The Latest Advances in Drug Manipulations of the Immune System
Uploaded by eeyore on Aug 09, 2001
INTRODUCTION
In 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 IMMUNITY
Innate 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 IMMUNITY
The 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 IMMUNITY
Humoral 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).
Lymphokines
The 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 complexes
Antibodies 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...