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The Latest Advances In Drug Manipulations Of The Immune System Essay, Research Paper

INTRODUCTIONIn order to provide a detailed analysis of recent pharmacological developments involving the human immune system, it is firstly necessary to introduce the innate and adaptive immune responses . Immunosuppressants and immunomodulators will be differentiated between and a selection of new and often experimental drugs belonging to each category will be provided. Specific drugs will be described including the pharmacokinetics and pharmacodynamics involved with each type. The possible clinical uses will be alluded to along with details from recent research.

INNATE IMMUNITYInnate immunity is the first line of defence and comprises physical (skin), biochemical (complement, lysozyme) and cellular (macrophages, neutrophils) mechanisms (Katzung, 1998). All these mechanisms are non-specific, anti-microbial agents which work in conjunction with adaptive immune responses to provide a more effective system (Downie et. al., 1995).

ADAPTIVE IMMUNITYThe adaptive immune system is split into two mechanisms: humoral immunity and cell-mediated immunity. A basic understanding of these concepts is necessary for the purpose of understanding the specific effects of different immunopharmacological agents.

HUMORAL IMMUNITYHumoral or antibody-mediated immunity is associated with B-lymphocyte cells. Antigens are foreign molecules that initiate an immune response, they have inherent immunogenicity (Tortora & Grabowski, 1996). Upon contact with an antigen, B-cells divide to produce a clone of plasma cells capable of the production of antibodies. Antibodies are immunoglobulins, modified blood proteins with a specific action against antigens. Five main sub-types of immunoglobulins have been identified of which IgG is the most abundant in bodily fluids (Hopkins, 1995). Several cells are known to initiate the process of plasma cell differentiation and are known collectively as antigen presenting cells (APCs) (Waller & Renwick, 1994).

LymphokinesThe antigen on the surface of the APC triggers TH-cells to produce hormone-like lymphokines (Lessof, 1993). Lymphokines are cytokines, regulators of the immune reactions which are produced by lymphocytes. Examples of these chemicals include interleukins, interferon and tumour necrosis factors. Their action involves the regulation of the proliferation, differentiation and activity of leukocytes (Dale et. al., 1994). The nature of lymphocyte stimulation will determine which class of immunoglobulin will be produced (Waller & Renwick, 1994).

The role of complement & antibody-antigen complexesAntibodies have two distinct functions: to recognise and combine with an antigen, and to activate a defence mechanism for example by activating the complement sequence (Dale et. al., 1994). This sequence involves more than thirty proteins (Mollnes & Harboe, 1996) and has the function of the destruction and removal of invading micro-organisms and subcellular debris and to promote clearance of antigen-antibody complexes (Dale et. al., 1994). These functions are achieved mainly via complement?s ability to attract leukocytes (Lessof, 1993). The interaction of antibody with specific antigen results in the formation of the antibody-antigen complex. This complex has several functions: for instance, to immobilise an antigen therefore preventing attack upon host cells, to block active toxic regions of particular bacteria, and to allow phagocytic attack.

Memory cellsOnce the antigens have been destroyed the plasma cells disappear leaving a few as memory cells which enable a swift response upon second exposure to the antigen (Trounce, 1997). Memory cells are the basis of active immunisation against bacteria (Downie et. al., 1994). Humoral immunity is most efficient against antigens dissolved in body fluids, that is extracellular pathogens, primarily bacteria whereas cell-mediated immunity is most effective against intracellular pathogens such as viruses (Tortora & Grabowski, 1996).

CELL-MEDIATED IMMUNITYCell-mediated immunity is mainly concerned with T-lymphocytes. It is this form of immunity that is thought to be responsible for tissue transplantation rejection (Tortora & Grabowski, 1996). T-cells possess receptors upon their surface which recognise antigens, these receptors are similar to the antibodies released by B-cells. Upon contact with an antigen, T-cells produce memory and effector cells as do the B-cells. However, T-cells produce a variety of effector cells (Downie et. Al., 1995).

TC-cells & TH-cells The cells produced are mainly Cytotoxic cells (TC-Cells or CD8+) or Helper cells (TH-cells, or CD4+). TC-cells recognise and destroy virally infected host cells, hence they are also known as killer-cells (Trounce, 1997). It is also thought that cancerous cells can be destroyed by the same mechanism (Dale et. al. ,1994). TH-cells release lymphokines which activate local macrophages (Waller & Renwick, 1994). Meaning ?big eaters? macrophages engulf micro-organisms and secrete lysosomal enzymes, complement components and some lymphokines (Dale et, al., 1994).

IMMUNOSUPPRESSION & IMMUNOMODULATIONBy providing an overview of the adaptive immune responses it becomes apparent that two areas of pharmacological enquiry are of interest: immunosuppression and immunomodulation. The former concept involves developing agents that suppress the immune responses. This area is important in the treatment of organ and tissue transplant rejection and also the treatment for certain diseases resulting from immune system irregularities. The latter area involves agents that augment or alter certain components of the immune system and are therefore important in cancer and AIDS management (Katzung, 1998).

NEW IMMUNOSUPPRESSANTSThe prototype immunosuppressant, cyclosporine was discovered in the 1970s Almost three decades later there is

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