Definitions and Outline Structure of the Immune System

DEFINITIONS AND OUTLINE STRUCTURE OF THE IMMUNE SYSTEM

The primary function of the immune system is to defend against and eliminate ‘foreign’ material, and to minimize any damage that may be caused as a result of the presence of such material. The term ‘foreign’ includes not only potentially pathogenic microorganisms but also cells recognized as ‘non-self’ and therefore foreign such as the human body’s own virally infected or otherwise transformed (e.g. cancerous) host cells. Foreign material would also include allogeneic(within species) or xenogeneic (between species) transplant tissue and therapeutic proteins administered as medicines if they arose from a different species or were of human origin but had undergone inappropriate post-translational modifications during manufacture or contained impurities. It is also possible that small organic-based drugs may form adducts with endogenous proteins leading to the generation of an immunogen. A good example of such adduct formation is that between the serum protein albumin and the glucuronide metabolite of some non-steroidal anti-inflammatory drugs. This adduct is proposed as the basis of some hypersensitivity reactions.

For clarity there are a number of terms that should be defined at this point. An organism which has the ability to cause disease is termed a pathogen. The term virulence is used to indicate the degree of pathogenicity of a given strain of microorganism. Reduction in the virulence of a pathogen is termed attenuation; this can eventually result in an organism losing its virulence completely and it is then said to be avirulent.

An antigen is a component of the ‘foreign ’material that gives rise to the primary interaction with the body’s immune system. If the antigen elicits an immune response it may then be termed an immunogen. Within a given antigen, e.g. a protein, there will be antigenic determinants or epitopes, which actually represent the antigen recognition sites for our adaptive immune system (see below). For example, within a protein antigen, an epitope for an antibody response will consist of 5–20 amino acids that form either part of a linear chain or a cluster of amino acids brought together conformationally by the folding of the protein. Antibodies (otherwise known as immunoglobulins —Ig) are produced and secreted into biological fluids by our adaptive immune system, are widely used in in vitro diagnostics and have been investigated in therapeutics as a means of targeting drugs to specific sites in the body. A monoclonal antibody is an antibody nominally recognizing only a single antigen (e.g. a single protein) and within which only a single common epitope (e.g. clusters comprising a common single specific amino acid sequence or pattern) is recognized. In contrast, a polyclonal antibody is an antibody nominally recognizing only a single antigen but within which a number of different epitopes (e.g. clusters comprising different amino acid sequences or patterns) are recognized.

The immune system is broadly considered to exhibit two forms of response:

·        The innate immune response, which is non-specific, displays no time lag in responsiveness, and is not intrinsically affected by prior contact with infectious agent.

·        The adaptive immune response, which displays a time lag in response, involves highly specific recognition of antigen and affords the generation of immunological memory. An example of immunological memory is that provided by the generation of specific lymphocyte memory cell populations following vaccination with an antigen (e.g. diphtheria toxoid). These memory cells reside over a long term in our lymphoid tissue and permit a more rapid and pronounced protective immunological response on future exposure to the same antigen. The adaptive immune system is further subdivided into:

·        Humoral immunity, within which the effector cells are B-lymphocytes and where antigen recognition occurs through interactions with antibodies.

·        Cell-mediated immunity, within which the effector cells are T-lymphocytes and where antigen recognition occurs through interactions of peptide antigen (presented on the surface of other cell types) with T-cell receptors (TCR) on the plasma membrane of T-lymphocytes. In cell-mediated immunity the peptide antigen must be presented to T-lymphocytes by other cell types in association with a class of plasma membrane molecules termed major histocompatibility complex (MHC) proteins.