Immunology. Supplement最新文献

T cells and their subpopulations have many different functions important for (i) the regulation of immune responses through the release of antigen non-specific lymphokines and (ii) as effector cells to rid the host of intracellular pathogens, be they bacteria, parasites or viruses. In this short summary only a few features of T-cell function can be summarized, and studies in virus infection will serve as illustrations.

Although some gaps remain, the major histocompatibility complex (MHC) has now been mapped in considerable detail in both humans and mice. From the results of DNA cloning and sequencing, there is now a detailed knowledge of which genes are expressed and the composition of the proteins encoded by them, as well as the structural basis of the polymorphism. The problem that can now be addressed is how the sequences of the polymorphic domains relate to the function of HLA molecules and to the diseases associated with the MHC.

The application of recombinant DNA technology to the investigation of lymphokines has provided homogeneous material for experimentation. The general biochemical and biological properties of these lymphokines are reviewed here. The available information suggests that lymphokines have diverse and synergistic effects on multiple target cells and organs. The biological significance of these effects is discussed.

The responses of B cells to specific antigens are modulated by secondary signals delivered by a variety of cell surface receptors. Besides surface immunoglobulins, these include class II MHC antigens, Fc and C3 receptors, in addition to those for various lymphokines. The current knowledge of the second messengers used by various receptors and their roles in B-cell activation are discussed here.

The major histocompatibility complex (MHC) was discovered originally as a genetic locus controlling rapid rejection of tissue grafts. Subsequently, study of antibody responses in vivo and T-cell responses in vitro to MHC antigens identified the presence of a number of closely linked loci within the MHC. Immune response (Ir) genes also mapped to the MHC. The discovery of MHC restriction and the molecular identification of MHC genes and their products has led to a unified theory of the principal function of MHC molecules to act as guidance molecules for T-cell responses. Additional functions are suggested by their association with cell surface receptors.

At the protein level, antibodies show several types of variability. One is the diversity of the variable (V) regions of heavy (H) and light (L) chains, leading to antibody-combining site specificity; another is the existence of two types of light chain (kappa and lambda); a third is the diversity of heavy chain-constant (CH) regions associated with different effector functions. At the DNA level, V-region variability is coded partly through the large number of VL- and VH-region genes and partly generated by integrating complete V genes from combinations of shorter segments (VL-JL for the light chain, VH-D-JH for the heavy chains), together with somatic mutational events (Tonegawa, 1983). kappa, lambda and H chains are coded independently on different chromosomes and have their own V- and C-region genes (Honjo, 1983). CH-region diversity results from a set of CH genes corresponding to the different Ig subclasses. During B-cell development, rearrangement of DNA occurs both in the VL/VH- and CH-region genes. V-region rearrangements take place at the pre-B-cell stage and produce the complete V-region genes for the heavy and light chains which will permanently characterize an individual clone; CH-region rearrangements enable mature B cells to secrete their V regions on different Ig classes (class switching). This article will review the structure and organization of V and C genes and the control of their expression.

Interferon (IFN)-alpha and -beta are produced by virus-infected cells; IFN-gamma is produced as a primary response of T lymphocytes to mitogenic stimulation, IFN-gamma gene activation being brought about by changes in Ca2+ and phosphatidyl inositol metabolism. IFNs act by binding to cell surface receptors and triggering activation of IFN-responsive genes, probably via specific base sequences located in the 5' non-coding region of such genes, resulting in changes in cell function. Important genes activated in this way are the MHC antigen genes; class I induced by all IFNs, class II by IFN-gamma only. This MHC activation may have important consequences for lymphocyte function.

Antigen-specific T-helper and -suppressor molecules usually have a two-moiety, disulphide-bonded structure. One chain binds antigen, while the other chain bears I-A in the case of helper factor and I-J in the case of suppressor factor. Their genetic restriction, when it exists, parallels the 'MHC' determinants that they carry and probably reflects the fact that helper cells are activated by antigen in the context of I-A, while suppressor cells are activated by antigen in the context of I-J. T-helper factor probably augments the induction of contact sensitivity by approximating antigen with its own I-A determinants. Different factors act at the induction and the effector stage and they may be antigen or idiotype directed. The antigen-specific factors characteristically are part of complex circuits involving both antigen-specific and non-specific cells and factors and often have a mode of action through the macrophage.