The Body's Defence

7/17/2019 The Body's Defence

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Chapter 43 Caesar Tin-U, Danh Vu


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Contents.

! 1stdefence: Nonspecific Defences

! 2nddefence: Inflammation

! 3rddefence: Specific Immunity

! Immune Response

! Immunity in Health and Disease


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Foreign Invaders

! Called Pathogens" Viruses, bacteria or

other living thing thatcausesdisease/immune

response.

! Antigens" Toxins that pathogens

produce that cause

harm to an organism.


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#$ They dont distinguish between foreign organisms

%$ Can be viewed in relation to a besieged city:

#$ 1stline of defence Skin = City walls

2ndline of defence Phagocytes = Foot soldiers

3rdand last defence Immune system = Secret Agents

Nonspecific Defences


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Nonspecific Defenses

Against Infection! Organisms must find a means of defence against

antigens such a viruses described on the previouspage.

! If this was not the case, bacteria, fungi and viruseswould replicate out of control inside other organismswhich would most likely already be extinct.

! Therefore organisms employ many types of defence tostop this happening.

! Means of defence can be categorized into first andsecond lines of defence, with the first line usuallyhaving direct contact with the external environment.


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The First Line of Defence

Got own3d?


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The First Line of Defence

! First Lines of Defence

! Skinis an excellent line of defence because it provides an almost

impenetrable biologicalbarrierprotecting the internal environment.

ALactobacillusspecies, possiblyDoderlein's bacillus, in association

with a vaginal epithelial cell.

(Squamous epithelial)


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!

Lysozymeis an enzyme found in tears and saliva that haspowerful digestive capabilities, and can break down foreign

agents to a harmless status before they enter the body.

! It damages bacterial cell walls by catalyzing

hydrolysis of 1,4-beta-linkages between

N-acetylmuramic acid andN-acetyl-D-glucosamine residues in a

peptidoglycan and between

N-acetyl-D-glucosamine residues in

chitodextrins.

! (In Plain English: It just disassembles their cell walls)

(They can also be found largely in your favorite product: eggwhites)

Lysozyme


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The primary structureof egg white

lysozyme - shown here - is a single

polypeptide chain of 129 amino acids.

There are four pairs of cysteinesthat

form disulfide bridges between positions

6 and 127

30 and 115

64 and 80

76 and 94

(counting from the N-terminallysine).

These cross-bridges force us to realize

that this polypeptide is not a straight

chain (like cellulose, for example).

Rather the chain must fold to allow these

cysteines to be close to each other.


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And the rest of the stuff!

Mucusand ciliafound in the nose and throat can catchforeign agents enteringthese open cavities then sweepthem outside via coughing, sneezing and

vomiting.

! The cell wallof plants consists of fibrousproteins which provide a barrierto

potential parasites (antigens).

! If these first lines of defence fail, then there are further defenses found within

the body to ensure that the foreign agent is eliminated.

Figure 1. Gram stain of a species of Micrococcus,commonly isolated from the skin and nasal membranes of humans.


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Contents.




! Immune Response



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The 2ndline of defence.


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These series of slides will take you though thebasic response to outside stimuli and bodily

responses of tissue injury.

The Inflammatory Response

Summary


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InjuryTissue injury occurs

Sequence 1: Tissue injury


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#$ Tissue injury

#$ Causes release of pain

mediators

%$ Release of ATP,

acetycholine and serotonin.

#$ Forms prostaglandin E2= bradykinin release

&$ Bradykinin +

Prostaglandins=

#$ Vasodilatation & flag for

leucocytes to follow.

Pain inflammatory mediators


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Which leads to the actions of the 2ndline of defence.


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Pha -> Go -> Cytosis!

Second lines of defence dealwith antigens that have

bypassed the first lines of

defence and still remain a

threat to the infected

organism.

-WBC home on to

Interferons, chemical signals

released by cells under attack.

(Click for video)


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These phagocytes contain digestive enzymes in

their lissome (an organelle in phagocytes) such

as lysozyme.

White blood cells such as a neutrophilor a

monocyte are capable of undergoingphagocytosis, which is illustrated below.

Monocyte:

(Video)

Neutrophil: (Video)


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Copyright 2006 American Society of Hematology. Copyright restrictions may apply.

