Small Pox

In what century was it written about?

in ____ what physician used cow pox to immunize against  small pox?

10th century

1798, Dr. Edward Jenner

History

Who published bacteria in ____ _______?

In 1800, who was responsible for formulating ____ postulates?

Pastuers Germ Theory

1800, Koch's Postulates

When/who was responsible for the concept of Anti-bodies?

Later around that time, what theory was developled?

Who was further credited with the concept of anti-bodies (aka: antitoxins)?

1800's, Von Behring was credited with the concept of anti-bodies.

Later the theory of toxiods was developed.

Paul Ehrlich was further credited with the concepts of antibodies.

In 1899, Jules Bordet was credited with this discovery:

When was the Arthus Phenomenon (as inappropriate human response to substances) published? 

Who was credited with the ABO blood typing system?

Jules Bordet was credited with the Theory of Alexin.

in the 1900's, Maurice Arthus published Arthus Phenomenon.
Landsteiner was creditied with the ABO system.

When and Who was creditied with the theory of Phagocytosis?

1884 Metchnikoff was credited with phagocytosis.

*side note: two sides of immunology was developed.

*most investigators held for antibodies and ignored phagocytosis (cellular immunity)

Metchikoff (champion of cellular immunity)

Erhlich (champion of antibody, humoral immunity)

Differentiation self vs. non-self

The immune system must be able to: 

What is the main function of the immune system? Self and non-self?

Immune system must be able to distinguish between normal components of the human body (itself) and sustances that are not part of the normal human body (non-self)

Function of the immune system is to remove the "non-sel" sustances that enter the body and protect the "self" components by inate or acquired immunity.

Give some example of non-self:

there are 7

Bacteria

Viruses

Parasites

Fungi

Allegans

Toxins (bacterial, chemical)

Malignant cells

Non-self aka antigen

What is an antigen? 

non-self substances aka antigen

Antigen is a substance which stimulates the immune system and cause a immune response.

Most antigens are not normally found in the human body, thus they are non-self.

What are the characteristics of antigens:

Immunogenicity: 

Rectivitity: 

Immunogenicity refers to the ability of the antigen to stimulate the immune system.

Reactivity is the ability of the antigen to react with the immune system.

Antigens:

 What is the largest size? 

What are common antigens? 

Which are the strongests antigens?

Which are the weakest antigens?

largest is 10,000 daltons

Common antigens are: protiens, polysachs, glycoprotiens (plus complexes of these)

Protiens are strongest due to diversity

Polysach are weakest due to lack of diversity

Specific Immunologic Tolerance

 State the Theory of Humans

*when does it occur?

*fetal response?

Who was credited with this theory?

Theory of humans recognizing own cells as "self" and immunologically responding to "non self" substances (antigens)

* occurs before birth

* fetal turn-off of responding to own cells

*theory by Frank MacFarlane Burnet (nobel prize) and David Talmadge.

Two types of immunity

Natural Immunity: aka non specific, aka innate

Acquired Immunity: aka specific immunity

Natural: present at birth, consists of anatomical barriers, secretory molecules, blood components

Acquired: occurs after birth, B and T cells major players

Name some Characteristics of natural/innate immunity

 There are 7

-is the first line of defense against non-self substances aka antigens

1. preformed or rapidly made components

2. immediate resonse

3. no specificity

4. upon repeat exposure of antigen, no enhancement or memory of response.

5. uses pattern recognition molecules

6. Occurs in all members of animal kingdom-ancient system

7. rarely malfunctions

name some characteristics of Acquired Immunity:

 There are 7 of them

1. B and T lymphocytes are the main components

2. Time Lag-takes days to respond

3. Highly specific

4. Uses antigens recognition molecules

5. Develops memory (2nd exposure)

6. Occurs in vertebrates (later evolved)

7. Can malfunction

Innate Immunity

What are the components of innate immunity?

(3)

1. Anatomical Barriers

2. Secretory molecules

3. Cellular components

Anatomical barries innate immunity

 What is the function of the External Skin? 

What are the functions of mucuous membranes?

What are the functions of ciliated cells?

External Skin: squamous epithelial cells provide dry envirmoment inhibitory to bacteria

Mucuous Membranes: lining of entire digestive system, respiratory system, urogenital system-effective protective barrier.

