The following points highlight the top two types of immune response. The types are: 1. Humoral Immune Response 2. Cell Mediated Acquired Immune Response.
Type # 1. Humoral Immune Response:
After first contact of the tissue with the antigen, there is an interval of about two weeks before antibody can be found in the blood and during this initial period, there is intense activity in the antibody forming tissues. After primary antigenic stimulation, there is a rapid increase in cell proliferation and in the synthesis of protein in cells of the lymphoid organ.
The antibody which can be detected during the primary immune response does not reach its peak. Then, after a day or two, there is a remarkable rise in the level of antibody which reaches its peak. This “secondary immune response” can be boosted to even higher levels by a further injection of antigen (booster or recall dose) until no further increase occurs and it slowly fails.
Once an animal has responded to a single dose of a live attenuated antigen (e.g. small pox or polio vaccine) the animal retains a “memory” of the antigen so that months or years later it responds with a rapid mobilisation of anti-forming cells.
Vaccination with even non-living agent such as tetanus or diphtheria toxoid, if given in two spaced doses, provides several years of useful protection against infection even though after vaccination the level of antibodies falls to a low level, the “memory” is retained.
To obtain a maximum response, the interval between the primary and secondary injections should not be too short and an interval of less than ten days is likely to reduce the level of the secondary response. This allows time for a maximal increase in the number of antibody forming cells which can be stimulated by subsequent injection.
Determinants of Acquired Specific Immunity:
The natural ability of antigen to induce an immune response may be enhanced by altering or mixing it with another substance known as adjuvant. The antigen can be absorbed on a mineral gel such as aluminium hydroxide or aluminium phosphate—e.g. Alum precipitated antigen.
Such particulate form of antigen seems to be able to initiate antibody production much more effectively than the same antigen in non-particulate form. The effect is not yet fully understood, but it may be due to the direct effect of the particulate antigen on the lymphoid cell membrane—leading to more effective transformation of the cell for antibody formation than that can be brought about by antigen in solution.
Another method has been developed to enhance antibody response i.e. preparation of a water-in-oil emulsion. The emulsion forms a depot of antigen in the tissues from which small quantities of antigen are released continuously, sometimes for a year or more. Example, Influenza vaccine.
If an antigen is given intravenously, most of the antibody is produced by spleen, and some in lung, bone marrow, if given subcutaneously or intradermally—the antigen travels via lymphatic’s to local lymph nodes where antibody is produced initially.
The antibody response is proportionate to the dose of antigen. If the antigen dose is increased, the immune response is small, so if a particular level of antigen is increased then there will be specific paralysis of the antibody forming tissues—Immunological tolerance.
Type # 2. Cell Mediated Acquired Immune Response:
Cell mediated immunity occurs particularly in infections by microorganisms that enter and grow within the tissue cells such as viruses, tubercle bacilli, brucella and some salmonella. It seems likely that the cell mediated immune response is involved in protection against infective agents—particularly those causing intracellular infection.
Cell mediated immunity is manifested by delayed hypersensitivity around the site of infection. The cell mediated response is initiated in different areas of spleen and lymph node (white pulp of spleen and Para cortical areas of lymph). These areas are controlled by thymus —so these lymphocytes are called as T-cells.
Very recently a number of yet uncharacterized non-antibody lymphocytic factors (nonspecific antibodies) are described and are called lymphokines. In 1969, Dudley Dumonde suggested the term lymphpkine. They are released by sensitized lymphocytes, T-cells in contact with antigen.
(i) The property of inhibition of the in vitro migration of macrophages on glass slide;
(ii) Macrophages can be grown in culture in capillary tube and will normally migrate out of the open end of the tube into the culture fluid.
(iii) A factor released by lymphocytes exposed to antigen will prevent this migration by causing the macrophages to stick together. This factor is likely to be released also in vivo and may be responsible for the accumulation of macrophages in cell mediated immune reaction.
(iv) Another factor released from sensitized lymphocytes after exposure to antigen causes stimulation and proliferation of normal unsensitised lymphocytes. This is known as mitogenic factor.
(v) Another lymphokine has a chemotactic effect on macrophages attracting them to the site of the inflammatory responses.
(vi) A cytotoxic effect due to a lymphokine (lymphotoxin) has been demonstrated to damage the different types of cell.
(vii) A factor which increased capillary permeability (skin reactive factor) can also be shown to be released by sensitized lymphocytes.
(viii) It is generally thought that the lymphokines are the main effector mechanisms in the cell mediated response.
Tissue Involved in Immune Response:
Lymph nodes, spleen and bone marrow are mostly engaged in the immune response, while lung and, to some extent, the liver, can take part in immune response. The specialised lymphoid organs (spleen and lymph nodes) take up foreign antigen and initiate the immune response.
The lymph nodes and spleen are made up of three types of cells which are involved in the initiation of the immune reaction, the three types of cells are lymphocytes, plasma cells and phagocytic cells of reticulo-endothelial system. The lymphoid tissues responsible for humoral antibody production are associated developmentally with the gut and consist of lymphocytes and plasma cells of the lymph nodes and spleen.
In the humoral immune response, immunoglobulin’s are secreted into the blood by the lymphoid cells, predominantly plasma cells situated in the spleen and lymph nodes.
In man, lymphoid tissues appear first in the thymus at about eight weeks gestation. Peyer’s patches are distinguishable by the fifth month and immunoglobulin secreting cells appear in the spleen and lymph nodes at about 20 weeks.
From this period onwards, both IgM and IgG globulins are synthesized by the foetus with IgM predominating. At birth, the infant has a blood concentration of IgG comparable to—or sometimes higher than that of maternal serum having received IgG but not IgM via placenta from the mother.
The rate of synthesis of IgM in the infant increases rapidly within the first few days of life and does not reach adult levels until about a year. Cell mediated immune reactions can be stimulated at birth but these reactions may not be as powerful as in the adult.
Cells Concerned in the Antibody Production:
Cell cooperation between thymus dependent (T) lymphocytes and bone marrow derived (B) lymphocytes has been shown to occur. The (T) lymphocytes assist (B) lymphocytes in some as yet undefined way, possibly by concentrating antigen on their surface and presenting it to B cells or perhaps by releasing a lymphocyte activation product (lymphokine) to stimulate the B cells to respond to antigen.
In the spleen, the cells engaged in antibody production are found in the red pulp, whereas, in lymph nodes, they are found in germinal centres of the cortex.
Individual immunoglobulin producing cells synthesise the whole molecule of immunoglobulin—both heavy and light polypeptide chains. Individual cells make only one class of immunoglobulin and the light chains are restricted to one of the two types (K and L). T and B lymphocytes are morphologically similar.
Initially, B cells produce Ig M antibody and then switch over to IgG production. Antibody secreting “Russell body” is found in plasma cell. B cells are responsible for immunoglobulin (Ig) synthesis, and can either react to the direct contact with antigen or cooperate with T cells which are helper cells.