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DEFINITION AND PROPERTIES OF ANTIGEN
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• Antigen (Ag) - any substance, which is recognized by the mature immune system of a given organism
– antigenicity - specific reactivity with cells or molecules of the immune system
– immunogenicity - capability to elicit an immune response
– tolerogenicity - capability to induce immunological tolerance
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Antigenic determinant (epitope)
part of the antigen which are recognized by a defined immunoglobulin (B cell receptor or antibody) or by T cell receptor
COMPLEX ANTIGENS CONSIST OF THE CARRIER AND MULTIPLE ANTIGENIC DETERMINANTS (EPITOPES)
Carrier
part of the antigen directly not involved in connection with antibody
These terms can only be used to describe the interaction of particular antigenic determinant and single immunoglobulin or T cell receptor
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B cell epitope T cell epitope
recognized by B cells
proteinspolysaccharideslipidsDNAsteroidsetc. (many artificial molecules)
cell or matrix associated or soluble
recognized by T cells
proteins mainly (8-23 amino acids) requires processing by APC
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T-INDEPENDENT ANTIGENTI-1
T-INDEPENDENT ANTIGENTI-2
B cell activation without the help of T cells
Strong crosslinking of BCR by repetitive polysaccharide or protein
epitopes. Cytokine help provided by T, NK cells etc.TI-2 usually do not act as
polyclonal B cell activators.
Complete absence of T-cell help. No interactions no cytokines. At high
concentration B-cell mitogens. Simultaneous activation of BCR and other
receptors on B cells (i.e. LPS binding protein /CD14/TLR4) induces the B cells to
proliferate and differentiate
B cell
B CELL ACTIVATION
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carrier + hapten
Small chemical structures cannot induce B cell response on their own (e.g. drugs, reactive compounds)
hapten
(i.e. DNP:dinitrophenyl)
-
+
HAPTENS
hapten +
1.
2.
primed
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Factors influencing immunogenicity I.
• Foreignness• Size• Genetics
– Species– Individual
• Responders vs non-responders
• Age
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Factors influencing immunogenicity II. • Dose• Route
– Subcutaneous > intravenous,> oral > intranasal• Adjuvant
– substances that enhance an immune response to an antigen
(alum, LPS, Freund’s adjuvant, TLR ligands)COMPLEX EFFECTS
depo effect – slow antigen intake by antigen presenting cells
activation of innate immunity
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• Physical status- corpuscle (cell, colloid) or soluble- denaturated or native
• Degradability- antigen presentation by APC
Factors influencing immunogenicity II.
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Superantigens
conventional antigen
monoclonal/oligoclonal
T cell response
1:104 - 1:105
superantigen
polyclonal
T cell response
1:4 - 1:10
Microbial proteins that bind to and activate all the T cells in an individual that express a particular set or family of TCR molecules
107 – 108 / 1012 1011 / 1012activated T cells
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Immunoglobulins• Definition:
Glycoprotein molecules that are present on B cells (BCR) or produced by plasma cells (antibodies) in response to an immunogen
Immune serumAntigen adsorbed serum
α1 α2 β
+ -
albumin
globulins
Mobility
Amou
nt o
f pro
tein
γ
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Immunoglobulin Structure
• heavy and light chains
• disulfide bonds– inter-chain– intra-chain
hinge region
carbohydrate
disulfide bond
CH1
VL
CL
VH
CH2 CH3
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Immunoglobulin Fragments: Structure/Function Relationships
antigen binding
complement binding site
placental transfer
binding to Fc receptors
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Immunoglobulin Structure• variable and
constant regions• hinge region
• domains– VL & CL
– VH & CH1 - CH3 (or CH4)
• oligosaccharides
hinge region
carbohydrate
disulfide bond
CH1
CL
VH
CH2 CH3
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Ribbon structure of IgG
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•cell surface antigen receptor on B cells
allows B cells to sense their antigenic environment
connects extracellular space with intracellular signalling
machinery
•secreted antibody
neutralization
opsonization
complement fixation
Immunoglobulin Structure-Function Relationship
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Human Immunoglobulin Classesencoded by different structural gene segments (isotypes)
• IgG - gamma (γ) heavy chains• IgM - mu (μ) heavy chains• IgA - alpha (α) heavy chains• IgD - delta (δ) heavy chains• IgE - epsilon (ε) heavy chains
light chain types• kappa (κ)• lambda (λ)
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Ig isotype Serum concentration
Characteristics, functions
12-14 mg/ml
Major isotype of secondary (memory) immune response
Complexed with antigen activates effector functions (Fc-receptor binding, complement activation
Trace
amounts
The first isotype in B-lymphocyte membrane
Function in serum is not known
Trace amounts
Major isotype in protection against parasites
Mediator of allergic reactions (binds to basophils and mast cells)
3-3,5 mg/ml
Major isotype of secretions (saliva, tear, milk)
Protection of mucosal surfaces
1-2 mg/ml
Major isotype of primary immune responses
Complexed with antigen activates complement
Agglutinates microbes The monomeric form is expressed in
B-lymphocyte membrane as antigen binding receptor
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Antibodies with different isotypes differ in their Binding affinity, effector functions and theirTransport.
Carbohydrate antigens are usually recognized By IgM type antibodies.
Differences in transport makes all the differece:Antibodies spec. to blood group antigens
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PRODUCTION OF IMMUNOGLOBULINS
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IgG
IgM
IgA
A F T E R B IR T H
breas t milkIgA
0
1 0 0 %( a d u l t )
3 3y e a r
2 546 a d u l t9 1m o n t h
maternal IgG
B E F O R E B IR T H
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Ig . C onc entra tion
na p o k
p rim er response
„A” a ntig né
IgM
IgGIgAIgE
Szekund er ’la syec ond a ry response
„A” és a ntig én
„B”
5 10 15 20 25 30
IgM
secondary response against antigen A
primary response against antigen A
level of antibodies
napok
primary response against antigen B
Antigen A
days
Antigen A and B
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Polyclonal antibody response Ag
ImmunserumPolyclonal antibody
Ag
Ag
Set of B-cells
Activated B-cells Antibody-producing
plasma-cellsAntigen-specific antibodies
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Structures of the ABO blood group antigens
Defined by specific enzymes inherited co-dominant genes (Mendelian rules)
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Donors and recipients for blood transfusion
-
-
-
-
-
+
-
-
- -
+ +
+
+
+
+
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Rhesus (Rh) blood group antigen (D)
IgG type antibody - incomplete
no direct agglutinationbut human immunglobulin-reactive 2. antibody can cause agglutination
indirect agglutination
POLYPEPTIDE TYPE ANTIGEN
cytoplasm membrane
extracellular space
intracellular space
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Pathological consequences of placental transport of IgG(hemolytic disease of the newborn)
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Effects of agglutination in vivo
ABO incompatibility intravascular haemolysis(complement mediated haemolysis)
Rh incompatibility haemolytic disease of the newborn (erythroblastosis
fetalis)(opsonisation of red blood cells, which
are then phagocytosed by macrophages and granulocytes)
Rh profilaxis