood that flows

through it.

If the spleen is damaged or removed, the individual is more susceptible toinfections.

Lymph node

Lymph nodes filter and purify lymphSpleen filters and purifies blood

(Antigen Presenting Cells)

Lymphoid organs

The bone marrow and thymus are called primary lymphoid organs because theprimary or initial differentiation of lymphocytes occurs in these organs.

After they are formed they migrate through the lymph and blood to the lymph nodes and

spleen that are called secondary lymphoid organs.


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ImmunityPathogens are destroyed bythree mechanisms: (1) Nonspecific innate

immunity-phagocytes(2) Specific humoral

antibody-mediatedimmunity

(3) Specific cell-mediatedimmunity.

Innate immunity: PhagocytesTwo types1. Polymorphonuclear leukocytes (PMNs or neutrophils) actively motile granulocytes

that contain lots of lysosomes. Derived from myeloid stem cells. Found normally

in the blood and bone marrow but migrate to sites of infection as part of the

inflammatory response.2. Monocytes and macrophages

a.Monocytes circulate throughout blood and lymph-precursors of macrophages.b.Macrophages are attached to tissue surfaces and are found primarily in the

secondary lymphoid tissues (What are these? spleen and lymph nodes). These are

antigen presenting cells-APC. When a macrophage eats a bacterium or other foreign particle it digests it andtakes the antigens from the particle and passes them through it's membrane to the

macrophage cell surface. These macrophages then contact the T-cells and B-cells and "show" them theirantigens. This lets the T and B cells know what they're up against and they then beginforming an immune response.

Neutrophil (PMN)

Note segmented nucleus and granular cytoplasm.

Monocyte


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MHC

TCR

Antigenprocessing

Antigen presentation

PRM

Antigendestruction

Pathogens with PAMPsand antigens

Adaptive immunity

Innate immunity

T cell

1

Antigenbinding

Complement,opsonization

2 Antigen-specific,antibody-mediatedimmunityActivate

B cells

Produceantibody

Innate immunityPathogen recognition by phagocytes involves an

interaction between the surface molecules of the

pathogen and the surface molecules of the

phagocytes called Pattern Recognition

Molecules (PRMs).

The PRMs on the phagocyte recognize unique

molecules or molecular arrangements found in

bacteria or viruses called Pathogen-Associated

Molecular Patterns (PAMPs).

For instance there is a PRM that recognizes LPS

which allows phagocytes to identify what type

of bacteria?

Others recognize peptidoglycan and even

unmethylated CpG-unique to bacterial DNA.When detected, the PAMP-PRM interaction

causes a transmembrane signal to occur and this

stimulates the transcription of several genes

involved in host defense. Some of these are involved in making toxic

oxygen species.

Antigendestruction

Killing

Inflammation

Cytokine andchemokine production

Antigen-presenting cell

PRM

Activatephagocytes

T cell

ActivateT cells

3


Cell-mediatedimmunity


MHC

TCR

InflammationThis is a nonspecific response to toxins

and pathogens that is mediated by the

release of cytokines and chemokines by

immune cells, especially phagocytes

and lymphocytes. Cytokines and chemokines are types of

proteins involved in inflammation and

the difference between them is

primarily based on their molecular

structures. Chemokines are

chemotactic cytokines-they cause

chemotaxis of immune cells toward the

site of injury. They also cause a

number of other physiological changes

such as vasodilatation and increased

vascular permeability (producing

swelling and redness).

Antigendestruction

Killing

Inflammation



PRM

Activatephagocytes

T cell

ActivateT cells

3




MHC

TCR

Septic Shock

Inflammation usually localizes the

infection and destroys the pathogen and

damaged tissue and generally helps

overcome the infection.Occasionally, a severe inflammatory

response becomes overwhelming and

spreads the inflammatory cells and

molecules throughout the lymph or

circulatory systems causing septic

shock.


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Antigendestruction

Killing

Inflammation



PRM

Activatephagocytes

T cell

ActivateT cells

3




MHC

TCR

Septic ShockOften caused by Gram negatives. This

can happen when an infection by

Salmonella orE. coli becomes systemic or

as a result of bowel injury resulting in the

release of enterics into the blood stream. The LPS on the surface of the G- bacteria

causes the release of cytokines and

chemokines which facilitate the destruction

of the bacteria but also act as endogenous

pyrogens, causing high fever. Widespread vasodilatation and increased

vascular permeability also occurs causing

movement of fluid from the bloodstream

into the tissues. This causes severe edema in the tissues and

a dramatic loss of blood pressure and is

fatal in about 30% of the patients affected.

