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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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The end