IMMUNOGENICITY

Introduction

Immune responses arise as a result of exposure to foreign stimuli. The compound that evokes the response is referred to either as antigen or as immunogen. The excellence between these terms is functional. An antigen is any agent capable of binding specifically to components of the immune system, like the B cell receptor (BCR) on B lymphocytes and soluble antibodies. against this, an immunogen is any agent capable of inducing an immune reaction and is therefore immunogenic. the excellence between the terms is necessary because there are many compounds that are incapable of inducing an immune reaction, yet they're capable of binding with components of the system that have been induced specifically against them. Thus all immunogens are antigens, but not all antigens are immunogens. This difference becomes obvious within the case of low molecular weight compounds, a gaggle of drugs that has many antibiotics and medicines. By themselves, these compounds are incapable of inducing an immune reaction but when they are including much larger entities, such as proteins, the resultant conjugate induces an immune reaction that is directed against various parts of the conjugate, including the low relative molecular mass compound. When manipulated in this manner, the low relative molecular mass compound is referred to as a hapten (from the Greek hapten, which means “to grasp”); the high relative molecular mass compound to which the hapten is conjugated is mentioned as a carrier.

Thus a hapten may be a compound that, by itself, is incapable of inducing an immune reaction but against which an immune response is often induced by immunization with the hapten conjugated to a carrier. Immune responses are demonstrated against all the known biochemical families of compounds, including carbohydrates, lipids, proteins, and nucleic acids. Similarly, immune responses to drugs, antibiotics, food additives, cosmetics, and little synthetic peptides also can be induced, but only these are coupled to a carrier.

Requirements for Immunogenicity

A substance must possess the subsequent characteristics to be immunogenic: (1) foreignness; (2) high molecular weight; (3) chemical complexity; and, in most cases, (4) degradability and interaction with host major histocompatibility complex (MHC) molecules.

Foreignness

Animals normally don't respond immunologically to themselves. Thus, for instance, if a rabbit is injected with its own albumin, it'll not mount an immune response; it recognizes the albumin as self. against this, if rabbit albumin is injected into a guinea pig, the guinea pig recognizes the rabbit albumin as foreign and mounts an immune reaction against it. To prove that the rabbit, which didn't answer its own albumin, is immunologically competent, it is often injected with guinea pig albumin. The competent rabbit will mount an immune reaction to guinea pig albumin because it recognizes the substance as foreign. Thus, the primary requirement for a compound to be immunogenic is foreignness. The more foreign the substance, the more immunogenic it's. Generally, compounds that are a part of self aren't immunogenic thereto individual. However, there are exceptional cases during which a private mounts an immune reaction against his or her own tissues. This condition is termed autoimmunity.

High Relative Molecular Mass

The second feature that determines whether a compound is immunogenic is its relative molecular mass. Generally, small compounds that have a relative molecular mass of but 1,000Da (e.g., penicillin, progesterone, aspirin) aren't immunogenic; those of molecular weights between 1,000 and 6,000Da (e.g., insulin, adrenocorticotrophic hormone [ACTH]) may or might not be immunogenic; and people of molecular weights greater than 6,000Da (e.g., albumin, tetanus toxin) are generally immunogenic. In short, relatively small substances have decreased immunogenicity whereas large substances have increased immunogenicity.

Chemical Complexity

The third characteristic necessary for a compound to be immunogenic may be a certain degree of physicochemical complexity. Thus, for instance, simple molecules like homopolymers of amino acids (e.g., a polymer of lysine with a relative molecular mass of 30,000Da) are seldom good immunogens. Similarly, a homopolymer of poly-γ-D glutaminic acid (the capsular material of Bacillus anthracis) with a relative molecular mass of fifty, Da isn't immunogenic.

The third characteristic necessary for a compound to be immunogenic may be a certain degree of physicochemical complexity. Thus, for instance, simple molecules like homopolymers of amino acids (e.g., a polymer of lysine with a relative molecular mass of 30,000Da) are seldom good immunogens. Similarly, a homopolymer of poly-γ-D glutaminic acid (the capsular material of Bacillus anthracis) with a relative molecular mass of fifty, Da isn't immunogenic. not only against the coupled low relative molecular mass compounds but also against the high relative molecular mass homopolymer. Generally, a rise within the chemical complexity of a compound is amid a rise in its immunogenicity. Thus copolymers of several amino acids, like polyglutamine, alanine, and lysine (poly-GAT), tend to be highly immunogenic.

Because many immunogens are proteins, it's important to know the structural features of those molecules. Each of the four levels of protein structure contributes to the molecule’s immunogenicity. The acquired immune reaction recognizes many structural features and chemical properties of compounds. for instance, antibodies can recognize various structural features of a protein, like its primary structure (the aminoalkanoic acid sequence), secondary structures (the structure of the backbone of the polypeptide chain, like an α-helix or β-pleated sheet), and tertiary structures (formed by the three-dimensional configuration of the protein, which is conferred by the folding of the polypeptide chain and held by disulfide bridges, hydrogen bonds, hydrophobic interactions, etc.). They will also recognize quaternary structures (formed by the juxtaposition of separate parts, if the molecule consists of quite one protein subunit).

Degradability

In contrast to B cells, so as for antigens to activate T cells to stimulate immune responses, interactions with MHC molecules expressed on antigen-presenting cells (APCs) must occur. APCs must first degrade the antigen through a process referred to as antigen processing (enzymatic degradation of antigen) before they will express antigenic epitopes on their surface. Epitopes also are referred to as antigenic determinants. they're a part of an antigen that's recognized by the system and are the littlest unit of antigen that's capable of binding with antibodies and T-cell receptors. Once degraded and noncovalently sure to MHC, these epitopes stimulate the activation and clonal expansion of antigen-specific effector T cells. A protein antigen’s susceptibility to enzymatic degradation largely depends on two properties: (1) it's to be sufficiently stable in order that it can reach the location of interaction with B cells or T cells necessary for the immune reaction, and (2) the substance must be vulnerable to partial enzymatic degradation that takes place during antigen processing by APCs. Peptides composed of D-amino acids, which are immune to enzymatic degradation, aren't immunogenic, whereas their L-isomers are vulnerable to enzymes and are immunogenic. against this, carbohydrates aren't processed or presented and are thus unable to activate T cells, although they will directly activate B cells.

In general, a substance must have all four of those characteristics to be immunogenic; it must be foreign to the individual, have a comparatively high relative molecular mass, possess a particular degree of chemical complexity, and be degradable.

Haptens

As noted earlier, substances called haptens fail to induce immune responses in their native form due to their low relative molecular mass and their chemical simplicity. These compounds aren't immunogenic unless they're conjugated to high relative molecular mass, physiochemically complex carriers. Thus an immune reaction is often evoked to thousands of chemical compounds—those of high relative molecular mass and those of low relative molecular mass, provided the latter are conjugated to high relative molecular mass complex carriers.

References :

1. Immunology 7th Edition by Richard Coico and Geoffery Sunshine.

2. The image is from Vecteezy.com.