Immunity
The word immunity was derived from Latin word “immunis,” meaning “exempt.” Immunity is the ability of an individual to protect against invading pathogenic microorganisms and cancer through interlinking networks of cellular and biochemical mechanisms collectively known as the immune system.
Two key features of the immune5.1.1 Classification of Immunity
The immunity can be classified on the basis of recognition of antigens or developmental and hereditary characteristics. On the basis of immune recognition, immunity can be classified into specific and nonspecific immunity. Nonspecific immunity responds equally to all pathogens to eliminate them. In
Table 5.1 Factors determining the antigenicity
| Foreignness | To elicit an immune response, an antigen must be treated as a foreign substance to the individual. |
| Chemical nature | Proteins have good immunogenic response followed by polysaccharides and lipopolysaccharides. The nucleic acids are poor immunogenic. The lipids usually lack immunogenicity. |
| Molecular size | The molecules having a molecular mass of 100,000 Da have good immunogenic potential. Substances with a molecular mass less than 5000-10,000 Da have poor immunogenicity. |
| Physical form | Particulate and denatured antigens are more immunogenic compared to soluble and native form, respectively. |
| Genetic factor | Some antigens are able to induce immunogenicity in a particular species. Bovine serum albumin is nonimmunogenic to cow, poorly immunogenic to goat, but strongly immunogenic to chicken. |
| Dose of the antigen | All antigens require a particular dose to elicit immune response. The optimal immune response will not be achieved above or below this dose level. |
| Route of administration | Intravenous administration of antigens carried first to spleen but antigens administered carried first to local lymph nodes. Therefore, subcutaneous route is better compared to intravenous route. |
| Age | Very young or very poor individuals have diminished immunogenic response against an antigen. |
| Degradability | To elicit an immune response, the antigens must be processed by antigen-presenting cells. Therefore, antigens that can be easily phagocytosed are having good immunogenic response. |
contrast, specific immunity uses different strategies for different microorganisms to neutralize them. On the basis of hereditary features, immunity can be classified as innate and adaptive immunity. The innate immunity is inborn and present before the onset of infection. Adaptive immunity comes into action after the pathogenic exposure. The innate immunity thus provides the first line of defense against invading pathogen and is less specific. In contrast, adaptive immunity is highly specific. The adaptive immune responses developed slowly after the exposure of pathogens or foreign materials, but a rapid response against pathogens was achieved in innate immune system that destroys the pathogens during the first critical hours of its exposure. One of the striking features of adaptive immunity is the memory, which means the initial exposure of any pathogen results in memory response and a quick and stronger response is achieved after the second exposure of the same pathogen.
5.1.2 Antigens
The molecules that induce humoral and cell-mediated immune response are called immunogens, and their ability to induce immune response is termed as immunogenicity. Immunogens after binding with B cells generate activated B cells to produce antibody.
The binding of antigens with T-cell receptors leads to activation of T cells (cytotoxic T lymphocytes). The term antigens are not synonymous with immunogens. Antigens are the molecules that bind specifically with products of immune response induced by immunogens (i.e., antibodies or cytotoxic T lymphocytes), and this property is called antigenicity. An antigen may not be immunogenic if it fails to induce an immune response. Certain molecules like haptens (discussed later) can bind with T or B cells but fail to activate them. An antigen is said to be immunogen only when it can be able to induce an immune response (activation of humoral or cell-mediated immune response). Thus, it can be said that all immunogens are antigens, but not all antigens are immunogens. Some body cells like sperm and corneal cells may cause immunoreaction if injected in the same animal.5.1.2.1 Determinants
of AntigenicityZImmunogenicity
There are several factors that determine the antigenicity (Table 5.1).
5.1.2.2 Types of Antigens
The antigens can be classified on the basis of their source and immune response.
5.1.2.2.1 Classification Based on Source
Exogenous antigens: They enter inside the body from outside and are processed by antigen-presenting cells. Some antigens are exogenous at the beginning but later become endogenous, e.g., viral antigens.
Endogenous antigens: These antigens are produced within the body. They are usually body’s own cells or cell products such as corneal tissue, blood group antigens, and HLA (histocompatibility leukocyte antigens). There are several types of endogenous antigens like autoantigens (person’s own self antigens, e.g., thyroglobulin, corneal tissue, DNA) and alloantigens (found in different members of the same species, e.g., red blood cell antigens A and B).
5.1.2.2.2 Classification Based on Immune Response
Complete Antigen or Immunogen: They are capable to induce immune response by their own. They are usually proteins or polysaccharide in nature having a molecular weight above 10,000 Da.
Incomplete Antigen or Hapten: They are low-molecular- weight (below 10,000 Da) substances that react with its corresponding antibody but unable to induce immune
Table 5.2 Different components of innate and adaptive immunity
| Immunity | Anatomical barrier | Physiological barrier | Cellular | Humoral |
| Innate immunity | Skin and mucous membrane | Body temperature, pH | Dendritic cells, granulocytes, mononuclear phagocytic system (MPS), dendritic cells (DCs), innate lymphoid cells (ILCs), natural killer (NK) cells, epithelial and endothelial cells, platelets, pattern recognition receptors | Inflammatory serum proteins/acute-phase proteins (APPs), antimicrobial peptides (AMPs), complement system, cytokines, interferons |
| Adaptive immunity | B lymphocytes, T lymphocytes | Antibodies |
response by their own. Their immunogenic property can by augmented by carrier molecules (albumin or globulin), e.g., pneumococcal capsular polysaccharide, polysaccharide C of Streptococci, and cardiolipin antigens.
Superantigens: These antigens are able to activate a large proportion of T cells (up to 25%) in comparison to conventional antigens that are able to induce only 1-2% T cells. The superantigens cause hyperactivation of immune system. Pyrogenic exotoxins (lead to shock) and enterotoxins (lead to food poisoning) of Staphylococci are the examples of superantigens.
5.1.2.3 Epitopes
Epitopes are the antigenic determinants, a small site of an antigen that can activate immune response by activating T or B cells. Based on the specificity of binding, epitopes can either be B-cell epitopes or T-cell epitopes.
B-cell epitopes bind with antibody, and T-cell epitopes bind with T-cell receptor after presented with MHC molecules by antigenpresenting cells. The properties of an epitope are required to design vaccines.5.1.2.4 Adjutants
Adjuvants are the substances that enhance the immunogenicity of an antigen by one of the following mechanisms:
• Acting as a depot and leading to sustained release of an antigen from the site of delivery
• Stimulating the production of cytokines and chemokines
• Facilitating the recruitment of immune effector cells at the site of delivery
• Helping in antigen uptake and further processing and presentation by antigen-presenting cells
• Activating inflammatory mediators
The common examples of adjuvants are Freund’s complete adjuvant (containing inactivated Mycobacterium tuberculosis in oil, alum nonionic surfactants, and muramyl peptides). There are adjuvants licensed for human use such as MF59, AS04, and virosomes.
5.1.3 ComponentsofImmuneSystem
The immune system is equipped with several components like anatomical and physiological barriers, immune effector cells and cell surface receptors, inflammatory serum proteins, antimicrobial peptides, and antibodies to inhibit the entry pathogens, which resist the establishment of infection along with clearing of host and microbial debris from the site of infection. Some of the components are cellular, and some components circulate freely in the body fluids called humoral factors. Table 5.2 summarizes different components of innate and adaptive immunity.
5.2