 Ciliated cells: movement prevents attachment and provideds sweeping, cleansing system.

Secretory components innate immunity

Nasopharynx

Oral Cavity

Eye

Nasopharynx: mucus traps and flushes out bacteria/viruses

Oral Cavity: saliva-thiocyanate-flushing

Eye: tears contain lysozomye which destroys peptidoglycans of bacteria.

Serum secretory components innate immunity

 Define each term

Lysozyme

Transferrin and lactoferrin

 Interferon

Tumor Necrosis factor alpha (TNFalpha)

Lysozyme: destroys bacteria walls

Transferrin and lactoferrin: deprives bacteria of iron

Interferron: inhibits viral replication and activiates other cells to kill viruses

TNFalpha: depresses viral growth and activates phagocytes.

Serum secretory components innate immunity

Complement

Acute phase protiens

Complement: helps to destroy bacteria

Acute phase protiens: specific protiens produces in the early (acute) stages of infection, an example is: C-Reactive Protien

Cellular components innate immunity

Neutrophils

Macrophages

Eosinophils

Basophils and mast cells

Neutrophils aka segemented cells

name the characteristics of this cell: 

Polymorphonuclear white blood cells

Abundant in blood

live several days

motile

respond within first day of inflammation

contains granules-phagocytosis, inflammation

Granules of neutrophils

Primary azurephillic granules: 

Secondary granules:

Primary azurephillic granules: are found in young, immature neutrophils; contain proteases, cationic protiens, lysozyme, myeloperoxidase

Secondary granules: are more common in mature neutrophils; contain lysozyme, NADPH oxidase cofactors, most characterically lacterferrin and B-12 binders.

Monocytes/Macrophages

Where are they found?

How long do they live for?

what is thier function?

Monocytes are found in the blood and become macrophages in tissues

Small numbers in blood, larger numbers in tissues

They live for months

Function inflammatory and phagocytosis process

What are the Major Fuctions of Neutrophils and Monocytes?

Other blood cells:

Eosinophils: 

Basophils: 

Eosinophils: Predominant cell in allergic reactions or parasitic worm infections.

Basophils: (in blood) and become mast cells in tissues.

Are important for allergies.

Natural Killer cells:

What are thier functions?

1. Large, non-phagocytic, cells

2. destroy viral infected or neoplastic cells by release of toxic compounds.

3. Toxic compounds cause holes in membranes or stats apoptosis (programmed cell death).

Innate immunity

How does innate immunity system recognize pathogenic (disease causing) microorganisms such as bacteria, biruses, fungi, and parasites?

 At what range does the immune system recognize to?

What are these structures called?

10 to the 10th to 10 to the 14th.

The are called PAMPS: pathogen associated molecular patterns.

Important characteristics of PAMPS:

Where are they found?

What classes of pathogens are PAMPS shared by?

How many pamps does the innate system recognize?

1. The are found in only microbial pathogens and NEVER IN HUMANS.

2. PAMPs are needed for survival or pathogeniticity of the microorganism (dont mutate, geneticall conserved)

3. PAMPs are shared by entier classes of pathogens.

4. Innate system recognizes only Hundreds.

What are the two major types of patterns recognized by PAMPs?

Endocytic pattern recognition receptors

Signaling pattern recognition receptors

Endocytic Pattern Recognition receptor:

Mannose Receptors: 

Scavenger receptors: 

Mannose Receptors: bind to terminal mannose or frucrose grous on microbial glycoprotiens or glycolips. (humans dont have these terminal groups)

Scavenger Receptors: bind to bacterial cell wall components and help clearing bacteria from the human host.

Endocytic pattern recognition receptors:

Where are they located? What are thier functions?

Signaling pattern-recogntion receptors:

What do they bind to? 

What do they synthesize?

Why are cytokines crucial to innate immune response?

How many different types of TLR's are there?

When were they discovered?

Toll is german for ?

where are TLR's found?

There are 11 TLR's

First discovered in 1966 on fruit flies first found in a human in 1997

Toll is german for "amazing" or "mad"

TLR's are found in plants, animals, etc.

Decribe TLR's

What do they bind to and secrete?