Fukumoto, J. et al. ASH Image Bank 2006;2006:6-00023

Pathology:Hemophagocytosis

Associated with:

EpsteinBarr virus-T-

cell lymphoma.

EpsteinBarr virus

(EBV) can infect T

lymphocytes and

manifests as

hemophagocyticlymphohistiocytosis

(HLH), a distinct entity

of hemophagocytic

syndrome (HPS)

characterized by fever,

hepatosplenomegaly,

cytopenia,hypercytokinemia, and

systemic macrophage

activation with

hemophagocytosis.


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Maslak, P. et al. ASH Image Bank 2002;2002:100540

Figure 1. Histiocytes ingesting red cell precursors may be seen in response to certaininfections


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Pyrogens- High-molecular-weight substances of

polymerous nature, like lipopolysacharids.

They increase the temperature of the body contributing todefence.

Inhibits growth of some microorganisms.

Facilitates phagocytosis

Catalyses bodily reactions (tissue synthesis)

Sometimes responsible for septic shock

Body temperature exceeds normal fever.


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The phagocytes:

Eosinophils

Natural killer (NK) (T

cells)

Monocytes

Neutrophils


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Maslak, P. ASH Image Bank 2005;2005:101382

Natural Killer (T-Cell)


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Monocytes may be increased in chronic infections, chronic inflammatory disorders and

some forms of MDS and myeloid leukemia


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Plasmacytoid lymphocytehas an oval nucleus with condensed

chromatin


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Lazarchick, J. et al. ASH Image Bank 2005;2005:101296

Figure 1. Peripheral smear from a 17 year old female with Chediak-Higashi syndrome is

shown


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Figure 1. Lymphoblastsin the peripheral blood


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Contents.




! Immune Response



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Cytokines (chemokines)Structure of interleukin 2

Schematic overview of the highaffinity

interleukin2 receptor complex, including

the receptor chains, downstream signaling

components and target genes

Fig. 1

Fig. 2


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exposed surface

hidden surface

hinge region

carbohydrate

Previously

hidden surface

Lambda

Kappa

Intact Immunoglobulin Free Light Chain

Bradwell, Serum free light chain assay


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Chemokines:

-50 different proteins-Induces inflammation

-Induces toxin production in lymphocytes

Called

chemo-taxis.

(like taxiing)


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Contents.




! Immune Response



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The last line of defence.


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Antibodies

Interferons

How Specific Immunity Arises

Lymphocytes are the key cells to immunity

and bodily defence.

They generate the key responses thateliminate infections.


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This is a specific response to a specific

pathogen/antigen.

! The response involves the creation ofAntibodies.

Third Line of Defense Specific Immune Response


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Antibodies

! Y-shapedproteinmolecule.

! Made up of variableandconstantregions.

! Made up of Heavyand

Light chains.! Produced by B-

Lymphocytes

! Function:Recognizeantigens, bind to anddeactivate them.

" Note: Variable regionrecognizes the anitgens.


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How an antibody operates/works?

Deactivation of a bacterium by an antibody.


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Lymphocytes

1. 2 types:

1. B Lymphocyte (B-Cells)

2. T Lymphocyte (T-Cells)

2. Along with their variations:

1. Helper T Cells

2. Cytotoxic T cells

They display specificityonly targeting foreign cells

Lymphocytes detect foreign molecule marker

Antigen

Countered withAntibodies. (Antigen = Short for Antigen-

generator)

Created by B Cells

Video


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Origin of lymph


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How to Identify Friend or Foe?

While B cells and T cells are maturing in the

bone marrow and thymus, their antigen receptors

are tested for potential self-reactivity.

Lymphocytes bearing receptors for molecules

already present in the body are destroyed byapoptosis

Normally has lymphocytes that react against its

self

Failures of selftolerance leads to

autoimmune diseases.


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Autoimmune Disease

! Autoimmune diseases are diseases where theimmune system begins to attack itself.

" Ex:

! Rheumatoid Arthritis crippling disease of the

joints.! Lupus disease of blood and organs.

! Multiple Sclerosis disease of nervous system

! Cause(s): unknown

! Cures/Treatments: No known cures. Usually treatedwith drugs.


