Antibody Affinity: Its Relationship to Immune Complex Disease and the Effect of Malnutrition

Abstract

There is an impressive body of evidence in the literature to support the view that malnutrition is a major cause of secondary immunodeficiency in man. The malnourished state leads to impaired cell-mediated and humoral immune mechanisms with a consequent predisposition of affected individuals to severe infections. Serum immunoglobulin levels in malnourished individuals are not related o the degree of nutritional impairment and these levels can be high or normal⁽¹⁾. However, it is clear that specific antibody responses in malnutrition can be adequate or reduced⁽²⁾. Whilst it is clear that the amount of antibody an individual makes is important, perhaps more critical to the function of the antibody response is its quality. Antibody affinity is one of the means of expressing antibody quality and is a measure of the strength of interaction of the antibody combining sites with the corresponding antigenic determinants. A high affinity antibody forms complexes with the antigen which have a lesser tendency to dissociate than do complexes formed with a low affinity antibody. In terms of antibody function, high affinity antibody is superior to lower affinity antibody in a number of antibody-mediated immune functions. These include complement fixation, immune elimination, and protective capacity against bacterial infection. Therefore circumstances which interfere with the production of antibody of an appropriate high affinity will result in impaired immune function. The production of antibody of low affinity may be viewed as a form of immunodeficiency⁽³⁾ leading to the failure of elimination of antigen or infectious agent with the corresponding persistence of infection or the production and subsequent tissue deposition of antigen excess antigen: antibody complexes. The purpose of this paper is to discuss the production of low affinity antibody as an example of a primary immunodeficiency which may predispose to the induction of chronic disease, and to consider how secondary immunodeficiency arising from malnutrition may contribute to disease susceptibility through its effect on antibody affinity.