Clinics in Immunology and Allergy最新文献

Malignant transformation results in major changes in cellular growth control and interaction with surrounding cells. In many experimental systems, transformed cells are recognized specifically by the immune system; but in human cancer, evidence for such recognition remains equivocal. Rejection of experimental tumours depends primarily on cellular immune responses, although the relative importance of cytotoxic T cells, helper/inducer T cells, and less specific effector cells such as macrophages and NK cells varies between tumour systems. A variety of mechanisms by which tumours may escape immunological control have also been defined, including antigen loss, suppression and the development of factors which interfere with cellular immunity. Antibodies may be useful as an agent of immunological attack against tumours, either functioning with effector cells or complement, or as the vehicle to carry drugs or toxins to the tumour.

Macrophages were originally thought to play an important role in host defence against intracellular pathogenic micro-organisms. This observation led to the development of the concept of macrophage activation. The events required for macrophage activation have been extensively studied and clearly demonstrate that activation is brought about by soluble mediators secreted by stimulated T cells. Both natural and recombinant γ-IFN preparations have been shown to be capable of activating macrophages. The possibility that lymphokines other than γ-IFN, present in antigen- or mitogen-stimulated T-lymphocyte culture supernatants, participate in macrophage activation remains to be resolved. There seems to be little doubt that activated macrophages contribute to host defence mechanisms in the control of neoplasia. It has been shown that oxygen-dependent as well as independent mechanisms participate in the destruction of micro-organisms and neoplastic cells. Several soluble factors that kill bacteria and tumour cells in vitro and in vivo, released by activated macrophages, have been described. Of these, only TNF has been fully characterized by gene cloning studies and its amino acid sequence analysis. Similar studies need to be performed with guinea pig, mouse and human factors to confirm whether their activity is due to protein(s) coded by a single gene or family of genes.

Studies performed during the last 20 years have clearly established that macrophages, in addition to their function as effectors in host defence mechanisms, play a critical role in induction and regulation of immune response. Thus, it has been demonstrated that macrophages are required during the early events that lead to antigen-specific stimulation of T and B cells. These T cells, especially the helper subset, do not respond unless the antigen has undergone a processing and is associated with the products of the I-region of MHC. The macrophages, because of their innate capacity to take up and catabolize antigens and to express Ia, provide the necessary signals to helper T cells. This interaction between la-positive macrophages containing processed antigen and helper T cells results in secretion of lymphokine and DNA synthesis by T cells and synthesis of Ia molecules and lymphostimulatory molecules such as IL-1 by macrophages. However, the contribution of other la-positive cells in the induction of the immune response and the question of whether macrophages are the only cells that participate in immune induction requires further study.

The immune response to virus infection protects the host against the pathogenic effects of the virus, limits dissemination of infection, and clears the infecting agent. Virus infection results in the expression of a number of different antigens, both structural (virion) and non-structural, which vary during different stages of the replicative cycle. Antibody responses are predominantly directed against structural antigens but some of these are also expressed on infected cells, which may then be lysed by complement or ADCC. Virus-specific T cells are probably the most important response against virus-infected cells. They recognize viral antigens in conjunction with MHC determinants, although the precise nature of this association is unknown. Cytotoxic T cells and T cells mediating delayed-type hypersensitivity have been shown to be directly protective but these require T helper and other cells for their generation. Lymphokines, such as interferon, released by antigen-specific T cells, may also be directly protective or act by enhancing the activity of non-specific effector cells such as macrophages and NK cells. However, antibody- and cell-mediated responses can be suppressed by viruses which directly infect immunocompetent cells and, in addition to its protective effects, the immune response can prove more damaging to the host than the infecting virus. Therefore, a detailed understanding of the many facets of the immune response to virus infection is required for the future development of effective preventative and therapeutic measures.

Although a knowledge of the cellular pathology underlying many secondary immunodeficiencies is essential to an understanding of the clinical presentation and management of these common conditions, the specific role of the diagnostic immunology laboratory is strictly limited in many of them. While basic biological mechanisms are not illustrated as clearly as they are in congenital disorders, the underlying defects in secondary immunodeficiency can generally be discerned. Even in AIDS and related conditions caused by the T lymphotropic retrovirus HTLV-III/LAV, immunological tests form only a part of the pattern recognition in diagnosis and are not pathognomonic; their relevance can only be established with reference to the clinical state. However, AIDS, with its precisely defined aetiology and its increasingly well-understood immunopathogenesis, has helped to clarify the relevance of different assays in both this and other diagnostic settings. The relative lack of specificity of such assays and the limitations inherent in the use of peripheral blood have been underlined by this remarkable disease. AIDS has highlighted the importance of defining the clinical context in which laboratory abnormalities are found.