Antigen - Definition, Types, Structure, Properties

Antigen Definition

Antigens are molecules that stimulate the development of antibodies and provoke an immunological response.

Antigens are defined as molecules that can be identified by the immunoglobulin receptor of B cells or the T-cell receptor when complexed with major histocompatibility complex (MHC).

Antigens are big protein molecules found on the surface of pathogens like bacteria, fungi, viruses, and other foreign particles.

When these hazardous chemicals enter the body, they stimulate the formation of antibodies by the immune system.
For instance, when a typical cold virus enters the body, it triggers the production of antibodies to avoid illness.

Antigen is an abbreviated abbreviation of the phrase “antibody generator.”
Immunogens are chemicals that elicit an immunological response.
In the majority of instances, antigens and immunogens are used interchangeably.

Haptens are antigens that are not immunogenic but can nonetheless trigger immunological responses.
Immunogenicity refers to the ability of an antigen to trigger an immune response in the form of a B-cell or T-cell response, whereas antigenicity refers to the ability of an antigen to combine precisely with the products of the aforementioned responses.
Immunogenic molecules are also antigenic, although antigenic molecules cannot all be deemed immunogenic.

Consequently, haptens lack immunogenicity.

Properties of Antigens

These are the qualities of antigens:

The antigen must be a foreign material in order to elicit an immunological response.

Antigens have a molecular weight between 14,000 and 6,000 Da.
They consist primarily of proteins and carbohydrates.
The greater their molecular complexity, the greater their immunogenicity.

Antigens are particular to a species.
Age has an effect on immunogenicity. Very young and elderly individuals have a very low immunogenicity.

Structure of antigens

Antigens are typically proteins, peptides, or polysaccharides that make up the components (coats, capsules, cell walls, flagella, fimbrae, and poisons) of bacteria, viruses, and other microbes.

Epitope is the smallest unit of antigen that is recognised by immune cells; it is also known as antigenic determinant.
Epitope consists of 4-5 amino acid residues or monosaccharides.
Have a distinct chemical structure, electric charge, and spatial arrangement.

It is possible for a single antigen to have many types and copies of epitopes.
The epitopes interact with the paratope on the antibody.

Characteristics/ Determinants of Antigenicity/ Factor affecting the Antigenicity of Antigen

Several factors have been identified that contribute to the immunogenicity of a drug. Among the most important antigenicity determinants are: 1. Molecular size 2. Extraterritoriality 3. Chemical-structural complexity 4. Stability 5. Other variables

The Nature of the Immunogen Contributes to Immunogenicity

1. Molecular Size

Protein molecules with a high molecular weight are typically highly allergenic.
In general, compounds having molecular weights of less than 5000 Da are not immunogenic.
Using high molecular weight proteins such as bovine gamma globulin (MW 150,000 Da) to elicit an immunological response has been utilised to leverage this characteristic in experimental research.

Low-molecular-weight substances can be rendered antigenic by adsorption on carrier particles such as bentonite, kaolin, and other inert particles.

2. Foreignness

A molecule must be recognised as nonself, or foreign, in order to be immunogenic.
The immune system classifies the molecule as self or nonself depending on whether or not it was exposed to the immune system during foetal development.

Foreignness entails the host’s capacity to accept selfantigens.
Tolerance to self-antigens develops by contact with them throughout the early stages of immune system development, namely during lymphocyte development.
The less closely two species are related, the greater the immunogenicity of a molecule from one species when exposed to the other.

The bovine serum albumin, for instance, is more immunogenic in chickens than in goats.
A graft from an unrelated human will be rejected within two weeks if immunosuppressive medicines are not utilised, however a chimpanzee graft will be rejected within hours regardless of the use of drugs.
In contrast, a kidney transplant from an identical twin is readily approved.

3. Chemical-Structural Complexity

The most potent immunogens are proteins, followed by polysaccharides.
Although they may serve as haptens, nucleic acids and lipids are ineffective at inducing a strong immunological response.
Complexity of a protein’s structure contributes to its immunogenicity.