Identify what each TLR binds to:

First 5 TLRs

TLR1: triacyl lipoprotiens

TLR2: peptidoglycans, lipoteichoic acids

TLR3: double stranded RNA

TLR4: Lipopolysaccharides

TLR5: bacterial flagella, and so on.

TLRs Function:

When TLRs bind to bacterial components and viral components, explain what happens.

Many TLRs especially those binding to bacterial components stimulate release of cytokines that trigger innate immune responses such as inflammation, fever and phagocytosis (immediate response)

TLRS that bind to viruses stimulate release of special cytokines called interferons that block viral replication inside host cells.

TLRs Function:

Without innate imune responses there is no acquired immunity.

Mannose Receptors:

Give the general structure, where are the mannose receptors located?

Where are they found?

Many bacteria have glycoproteins that end with mannose (human cells end with sialic acid or N-acetylgalactosamine)

Mannose receptors are found on human phagocyte cells.

N-formyl Methonyl Receptors:

Where is the receptor found?

Where does it bind on the bacteria?

Characteristics of Receptors:

Where are the receptors found?

Where are the receptors at?

Does not reconize host cells or express molecules because?

Found on the surfaces of neutrophils or macrophages (monocytes)

Receptors are encoded in the germline

No somatic recombination of genes

Do not recognize host cells or express molecules that prevent recognization by innate system.

Fever

Phagocytosis

Inflammation

Fever:

Explain the process.

After macrophages recognize PAMPs (via TLRS), they release cytokines, Interleulin l, Interleukin 6, and Tumor Necrosis Factor.

These cytokines bind to hypothalmus receptors which responds by increasing temperature (fever) to destroy microorganisms

1. attachment of antigen to phagocyte

2. engulfment of antigen, formation of phagosome

3. fusion of phagosome with lysosome forming a phagolysosome

4. Destruction of antigen (often respiratory burst)

Destruction of Macroorganism:

What are the two destructive mechanisms?

1. Oxygen dependent myeloperoxidase

2. Oxygen independant mechanism

Oxygen Dependent Myeloperxidase:

Explain the process inside the phagolysosome: 

1. NADPH oxidase catalyzess the formation of superoxide radicals.

2. Myeloperoxidase catalyzes the formation of hypochloite ion (bleach) 

3. Hydroxyl radicals formed spontaneously

-all this accompanied by transitory increase in oxygen called respiratory burst.

Oxygen Dependent myeloperoxidase system

-explain this transaciton

Oxygen Dependent Mechanisms

what are microorganisms destroyed by?

explain lysosomal enzyme digestion:

1. Microorganisms destroyed by pH changes in phagolysome (acidic)

2. By lysosomal enzyme digestion of microorganism by proteases, hydrolases, or nucleases.

Accute local inflammation: due to physical, chemical, or biological agents.

Systemic inflammations: spreads from site of injury to other tissues or organs.

Run Call the DOCTOR:

Rubor: reddening (blood accumulation)

Calor: warmth from heat of blood

Tumor: swelling from the accumulation of fluid

Dolar: pain from the injury

What are the characteristics of Acute local infammatory cascade?

5 steps: 

1. vasodialation

2. WBCS emigration

3. Chemotaxis

4. Phagocytosis

5. tissue inflammated from phagocytosis products, necrotic tissue, acute phase protiens.

This type of immunity develops after birth:

1. Develops after days

2. Specific response occurs

3. After repeated exposure to "non-self" aka antigen, response is enhanced (memory)

Active: host develops the immunity

Passive: a different host develops the immununity and the immunity is transfered o a receipiant host.

Naturally aquired active immunity

Artificially aquired active immunity

Naturally active passive immunity

Artificially acquired passive immunity

Natural acquired active: you had the disease and made your own immunity

Artificial acquired active: you recieved a vaccine and made your own immunity

Natural acquired passive: maternal antibodies and or/ colostrum

Artificial acquired passive: horse serum with antibodies (receive passively) 

Acquired Immunity:

Acquired immunity consists of two major divisions, what are these?

