Cytotoxic immune response

Type II, or cytotoxic immune, responses can be complement-independent or complement-dependent in nature. In the former case, IgG antibodies bind to antigens attached to the surface of normal cells (e.g., erythrocytes, platelets, etc.). Cytotoxic cells (macrophages, neutrophils, and eosinophils) then attach to the crystallizable fragment (Fc) portion of the antigen, release cytotoxic granules, and lyse the cell. 

Immunoallergenic reactions Chemically generated neoantigens trigger a cytotoxic immune response to those hepatocytes that have such neoantigens on their surface. 

One recent area of intense research interest is the effects of various thymic factors on the production of soluble mediators (lymphokines) by T cells, most notably T cell growth factor [TCGF or interleukin-2 (IL-2)] and 7 interferon (IFN-7). Interleukin-2 is released by activated T cells and plays a pivotal role in sustaining both proliferative and cytotoxic immune responses. Interferon, on the other hand, augments T cell cytotoxic activity but exhibits antiproliferative effects. It has been demonstrated that Toj can increase IFN-7 production in vitro in human peripheral blood lymphocytes (Svedersky et al., 1982), whereas TF5, but not Taj, has a pronounced effect on increasing IL-2 production (Zatz et al., 1984a). Similar effects have been demonstrated with thymulin in animals (Palacios, 1983). Thus, it is possible that the variable effects of thymic hormones observed to date in human fiinctional assays may be related to differences in their ability to influence lymphokine production. 

Weber KS. Selective recruitment of Th2-type cells and evasion from a cytotoxic immune response mediated by viral macrophage inhibitory protein-II. Eur J Immunol 2001 31(8) 2458-66. 

Some of the humoral and cytotoxic immune responses to MUCl in cancer patients are known to be directed to specific sequences in the tandem repeat. As a result, and because there are many pragmatic advantages in using relatively short defined amino acid sequences, the clinical studies involving the use of peptides as the immunogen have concentrated on the tandem repeat of MUCl. Phase 1 studies have been reported that use tandem repeat peptides coupled to diphtheria toxid, BCG or KLH (for review see [62]). In the latter trial, class I restricted CTL were demonstrated after immunization with 16 amino acids from the tandem repeat coupled to KLH, and increase in CTL precursor frequency has been reported when patients have been immunized with five tandem repeats mixed with BCG. 

The mammalian and avian immune systems function similarly both incorporate humoral and cell-mediated cytotoxic mechanisms, " and are thought to share a 160m year old relationship with the reptilian immune system. The immune system of mammals shows sexual dimorphism " a greater immune response is normally observed in females, which has been attributed to differences in steroid hormone concentration. In the toad Bufo regularis, sexual dimorphism of the immune system is also apparent. ... 

A recent example of a CA model of the immune response in AIDS is Pandley s four-cell model using interactions among macrophages (= M) containing parts of the virus on their surface, helper T cells (= H), cytotoxic T cells (= C) and the virus (= V) ([pand89], [pandQl]) ... 

The field of DNA vaccination started when eukaryotic expression vectors were injected into the muscle of laboratory animals [2]. The authors observed protein expression for more than 2 months after injection and noted that no special delivery system was required to obtain this expression. Subsequently, it was demonstrated that antibodies can be induced simply by injecting plasmid DNA into the muscle of mice [3]. Subsequent studies found that the injection of expression plasmids also leads to the induction of a cytotoxic T-cell response. After injection, the DNA enters cells of the vaccinated host and the encoded gene becomes expressed. This eventually leads to the induction of a cellular cytotoxic T-cell, T-helper, and/or humoral (antibody) immune response. 

Although a humoral immune response is the primaiy protection against most viral and some bacterial diseases, protective defense against other pathogens such as HIV, Plasmodium and Mycobacterium tuberculosis requires a cytotoxic response mediated by CD8+ T-cells (CTL response). Since the introduction of the vaccination concept by Jenner almost 200 yeats ago, only few vaccines have been developed that are able to induce a CTL response. These vaccines are usually attenuated live vaccines that are accompanied by certain risks and are not readily available for most pathogens. The immense appeal of DNA vaccines can be attributed to a considerable part to the fact that they are able to induce... 

Immune Defense. Figure 2 Cytokines involved in the development of adaptive immune responses in secondary lympoid tissues such as the lymph nodes or spleen. Abbreviations B B-lymphocyte, IFN interferon, Ig immunoglobulin, IL interleukin, NK natural killer cell, TE T-effector (cytotoxic) lymphocyte, TH T-helper lymphocyte... 

Several cytokines are in clinical use that support immune responses, such as IL-2, DFNs, or colony-stimulating factors. IL-2 supports the proliferation and effector ftmction of T-lymphocytes in immune compromised patients such as after prolonged dialysis or HIV infection. IFNs support antiviral responses or antitumoral activities of phagocytes, NK cells, and cytotoxic T-lymphocytes. Colony-stimulatory factors enforce the formation of mature blood cells from progenitor cells, e.g., after chemo- or radiotherapy (G-CSF to generate neutrophils, TPO to generate platelets, EPO to generate erythrocytes). 

Helper T cells (CD4+) are the great communicators of the immune response. Once activated, they proliferate and secrete cytokines that regulate effector cell function. Some helper T cells secrete cytokines that recruit cytotoxic T cells, B cells, or APCs, whereas others secrete cytokines that turn off the immune response once an antigen has been destroyed. 

After activation, cytotoxic T cells emerge from lymphoid organs to infiltrate the graft and trigger the immune response. These cells have been shown to induce graft destruction via two mechanisms (1) secretion of the cytotoxic proteins perforin and granzyme B, and (2) induction of cellular apoptosis... 

During the early stages of infection, approximately 10 billion viruses can be produced each day. Most of the cells containing these viruses will be lysed as a result of budding virions, killed by cytotoxic T-lymphocytes, or undergo apoptosis. However, virus will be protected within some cells, which can stay dormant for years. The initial immune response against... 

Vaccination to induce an adaptive immune response is expected for a broad range of infectious diseases and cancers. Traditional vaccines are mainly composed of live attenuated viruses, whole inactivated pathogens, or inactivated bacterial toxins. In general, these approaches have been successful for developing vaccines that can induce an immune response based on antigen-specific antibody and cytotoxic T lymphocyte (CTL) responses, which kill host cells infected with intracellular organisms (Fig. 1) [1,2], One of the most important current issues in vaccinology is the need for new adjuvants (immunostimulants) and delivery systems. Many of the vaccines currently in development are based on purified subunits, recombinant... 

It is also more or less accepted that T-cells, in particular T-helper cells (CD4+), may develop into either Thl cells or Th2 cells. By doing so, T-helper cells orchestrate the ensuing immune response by the types of cytokines they produce. Thl cells, by producing IL-12 and y-IFN, stimulate macrophages and/or cytotoxic T-cells to kill and destroy infected or malignant cells, or to initiate a delayed type hypersensitivity (DTH) reaction Th2 cells, by producing IL-4, IL-5, IL-10, IL-13, trigger B-cells to initiate antibody production. 

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