Single-amino acid or single-sugar chains are not very immunogenic, but when many amino acids or sugars are joined inside the same molecule, the immunogenicity is substantially boosted.
In cell-mediated immunity, the response of T cells to the peptide component of proteins is dependent on the manner in which the peptide is detected and presented by MHC cells.
Consequently, the shape of a protein plays a significant impact in its immunogenicity, particularly in eliciting cellular immunity.

Since lipid-specific antibodies are difficult to manufacture, they do not play a significant role in immunity.
Nonetheless, these antibodies play an important role in the assessment of particular lipid-based compounds and medications.
These antibodies are created by first treating lipids with haptens, followed by conjugation with appropriate carrier molecules, such as proteins (e.g., hemocyanin or bovine serum albumin).

4. Stability

Immunogenic are not things that are highly stable and nondegradable, such as some polymers, metals, or chains of D-amino acids.
This is due to the fact that internalisation, processing, and presentation by antigen-presenting cells (APCs) are always required for an immune response to be mounted.
Therefore, extremely stable compounds (such as silicon) have been effective as nonimmunogenic materials for reconstructive procedures, such as breast augmentations.

In contrast, if a chemical is extremely unstable, it may degrade before an APC can internalise it, hence becoming immunogenic.
Large, insoluble complexes are also more immunogenic than smaller, soluble ones. This is because macrophages find insoluble complexes easier to phagocytose, breakdown, and present than soluble ones.

5. Lipids As Antigens

Lipoidal antigens that are appropriately delivered can stimulate B- and T-cell responses. Lipids are employed as haptens and coupled to suitable carrier molecules, such as the proteins keyhole limpet hemocyanin (KLH) or bovine serum albumin, for the stimulation of B-cell responses (BSA).

By immunising with these lipid-protein conjugates, antibodies that are highly specific for the target lipids can be produced.
Using this method, antibodies against a wide range of lipid compounds, including steroids, complex fatty-acid derivatives, and fat-soluble vitamins such as vitamin E, have been produced. Numerous clinical assays for the presence and quantities of medically significant lipids are antibody-based, hence these antibodies are of great practical value.
A determination of the amounts of leukotrienes, a complicated group of lipids, can be helpful in evaluating asthma patients, for instance. Prednisone, an immunosuppressive steroid, is frequently used as part of the endeavour to prevent organ rejection.

6. Susceptibility To Antigen Processing And Presentation

T cells must engage with antigen that has been processed and presented in conjunction with MHC molecules for the establishment of both humoral and cell-mediated immune responses.
Large, insoluble macromolecules are often more immunogenic than small, soluble macromolecules, as the larger molecules are more readily phagocytosed and digested.
Immunogens that cannot be destroyed and delivered to MHC molecules are ineffective. This is exemplified by polymers of D-amino acids, which are stereoisomers of naturally occurring L-amino acids.

Due to the fact that the degradative enzymes within antigen-presenting cells can only degrade proteins containing L-amino acids, polymers of D-amino acids cannot be digested and are therefore ineffective immunogens.

The Biological System Contributes to Immunogenicity

1. Biological system

In determining the immunological effectiveness of an antigen, biological system also plays a crucial role.
Certain chemicals are immunogenic in some people but not others (i.e., responders and nonresponders). Individuals may lack or have altered genes that code for antigen receptors on B cells and T cells, or they may lack the genes required for APC to transmit antigen to helper T (TH) cells.

2. Immunogen Dosage And Route Of Administration

Antigen immunogenicity is also affected by the antigen’s dosage and the method through which it contacts the immune system.
Extremely low antigen doses do not activate immunological response, either because too few lymphocytes are touched or because a nonresponsive condition is induced.
In contrast, an exceedingly high dose does not induce tolerance. It may be necessary to administer antigens repeatedly (booster doses) to improve the immunological response of the host to certain antigens.

In the case of vaccines, when a minimum degree of immunity must be obtained, this is of special significance. To ensure adequate levels of protective antibodies, booster doses of vaccines such as DPT (Diphtheria, Pertussis, Tetanus), DT (Diphtheria, Tetanus), etc. are administered.
Antigens are typically delivered parenterally in order to create enough levels of antibodies.
Antigens can be administered intravenously, subcutaneously, intradermally, intramuscularly, intraperitoneally, and mucosally.