Phagocytic killingPhagocytes kill bacteria in a number of ways:

1. Acid-When they ingest bacteria they enter into fermentative metabolism andas a result they produce lactic acid.

Hydrolytic enzymes in phagolysosomes are most active in acid pH so

when the pH drops, these enzymes become very active and digest the

bacteria more efficiently. These include proteases, lipases, nucleases,and lysozyme.

2. Phagocyte stimulation. The phagocyte becomes10 times more active aftereating its first bacterium.

3. Toxic oxygen. Phagocytes contain several enzymes that produce toxic formsof oxygen that in turn destroy the phagocytized bacterium.

Toxic oxygen species

Peroxide, singlet oxygen, nitric oxide, hypochlorous acid and superoxide are

all toxic forms of oxygen that are formed in phagocytes to kill bacteria.


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Countermeasures against phagocytesSome bacteria carry antioxidants with them that make them resistant to

phagocytic death.

Staphylococcus aureus (aureus means golden) gets its characteristic

yellowish color from the presence ofcarotenoid pigments that act as

antioxidants and make this organism very resistant to oxidative death and

therefore phagocytic killing. Carotenoid pigment is therefore a virulence

factor.

Mycobacterium leprae (leprosy) and M. tuberculosis can actually grow in

phagocytic cells because they make a group of membrane associated

glycolipids that inactivate toxic oxygen compounds.

Another Staphylococcus aureus

virulence factor

Countermeasures against phagocytesMany of the disease causing streptococci and staphylococci produce

compounds that kill the phagocytes.

These are called leucocidins. The dead phagocytes form what iscommonly called pus and these compounds are referred to as pyogenic-

pus forming. Streptococcus pyogenesstrep throat, also

Staphylococcus aureus produce leucocidins.

Capsules: Size and blocks adherence of the phagocyte to the bacterialcell. Streptococcus pneumoniae best example. Strains with no capsule

cannot cause disease.


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Characteristics of theAdaptive

immune responseThree fundamental characteristics of the specific immune

response.

Specificity

Memory

Tolerance

Specificity1. Specificity-highly specific-organism, protein, even epitope.

Memory2. Memory-The first time an antigen is introduced the immune response takes

a while to develop. However, if the antigen ever enters the body again, it

is recognized and the immune response happens immediately.


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Tolerance3. Tolerance; We generally don't make an immune response against

ourselves. In some cases this happens and it causes disease-Multiplesclerosis. These are calledautoimmune diseases.

Cells of the immune response

LymphocytesPhagocytes

Lymphocyte

Note: Very little cytoplasm and smaller than phagocytes


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Specific immunity-lymphocytesLymphocytes very common in blood and lymph. Tissues that contain lymphocytes are

called lymphoid tissues. All come from stem cells in the bone marrow. However,

they mature into different types of cells in other tissues. 1. B-cells: Stem cells that mature in the bone marrow.

a. Responsible for antibody interaction and antibody production.b. Have a single type of antibody molecule on their surface that recognizes a

single antigenic determinant (epitope) and this causes the B-cell to begin

producing a particular type of antibody. 2. T-cells: Stem cells that mature in the thymus.

T-Cells have antigen-specific T-cell receptors (TCRs)on their surface that allows

them to recognize a specific antigen. These receptors have two chains and

resemble antibody molecules. The part that binds antigen is called the variable

region and is specific for each different antigen. The other part that is stuck in the

membrane is called the constant region. Therefore these cells are as specific as

antibodies at recognizing foreign substances (antigens).

AntigensAntigens are substances that react with either antibodies or with

antibody-like molecules on the surface of T-cells called T-cell

receptors (TCRs).Immunogens are substances that induce an immune response.

Most (but not all) antigens are immunogens (see Haptens-below). Haptens are antigens that bind to antibodies but cannot induce an

immune response by themselves. Must be bound to a carrier

molecule. Penicillin is a hapten. It binds to glycoproteins that act

as carriers present in some individuals and stimulates an immune

reaction against the carrier-hapten conjugate in these individuals.

Antigens and haptens are both immunogens.

AntigensThree intrinsic factors affect the ability of a molecule to induce an

immune response:1. Molecular size: Small molecules are generally not

immunogenic. Sugars are bad immunogens, proteins are goodimmunogens.

