Antibodies effector mechanisms

Humoral immunity depends on soluble, noncellular effector mechanisms of the immune system. These include defensins and complement components (proteins of the innate immune system) and antibodies (products of the adaptive immune system). They are capable of reacting with foreign substances (e.g., bacteria and viruses) to produce detoxification and elimination. 

Else, K.J. and Grencis, R.K. (1996) Antibody-independent effector mechanisms in resistance to the intestinal nematode parasite Trichuris muris. Infection and Immunity 64, 2950-2954. 

Effector Mechanisms Antibody-Mediated Versus Cell-Mediated Damage.425... 

EFFECTOR MECHANISMS ANTIBODY-MEDIATED VERSUS CELL-MEDIATED DAMAGE... 

By the time they have reached the lungs, schistosomula are innately resistant to immune effector mechanisms that are capable of killing schistosomula newly transformed from cer-cariae. In part, this is a reflection of the fact that growing schistosomula develop the ability to avoid activating complement and to evade recognition by antibodies (see below), and therefore are no longer susceptible to antibody or complement-mediated cellular cytotoxicity. However, studies in which these evasion mechanisms have been experimentally bypassed have revealed underlying resistance to immune effector molecules (Moser et al., 1980) the basis of this resistance is unknown. 

Monoclonal antibody therapy (MAT) makes use of all the major features of the immune response. It involves vaccination/ immunization, albeit in experimental animals, to induce the desired specific immune response. It exploits the high specificity, selectivity, and affinity of the antibody CDR toward the target antigen to be recognized, highlighted, inactivated, or eliminated, using the characteristics of the Fc portion of an immunoglobulin to facilitate the means for such inactivation or elimination and for selection of appropriate effector mechanisms. Finally, MAT represents a modern form of serotherapy, in which parenteral administration of whole serum or Ig preparations has been replaced by recombinant antibody molecules of a defined specificity. 

Egg-induced immunity appears to involve stage-specific immunogens against (a) the tissue phase of egg challenge (early response) and (b) the lumen phase of cysticercoid challenge (late response). This immunogenetic pattern is thus similar to the development of early and late immunity in larval taeniid cestodes (Fig. 11.7). The effector mechanism of the early response has been shown to be thymus dependent, X-irradiation sensitive, cell mediated and antibody mediated the response is visualised by eosinophilia infiltration around the invading oncospheres (Fig. 11.6) (353). 

Latov N, Renaud S. Effector mechanisms in anti-MAG antibody-mediated and other demyelinating neuropathies. J Neurol Sci 2004 220(1-2) 127-129. 

IgA is the principal antibody present in a number of secretions and is the major antibody associated with the external immune system. IgA lacks the effector functions identified previously and acts mainly in immune exclusion (prevention of entry of potentially infectious entities into the body). As noted previously, there are differences in the immune effector mechanisms associated with the internal immune system or systemic immunity and the external immune system or local immunity. Systemic immunity is mediated by IgM and IgG, the latter is the major form of Ig found in the blood. Local immunity is mediated primarily by IgA and IgE. The contribution by the external immune system should not be underestimated because about half of the body s lymphocytes are associated with this system. 

In addition to those mentioned above, other chemicals have been implicated in the induction of occupational asthma. Some of these are listed in Table 1.1 and more comprehensive details are available elsewhere (Chan-Yeung and Malo, 1993). It is important to emphasize, however, that the inclusion of a chemical in such lists does not necessarily imply that respiratory symptoms result in all instances from allergic sensitization. For many chemicals associations have been found between respiratory effects and the presence of homocytotropic (IgE or IgG4) antibodies. Such associations are not universal and there is some uncertainty about the nature of immune effector mechanisms, and indeed the requirement for immune processes per se, in some forms of chemical-induced asthma. The subject of this book is allergic sensitization... 

Complement system. A group of serum proteins with the capacity to interact with each other when activated. The chain reaction of the activated complement components results in formation of a lytic complex and several biologically active peptides of low molecular weight (anaphylatoxins). The system can be activated by antigen-antibody complexes (classical pathway) and by other components, e.g. bacteria (alternative pathway). As an effector mechanism of the humoral immune response, the activated complement system facilitates opsonization, phagocytosis, and lysis of cellular antigens. Some defects in components of complement are associated with autoimmune diseases (see complement deficiency). 

From these considerations it is clear that the optimal format of the antibody is dependent on the exact mode of action, its location, the effector mechanism, whether the antibody has been fused or conjugated with a toxin and what kind of toxin or toxic radioisotope is used. The use of an IgG is thus only one of many options. The advent of molecular engineering is thus pivotal to the further development of these therapeutic modalities. 

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