Typically, subcutaneous injection is superior to intravenous treatment for triggering an immunological response.

3. Adjuvants

Adjuvants are chemicals that, when combined with an antigen and injected with it, enhance the antigen’s immunogenicity. Adjuvants enhance the intensity and persistence of an immunological response. In numerous ways, adjuvants augment the immunogenicity of antigens:

4. Genotype Of The Recipient Animal

The genetic makeup (genotype) of an inoculated animal determines both the type and intensity of the immunological response the animal displays.

Hugh McDevitt demonstrated, for instance, that two distinct inbred mouse strains respond quite differently to a synthetic polypeptide immunogen.
One strain produced large quantities of serum antibody after exposure to the immunogen, while the other strain produced modest levels.
When the two strains were crossed, the F1 generation exhibited a moderate immunogenic response.

The gene governing immunological response was localised to a subregion of the major histocompatibility complex by backcross research (MHC).
Numerous trials with simply specified immunogens have proven genetic control of immunological responsiveness, which is predominantly confined to MHC genes.
These findings suggest that MHC gene products, which serve to present processed antigen to T cells, play a crucial role in regulating the degree to which an animal responds to an immunogen.

The response of an animal to an antigen is also affected by genes encoding B-cell and T-cell receptors as well as genes encoding proteins involved in immune regulation systems.
The immunogenicity of a specific macromolecule varies among animals based on the genetic diversity of these genes.

Specificity of Antigen

1. Antigenic Specificity

The antigen’s antigenic specificity is determined by antigenic determinants or epitopes.

Epitopes

A portion of an immunogen that binds to antigen-specific membrane receptors on lymphocytes or released antibodies is referred to as an epitope.
The interaction between immune system cells and antigens occurs on multiple levels, and the complexity of an antigen is reflected in its epitope.
B-cell epitopes and T-cell epitopes are the two types of epitopes.

a. B-cell epitopes

B-cell epitopes are antigenic determinants recognised by B lymphocytes. Only if the antigen molecule is in its original state can B-cell epitope connect with its receptor.
It would appear that the corresponding surfaces of the antibody and antigen molecules are generally flat.
Typically, smaller molecules fit snugly within a specific depression or groove in the antigen-binding site of an antibody molecule.

The length of the B-cell epitope is approximately six or seven sugar residues or amino acids. B-cell epitopes are typically hydrophilic and frequently situated at protein structural bends.
They are also frequently located in areas of proteins that are more mobile; this may allow an epitope to shift slightly to fit into a nearly-perfect location.

b. T-cell epitopes

T cells detect amino acids in proteins but do not recognise polysaccharide or nucleic acid antigens.

This is why polysaccharides are regarded T-independent antigens whereas proteins are called T-dependent antigens.
Antigenic determinants identified by T cells are established by the main sequence of amino acids in proteins.
T cells do not identify free peptides, but they do recognise the complex of MHC molecules and peptide.

In order for a T-cell response to occur, the T-cell must recognise both the antigenic determinant and the MHC; consequently, it is MHC restricted.
In general, the length of T-cell epitopes or antigenic determinants is between 8 and 15 amino acids.
Antigenic determinants are restricted to antigen regions that can bind to MHC molecules.

Given that MHC molecules are vulnerable to genetic diversity, T-cell responses to the same stimuli can vary between individuals. Each MHC molecule can bind numerous peptides, but not all.
In order for a peptide to be immunogenic in a certain individual, that individual must possess MHC molecules capable of binding to it.

Processing of an antigen by APCs

Antigen processing by APCs is extremely important for T cell recognition. Two distinct methods of processing can prepare a protein antigen for presentation as an antigen. These consist of:

Processing externally generated antigens: In this process, phagocytic cells, such as macrophages, destroy and lyse phagocytosed microorganisms. The bacterium fragments are subsequently given within the framework of class II MHC molecules.
Processing of endogenously produced antigens: In this step, viral proteins created within a cell are processed and displayed in the context of class I MHC molecules.

2. Species Specificity

Certain species-specific antigens are present in the tissues of every member of a species. However, there is some cross-reactivity across antigens from closely related species. The specificity of the species indicates phylogenetic relationship. The phylogenetic relationship is useful for:

tracing species’ evolutionary relationships.
In forensic medicine, the identification of species from blood and seminal fluid stains.