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Autoimmune diseasesAcute disseminated encephalomyelitis(ADEM) yes G04.0 is a form of encephalitiscaused by an autoimmune reaction and

typically occurring a few days or weeks after a viral infection or a vaccination.Addison's diseaseyes E27 is often caused by

autoimmune destruction of the adrenal cortex.Ankylosing spondylitisyes M08.1, M45. is a chronic, painful, progressive

inflammatory arthritis primarily affecting spine and sacroiliac joints, causing eventual fusion of the spine.Antiphospholipid

antibody syndrome(APS) yes D68.8 affects the blood-clotting process. It causes blood clots to form in veins and/or arteries.

Aplastic anemiano D60 is often caused by an autoimmune attack on the bone marrow.Autoimmune hepatitisno K75.9 is a

disorder wherein the liver is the target of the body's own immune system. Autoimmune Oophoritisno N70 is a disorder in

which the immune system attacks the female reproductive organs. Celiac diseaseno K90.0 is a disease characterized by

chronic inflammation of the proximal portion of the small intestinecaused by exposure to certain dietary glutenproteins.

Crohn's diseaseno K50 is a form of inflammatory bowel diseasecharacterized by chronic inflammation of the intestinal tract.

Major symptoms include abdominal pain and diarrhea. There is also a theory that Crohn's Disease is an infectious disease

caused by Mycobacterium avium paratuberculosis. Diabetes mellitus type 1yes E10 when it is characterized by a deficiency

or absence of insulinproduction (Type I), is often the consequence of an autoimmune attack on the insulin-producing beta

cellsin the islets of Langerhansof the pancreas. Gestational pemphigoidno O26.4 is a pregnancy-related blistering condition

where autoantibodies are directed against the skin. Goodpasture's syndromeyes M31.0 is a disease characterised by rapiddestruction of the kidneys and haemorrhagingof the lungs through autoimmune reaction against an antigen found in both

organs. Graves' diseaseyes E05.0 is the most common form of hyperthyroidism, and is caused by anti-thyroid antibodies

that have the effect of stimulating (agonist) the thyroidinto overproduction of thyroid hormone. Guillain-Barr syndrome

(GBS) yes G61.0 is an acquired immune-mediated inflammatory disorder of the peripheral nervous system(i.e., notthe brain

and spinal column). It is also called acute inflammatory demyelinating polyneuropathy, acute idiopathic polyradiculoneuritis,

acute idiopathic polyneuritis and Landry's ascending paralysis. Hashimoto's diseaseyes E06.3 is a common form of

hypothyroidism, characterised by initial inflammation of the thyroid, and, later, dysfunction and goiter. There are several

characteristic antibodies (e.g., anti-thyroglobulin). Idiopathic thrombocytopenic purpurayes D69.3 is an autoimmune disease

where the body produces anti-platelet antibodies resulting in a low platelet count Kawasaki's Diseaseno M30.3 is often

caused by an autoimmune attack on the arteries around the heart. Lupus erythematosusyes L93, M32 is a chronic (long-

lasting) autoimmune disease wherein the immune system, for unknown reasons, becomes hyperactive and attacks normaltissue. This attack results in inflammation and brings about symptoms. This is a "Non-organ-specific" type of autoimmune

disease. Mixed Connective Tissue Diseasehas features of other connective tissues diseases lupus, rheumatoid arthritis,

scleroderma and polymyositis. The presence of a specific antibody called U1-RNP is needed for diagnosis. Multiple

sclerosisyes G35 is a disorder of the central nervous system(brain and spinal cord) characterised by decreased nerve

function due to myelinloss and secondary axonaldamage. Myasthenia gravisyes G70.0 is a disorder of neuromuscular

transmissionleading to fluctuating weakness and fatigue. Weakness is caused by circulating antibodies that block

(antagonist) acetylcholinereceptors at the neuromuscular junction. Opsoclonus myoclonus syndrome(OMS) n/a n/a is a

neurological disorder that appears to the result of an autoimmune attack on the nervous system. Symptoms include


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AllergiesAllergy

- An exaggerated response by the immune system to an allergen.