2. Complexity: Greater diversity = greater immunogenicity.Proteins are very good immunogens-Nucleic acids are not.

3. Form: The more particulate and insoluble an antigen, the betterit is taken up by phagocytes and the better immunogen it is.Precipitated proteins make better antigens than soluble proteins.


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AntigensThree extrinsic factorsalso affect the ability of a molecule to

induce an immune response:1. Dose: Because of tolerance, more is not always better.

Generally dose is between 10 g and 1 gm. 2. Route: Injections are usually (but not always) more effective

than oral or topical.3. Foreign nature: More different from host molecules, better

antigen (because of tolerance).

Antigenic determinants-epitopesThe entire antigen does not interact with the antibody or TCR.

The region on an antigen that specifically reacts with the antibody

or TCR is known as the antigenic determinantor epitope.

AntigensSometimes an antibody will recognize and bind to a

molecule other than the one it was made to recognize

(similar epitope).

In this case the antigen that was used to stimulate theresponse is called the homologous antigen and the one

that it binds to it " accidentally" is the heterologous antigen.

The interaction of an antibody with a heterologous antigen is

called a cross reaction.


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The immune response1. Antigens are processed (partially digested) by antigen

presenting cells (APCs) and the pieces are moved to the

surface of the APCs.2. APCs have proteins on their surface called Major

Histocompatibility Complex (MHC) proteins that hold the

antigen pieces on the surface of the cell so other cells can bump

into them. The cells that bump into the APCs are T-

lymphocytes (T-cells) and they have special antigen

recognition proteins on their cell surfaces call TCRs (T-cell

receptors)3. The APCs present the antigen pieces to the T-cells so that they

can begin forming an immune response. This is called antigen

presentation.

The immune response4. Some T-cells interact directly with invading cells that have the

antigen and destroy the invader. These T-cells are called

cytotoxic T-cells or TC cells.

5. Other T-cells called T-helper cells (TH cells) interact withantigen and secrete proteins called cytokines that activate

several types of host defense cells to destroy the invading

antigen containing invaders. Destruction of invading antigen

by host cells is called the cell mediated immunity.

The immune response6. The TH cells also interact with another group of antigen specific

cells called B-lymphocytes or B-cells. When this interaction

occurs, the B-cells that come in contact with the TH cells are

stimulated to produce proteins called antibodies that very

specifically recognize and bind to the antigen that stimulated

the initial response. Immunity that occurs because of antibodies

is called humoral immunity.


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The immune response1. Antigens are processed and passed along to T-lymphocytes (T-cells). Th is is

called antigen presentation.

The immune response2. Some T-cells interact directly with invading cells that have the antigen and

destroy the invader. These T-cells are called cytotoxic T-cells or TC cells.

The immune response3. Other T-cells called T-helper cells (TH cells) interact with antigen and

secrete proteins called cytokines that activate several types of host defense

cells to destroy the invading antigen containing invaders. Destruction of

invading antigen by host cells is called cell mediated immunity.


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The immune response4. The TH cells also interact with another group of antigen specific cells called B-

lymphocytes or B-cells. When this interaction occurs, the B-cells that come in

contact with the TH cells are stimulated to produce proteins called antibodies that

very specifically recognize and bind to the antigen that stimulated the initialresponse. Immunity that occurs because of antibodies is called humoral

immunity.

T-cell Receptors (TCRs)TCRs are surface proteins that pass through the T-cell membrane. Each T-cell has thousands ofidentical TCR molecules on its

surface.TCR1. Alpha chain ()variable domain (V)constant domain(C)2. Beta chain ()variable domain (V)constant domain(C)The V and V combine to

form the antigen binding

site.

Major Histocompatibility Complex (MHC)MHC proteins are present in all vertebrates. Also known as Human

leukocyte antigens (HLAs) First discovered because of their role in tissue rejection in transplant

patients.


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Major Histocompatibility Complex (MHC)MHC proteins are essential

components of the immune

system.They function as antigen-

presenting molecules and

they interact with antigens

and with T-cell receptors.

(MHC)

(Antigen)

T-cell receptor

Major histocompatibility complexThere are two classes of MHC proteins, Class I and Class IIVariations in the MHC proteins from one individual to another are responsible for

tissue rejection.

Class I: Found on surface of all cells with nuclei. Primarily involved in defenseagainst viral infection or tumors.

Class II: Only on surface of phagocytes, B lymphocytes, and other Antigen PresentingCells.

