Immune effectors mechanisms

Gene Therapeutic Strategies that Act via Host Immune Effector Mechanisms.283... 

Flatworm parasites are well recognized for their ability to live for decades in environments where they are in contact with potentially damaging immune factors. This adaptability reflects the fact that these parasites have evolved mechanisms to evade immune effector mechanisms, and more remarkably, to sense and utilize components of the host immune system for their own development. Schistosomes, digenetic trematodes, are undoubtedly the most well-studied parasitic flatworms. These parasites infect over 200 million people in tropical and subtropical zones, and cause severe disease in approximately 5% of those infected. Of immunological interest is the fact that pathology in schistosome-infected individuals is caused largely by the immune response... 

Cytokines and chemokines made by cells such as keratinocytes, macrophages and LC might be expected to recruit and activate leukocytes, which have the potential to kill schistosomula before the development of any adaptive immunity. In vitro, schistosomula have been shown to be susceptible to a wide array of immune effector mechanisms mediated by eosinophils and neutrophils (Butterworth, 1984 Capron and Capron,... 

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. 

In recent years it has become clear that the nature of the immune response initiated by CD4 T lymphocytes is at least partly dependent on the selection or preferential activation of particular subsets of CD4 T lymphocytes which secrete defined patterns of cytokines (Table 2.3). These patterns of cytokine release result in the initiation and propagation of distinct immune effector mechanisms. Initial studies of mouse CD4 T lymphocyte clones revealed that these could be divided into two basic fiinaional subsets termed ThI and Th2. ThI T lymphocytes were characterized by the predominant secretion of IL-2, interferon y (IFNy) and tumour necrosis factor 8 (TNF/3), while Th2 cells characteristically... 

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. 

The sequence of events that underlies graft rejection is recognition of the donor s histocompatibility differences by the recipient s immune system, recruitment of activated lymphocytes, initiation of immune effector mechanisms, and Anally graft destruction. 

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... 

Relevant Immune Effector Mechanisms Passive Immunization... 

Soares MM, Mehta V, Finn OJ. Three different vaccines based on the 140-amino acid mud peptide with seven tandemly repeated tumor-specific epitopes elicit distinct immune effector mechanisms in wild-type versus mucl-transgenic mice with different potential for tumor rejection. J Immunol 2001 166 6555-6563. 

Because immune mechanisms of "disorders of immune function appear to contribute importantly to both conditions, a review of immune effector mechanisms is in order when one considers these two uncommon diseases. 

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. 

While cells of the innate immune system can combat invading microbes autonomously, their effector mechanisms are also used and greatly enforced by the... 

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. 

Ferrant, J.L. et al., The contribution of Fc effector mechanisms in the efficacy of anti-CD154 immunotherapy depends on the nature of immune challenge, Internal Immunol., 16, 1583, 2004. 

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