Chapter 3: Immunogen and Antigen
Definition of the immune response:
When foreign substances (Anigen, Ag) are introduced into the body, they lead to anti-foreign substance (Antibody – Ab) formation. These foreign substances may be bacteria, viruses, parasites, foreign proteins, etc when enter into the body give rise to immune response.
Immune response means antigenic challenge leads to activation of either B-lymphocytes or T-lymphocytes.
These foreign substances may be:
- Immunogenic when they are able to produce a specific immune response; that they will stimulate immune cells and then give rise to immunological reaction (Humoral or cellular).
- Antigenic substances cannot yield directly immune response but need some help from some proteins (carrier proteins) and then they can react with antibodies.
All immunogens are antigenic but not all antigens are immunogenic. In daily life, the word antigen is more commonly used.
The antigen may be:
- Incomplete called Haptens
Properties of Antigen (Foreign Substances) to be Immunogenic:
This is the most important factor that the substances should be recognized by the immune systems as foreign (non-self).
The immune system develops a tolerance to self-antigens. In some of the diseases, there may be antibodies reacting against the self-antigens.
The cell membrane consists of protein, phospholipids, cholesterol, and a trace of carbohydrate which are in the form of glycoproteins and glycolipids. there are certain areas which are antigenic determinants called epitopes. The bacterial capsule is also immunogenic while bacteria without capsule have the surface structure which is immunogenic.
- Autologous antigens are self-antigens and there will be no immune response.
- Allogenic antigens are from the same species and there may be a reaction, e.g. blood transfusion, kidney transplant, etc.
- Heterologous antigens are from different species. These will be rejected and there will be a severe immune response.
- Antigens that degrades quickly can not stimulate the immune system, so the immune system needs adequate time for exposure to the antigen.
B. Chemical Nature
Antigens or immunogens are either proteins or large polysaccharides molecules and rarely if ever lipids.
These are cell surfaces or membrane-bound antigens.
The antigens or immunogens are the large organic molecules which may be:
- Proteins: These are very strong antigens. These are strong antigens because of their high molecular weight and structural complexity.
- Lipoprotein: These are part of the cells.
- Lipopolysaccharides: These are endotoxin, capsular polysaccharides of pneumococci, and other haptens.
- Carbohydrates (polysaccharides) are too small to be antigenic. But in the case of red blood cells protein or lipid carrier gives rise to an increase in their size and polysaccharides are present in the form of side chains and give rise to antigenicity.
- Red blood cell surface antigens are glycoproteins.
- Nucleic acid: These are non-immunogenic except single-stranded DNA. These poor antigens because of the simplicity of the structure, molecular flexibility, and rapid degradation.
- Polypeptide: These are hormones, insulin and these are weak antigens.
- Nucleoproteins: These are strong antigens.
- Lipids: These are non-immunogenic except cardiolipin. These are very weak antigens because of simplicity and lake of structural stability. When these are combined with polysaccharides or proteins then they may act as an antigen.
C. Molecular size (molecular weight)
The higher the molecular weight, the better the molecule will act as an antigen. The number of epitopes is directly proportional to the size of the antigen.
Haptens are very small molecule, so need to combine with the carrier (larger molecule) to be antigenic.
The larger molecules of antigens are more immunogenic because:
- These are easily phagocytosed.
- Antibody formation is increased if the antigens are processed by antigen-presenting cells (APC)
- The antigen which is difficult for phagocytosis is not immunogenic. If the molecular weight is >10,000, these are more immunogenic than the molecular weight of <10,000. See the example in the following table:
In addition, amino acids and monosaccharides are not immunogenic.
D. Molecular Structure
The structural stability for the antigens is very important and always needed. If the structure is unstable then it will be a very poor antigen.
This depends upon the chemical structural complexity. The more complex chemical structure is more potent immunogen than simple chemical structure substances, which are week immunogen.
For example: If protein consists of different aminoacid like A-B-C-D-G are strong immunogen in comparison to A-A-A-A substance, which is a weak immunogen.
E. Route of Entry
Route of entry also influences the immune response. If it is exposed to the skin then may see the localized reaction, if it enters blood circulation then there is a generalized reaction. Possible route of entries are:-
- Natural: Gastrointestinal tract, and respiratory system.
- Artificial: Subcutaneous, Intramuscular, and Intravenous.
F. The dose of the Immunogen
For adequate immune response always there is need for optimum dose otherwise there may be no reaction with a smaller dose and even with larger doses.
G. Genetic Host Relation
There is an immune response gene (1r gene) that influences the immune response; it is different in different individuals.
The epitope is an antigenic determinant and these are small in size. These may be 4-5 aminoacid or monosaccharides.
These may be present on:
- The surface called topographical.
- Internal only expressed after processing by the APC.
The antigen has a variable number of epitopes varying from one to hundreds and this is called valency of antigen.
An epitope can be altered in the configuration by combination with other substances.
This is the Greek word means to fasten. These are partial antigens. These are not immunogenic. Mostly too small to be immunogenic.
Hapten needs carrier proteins like albumin, globulin, and synthetic polypeptide to become immunogenic.
Karl Land Steiner did an experiment:
He injected hapten with a carrier protein to Guinea Pig. The immune response took place, there was Antibody formation. Now he found that the antibody formed reacted with the hapten.
Examples are antibiotics, analgesic, penicillin, and alpha-methyldopa.
Therefore, haptens are antigenic, and not immunogenic.
This word is from Latin means “aiding and these are immunopotentiating agents. These are of two types:-
- General: – These potentiate both humoral and cellular immune response.
- Specific: – These potentiate only one class either B-lymphocytes (Humoral response) or T-lymphocytes (cellular response).
- The basic mechanism is that adjuvants give a slow release of antigen- adjuvant complex to the immune cells, so exposure time is prolonged.
- Adjuvants increase the size of the antigen.
- Adjuvants increase the efficiency of APC and increase lymphokines.
- Adjuvants increase antibody production.
- There is a decrease threshold dose of antigen.
- Adjuvants make weak antigens as potent and strong antigens.
General Adjuvant Examples
- Water and oil
- Aluminum hydroxide (Gel)
- Synthetic polynucleotide
- Bacterial endotoxin
Specific Adjuvants Examples
- Transfer factor (in cell-mediated immunity)
- Helper factor
Freunds Complete Adjuvant
It consists of killed Mycobacterium Tuberculosis and oil (in water emulsion). It increases cell-mediated response and antibody synthesis.
Freunds Incomplete Adjuvants
It consists of water in oil emulsion (water phase). It only increases the humoral response.