Humoral Immunity

Cellular Immunity aka CMI (cell mediated immunity)

1. B lymphocytes (differentiate into plasma cells)

2. antibodies

3. compliment

4. Assisted by T-lymphocytes

Cell immunity aka cell-mediated immunity:

Name the components of cellular immunity: 

1. T-Lymphocytes

2. Antigen presenting cells

Lymphoid System:

What are the two divisions of the lymphoid system:

Cells involved in the immune response are found in tissues and orgians that are collectively know as the Lymphoid system.

1. Primary Lymphoid organs

2. Secondary lymphoid organs and tissues

Thymus Gland: produce T-lymphocytes

Bone Marrow: produce B-Lymphocytes

-Primary Lymphoid organ

-B-lymphocyte differentiates in the Fetal Liver, then bone marrow after birth

-Mature B-lymphocytes develop antigen specific receptors.

Secondary Lymphoid

What are the two major structures? 

What are the minor structures?

Primary: spleen, lymph nodes

Minor: tonsils, adenoids, appendix, Peyer's Patches, mucosal tissue with lymphoid aggregates.

-Removes foriegn antigens (filters) from blood

-Site of antibody synthesis

-Consists of red pulp and white pulp

-White pulp-50% B cells in follicles

-35% T-cells in periarteriolar sheet

MHC

What are they? 

What are thier functions?

MHC are specific protiens

2 fxns are: identity marker and present foriegn antigen to T-cell

Class 1 MHC:

How many peptides are MHC composed of?

What are thier functions?

All nucleated cells have class 1 MHC molecules

-MHC class 1 are composed of 2 peptides 

-Transmembrane polypeptide noncovalently associated with beta 2 microglobulin

-Binds to protiens made inside the cell.

Class II MHC

Name some characteristics: 

-Cell surface glycoprotien composed of two polypeptide chains

-Class II MHC on surface of antigen presenting cells (APC's) = macrophages 

-B-cells, dendritic cells

-MHC presents to T-cell exogenous protien acquired by ponocytosis or phagocytosis

Humoral Immunity

Give some characteristics of Antigens aka immunoglobulins

Major functions of antibodies

-Neutralization of toxins and viruses

-Opsonization of bacteria

-Activation of compartment

Structure of an antibody:

Basic units are glycoprotiens with carbohydrate content ranging from 2-14%

-Two identicallight chains (L-chains)

-Two identical heavy chains (H-chains)

-Disulfide bonds bind L to H and H to H

Fab and Fc

anti bodies break into ?

what does Fab consist of?

Give some details on FE

Enzyme, papain, breaks into Antibody into fragments, Fab and Fc

-Fab (fragment-antigen binding) consists of 2 identical fragments-bind antigen

-Fe (fragment-crystallizable) no antigen binding, binds complement and mast cells transplacental passage

Classes of Light Chains

name the two classes of light chains

Kappa

Lambda

-Each antibody has either kappa or lambda but not both.

How many classes of heavy chains are there?

5: mu, delta, alpha, gamma, epsilon

-antibodies classified according to H chains.

IgM-has a Mu H chain

IgD has a Delta H

IgG has a gamma H

IgA has a alpha H

IgE has a epsilon H

Constant and Variable regions:

What does "Constant" stand for?

What does "Variable" stand for?

What does the v region bind to?

how many sites does each antigen site bind to?

Constant region is identical for all Igs and determines biological action

Variable region binds uniquely to antigen

V region of ohe h and one L to antigen

Each antibody has 2 antigen binding site (divalent and bivalent)

IgM

What does the M stand for?

How large is it?

 it is __% of the Ig pool?

IgM is a receptor of which lymphocyte?

IgM is the largest (M stands for Macro)

970,000 daltons

10% f Ig's pool

IgM is a protien receptor for B-lymphocyte

Half Life 10 days: first to form

IgM

Why is it intravascular?

When does it form?

What is its major FXN?

IgM is first to form

Intravascular due its large size and its more efficient against blood bourne bacteria

Inflammation: extravascular to tissues and interstitial spaces.

Not as efficient as IgG neutralizing toxins or viruses

Cannot cross human placentia

Develops after 5 months of fetal life

If fetus forms IgM that indicates congenital infection

FIRST FORM OF RESPONSE!

IgG

what percentage of pool does this represent?

what is its molecular weight?

how is it distributed?