3. Isospecificity

Isospecificity is determined by the presence of isoantigens or histocompatibility antigens.

Isoantigens

Isoantigens are antigens found in a subset of a species’ members.
A species can be classified based on the existence of distinct isoantigens in its individuals.
These are decided genetically. Human erythrocyte antigens, which are used to classify individuals into various blood groups, are the best examples of isoantigens in humans.

The blood types play a crucial role in:
- Blood transfusion and transfusion of blood products.
- Isoimmunization during pregnancy.
- Providing crucial evidence in paternity disputes, the results of more modern DNA fingerprinting tests enhance these results.

Histocompatibility

Antigens Histocompatibility antigens are the species-specific biological determinants for each individual.
These antigens are connected with tissue cell plasma membranes.

Human leukocyte antigen (HLA) is the primary histocompatibility antigen that determines the rejection of a homograft.
Before transplanting tissue or organs from one individual to another, HLA typing is therefore critically necessary.

4. Autospecificity

In general, self-antigens are not antigenic. Sequestered antigens (such as protein from the eye lens and sperm) are exceptions, as they are not identified as selfantigens.

This is because the immune system never encounters ocular tissue or sperm during the establishment of self-antigen tolerance.
Therefore, if these tissues are unintentionally or experimentally discharged into the blood or tissues, they become immunogenic.

5. Organ Specificity

Antigens that are specific to a particular organ or tissue are known as organ-specific antigens. The antigen specificity of these antigens discovered in the brain, kidney, and lens tissues of diverse animal species is identical.

Antigens unique to organs, such as brain-specific antigens, are shared by the human and sheep brains.
When administered, antirabies vaccinations made from sheep brain may provoke an immunological response in some humans, resulting in harm to the recipient’s neural structures.
Some individuals may get neuroparalytic problems as a result.

6. Heterophile Specificity

The presence of heterophile antigens determines the specificity of heterophiles. Heterophile antigens are identical or closely related antigens that are sometimes found in the tissues of distinct biological species, groups, or kingdoms.
Antibodies against heterophile antigens produced by one species react with antigens produced by other species.
This characteristic is utilised for the diagnosis of numerous infectious disorders. Examples of serological assays that involve heterophile antigens include the Weil–Felix reaction, the Paul-Bunnell test, and cold agglutination tests.

Types of Antigens

Types of Antigens On the basis of Origin

Different types of antigens exist based on their origin:

1. Exogenous Antigens

Exogenous antigens are antigens that enter the body externally, such as via inhalation, injection, etc.
These include allergens in food, pollen, and aerosols, among others, and are the most prevalent type of antigens.

Responses of the immune system to foreign antigens are frequently subclinical. Exogenous antigens are taken up by antigen-presenting cells (APCs) via endocytosis or phagocytosis and fragmented.
APCs subsequently deliver the fragments to T helper cells (CD4+) via their surface molecules of class II histocompatibility. Specific T lymphocytes recognise the peptide:MHC complex.
They get activated and begin to generate cytokines, which stimulate the activation of cytotoxic T lymphocytes (CTL), antibody-secreting B cells, macrophages, and other particles.

Some antigens begin as exogenous and eventually transform into endogenous (for example, intracellular viruses).
Upon the demise of the infected cell, intracellular antigens can be reintroduced to circulation.

2. Endogenous Antigens

Due to viral or bacterial infections or cellular metabolism, endogenous antigens are produced within the body.

Normal cells develop endogenous antigens as a result of normal cell metabolism or a viral or intracellular bacterial infection.
The fragments are displayed on the cell surface in the presence of MHC class I molecules.
If activated cytotoxic CD8+ T cells recognise them, they produce a variety of poisons that result in the lysis or death of the infected cell.

To prevent the cytotoxic cells from killing cells just by presenting self-proteins, the self-reactive T cells (cytotoxic cells) are destroyed as a result of tolerance (negative selection).
There are three types of endogenous antigens: xenogenic (heterologous), autologous, and idiotypic or allogenic (homologous). Antigens are sometimes a part of the host in autoimmune diseases.