Allergen:a normally harmless substance that causes an allergicreaction.

ex: dust, pollen, mould, food, insect stings

Types of Allergic reactions

There are two types of allergic reactions.

a. Immediate occurs within seconds and normally lasts for about30 mins.

b. Delayed takes longer to react and can last for a much longertime.


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What happens during an allergic reaction?! During an allergic reaction antibodies cause histaminesto be

released from certain cells.

Histamines cause:

a. Swelling of tissues

b. Release of fluids (runny noses and eyes)

c. muscle spasms (some cases)

Anaphylaxis or anaphylactic shock:This is the sudden and severe allergic reaction to a substance thatcan cause death.

Treatments for Allergies

1. Avoidance of material especially food.

2. Epinephrine epi pen3. Antihistamines -- benadryl


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Autoimmune disease - MS

Multiple sclerosis (MS) is typically considered to be a disease of young

adults.

Environmental triggers Environmental exposure to a specific

infectious agent during a window of immunologic vulnerability in

childhood may predispose some individuals to the development of MS

[9] . Many viral and bacterial pathogens have been putatively linked todemyelination. Of these, the Epstein-Barr virus (EBV) has attracted

much attention.

Exposure to EBV results in persistent B-cell infection, expansion of

EBV-transformed B-cell clones, and the production of antibodies

directed against specific EBV viral antigens as well as lifelong T-cell

surveillance of infected B-cells [10] . EBV nuclear antigen has a similar

structure to myelin basic protein, a major component of central nervous

system (CNS) myelin. T-cells directed against EBV antigens may be

redirected to attack CNS myelin because of similarity between the

antigens, a process termed molecular mimicry.


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Treatment of MS

No cureOnly management tehniques

administration of high doses of intravenouscorticosteroids, such as

methylprednisolone.

(This will end the attack sooner, and prevent major damage)

Side effects include: osteoporosis, and impaired memory.

Immunosuppressantalso used in cancer chemotherapy(Approved only in the USA.)

Alternative treatments

Different alternative treatments are pursued by many patients

Dietaryregimens

Herbal medicine

On the other hand the therapeutic practice of martial artssuch as tai chi,

relaxation disciplines such as yoga, or general exercise, seem to mitigate

fatigue and improve quality of life.


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A) Axial FLAIR MRI demonstrating largetumefactive areas of demyelination. B)

Axial T1 with gadolinium contrastdemonstrating enhancement of the lesion

margins.FLAIR: fluid-attenuated inversion recovery;MRI: magnetic resonance imaging.

T1-weighted MRIscans (post-

contrast) of same brain slice

at monthly intervals. Bright

spots indicate active lesions.


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Ergo Break~~

5 minutes


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What is the Major histocompatibility complex (MHC)?

It is a native molecule

TWO main classes of MHC

Mark body cells as self

Class I MHC molecules are found on almost all

nucleated cells - that is, on almost every cell.

Class II MHC molecules are restricted to a fewspecialized cell types, including macrophages, B

cells, activated T cells, and those inside the thymus.

The MHC provides a biochemical fingerprint virtually

unique to each individual.

NUMBER ONE REASON why transplant operations

fail.


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IdentificationClass I MHC molecules, found in almost all cells,

are poised to present fragments of proteins madeby infecting microbes, usually viruses, to

cytotoxic T cells.

Cytotoxic T cells respond by killing the infected cells.

Because all of our cells are vulnerable to infection by

one or another virus, the wide distribution of class I

MHC molecules is critical to our health.

Class II MHC molecules are made by only a few

cell types, chiefly macrophages and B cells.

These cells, called antigen-presenting cells (APC

in this context, ingest bacteria and viruses and then

destroy them.

Class II MHC molecules in these cells collect peptid

remnants of this degradation and present them to

helper T cells.

In response, the helper T cells send out chemical

signals that incite other cell types to fight the

pathogen.


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Were almost done


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Contents.




! Immune Response



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Got lazy?...

I i


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Immunity


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The Pathway of Specific Immune Response

Pathogens

Pathogens eaten by Macrophage

Displays portion of Pathogen

on surface

Helper-T cell recognizes

Pathogen

Step 1

Step 2

Step 3


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Activates B- CellActivates Cytotoxic

T- Cell

Memory B-CellMemory T-Cell

Kills Infected CellsAntibodies


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Cellular Immunity .vs. Antibody Immunity

! Carried out by T-Cells

! Infected cells are killed

by Cytotoxic T Cells.

