Antigen

Antigen.

Antigen are molecule that have ability to combine specifically with the final product of immune response i.e. secreted antibodies &/ or surface receptors on T cells.

Antigenicity is the ability of a molecule (an antigen) to combine specifically with the final products of immune responses (antibodies & TCR).
Antigen may or may not immunogenic and Serve as the target of an immune response.

 

Immunogen

Immunogen is high molecular weight foreign substance usually protein or polysaccharide in nature, which when introduced into a suitable host by suitable route produce immune response that may be humoral or cellular or both.
Immunogenecity is the ability of a molecule to induce a humoral and/ or cell mediated immune response.

 

Antigen & immunogen

 All immunogens are antigen but all antigens are not immunogen i.e. all molecules that have the property of immunogenecity also have the property of antigenicity. But the reverse is not true.
 For example hapten are antigenic but incapable by themselves of inducing an immune response – they lack immunogenecity.

 

Hapten

Haptens are low molecular weight substances,antigenic but incapable by themselves of inducing a specific immune response & when combine with carrier protein it induces antibody production with which it reacts specifically. E.g. penicillin, poison oak, poison ivy, dinitrophenol, aminobenzene etc.
Haptens are usually small molecules, but me high molecular weight nucleic acids are haptens as well.

Haptens are not immunogenic because they cannot activate T cells. Because they cannot bind to MHC as they are not peptide.
They are univalent & cannot activate B cells by themselves. Example of carrier protein BSA (bovine serum albumin). Hapten-protein combination becomes immunogenic.

When hapten-carrier protein conjugate inject antibodies produce against 3 types of antigenic determinants –

 

Immunology | Immune system| Immunity: Haptens and the Study of  Antigenicity.|Hapten carrier
Hapten- carrier conjugate

 

Properties of good immunogen / antigen

A. Foreignness – to elicit an immune response, a molecule must be recognized as nonself by immune system. Self molecules usually not immunogenic.


B. Molecular size – ˃100,000 dalton – most immunogenic; <5000 to 10,000 Da – poor immunogen; but in few instances <10,000 Da have proved to be good antigenic. E.g. glucagon (3,800 Da), insulin (6,000 Da).

C. Chemical composition & heterogenecity – chemically proteins are good antigen. Polysaccharide also good antigen. Appropriately presented lipid can induce B cell response. Homopolymers of amino acids regardless of their size less immunogenic. Heteropolymers are more immunogenic.

D. Susceptibility of antigen processing & presentation – development of both humoral & CMI requires interaction of T cells with antigens that has been processed & presented together with MHC.

E. Genotype of recipient animal – ability to response to a particular antigen varies with genetic make up e.g. pure polysaccharide are immunogenic when injected into mice or human but not to guneapig.

F. Immunogen dosage & route of administration – optimal dosage & route of administration induce a peak immune response. Insufficient/ excessive dose will not produce immune response or develop tolerance.

G. Adjuvants.

Adjuvant

They are substances that when mixed with an antigen & injected with it, enhance the immunogenicity of that antigen. They are used when an antigen has low immunogenicity or when only small amounts of an antigen are available. • Aluminum potassium sulfate (Alum)is the only adjuvant approved for human use.

• Effect of adjuvants are following –

  • Antigen persistence is prolonged.
  • Costimulatory signals are enhanced.
  • Stimulate influx of macrophages or other immune cell types at the site of injection
  • Local inflammation is increased.
  • Increase the effective size of immunogen & promote phagocytosis & presentation by macrophages.
  • Non specific proliferation of lymphocytes is stimulated.

Epitope

The portion of antigen when combine with the corresponding antibody or TCR is called epitope or antigenic determinant.


Paratope

The portion of antibody which bind with the epitope (corresponding antigen) is called paratope.


Cross reaction 

When antibody reacts with similar substance which is not responsible for its production is called cross reaction. This is also called molecular mimicry.

Classification of antigen.

1. On the basis of chemical nature –

a. Protein – all proteins are antigenic.
b. Polysaccharide – not always antigenic.
c. Lipid – may act as hapten.
d. Nucleic acid – usually not antigenic.


2. On the basis of mode of action –

a. T-dependant (TD) – they require help from T cells for the induction of immune response. They are protein in nature. E.g. microbial proteins, non-self or altered-self proteins.
b. T-independent (TI) – they do not require help from T cells. They can directly induce immune response. They are polysaccharide in nature. 2 types TI-1 & TI2. e.g. capsular polysaccharide.

Differences shown between TD & TI antigen
Differences between TD & TI antigen
Comparison of antigen recognition by T & B cells
Comparison of antigen recognition by T & B cells

Super antigen


 Superantigens are bacterial or viral proteins that bind simultaneously to the Vβ domains of a TCR & to the α chain of a class II MHC molecule.

Antigen and superantigen recognition via the MHC/T-cell receptor complex. |  Download Scientific Diagram

Conventional Ag activates one or few T cells, but superantigens activate a large number of TH cells.
Because superantigens bind outside the TCR Ag binding cleft without processing any T cell expressing Vβ domains will be activated. This activation is polyclonal & can affect a significant % of total TH cells. This result in over production of cytokines leading to systemic toxicity.
• E.g.:
▪ Staphylococcal enterotoxin
▪ Staphylococcal toxic shock syndrome toxin
▪ Staphylococcal exfoliating toxin
▪ Staphylococcal pyrogenic exotoxins
(erythrogenic toxin)



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