3. Autoantigens

Due to genetic or environmental modifications, autoantigens are’self’ proteins or nucleic acids that are attacked by the body’s immune system, resulting in autoimmune disorders.

Autoantigens are often self-proteins or protein complexes (and occasionally DNA or RNA) that are recognised by the immune system of patients with a particular autoimmune illness.
These self-proteins should not be the target of the immune system under normal circumstances, but in autoimmune disorders, their associated T cells are not eliminated and instead assault.

4. Tumour Antigens

MHC-I and MHC-II are examples of antigenic substances found on the surface of tumour cells that induce an immunological response in the host.

Numerous tumours evolve mechanisms to elude the body’s immune system.
Tumor antigens are effective tumour markers for detecting tumour cells with diagnostic testing and are possible therapeutic agents for cancer.
Cancer immunology is the study of such subjects.

On the basis of their pattern of expression, tumour antigens were initially generally divided into two types.
1. Tumor-Specific Antigens (TSA): antigens found exclusively on tumour cells and no other cells.
2. Tumor-Associated Antigens (TAA): antigens that are found on both normal and tumour cells.

5. Native Antigens

Native antigens are antigens that have not yet been processed by an antigen-presenting cell.

Types of Antigens On the Basis of Immune Response

Based on the immunological reaction, antigens are categorised as:

1. Complete antigens/ Immunogen

Immunogens or complete antigens are antigens that induce a specific immune response.

These antigens can stimulate an immunological response without the need for carrier particles.
High molecular weight proteins, peptides, or polysaccharides are typically present (greater than 10,000 Da).

2. Incomplete antigens/ Hapten

These are non-protein, foreign compounds that necessitate a carrier molecule in order to elicit an immune response.

Haptens are antigenic but not immunogenic tiny chemical compounds. They lack immunogenicity because they are incapable of activating T helper cells.
They cannot bind because they are not proteins, and only proteins can be presented by MHC proteins.
Moreover, because haptens are univalent, they cannot independently activate B cells. However, the haptens can activate B cells when covalently attached to a “carrier” protein.
They create an immunogenic hapten–carrier combination when attached to a carrier molecule.
During this process, the haptens connect with an IgM receptor on the B cells, resulting in the internalisation of the hapten–carrier protein complex.
A peptide of the carrier protein is delivered to helper T cells in conjunction with a class II MHC protein. Activated helper T cells subsequently create interleukins, which drive B cells to produce antibodies against hapten.
Animals inoculated with such a compound generate antibodies specific for (a) the hapten determinant, (b) unmodified epitopes on the carrier protein, and (c) novel epitopes created by the combination of portions of the hapten and carrier.
The hapten epitopes bind the hapten-carrier molecule to the surface immunoglobulins of B lymphocytes.
These B cells and TH cells then absorb the hapten–carrier molecule, digest it, and present fragments of the carrier.
The synthesis of hapten–carrier conjugates in the body is the cause of drug-induced allergic reactions, such as penicillin hypersensitivity.

Antigen Presenting Cells (APCs)

Antigen-presenting cells are cells that can absorb antigen and provide pieces to T cells (APCs). In the body, there are three types of antigen-presenting cells: macrophages, dendritic cells, and B cells.

Different Types of Antigen Presenting Cells

1. Macrophages

Typically, macrophages are present in a resting state. When induced to become activated macrophages, their phagocytic capacities are significantly enhanced.
Almost all lymphoid tissues contain macrophages alongside lymphocytes, such as monocytes as blood macrophages and histocytes as tissue macrophages.

2. Dendritic Cells

These cells are distinguished by their lengthy cytoplasmic processes.
Their principal job is to serve as very efficient antigen-capture and antigen-presentation cells.
These cells are incapable of phagocytosis. The lymph nodes, spleen, thymus, and skin contain these cells.
These are the various types of dendritic cells:
- Langerhan’s dendritic cells: The epidermis of skin contains dendritic cells of Langerhans that capture organisms coming into touch with the body surface.
- Dendritic cells in spleen: The spleen contains dendritic cells that capture the antigen in the blood.
- Follicular dendritic cells: In lymph nodes, follicular dendritic cells capture the antigen in the lymph.
Therefore, macrophages and dendritic cells play a crucial role in the capture and presentation of antigens to T and B cells in order to trigger an immune response.
Steinman received the 2011 Nobel Prize for his discovery of the dendritic cell and its function in adaptive immunity.