! Carried out by B-cells

! Antibodies are produced

and dumped into blood

stream.

! Antibodies bind toantigens and deactivate

them.

Cellular Immunity Antibody or Humoral Immunity


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Immune Response Explained

1. Antigen infects cells.

2. Macrophage ingests antigen and displays portion on itssurface.

3. Helper T- Cell recognizes antigen on the surface of themacrophage and becomes active.

4. Active Helper T-Cell activates Cytotoxic T-Cells and B-Cells.5. Cytotoxic T-Cells divide into Active Cytotoxic T-cells andMemory T Cells.

6. Active Cytotoxic T-Cells kill infected cells.

7. At the same time, B-Cells divide into Plasma Cells andMemory B- Cells.

8. Plasma cells produce antibodies that deactivate pathogen.

9. Memory T and Memory B cells remain in the body to speedup the response if the same antigen reappears.

10. Supressor T-Cells stop the immune response when allantigens have been destroyed.


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Immune Response Summary

Antigen

Macrophage

Helper T - Cell

Active Cytotoxic T-Cell Active B - Cell

Kills Infected Cells Memory T- Cell Plasma Cell Memory B-Cell

Antibodies

Deactivates Antigens

Displays copy of antigen

on surface of cell

Cellular ImmunityAntibody Immunity


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Primary .vs. Secondary Immune Response

! Primary Immune Response

" This is a response to an invader the First time the

invader infects the body.

! No measurable immune response for first few days.

! Next 10 15 days antibody production grows steadily

! Secondary Immune Response

" A more rapid response to an invader the 2ndtime it

invades the body.! Antibody production increases dramatically and in a much

shorter time period..


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Primary .vs. Secondary Immune Response


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Passive .vs. Active Immunity1. Active Immunity

This is immunity where the body is actively producing antibodies

to fight infection.Ex: You have a throat infection and you are actively creating

antibodies to fight it.

Vaccination: An injection of a weakened strainof aninfectious microbe (pathogen) that causes the body to undergoactive immunity (produce antibodies).

2. Passive Immunity

This is immunity where antibodies are given to aperson from the blood of another person or animal.

This immunity only lasts for a short period of time.

ex: Breastfeeding mothers pass antibodies to theirchildren through the milk.


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! HIV is a retrovirus.

! A more specific name is Lentivirus.

! Retroviruses have an RNA genome that isreplicated via a DNA intermediate in infected

cells. DNA also integrates in the hostgenome to form provirus.


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Structure of HIV

Sarcophagus-shaped capsid

contains 2 copies of RNA genome

(SS (+) strand), a reversetranscriptase, integrase, and

protease.

P7 coats the RNA, and P24 forms

the nucleocapsid structure, which

is enclosed by a lipid bilayer.

Lipid bilayer comes from the host

cell, but contains two viral-

encoded glycoproteins, gp41 (41

kDa) and gp120 (120 kDa).

gp120 binds the CD4 receptor on

helper T cells.


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Infection

gp120 and gp41 associate with one

another. The complete complex is

probably trimeric (3 copies of each

protein).

Beta turns in C3 and C4 regions are

important for binding to the cell-

surface CD4 receptor.

Primary Target: CD4 helper T cells.

The normal role of these cells is to stimulate macrophages to destroy

pathogens, and coordinate the immune response. They have on their

surface, a glycoprotein called CD4. The viral protein gp120 binds CD4.

Gp120 also binds the chemokine co-receptor. gp41 causes membrane

fusion (between virion and cell).

H d HIV kill ll ?


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How does HIV kill cells?

Virus budding from cell membrane is not lethal. Cells die by autofusion, syncytial

formation, and apoptosis. Other mechanisms?

1. Autofusion

CD4 and gp120/41 proteins

mediate fusion and intracellular

vesicle formation.


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2. Syncytium formation

gp120/41 proteins on

infected cells bind to CD4

receptors on normal cells,

causing cell fusion. Thegiant multi-nucleated

syncytium dies before

long.

