Factors affecting production of antibodies
Many factors affect the production of antibodies. These factors are discussed below:
Genetic factors influence the response of the host to antigen. Persons responding to antigens are called responders, while persons not responding are called nonresponders. These dif-ferences are controlled genetically and are being controlled by immune response (Ir) gene located in the short arm of the 6th chromosome.
The embryo and the infant, at birth, are not fully immunologi-cally competent. Full competence is achieved by about the age of 5–7 years for IgG and 10–15 years for IgA by the development of lymphoid organs.
Malnutrition affects both the humoral and cell-mediated immunities. Deficiencies of amino acid and vitamins have shown to decrease the production of antibodies.
Induction of immune response in a host depends on the route of administration of the antigen. Parenteral administration of the antigen induces a better immune response than the oral or nasal routes.
A minimum critical dose of antigen is essential to elicit an opti-mum immunological response. A very high or small dose fails to stimulate the immune system. This phenomenon is referred to as immunological paralysis.
Antibody responses vary when two or more antigens are admin-istered simultaneously. Antibody responses to one or more of them may be diminished due to antigenic competition, or enhanced as seen after vaccination with triple vaccine (diph-theria, pertussis, and tetanus), or may be similar. Hence, the nature and relative proportions of different antigens should be carefully adjusted for optimal effect.
Adjuvants are the substances that enhance the immuno-genicity of an antigen. The adjuvants delay the release of an antigen from the site of injection and prolong the anti-genic stimulus. The substances that are used as adjuvants include:
a) Freund’s incomplete adjuvant (protein antigen incorpo-rated in water phase of water in oil emulsion);
b) Freund’s complete adjuvant (incomplete adjuvant along with suspension of killed tubercle bacilli);
c) Aluminum salts both phosphate and hydroxide; and
d) Others, such as silica particles, beryllium sulfate, endo-toxin, etc.
Immunosuppressive agents are those that suppress immune response. They are used in transplantation surgery and in situ-ations that require suppression of host immunity. The agents are as follows:
X-irradiation: Sublethal dose of irradiation is toxic to replicat-ing cells and is used to suppress antibody formation. Antibody production ceases after 24 hours of receiving irradiation.
Radiometric drugs: These include alkylating agents (such ascyclophosphamide, nitrogen mustard, etc.), which suppress antibody production. Cyclophosphamide, given for 3 days, completely suppresses the antibody response. It selectively prevents replication of B cells.
Corticosteroids: Corticosteroids are anti-inflammatory drugsthat diminish the responsiveness of both B and T cells. They alter maturation of activated cells by suppressing the production of interleukins. They suppress delayed hypersensitivity, but in therapeutic doses for a short period, they have little effect on the production of antibodies.
Antimetabolites: These include folic acid antagonists (such asmethotrexate); analogs of purine (6-mercaptopurine and azathi-oprine); and analogs of cytosine (cytosine arabinose); and uracil (5-fluorouracil). These substances inhibit DNA and RNA syn-thesis, thereby inhibiting the cell division and differentiation, which is essential for cellular and humoral immune responses. These are usually used for prevention of graft rejection.
Antilymphocyte serum: Antilymphocyte serum (ALS) is aheterogeneous antiserum raised against T lymphocytes. The ALS acts mainly against circulating lymphocytes but not against lymphocytes in lymphoid organs. It is mainly used to prevent graft rejection in transplantation surgery.
Antibodies that arise from a single clone of cells (e.g., myeloma) are homogenous and are called monoclonal antibodies. For example, in multiple myeloma, antibodies are produced by a single clone of plasma cells against a single antigenic determi-nant, and hence antibodies are monoclonal. The monoclonal antibodies differ from polyclonal antibodies, which are heter-ologous and are formed by several different clones of plasma cells in response to antigen.