3. B-cells

B-cells express intramembrane immunoglobulin (Ig) molecules that serve as V cell antigen receptors on their surface.
Due to the fact that all the receptors on a V cell are identical, each V cell can only connect to a single antigen.
This makes them significantly more effective antigen-presenting cells than macrophages, which must consume any foreign material they encounter.
Descendants of V-cells (plasma cells) generate antibodies.

Antigen-antibody Complex Formation

The antigen is not harmed by the antibody’s binding to the antigen. However, it triggers the elimination of pathogens via various immunological mechanisms, including agglutination, complement activation, neutralisation, opsonization, and antibody-dependent cell-mediated cytotoxicity.
In agglutination, antibodies bind to a large number of antigens, causing them to aggregate. Consequently, the number of infectious organisms that can be easily phagocytosed reduces.
Antibodies trigger the activation of the complement system, which produces inflammation and microbial lysis, during complement activation.
To neutralise a virus, antibodies surround it, preventing it from attaching to the host cell. Similar to how they can neutralise bacterial poisons.
The antigen-antibody complex or complement proteins can enhance pathogen uptake by phagocytic cells during opsonization.
Antibody-dependent cell-mediated cytotoxicity is similar to opsonization in which antibodies cover the antigen; but, in antibody-dependent cell-mediated cytotoxicity, the target cell is destroyed by natural killer cells or eosinophils that do not enter the target cell.
Some diseases are capable of evading the immune response against antigens by modifying their antigens, a process known as antigenic variation.

Antigen Processing and Presentation

Self-antigens are a natural constituent of the cells of the body. As a mechanism of autoimmune suppression, B and T cells that cannot recognise self-antigens are killed by apoptosis, but normal B and T cells disregard self-antigens.
Nevertheless, injury, infection, or defective apoptosis can stimulate the immune response to self-antigens, resulting in an autoimmune illness.
Antigens of intracellular pathogens that infect cells do not come into touch with circulating antibodies, hence they are not displayed.
Intracellular immunity can aid in the eradication of intracellular infections and aberrant cells, including cancer cells.
T-cells are responsible for the confronting of intracellular antigens; they are more prevalent in the lungs and gastrointestinal system, where the majority of intracellular antigens enter the body.
These antigens are then transferred to antigen-presenting cells or lymphocytes in order to be detected by antibodies by antigen-presenting cells or lymphocytes.
Antigen-presenting cells are cells that ingest antigens and present them to other immune cells in order for them to confront the antigen.
B-cells, dendritic cells, and macrophages are antigen-presenting cells. The antigen processing and presentation process is mediated by Major histocompatibility complex (MHC) class I and MHC class II located on the surface of antigen-presenting cells.
Dendritic cells and macrophages move to lymph nodes to deliver antigens to T-cells in lymph nodes following antigen uptake. Then, T-cells that are specific for this antigen travel to the antigen location to meet it.

Examples of Antigen

As stated above, there are various sorts of antigens. They can be categorised based on their origins as foreign antigens, endogenous antigens, and autoantigens, respectively. Exogenous antigens are digested and presented on MHC class II, whereas endogenous antigens are presented on MHC class I, hence inducing a variety of immune responses.
Exogenous antigens may originate from microbes, donated organs or tissues, or allergies. They are classified as MHC category II.
Endogenous antigens are antigens that are generated within the cell and are typically present due to viral or parasite infection. On changed cells such as tumour cells or infected cells, there are also endogenous cells.
The endogenous antigen is recognised by cytotoxic T-cells (CTL) on MHC class I, allowing CTL to assault infected or changed cells by releasing perforin, which creates pores in the cell membrane, resulting in the cell’s death.
Autoantigen is a self-antigen; it is a natural component of the cell that the immune system recognises, resulting in an autoimmune illness. Self-antigens normally do not stimulate an immune response because they are naturally present in the body. However, in autoimmune illnesses, the natural self-antigens trigger abnormal immune cells.