3.Apoptosis

An infected helper T cell can direct an uninfected T helper cell to undergo

apoptosis (programmed cell death). Apoptosis can be normal, forexample, to eliminate auto-reactive T lymphocytes to establish self-

tolerance.

Normal cell

Infected cell


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Current Therapies

1. Nucleoside analogues and other RT

inhibitors.

2. Active site inhibitors of the HIV

protease (part of the Pol gene).3. Interferon (stimulates anti-viral

response)

4. Cocktails of all 3.


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Whole virus vaccines

Attenuated viruses: Essentially intact, living HIV virions that havebeen chemically or genetically damaged.

Whole killed virus: Intact virions that have been damaged so badly

that they are completely nonfunctional (dead).

Subunit vaccines

Clone one gene from HIV, express the protein and use it to vaccinate

patients. The disadvantage is that the person only raises antibodies

against one target. With free virus, the targets are mainly the

envelope proteins; however, these are extremely variable proteins.

Six amino acids of the V3 loop of gp120 appear to be relatively

constant (some variability exists but most antibodies cross react with

the variants). Antibodies against cocktails of different V3's are being

tried.

Nucleic Acid Vaccines

Gene gun, muscle expression.

Vaccines?


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A Major Challenge in Maintaining

Control of HIV! HIV evolves rapidly! The RT is error-prone (no proof-

reading)

! ~ 1-2 mutations in each cDNA copy ofthe 9.8 kb RNA genome


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! Caesars little cancer cell fighting theory

applied to HIV / AIDS.

The Immune PathwayThink Michaelis-


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The Immune PathwayEffector Cell IL-2 Molecules

IL-2 ReceptorTumor

recognition site

Tumor

cells

Step 1

Step2

1. IL-2 binds IL-2 Receptor

2. Effector Cell with

bound IL-2

3. Effector Cell Activated

And Multiply

4. Tumor Eating

Site Activated

6. Attack Mode!

c ae s

Menton

5. Locates Tumor

Step 3Step 4

Step 5

Step 6

Calculus


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Calculus.

Change in

Effector cells

over time

Antigenicity

and size of

tumor

Death

rate

Death

rate

IL-2

StimulationEffector Cell

Injection

Change in

Tumor cells

Logistic

growth rate

of Tumor

Killing rate

by Effector

cellsChange in IL-2

Natural

production of IL-2IL-2

Injection


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Lupus

Lupus is a long-term autoimmune disease.

Immune system attacks body

causing inflammation and tissue

Symptoms:

Fatigue, fever, skin rashes, and muscle

and joint pain.

Some people may have severe episodes;

others have a milder form of the disease.

There is no cure for lupus.

More common in women than men.

The Epstein-Barr virushas been linked to lupus in children.


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References:

1. Kandel ER, Schwartz JH, Jessell TM, editors. Principles of

Neural Science (Fourth Edition). New York: McGraw Hill (Health

Professions Division). 2000;472-491.

2. Millan MJ. Progress in Neurobiology 1999;57:1-164.

3. Dickenson AH. Brit J Anaesthesia 1995;75:193-200.

4. Suzuki R and Dickenson AH. Neuroreport 2000;11:R17-21.

5. Waxman S. Pain 1999;6:S133-140.

References


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Works cited / Sources

! Kumar and Clark Clinical Medicine, 5thed.

! Campbell Reece Biology 6th& 7thed.

! Steven Zumdahl Chemistry 6thed.

! http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/L/Lysozyme.html

! http://www.textbookofbacteriology.net/normalflora.html

! https://reader008.{domain}/reader008/html5/0313/5aa7c1a67a4cd/5aa7c1d027586.jpg! http://www.georgiapainphysicians.com/l2_edu_pharma_mod2_slides.htm

! www.worldofteaching.com! www.hopkins-aids.edu/hiv_lifecycle/! www.who.int/hiv/en! hivinsite.ucsf.edu/InSite.jsp?doc=kb-02-01-02

! Chris Cunningham & Asad Usman Adoptive Immunotherapy


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And more sources

! Rosenberg, SA, Yang, JC, White, DE, et al. Durability of complete responses in patients with metastatic cancertreated with high-dose interleukin-2: Identification of the antigens mediating response. Ann Surg 1998; 228:307.