Class 1 Class II

Class I MHC proteinsSince viruses use host cells to

replicate, viral antigens are bound

by MHC Class I enzymes that are

made and assembled in the

endoplasmic reticulum along with

the foreign viral or tumor specific

proteins. Viral proteins degradedTransported through ER by TAP pore.Bind to MHC-ITransported to surfaceInteract with CD8 Tc cellsTc cells release cytokines and cytotoxins

killing the infected cell


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Class I MHC proteinsSome tumors make proteins that areunique to that type of tumor called tumor-

specific antigens.

When the Tc cells recognize a virus

infected cell or a tumor cell theysecrete lymphokines and cytotoxins

that kill the cell.

Kill me, I'm infected

with a virus!

Class II MHC proteinsClass II proteins are also

assembled in the cell

endoplasmic reticulum but

they are bound to a specific

blocking peptide called the

invariant chain (Ii) and

transported to a lysosome

(phagolysosome). This is

where degradation of foreign

material occurs. The Invariant chain is a

chaperone that prevents the

Class II proteins from

interacting with any otherproteins along the way.

Class II MHC proteinsIn the phagolysosome, the Ii is

removed and replaced with

antigens from the degraded

material and this complex

migrates to the surface of the cell

and presents the antigen to CD4-

THcells by interaction with the

TCRs and the CD4 receptor. When the foreign antigens are

recognized by TH cells they

secrete cytokines that stimulate

B-cells to produce antibody.


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Types of T-cellsTwo main groups of T-cells exist based upon the type of surface protein

they have.1. CD4: Have the CD4 protein on surface-Two groups

a. T-Helper 1 cells (TH1): Attract and activate cells involvedin non-specific cellular defenses such as macrophages.

b. T-Helper 2 cells (TH2): Stimulate B-cells to produce largeamounts of antibody.

2. CD8: Have CD8 protein on surface-One type: T-cytotoxic cell

(Tc) also known as cytotoxic T lymphocytes (CTLs). Destroy

invading cells after recognizing specific antigens on their

surfaces through direct contact with an antigen specific T-cell

receptor. Thus, these cells are responsible for tissue rejection.

Cell-cell contact is required and results from secretion of

perforin by Tc cells (perforates the cells)

Cell-mediated immunityNatural killer cells: Lymphocytes that are neither T or B cells but recognizeforeign cells in the absence of specific antigen and kill the cell. Effective defense

against tumor cells and virus infected cells.

CMI effector moleculesThe cell mediated response is initiated by a variety of

substances that are released by these cells in response

to foreign matter. These are called Lymphokines if produced by

lymphocytes and cytokines if produced by other cells

Interleukins and interferon-modulate immune

response.


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The humoral responseAntibody mediated response. TH2 cells stimulate B cells to produce

soluble proteins called antibodies. Humoral immunity can be

transferred in serum.

The Humoral Response: AntibodiesAntibodies: Also called immunoglobulins-or gamma globulins. A

type of protein that recognizes an antigen in a very specific

chemical way. They are found in the serum (hence term antiserum) and in most

secretions including milk.This is why breast feeding is generally better than bottle feeding. Mother has antibodies made to most pathogens that might threaten

the infant and infant has very poorly developed immune system

when born. In this way the motherpassively immunizes her baby when she is

feeding it.

AntibodiesBasic unit is four protein chains-2 long and 2 short shaped like Y and

held together by disulfide bonds (S-S) between cysteine residues.

Long chains are called the Heavy chainsShort chains are called the Light chains:

2 cysteines 1 cystine


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AntibodiesPapain is a protease that digests the antibody protein into three fragments. Toptwo parts are called the Fab (Fragment of Antigen Binding)-Binds antigen

Bottom part is called the Fc (Crystallizable)-Does not bind antigen.

Only a small part of the Fab is actually involved in antigen binding and this iscalled the variable region because it varies from antibody to antibody. The rest

of the antibody is called the constant region

AntibodiesThe Light chain has 2 regions: Variable (antigen binding) and Constant

The variable region binds antigen and is different from one antibody molecule to thenext.

AntibodiesThere are two types of constant regions found on the light chain: lambda andkappa. Each antibody molecule has either two lambda or 2 kappa portions. Never

two different types on the same molecule.

The heavy chains have one variable region and three constant regions CH1, CH2,and CH3.


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Types of antibodiesThere are five different classes of antibodies based on theirstructure, molecular weight and where they are found.

IgA

IgD

IgE

IgG

IgM

IgGImmunoglobulin GMost common antibody in blood. 80% of circulating antibody.

