Antigen, Biology tutorial

Introduction:

The antigen is stated as a substance which reacts by the antibody molecules and antigen receptors on the lymphocytes. The immunogen is an antigen which is acknowledged via the body as non-self and stimulates an adaptive immune response. For ease, both the antigens and immunogen are generally termed to as antigens. Antigen is any substance which causes your immune system to generate antibodies against it. An antigen might be a foreign substance from the environment like bacteria, chemicals, viruses and pollen. An antigen might as well be made in the body, as by bacterial toxins or tissue cells.

Specific Terminology:

To be immunogenic, an antigen should have three features: 

a) High molecular weight.

b) Show chemical complexity

c) Show foreignness (acknowledged as non-self through the body).

Antigens are the macro-molecules which elicit an immune response in the body. Antigens can be polysaccharides, proteins, conjugates of lipids having proteins (or lipoproteins) and polysaccharides (or glycolipids). 

Origin of Antigens:

The Antigens can be categorized in order of their class.

1) Exogenous antigens:

Exogenous antigens are the antigens which have entered the body from the outside, for illustration by means of ingestion, inhalation or injection. The response of immune system to exogenous antigens is frequently subclinical. By means of phagocytosis or endocytosis, exogenous antigens are taken into the antigen-presenting cells (APCs) and processed into the fragments. APCs then exhibit the fragments to T helper cells (CD4+) by the use of class II histocompatibility molecules on their surface. Several T cells are specific for the peptide: MHC complex. They become activated and begin to secrete the cytokines. Cytokines are substances which can activate cytotoxic T lymphocytes (CTL), antibody-secreting B cells, macrophages, and the other particles. 

Several antigens start out as the exogenous antigens and later become endogenous (for illustration, intracellular viruses). Intracellular antigens can be discharged back into the circulation on the destruction of the infected cell.

Antigen-presenting cells

a) An antigen-presenting cell overcomes the antigen through endocytosis. 

b) The endosome fuses by a Lysosome where the antigen is degraded into the fragments (example: short peptides). 

c) Such antigenic peptides are then exhibited at the surface of the cell nestled in a class II histocompatibility molecule. 

d) Here they might be recognized by CD4+ T cells.  

2) Endogenous antigens:

Antigens which are produced in a cell (example: viral proteins in any infected cell) are: 

a) Degraded into the fragments (example: peptides) in the cell and then

b) Shown at the surface of the cell nestled in a class I histocompatibility molecule. 

c) Here they might be recognized by CD8+ T cells. 

d) Most of the CD8+ T cells are cytotoxic and encompass the machinery to demolish the infected cell (frequently before it is capable to discharge a fresh crop of viruses to spread the infection).

Endogenous antigens are antigens which have been produced in previously-normal cells as an outcome of normal cell metabolism, or due to their viral or intracellular bacterial infection. The fragments are then represented on the cell surface in the complex having MHC class I molecules and activated cytotoxic CD8+ T cells be familiar with them. Whenever acknowledged, the T cells start to secrete different toxins which cause the lysis or apoptosis of the infected cell. In order to keep the cytotoxic cells from killing cells just for representing self-proteins, self-reactive T cells are removed from the repertoire as an outcome of tolerance (as well termed as negative selection). Endogenous antigens comprise xenogenic (that is, heterologous), autologous and idiotypic or allogenic (that is, homologous) antigens.

Autoantigens:

Autoantigen is generally a normal protein or complex of proteins (and at times DNA or RNA) which is acknowledged by the immune system of patients suffering from the particular autoimmune disease. Such antigens must, beneath normal conditions, not be the target of the immune system, however, due to primarily genetic and ecological factors; the normal immunological tolerance for such an antigen has been lost in such patients.  

Tumour antigens:

Tumour antigens or neoantigens are such antigens which are represented through MHC I or MHC II molecules on the surface of tumour cells. Such antigens can at times be represented by tumour cells and never by means of the normal ones. In this case, they are termed as tumour-specific antigens (TSAs) and, in general, outcome from a tumour-specific mutation. More general are antigens which are represented through tumour cells and normal cells, and they are termed as tumour-associated antigens (TAAs). Cytotoxic T lymphocytes which recognize such antigens might be capable to destroy the tumour cells prior to they proliferate or metastasize.