What is its half life?

is it active or passive immunity

70-75% of Ig pool

Monomer

M/w is 146,000 daltons

Distributed extra and intravascularly

half life is more than 20 days

Passive immunity.

Fxn of IgG

Fixes complement

opsonization

neutralize toxins and viruses

Fe portion binds to natural killer cells

And causes ADCC

IgA

is what % of pool?

how does it exist?

15% of Ig Pool

Exists as a monomer in serum

Exists as dimer (J-chain with secretory piece) in mucus, tears, saliva, gastric fluid, colostrum, sweat-prevents bacteria from attaching to GI and respiratory cells-prevents viruses from entering cells.

IgE

what is it made of?

How long is its life?

what is its total weight and what % does it occupy?

what is its function?

Monomer (2 H and 2 L chains)

very little serums because of its short life (2 days), slow syntheses, rapid binding to mast cells and basophils

188,000 daltons (0.1% of total Igs)

Allergies-parasitic infections.

IgD

what percentage does it occupy?

what is its size?

Less than 1%, serum function is unknown

IgD is present in large amounts of the surfaces of matur, naive B lymphocytes

184,000 daltons in size

Monomer

Fxn of antibodies?

neutralize toxins

neutralize viruses

opsonize bacteria

activate complement

Summary of Humoral Immunity

Bone Marrow: 

Secondary Lymphoid Tissue: 

B cells

Plasma cells

Bone marrow, stem cells mature, naive B cels

Secondary Lymphoid system B cells meet antigen

B cells proliferate, differentiate

plasma cells: antibodies

Bone marrow development
Fxn?

Apoptosis?

Now, mature naive B cells

Selection against self antigens

Programmed cell death if respond to self antigens

Now, mature naive B cells

B-Cell Development

Prior to birth, where do b-cells develop?

After birth, where do they develop?

Explain the overall maturation process of immature cells to naive cells.

Fetal Liver

Bone marrow

Overall maturation process is proliferation of immature cells, acquiring B cell receptor. and selection of mature, NAIVE B-cells.

Bone Marrow Development:

Starts as a _____ CELL

Which enzyme/process stimulates the proliferation of huge numbers of pro-b cells (WITHOUT RECEPTORS)

A pre-B cell aquires a single strand of Ig__?

Stem Cell

Growth factor, IL-7 stimulate huge numbers of PRO-B cells

Pre-B cell acquires a single strand of IgM

A _____ B cell develops into ____ ____ ___ which then develops complete IgM

What 2 Ig's are expressed in the transmembrane when an Immature B-cell develops into a mature b-cell?

Pre-B cell, Immature B-Cell, IgM

Immature B-cell develops into mature B-cell with both IgM and IgD expressed transmembrane.

Negative selection:

If the b-cell does not bind to a self-antigen then it?

If the b-cells binds strongly then it?

If the b-cell binds weakly, then it?

if does not bind to self antigen, cell dies (negative selection

if binds strongly, cell dies, (negative selection)

if binds wealky, lies and released as mature, naive b-cell

Secondary Lymphoids:

When mature, naive B cells leave the bone marrow (primary lymphoid) where does it travel to?

What does it does it do?

*Note: depending on the antigen present (protien or non protien) there are certain paths that are taken.

Secondary Lymphoid System

It stays here until an antigen is presented at which, the B-cell meets the antigen.

T-Cell Dependent Patway

When is this pathway taken?

B-cell then acts as ____ ___ ___?

Which MHC is expressed?

What type of bond is used to bind it to the MHC?

Protien present

Antigen-Presenting Cell

MHC II

Peptide bound to MHC II

When the T-cell recognizes MHC II what does it release?

B-cells then proliferate, differentiate into ____ cell and antibodies are produced.

When the B-cells are activated, it increases _____?

When cytokines are present, what do we see an increase of?

Cytokines

Plasma cells!

Ribosomes

B-cells proliferate and divide into clone B-cells.

Plasma Cells:

Explain the Morphology of the Plama Cell

What sites is it found?

it is unble to?

what is its FXN?

eccentric nuclei, perinuclear halo, abundant cytoplasm

Sites: lympoids, not blood or lymph

Unable to divide

Manufacture soluble antibodies.

T-Cell Independent Pathway

When is this pathway used?