Two light and two heavy chainsCan bind two antigens at same time (bivalent)

Four subclasses IgG 1=>4

IgG


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IgMActually 5 immunoglobulin molecules (pentameric) hooked together by shortproteins called J-chains.

Heavy chains have an extra Constant region-CH4First antibody to be made in response to bacterial infection

Multivalent: 10 antigen binding sites.

IgASecretory antibodyPresent in body secretions: Breast milk. Mothers give babies their antibodies

for protection.

Before being secreted it is a monomer but the secreted form consists of twoantibody molecules held together by a J-chain peptide and a peptide known as

the secretory piece that is responsible for the secretion of the IgA.

IgEFound in very low amounts in the serum but is responsible for allergic reactions.Extra constant region can bind to mast cells and this is responsible for

stimulating the allergic response.

CH1CH2CH3CH4 Extra constant region


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IgDFound in lowest abundance. Function is to binding antigen and stimulating new B-cellsin the spleen to start making antibody.

CH1CH2CH3CH4

The antibody response

(Booster)

(anamnestic [memory] response)

The antibody response1. Antigen binds to specific receptors on B-cell surface. 2. Antigen engulfed by endocytosis.3. Antigen digested.4. Antigen peptides moved to B-cell surface as part of Class II

MHC.5. B-cell presents antigen to T Helper cells T Cell Receptor and

CD4 molecule.6. T-Helper releases interleukins.

7. The dividing B-cells then form two types of B-cells

a. Plasma cells: Large, produce tons of antibody and have a

short life(


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The B cell functions as an antigen-

presenting cell (APC) and concentrates

antigen using antigen-specific

immunoglobulin receptors. After processing, antigen is presented to

the TH2 cell which then signals the sameB cell to proliferate and form plasma

cells (antibody producers) or memory

cells. After subsequent antigen exposure,

memory cells quickly convert to plasma

cells.

Interleukins

released

The Complement SystemA group of 11 proteins in the serum that act to destroy foreign cells by formingholes in their membranes. The complement system is not specific itself and is

always present. The specificity comes from antibodies that trigger thecomplement system when they are activated by binding to antigen.

Actions of the complement system:

1. Bacterial lysis-especially G-

2. Non-lytic killing.3. Phagocytosis. Cells such as Streptococcus pneumoniae that are not

normally phagocytized can be made susceptible to phagocytosis if they are

recognized by antibody in the presence of complement. This is an importantprocess called opsonization.

The complement system proteins function as anaphylatoxins that trigger the

release of histamine and other cytokines from mast cells or basophils. If thishappens too rapidly it can cause a life threatening allergic response known as

anaphylactic shock.

Complement cascadeEach of the proteins that are part of the complement system are assembled on the

invading cell surface and when they are all attached, they form a hole in the membrane

that causes lysis in many bacteria-especially G-.


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Immunity and diseaseOne of the greatest steps in the progress of science was the development

of methods to produce immunity to infection in individuals . This

can be done in 2 ways: 1. Active immunity: The immune response is stimulated in an

individual by the presence of antigen. This causes a permanent

change in the individual so he/she will always be able to produce an

immune response to subsequent encounters with the antigen. A. Natural-immunity following recovery from a disease.B. Artificial-Induced by injection of antigen-immunization.

Vaccination is commonly used but immunization is the proper

term. Note, this isNOT inoculation! You don't get inoculated

against a disease. If you inoculate someone you are giving them

the disease! Vaccination or immunization.

Immune diseasesHypersensitivity. An immune response that causes tissue damage that resultsfrom a preexisting immunity. Can be cellular or humoral.

Four types: I, II, III, IV

Type I: Immediate hypersensitivity:

This is mediated by antibodies. Allergies. 10-20% of the population

Type II-cytotoxic autoimmune diseases. Destruction of specific types of cells.

Type III-Immune complex disease. Antigen antibody complexes cause damageto several tissues.

Type IV-Delayed hypersensitivity.

Results from a special class of T-cells called TH1-helper cells.

Type I hypersensitivityFirst exposure to antigen: Specific antibodies of the IgE type aremade.IgE antibodies bind to Mast cells ( non-motile connective tissuecells-next to capillaries) and Basophils (motile white blood cells).The second time the IgE sees the antigen and the antigen binds totwo different antibodies at the same time then the mast cell orbasophil to which they are attached releases a variety ofphysiologically active chemicals such as histamine and seratonin. These cause dilation of blood vessels and smooth muscle

contraction. Thus a person experiencing an allergic reaction has difficultybreathing, flushed skin, lots of mucus production, itchy watery eyesetc. The severity of the reaction depends upon the individual and thedegree of exposure to the antigen.In some people the reactions are very severe and result in a severedrop in blood pressure (vasodilatation) the inability to breath. Theseindividuals can die immediately if they are not given adrenaline tocounteract the smooth muscle contraction.


