Antigens

Introduction
Antigen Substances capable of inducing a specific immune response

Immunologic Properties Of Antigens

Antigens can be defined on the basis of four immunologic Properties: [1] [2] [3] [4] Immuogenicity Antigenicity Allerogenicity Tolerogenicity
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[1]

Immunogenicity

Ability to induce humoral and/or cell-mediated immune response

B cells + Antigen Plasma cells + Memory Cells T cells + Antigen + MHC T effector cells + Memory Cells In this context, we can refer to an antigen as an immunogen

[2]

Antigenicity

Ability to combine specifically with the final product of the above responses (i.e antibodies and/or cell surface receptors) All molecules immunogenic are antigenic Reverse is not true

Example: Haptens = molecules that can bind to antibodies or surface receptors (antigenic). However, they cannot induce specific immune response alone (non immunogenic)
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hapten and carrier Hapten: substances which can combine with Ab, but cannot induce immune response independently. In another word, hapten only possess immunoreactivity. Carrier: hapten enhance the immunogenicity of

Complete antigen :possess both functions Hapten +carrier ----complete antigen

Haptens

Experiment using BSA carrier with DNP hapten

[3]

Allerogenicity

Ability to induce various types of allergic reactions

Allergens = Immunogen that specifically activates humoral and/or cell-mediated responses with allergic manifestations

[4]

Tolerogenicity

Capacity to induce specific immunologic nonresponsiveness in either humoral or cell-mediated responses

Tolerance induction is learned or acquired It is induced more rapidly in immature lymphocytes than in mature ones. Maintenance of tolerance depends on persistence of antigen Both B and T cells display tolerance
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FACTORS AFFECTING TOLERANCE

ROLE OF ANTIGEN
Factors which affect response
Physical form of antigen

Favor immune response

Large, aggregated, complex molecules, properly processed Subcutaneous or intramuscular Optimal dose

Favor tolerance
soluble, aggregate-free, simple small molecules, not processed Oral or, sometimes, intravenous Very large or very small dose

Route of injection

Dose of antigen

Factors Influencing Immunogenicity

Immune system protects against bacterial, viral, fungal and parasitic infections.
It recognises macromolecules in the structure of these infectious agents (Proteins/polysaccharides) Proteins are most potent immunogens with polysaccharides ranking second Lipids and nucleic acids do not serve as immunogens

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Figure A-2

Immunogen Contribution To Immunogenicity

Immunogenicity is determined by five properties of immunogen: 1) 2) 3) 4) 5) Foreignness Molecular weight Chemical Composition Complexity Degradability

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1)

Foreignness

Ability of lymphocyte to recognise self antigen occurs during MATURATION Any molecule not exposed to immature lymphocytes during this critical period = nonself or foreign Degree of immunogenicity depends on degree of foreignness The greater the phylogenetic distance between two species, the greater the genetic and antigenic disparity between them
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Bovine serum albumin (BSA) = more immunogenic in chicken than goat

Exceptions: @ @ Some macromolecules that are conserved cross species Sperm/corneal tissue are very sequestered from immune system If sperm or corneal tissue were to be injected into the same animal from which they originated Immunogenic

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2)

Molecular Weight

Molecular weight of 100,000 Da (100 kDa) = The best

Molecular weight < 500-10,000 Da are poor

3)

Chemical Composition & Heterogeneity

Synthetic homopolymers (single amino acid or sugar) lack immunogenicity regardless of molecular weight. Copolymers composed of different amino acids are immunogenic
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Addition of aromatic amino acids (e.g. tyrosine or phenylalanine) increases immunogenicity Primary, secondary, tertiary and quaternary structures of proteins affect immunogenicity

4)

Degradability

Macromolecules that cannot be degraded and presented by APC are poor immunogens

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Polymers of D amino acids cannot b degraded by macrophage enzymes therefore poor immunogens Large, insoluble macromolecules more immunogenic than small soluble ones

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FACTORS INFLUENCING IMMUNOGENICITY

METHOD OF ADMINISTRATION

Dose Route

Subcutaneous > Intravenous > Intragastric

Adjuvant Substances that enhance an immune response to an Ag

Low dose failure to activate enough lymphocytes or induces nonresponsiveness High dose lymphocytes enter nonresposnsivess state Single dose usually not enough to induce reaction Require repeated doses over a period of weeks to induce a strong immune response Repeated dosing BOOSTER increases clonal proliferation of antigen-specific B or T cells.
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Common administration routes = intravenous, intradermal, Subcutaneous, intramuscular and intraperitoneal.

Route of administration determines which immune organ and cell population will be deployed

Intravenous administration carried first to spleen Subcutaneous = Move first to lymph nodes
This generated differences due to differences in residing populations of cells

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Adjuvants
Substances that enhance immunogenicity of antigen when mixed and injected with it e.g. Antibody response to influenza vaccine is higher and prolonged when vaccine is administered with an adjuvant

Adjuvants used to boost immune response when:

1) Antigen has low immunogenicity

2) Small amounts of antigen are available

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Figure A-4

What is an Epitope?

Epitope: Any molecular structure that can be recognised by immune, or other, biological system T cell epitope: A short peptide that interacts with a T cell receptor while bound to a Major Histocompatibility Complex (MHC) molecule B cell epitope: Region of antigenic peptide bound by an antibody

TYPES OF ANTIGENS
Exogenous Antigens
1- Bacterial antigens:
a- Antigens related to bacterial cells - Somatic antigen (O): part of cell wall gm ve bacter. - Capsular antigen: usually polysaccharide - Flagellar Ag (H) : a protein made of flagellin - Fimbrial Ag: surface antigens in fimbriated bacilli b- Antigen secreted by bacteria:
- Exotoxins - Enzymes

TYPES OF ANTIGENS
Endogenous antigens

Human tissue antigens:

a- Blood group antigens: A, B and Rh antigens b- Histocompatibility antigens:
Glycoprotein molecules on all nucleotide cells: - Major histocompatibility complex antigens (MHC) - Human leucocyte antigen (HLA)

MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGENS (MHC)

* MHC has an important function in presentation of antigens to Tcells * Helper T-cells recognize foreign antigens on surface of APCs, only when these antigens are presented in the groove of MHC II molecule * Cytotoxic T-cells will only recognize antigens, on the surfaces of virus infected cells or tumor cells only when these antigens are presented in the groove of Class I molecule (MHC restriction)

ANTIGEN BINDING AND RECOGNITION MOLECULES

Antigens are recognized by and bind to: 1) B-cell receptors (BCR) :

- These are membrane-bound immunoglobulins

(IgM and IgD) on B-cells - BCRs can be secreted in plasma as antibodies 2) T-cell receptors (TCR) - and chains anchored to T-cells

- There is a groove which binds small peptides

presented by MHC on surface of APCs

3) MHC molecules

ACCORDING TO THE DEPENDENCE OF T CELLS WHEN AGS INDUCE HUMORAL IMMUNE RESPONSE
TD-Ag (thymus dependent Ag )

TI-Ag (thymus independent Ag)

1.TD-AG (THYMUS DEPENDENT AG )

the help of T cell

TD-Ag can stimulate B cell to produce Ab with

Most of TD-Ag are protein

Have many kinds of determinants Can induce HI and CMI

Stimulate B cell to produce :IgG, IgM, IgA

Have immune memory

2. TI-AG (THYMUS INDEPENDENT AG)

TI-Ag can stimulate B cells to produce Ab without the help of T cell

Most are polysaccharide Have more same or repeat determinants Only induce B cell to produce IgM Can not induce CMI No immune memory

Merci beaucoup a bientot