! Rosenberg, SA, Yang, JC, Topalian, SL, et al. Treatment of 283 consecutive patients with metastatic melanoma orrenal cell cancer using high-dose bolus interleukin-2. JAMA 1994; 271:907.

! Nicola NA (ed) (1994) Guidebook to Cytokines and their Receptors. Oxford: Oxford University Press.

! OstrandRosenberg S (1994) Tumor immunotherapy:the tumor cell as an antigenpresenting cell. CurrentOpinionin Immunology 6: 722727.

! Rosenberg SA. Lotze MT. Muul LM. Chang AE. Avis FP. Leitman S. Linehan WM. Robertson CN. Lee RE. RubinJT. et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killercells and interleukin-2 or high-dose interleukin-2 alone. [Journal Article] New England Journal of Medicine.316(15):889-97, 1987 Apr 9.

! Kirschner D. Panetta JC. Modeling immunotherapy of the tumor-immune interaction. [Journal Article] Journal ofMathematical Biology. 37(3):235-52, 1998 Sep.

! J.C. Arciero, T.L. Jackson, and D.E. Kirschner. A mathematical model of tumor-immune evasion and siRNAtreatment. [Journal Article] Discrete and Continuous Dynamical Systems: Series B. 4(1) 39-58, 2004 Feb.

! Dudley ME. Rosenberg SA. Adoptive-cell-transfer therapy for the treatment of patients with cancer. [Review] [97refs] [Journal Article. Review. Review, Tutorial] Nature Reviews. Cancer. 3(9):666-75, 2003 Sep.

! Chang W., Crowl L., Malm E.,Todd-Brown K., Thomas L., Vrable M. Analyzing Immunotherapy and Chemotherapyof Tumors through Mathematical Modeling. [Book] Department of Mathematics: Harvey-Mudd University, 2003Summer.


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Nonspecific Specific Immune ArisingImmunity In


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2 pt

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Nonspecific

Defense

Specific

Defense

Immune

Responses

Arising

ImmunityHealth and

Disease


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The ingestion ofinvading organisms by

certain type of white cells


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What is Phagocytosis?


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These are thephagocytic cells.


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What are neutrophils?


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The skin, mucous,membranes, and

secretions of skinand

mucous membranes.


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What is the firstline of defense?


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Phagocytic white bloodcells, antimicrobial

proteins theinflammatory response.


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What is the secondline of defense?


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This sets the bodys

thermostat at

a higher temperature.


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What are Pyrogens?


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White blood cells.


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What areLymphocytes?


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An antigen-bindingimmunoglobulin that functions

as the effector in an

immune response.


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What are antibodies?


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Lymphoctyes andAntibodies


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What is the thirdline of defense?


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Molecules secreted by blood

vessel endothelial cells

and monocytes.


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What are chemokines?


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A group of at least20 blood proteins that

cooperate withother defense mechanisms.


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What is thecomplement system?


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A protein that forms

pores in the target

cells membrane.


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What is perforin?


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A localized regionon the surface of an

antigen that ischemically recognized

by antibodies.


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What is a epitope?


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Can simulate antibody

production only withhelp from T helper cells


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What are T-dependentantigens?


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A process by which the

antibody binds to

and blocks the activity

of the antigen


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The activation of the complement

system by antigen-antibodyComplexes.


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What is complementfixation?


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A foreign molecule that

elicits a specific response

by lymphocytes.


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What are antigens?


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Short-lived cells that combat the

same antigen.


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What are effector cells?


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Long-lived cells bearing

receptors specific for

the same antigen.


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What are memory cells?


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Another term for

membrane antibodies.


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What is an antigenreceptor?


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The selective proliferationand differentiation of

lymphocytes that occurs thefirst time in the body is

exposed to an antigen.


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What is the PrimaryImmune Response?

A h f


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Another term for

immunization.


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What is vaccination?


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Another red blood cell antigen.


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What is the Rh factor?


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A life-threatening reaction

to injected or ingested

allergens.


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What is

anaphylactic shock?


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Temporary immunity obtained byacquiring ready-made antibodies

or immune cells.


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What is PassiveImmunity?


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The causative agent of AIDS.


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What is HumanImmunodeficiency

Virus (HIV)?

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The Body's Defence