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IgEFound in very low amounts in the serum but is responsible for allergic reactions.Extra constant region can bind to mast cells and this is responsible for

stimulating the allergic response.

CH1CH2CH3CH4 Extra constant region

Type I hypersensitivity

Hay

Fever

http://en.wikipedia.org/wiki/File:Mast_cells.jpg


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Type II and III hypersensitivitiesType II-cytotoxic autoimmune diseases. Destruction of specific typesof cells.

Type III-Immune complex disease. Antigen antibody complexes

cause damage to several tissues.

Juvenile diabetes-antibodies against insulin producing cells ( Type II).

Systemic lupus erythematosis-antibodies against everything (Type III).

Hashimotos disease-thyroglobulin destruction of thyroid gland. (Type II)The propensity to develop these and other autoimmune diseases is

probably determined genetically.

Type IV hypersensitivityDelayed hypersensitivity. Results from a special class of T-cells called T H1-helper cells. Can be caused by microbes or by chemicals.If it is caused by chemicals it is called contact dermatitis: Poison Ivy.The reaction to microbes is used to determine the preexisting exposure to

Mycobacterium tuberculosis: The Mantoux (man-too) tuberculin skin test (After Charles Mantoux (1877-1947),

French physician) involves injecting a very small amount of purified protein

derivative (PPD) fromM. tuberculosis just under the top layer of the skin

(intracutaneously). If the delayed hypersensitivity TH1-cells recognize the antigen

and are sensitized, then they will release lymphokines and this will cause the

formation of an inflammatory response in this area.Tissue destruction is caused by the lytic enzymes and phagocytic cells destroyingthe tissue that is bound to antigen.

SuperantigensThese are exotoxins that are not metabolically toxic but instead stimulate an

enormous immune response: This is the case with the pathogenic

Staphylococcus aureus during toxic shock syndrome. Also with Streptococcus

pyogenes and the flesh eating disease(necrotizing fasciitis). The exotoxins from these organisms bind to the beta chain of the T-Cell

Receptors (TCRs) in a different place than normally binds antigen. This can

cause an enormous cell mediated response and the release of lymphokines and

the cell mediated destruction is why these diseases are so dramatic and deadly.


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Immunity and diseaseOne of the greatest steps in the progress of science was the development

of methods to produce immunity to infection in individuals . This

can be done in 2 ways: 1. Active immunity: The immune response is stimulated in an

individual by the presence of antigen. This causes a permanent

change in the individual so he/she will always be able to produce an

immune response to subsequent encounters with the antigen. A. Natural-immunity following recovery from a disease.B. Artificial-Induced by injection of antigen-immunization.

Vaccination is commonly used but immunization is the proper

term. Note, this isNOT inoculation! You don't get inoculated

against a disease. If you inoculate someone you are giving them

the disease! Vaccination or immunization.

Immunity and disease2. Passive immunity: Temporary immunity due to the presence

of antibodies made by another individual or organism. No

permanent change in the individual. A. Natural-Infants have antibodies from their mothers whenthey are born and they get IgA in mothers milk. B. Artificial-The individual may receive injections of pre-formed antibodies (antiserum) such as those from another

individual or animal that has been immunized (gamma-

globulin injections). Frequently used to treat individuals

believed to have been exposed to Hepatitis A-clear the virus

before it can cause a full blown infection.

VaccinationVaccine: An antigen or mixture of antigens used to induce active

immunity.Toxoid: A vaccine composed of an inactivated toxin so that it can still

produce an immune response is no longer toxic. Example is tetanus

vaccine. Commonly inactivated with formaldehyde. For endotoxins the entire organism must be injected (why) so the entirecell must be killed. Cells are commonly killed with phenol or

formaldehyde.Antiserum: Serum containing antibodies against a particular antigen.Antitoxin: serum containing antibodies against a particular toxin such

as botulism or Diptheria.


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Vaccination Since children are susceptible to a number of infectious diseases, it is

desirable to immunize them as soon as possible. This is usuallybegun at a few months of age. The duration of immunization depends primarily upon the antigen.

Some antigens provide immunity for life while others require

boosters to initiate a secondary response.

Documents

Chapters 29 and 30, Immunology