1. + 2. the antigen & the receptor.pdf

7/28/2019 1. + 2. The Antigen & The Receptor.pdf

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The Antigen & The Receptors


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Objectives

To define structures involved in first step ofimmune response

A. Receptors:

Types General characteristics

B. Antigens:

Definition

Types of antigens

Characteristics and factors that influence their characteristics

Structure of antigen

Structural and chemical basis of antigen binding


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How Does the ImmuneSystem Work?

1. Recognition

2. Destruction

of the enemy


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Questions to ask

1. How do immune cells recognize foreign

molecules ?2. How do immune cells distinguish

between foreign and self ?

3. How do immune cells produce specificresponse to many different molecules ?


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A. Recognition-receptorsp


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First recognizedmicrobial products

Can be recognized in their natural state*only by the cells of II

Known aspathogen-associated molecular

patterns(PAMPs) Conserved among microbes PAMPs are recognized by plants as well

as animals, meaning this innate responsearose before the split between kingdoms Only vertebrates have evolved an

adaptive immune response


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RECEPTORS

INNATE

IMMUNESYSTEM

Pattern Recognition

Receptors (PRR)

ADAPTIVE

IMMUNE SYSTEM

Somatically Generated

Receptors (SGR)


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PRR SGRCELL SURFACERECEPTORS

PRRInnate System

preformed receptors

-recognize foreignstructures (non-self)

- similar on all IIS cells

- limited number (102)

-hard-wired ingenome

-common to all

individuals

- detect molecules onbacterial cells*

- 1st line of defense

SGR

Adaptive System

somatically generated

-recognize self &non-self

- each cell has itsunique receptor

- each individual hasgot its own set ofreceptors

- enormous number**

- Immunologicmemory

- 2nd line of defense


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Recognition of non-selfRECEPTORS

INNATE IMMUNESYSTEM

on cellular surface:

PatternRecognitionReceptors

(PRR)

-TLR (Toll-like R)

-KAR (killeractivator R)

-KIR (killerinhibitory

soluble form:

Complementreceptors

ADAPTIVE IMMUNESYSTEM

on cellular surface:

SomaticallyGeneratedReceptors

(SGR)

BCR (B cell R) TCR (T cell R)

soluble form:

antibodies


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Questions to ask

1. How do immune cells recognize foreign

molecules ?2. How do immune cells distinguish

between non-self and self ?

3. How do immune cells produce specificresponse to many different molecules ?


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Recognition of self

Is important because enables the cells ofmulticellular organisms to know whether Other cells with which they come into a contact

belong to the same organism

Interaction with them is safe

Self structures are normally absent from

invasive microbial cells abnormal cells of the body (cancer)

cells of other individuals


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Recognitionof self and absence of self

Every self cell present an identity cardrepresented by a set of cell surfacemolecules called major hstocompatibilitycomplex I (MHC I)

MHC I should be present on every normalnucleated cell of the body.

Cells that become abnormal owing to canceror certain viral infections may greatlyreduce/ eliminate entirely the expression ofMHC I molecules


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How Does the ImmuneSystem Work?

1. Recognition

2. Destruction

of the enemy

Recognition

Innate Immunity Receptors: PRR on phagocytes, NK cells

Adaptive Immunity Receptors: SGR on Lymphocytes B & T

(recognition/

Amplification)

Innate Immunity soluble factors: Complement

Adaptive Immunity soluble factors: Antibodies

Destruction ofmicrobe

Innate Immunity : phagocytosis, inflammation

Adaptive Immunity: Humoral Mediated Immune Response(B cell) & Cellular Mediated Immune Response (T cell)


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Who is the enemy?How it is called the enemy ?

B. Antigen:Any substance (ofexogenous /endogenousorigin)that can be recognized by

the immune system throughsoluble receptors (Ac) ormembrane receptors

f


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Types of AntigensExogenous Antigens

I. Bacterial antigens:

1- Antigens related to bacterial cells- Capsular antigen: usually polysaccharide(a)-Membranar/Somatic antigen (O): partof cell wall gm ve bacter(b)

- Flagellar Ag (H) : a protein made offlagellin

- Fimbrial Ag: surface antigens infimbriated bacilli (d)

2- Antigen secreted by bacteria (e):- Exotoxins- Enzymes

II- Parasite antigens:

-Somatic antigens (f)- Secretions (polypeptides withantigenic properties) (g)

III. Viral antigens (h):- protein coat viral antigens-soluble antigens (solublenucleoproteins as in influenza)

Bcterial Ags

Exogenous Ags

ab

c

d

ef

Parasite Ags

g

h


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Bacterial toxins: Exotoxins Secreted polypeptides

G+/- bacteria ligand + toxin

Endotoxins: LPS G- bacteria Induce Abs Systemic pathogenic

effects

ExogenousAntigens


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1.Tumor Ags :Ag present on the surface of tumor cells

a. Tumor specific Ag ( TSA): Onlyexpressed on the tumor cells but normalcells.

b. Tumor associated Ag (TAA): Highly

expressed on tumor cells but lowlyexpressed on normal cells, such as CEA.