Key Point

In the Weil–Felix reaction, strains of Proteus species (such as OX 19, OX 2, and OX K) are used to detect heterophile antibodies produced in response to rickettsial pathogens.
By demonstrating heterophile antibodies that agglutinate sheep erythrocytes, the Paul–Bunnell test is utilised to diagnose infectious mononucleosis caused by Epstein–Barr virus infection.
By demonstrating heterophilic antibodies, a cold agglutinin test is performed to diagnose primary atypical pneumonia caused by Mycoplasma pneumoniae.

What are Superantigens?

Superantigens are a class of molecules that can interact nonspecifically with APCs and T lymphocytes.
By interacting with MHC class II molecules of the APC and the Vb domain of the T-lymphocyte receptor, superantigens exert distinct effects.
This interaction activates a greater proportion of T cells (10%) than conventional antigens (1%), resulting in massive cytokine production and immunomodulation.
Staphylococcal enterotoxins, toxic shock syndrome toxin, exfoliative toxins, and certain viral proteins are examples of superantigens.

Examples of Bacterial Superantigens and their roles

Staphylococcal enterotoxins are the cause of food poisoning.
Toxic shock syndrome caused by the Staphylococcal toxin TSST-1
Scalding skin condition due to Staphylococcal exfoliating toxins
Streptococcal pyrogenic exotoxins (exotoxins A and B)

What is Adjuvant?

Adjuvants (from the Latin adjuvare, to aid) are chemicals that enhance the immunogenicity of an antigen when mixed with it and administered.
When an antigen has poor immunogenicity or when only a little amount of an antigen is available, adjuvants are frequently utilised to stimulate the immune system.
If BSA is delivered with an adjuvant, for instance, the antibody response of mice after immunisation with BSA can be boosted by a factor of five or more.
It is not totally understood how adjuvants enhance the immune response, however they appear to exert one or more of the following effects:
- Antigen persistence is prolonged.
- Co-stimulatory signals are enhanced.
- Local inflammation is increased.
- The nonspecific proliferation of lymphocytes is stimulated.
Aluminum potassium sulphate (alum) increases the antigen’s persistence. When an antigen is combined with alum, the salt causes the antigen to precipitate.
Injection of this alum precipitate causes a slower release of antigen from the injection site, hence increasing the effective exposure duration to the antigen from a few days without adjuvant to several weeks with adjuvant.
Additionally, the alum precipitate enlarges the antigen, hence boosting the possibility of phagocytosis. Additionally, water-in-oil adjuvants extend antigen persistence.
Freund’s incomplete adjuvant consists of antigen in aqueous solution, mineral oil, and an emulsifying ingredient such as mannide monooleate that disperses the oil into small droplets surrounding the antigen; the antigen is thus released very slowly from the injection site.
This treatment is based on Freund’s complete adjuvant, the first purposefully formulated, extremely efficient adjuvant, which was created by Jules Freund many years ago and contains heat-killed Mycobacteria as an extra component.
Muramyl dipeptide, a component of the mycobacterial cell wall, stimulates macrophages, rendering Freund’s complete adjuvant considerably more effective than its incomplete counterpart.
Activated macrophages are more phagocytic than unactivated macrophages and express more class II MHC molecules and B7 family membrane molecules.
The increased expression of class II MHC enhances the antigen-presenting cell’s capacity to present antigen to T-helper cells. B7 molecules on the antigen-presenting cell attach to CD28, a cell-surface protein on TH cells, inducing co-stimulation, an intensification of the T-cell immunological response.
In the presence of adjuvant, antigen presentation and the necessary co-stimulatory signal are often enhanced.
Alum and Freund’s adjuvants also induce a prolonged, local inflammatory response that draws both phagocytes and lymphocytes.
This infiltration of cells at the site of adjuvant injection frequently culminates in the creation of a granuloma, a thick, macrophage-rich mass of cells. Due to the activation of macrophages within a granuloma, this technique also promotes the activation of TH cells.
Other adjuvants (such as synthetic polyribonucleotides and bacterial lipopolysaccharides) improve the chance of antigen-induced clonal selection of lymphocytes by stimulating nonspecific lymphocyte proliferation.

References

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