There are many _____ _____.

Antigen is non-protien, antigen is polysaccharide, glycolipid, nucleic acid.

There are many repeating sites.

what is the first signal to the b-cell?

what causes the second signal?

Crosslinkage of multivalent antigens to surface molecules of IgM and IgD to start first signal.

Second signal is needed to start b-cell proliferation.

The second signal is from a breakdown component of complement.

Where does the complement product bind on the B-cell?

Once complement product is bound, what does it do?

The comlement product binds on the CR2 on the B-cell.

Once the complement product is bound it acts as a second signal for the B-cell to proliferate and differentiate into plasma cells.

T-cell independent product:PLASMA cells.

What do these plasma cells Produce? (Ig)

There is no ____ _____

what is the life span of these plasma cells?

These plasma cells produce only IgM.

There is no chain switching, somatic hypermutation, nor affinity maturation.

These plasma cells are short-lived and relase only IgM

T-cell independent pathway: Summary

active if antigen is ______

how is the b-cell activated?

Which Ig is mostly involved?

Heavy chain switching, affinity maturation, cytokines?

are there memory cells involved?

Antigen is non-protien

B-cell is activated by binding of antigen to surface of IgM, IgD molecules

IgM production mostly.

NO heavy chain switching, no affinity maturation, no CYTOKINES involved.

Little or no memory cells.

Primary Immune Response:

(antigen based)

When does primary response occur?

When does it occur?

Which Ig is produced?

Primary response is due to b-cell meeting anting antigen for the first time.

Occurs appoximately 5-6 days after antigen exposure

Intitally IgM is produced.

Does Heavy chain switching occur here?

Do cytokines play a role in heavy chain switching?

Does the variable region change or stay the same?

Which Ig is produced in LARGE AMOUNTS?

when does HC switching occur?

Heavy chain switching does occur.

Cytokines play a huge role in HC switching

Variable region stays the same

IgG is produced in LARGE amounts!

10 days after initial exposure

Secondary Response:

(antigen based)

When does this occur?

After how many days does it react?

Which Ig is produced in large amounts?

The second exposure of the B-cells to the antigen results in the secondary reponse.

1-2 days after second meeting.

IgG is produced in large amounts.

Heavy Chain Switching

what are the specific requires for HC switching?

requirements:

CD40 Ligand binding

Specific cytokines

switch recombination(specific genetic codes)

site such as mucosal tissues

Which Ig's are used at specific sites?

IFN gamma=

IL-4=

TGF-beta=

Mucosal Tissues=

IgG

IgE

IgA

IgA

Indep/Dep pathway: where does HC switching occur?

Why is there no heavy chain switching in the T-cell? and where does it occur?

Dependent because antigen has to be a protien

No heavy chain switching occurs if no T-cell=no cytokines are present.

Affinity Maturation:

Define affinity maturation, where does it occur and why?

Affinity maturation: how tightly antibody to antigen is bound.

Occurs in the t-cell dependent patway because antigen has to be a protien based antigen.

Name the two steps of affinity maturation:

Somatic hypermutation

Selection of B-cells by follicular dendrite cells.

Somatic Hypermutation:

Where does it occur?

Rapid proliferation occurs and produces how many cells per week?

it is __/100 base pairs/cell/division

What happens to the cell if selection does not occur?

Germinal Centers

5,000/per week

1/100 base pairs

Cell death happens if no selection occurs.

What is the FXN of the Follicular Dendrite?

Explain the efficiency of the B-cell bind.

FXN of follicular dendrite:

Selection of highest affinity B-cell

cell death for lower affinity B-cells

highest affinity B-cells often become memory cells.

The more efficient the B-cell binds, the more likely it will be selected to live.

Cytokines:

Isaacs and Lindermann's description of interferron

What is it called in todays terms?

in 1957, isaacs and lindermann described a factor that interred with viral replication in vitro: an interferon

IFN alpha

What are interferon, lyphokines, monokines, interleukins are referred to as today?

explain cyto

explain kines

Cytokines

Cyto: cell

Kine: hormones

Explain the composition of a cytokine.

What is its FXN?

Composition: soluble, antigen non specific protiens that bind surface receptors on variety of cells.