Endogenous Antigens


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2. Viral antigens :

viral antigensexpressed onthe structuresof cell surfaceof infected host

Endogenous Antigens


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Endogenous Antigens

3. Autoantigens:Ag that triggers a

self-reactiveimmune response:

Modified self Ags

Sequestered Ags


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II. Characteristics of Ag

1. ImmunogenicityThe ability of antigen to stimulatethe immune

system of individual in order to induce aspecific immune response.

2. Specificity/ antigenicityThe ability of antigen to combine withcorresponding Ab or specific receptor on Tlymphocyte.


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1.Immunogenicity

Ability to inducehumoral and/or cell-

mediated immuneresponse

Antigen + B cells Plasma cells + Memory Cells

Antigen + T cells + MHC T effector cells + MemoryCells

In this context, we canrefer to anantigenas animmunogen


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2. Specificity/ antigenicity

Ability to combine specifically with the final productof the above responses (i.e antibodies and/or cellsurface receptors of specific Tcell )

All molecules immunogenic are antigenic

Reverse is not true

Example: Haptens = molecules that can bind to antibodies orsurface receptors (antigenic). However, they cannot induce

specific immune response alone (non immunogenic)


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Terms of immunogenicity

Intrinsic:1. Foreignness

2. Size (GM)3. Complexity &heterogeneity

4. chemical

properties5. processability

Extrinsic:1. Genetic background

2. Degree of Maturity3. & Immunocompetence

1. Immunogenic dose

2. Route of administration3. Adjuvants


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Factors InfluencingImmunogenicity

I. related to immunogen

1. Foreignness2. Molecular weight3. Complexity & Heterogeneity

4. Chemical properties5. Degradability


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1. Foreignness (non-self)

Ability of lymphocyte to recognise self antigenoccurs during their MATURATION

Any molecule not exposed to immature lymphocytes

during maturation = non-self or foreign

Degree of immunogenicity depends on degree offoreignness

The greater the phylogenetic distance between twospecies, the greater the genetic and antigenicdisparity between them


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2) Molecular Weight (MW)Proteins with MW > 10 kDa more immunogenic

Proteins with MW < 500-10 kDa poor immunogenic

3) Complexity & Heterogeneity

Synthetic homopolymers ( single amino acid orsugar): lack immunogenicity regardless of MW Copolymers composed of different amino acids areimmunogenic

Addition of aromatic amino acids (e.g. tyrosine orphenylalanine) increases immunogenicity Primary, secondary, tertiary and quaternarystructures of proteins affect immunogenicity


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4) Degradability Macromolecules that cannot

be enzymatically degraded andpresented by APC are poorimmunogens

Polymers of D amino acidscannot be degraded bymacrophage enzymestherefore poor immunogens

Large, insolublemacromolecules are moreimmunogenic than small solubleones

Why ? More readily to be phagocytosed

and processed


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II. Characteristics of Ag

1. ImmunogenicityThe ability of antigen to stimulatethe immune

system of individual in order to induce aspecific immune response.

2. Specificity/ antigenicity

The ability of antigen to combine withcorresponding Ab or sensitized T lymphocyte.


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III. a. Structure of antigen

immunogenicity and antigenicity hapten and carrierHapten:responsible of specific combining with the receptors

Only possess specificityCarrier: capable to stimulate the immune responseEnhance the immunogenicity of hapten

Immunogens: possess both characteristicsHapten +carrier = complete antigen (immunogens)Hapten = incomplete antigen


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Types of antigens

1. complete antigen: (Immunogens) Composed by Hapten +carrier possess both characteristics

Hapten = incomplete antigen2. Incomplete antigen (hapten)

compose by haptenposses only the antigenicity


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Antigen determinants (epitope)

elementary structure and functional

unit of antigen moleculeDecide the specificity of the antigen

a subtle change (chemical composition, number

and conformation) can affect the specificity ofAg.

Antigen determinant is the site of Ag combiningwith Ab

III. b. Structure of antigenAntigen determinants (epitope)


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Structural and chemical basisof antigen binding

Polypeptide antigen----5-23amino acid residues

Polysaccharide antigen----5-7 monosaccharides

Nuclear acid antigen----6-8

nucleotide Functional epitopes (A,B,C,D)Cryptical epitopes (E,F)

l d h l b


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Structural and chemical basisof antigen binding

Epitopes:


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Functional Ag determinants :

The determinants existing on the surface of Ag which canbe recognized by receptors or combined with Ab easily.

Immune dominant determinant: Specially important

determinant. Sequestered Ag determinants:

The determinants existing inside of Ag which can not berecognized by BCR or combined with Ab easily.

Epitopes:classification by

accessibility


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