DEFINITION AND PROPERTIES OF ANTIGEN

• 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

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

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

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

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

Factors influencing immunogenicity I.

• Foreignness• Size• Genetics

– Species– Individual

• Responders vs non-responders

• Age

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

• Physical status- corpuscle (cell, colloid) or soluble- denaturated or native

• Degradability- antigen presentation by APC

Factors influencing immunogenicity II.

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

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

Immunoglobulin Structure

• heavy and light chains

• disulfide bonds– inter-chain– intra-chain

hinge region

carbohydrate

disulfide bond

CH1

VL

CL

VH

CH2 CH3

Immunoglobulin Fragments: Structure/Function Relationships

antigen binding

complement binding site

placental transfer

binding to Fc receptors

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

Ribbon structure of IgG

•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

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)

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

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

PRODUCTION OF IMMUNOGLOBULINS

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

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

Polyclonal antibody response Ag

ImmunserumPolyclonal antibody

Ag

Ag

Set of B-cells

Activated B-cells Antibody-producing

plasma-cellsAntigen-specific antibodies

Structures of the ABO blood group antigens

Defined by specific enzymes inherited co-dominant genes (Mendelian rules)

Donors and recipients for blood transfusion

-

-

-

-

-

+

-

-

- -

+ +

+

+

+

+

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

Pathological consequences of placental transport of IgG(hemolytic disease of the newborn)

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