FXN as chemical signals or messengers, also fxn's in immune system and other body systems.

Define:

autocrine

paracrine

endocrine

Autocrine: same cell secretes the cytokine and cytokine binds to the same cell

Paracrine: secreted cytokine bind to nerby cell

Endocrine: distant cell binds and is stimulated by the cytokine secreted into the circulation.

Characteristics of Cytokines: 

define the 4 characteristics of cytokines.

1. cytokines functin in innate and aquired immunity.

a. innate: bacteria or viruses stimulate macrophages to secrete cytokines.

b. aquired: t-cell recognition of foreign antigen and secrete cytokines.

2. Cytokine secretion is brief and self stimulated.

3. Cytokines act on many different cell types aka pleiotropism

4. Cytokines secreted by multiple diverse cells (not only immunity cells)

Interleukin 1

What cells produce IL-1?

What are the fxn's of IL-1?

What happens durring inflammation?

Macrophages produce IL-1

FXN: induces t-cells to make IL-2, enhances NKC.

Inflammation: moves WBCS from bone marrow to circulation, chemotaxis, liver makes c-reactive protien.

Increases bone resorption, increases temp

What stimulates CD4 to become a T-Helper cell?

What does IL-2 do?

IL-12 and INF gamma stimulate CD4 to become a T-helper 1.

IL-2 causes activated T-cells to proliferate, enhances NKC, Helps CD8 become cytotoxic, helps with chain switching.

What produces IL's 4-6?

What is their FXN?

T-helper cell 2 produces IL-4 thru IL-6

They function to stimulate growth and differentiation of B-cells to plasma cells.

TNF alpha

Cytotoxic to tumor cells, inflammatory response, fever, septic shock

MHC:

Define MHC

What is its FXN

What cells is MHC I found on?

What cells is MHC II found on?

MHC is a region of highly polymorphic genes which code for MHC molecules.

MHC molecules bind great diversity of peptides

MHC I is on ALL NUCLEATED CELLS

MHC II is on macrophages, B, dendritic cells (APC)

T-cells do not recognize?

What portion of the protien is recognized by the T-cell?

Explain T-cell activation, where does it occur?

T-cells do not recognize antigens in free or soluble form.

T-cells only recognize portions of protien antigens (peptides) that are non-covatently bound to MHC molecules.

T cells activation occurs locall while antibodies can be in circulation and bind to soluble agents.

MHC I: binds only to protiens produced in the cytoplasm of cells ( endogenously synthesized protiens)-viral protiens made inside an infected seed.

MHC II: binds to protiens exogenously generated by phagocytosis or pinocytosis. (protien taken inside the cell and broken down into peptides.)

STRUCTURE of MHC I

Describe the general structure of MHC I

1 peptide binding domain

2. IG like domain

3. transmembrane domain

4. Cytoplasmic domain

Consists of two separate polypeptide chains (alpha (heavy chains)

Smaller Beta chain known as Beta-2-microglobulin non covalently bound to alpha chain

3/4 of the complete polypeptide extends from the membrane into the enviroment.

MHC I:

How many AA's can bind to the cleft?

What does the small size of the cleft dictate?

9-11 amino acids

Small size of cleft dictates globular protien are broken down (processed ) into small pieces of peptides

What do these consist of?

Transmembrane Domain

Cytoplasmic Domain

MHC II:

describe the 4 domains of this structure:

1. peptide binding domain

2. IG like domain

3. Transmembrane domain

4. Cytoplasmic domain

Structure of MHC II:

what is it composed of?

how much of the chain extends into the extracellular space?

what domain consists of both alpha and beta chains?

where is the peptide binding chain located and how many amino acids does it bind to?

composed of 2 non-covalently associated polypeptide chains, alpha and beta

2/3 of each chain extends into the extracellular space.

peptide binding domain consists of parts of both alpha and beta chains.

the peptide binding cleft is located here and binds to 10-30 AA's

what are the major differences of the MHC I and MHC II?

How many AA's are MHC I and MHC II?

binding sites are different in each MHC

MHC I: 9-11 AA's

MHC II: 10-30 AA's

MHC I and II present antigens to which CD cells?

MHC I: CD 8-t-cell

MHC II: CD 4-t-cell