Tumour antigens can as well be on the surface of the tumour in the form of, for illustration, a mutated receptor, in which case they will be acknowledged through B cells.

Nativity:

The native antigen is an antigen which is not yet processed through an APC to smaller parts. T cells can't bind native antigens; however require that they be processed through APCs, while B cells can be activated through native ones.

Antigenic specificity:

Antigenic specificity is the capability of the host cells to recognize an antigen specifically as a unique molecular entity and differentiate it from the other by means of exquisite precision. Antigen specificity is mainly due to the side-chain conformations of the antigen. It is a measurement; though the degree of specificity might not be simple to measure and require not be linear or of the nature of the rate-limited step or equation.

Interaction of Antibody with Antigens:

The joining site of an antibody is positioned in the Fab part of the molecule and is made up from the hyper variable areas of the heavy and light chains. X-Ray crystallography studies of antigen-antibody interactions exhibit that the antigenic determinant nestles in a cleft made by the joining site of the antibody.

Therefore, theory of antigen-antibody reactions is one of a key (that is, the antigen) that fits into a lock (that is, the antibody).

Non-covalent Bonds:

The bonds which hold the antigen to the antibody joining site are all non-covalent in nature. These comprise electrostatic bonds, hydrogen bonds, Van der Waals forces and hydrophobic bonds. Multiple bonding among the antigen and the antibody makes sure that the antigen will be bound tightly to the antibody.

Reversibility:

As antigen-antibody reactions take place through non-covalent bonds, they are by their nature reversible.

Affinity and Avidity:

Affinity is basically the strength of binding of one molecule to a ligand. For illustration: the strength of binding of an antibody to the antigen. Affinity is presented through dissociation constant (Kd). Kd is basically the value of concentration of ligands require to occupy half of the molecules in a solution. In the perspective of antibody and antigen, it is the concentration of antigens required to occupy half of the antibody molecules. Smaller Kd points out that affinity is stronger, therefore less antigen is required to occupy the antibody sites.

Though 'avidity' is dissimilar from 'affinity' as avidity is the summation of net strength of binding of more than one molecule to ligand. The basic difference among them is that affinity is the binding strength of one molecule site to its ligand; however avidity and affinity are interrelated. The strength of avidity based on the affinity and the valency of interactions.

Specificity and Cross Reactivity:

Specificity:

Specificity signifies to the capability of an individual antibody joining site to react by just one antigenic determinant or the capability of a population of antibody molecules to react with just one antigen. Generally, there is a high degree of specificity in the antigen-antibody reactions. Antibodies can differentiate differences in:  

a) The primary structure of the antigen.

b) Isomeric forms of the antigen.

c) Secondary and tertiary structure of the antigen.

Cross reactivity:

The Cross reactivity signifies to the capability of an individual antibody joining site to react with more than one antigenic determinant or the capability of a population of antibody molecules to react by more than one antigen.

Factors affecting antigen-antibody reactions:

The merely way which one knows that an antigen-antibody reaction has occurred is to encompass some means of directly or indirectly detecting the complexes formed among the antigen and antibody. The easiness by which one can detect antigen-antibody reactions will base on a number of factors.

Affinity

The higher the affinity of the antibody for an antigen, the more stable will be the interaction. Therefore, the easiness by which one can detect the interaction is improved.  

Avidity

Reactions among multivalent antigens and multivalent antibodies are much more stable and therefore simpler to detect.

Antigen to antibody ratio:

The ratio among the antigen and antibody affects the detection of antigen-antibody complexes due to the size of the complexes made is associated to the concentration of the antigen and antibody.

Physical form of the antigen:

The physical appearance of the antigen affects how one detects its reaction by an antibody. When the antigen is a particulate, one usually looks for agglutination of the antigen via the antibody. When the antigen is soluble one usually looks for the precipitation of the antigen subsequent to the production of big insoluble antigen-antibody complexes.

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