The Cellular Immune Response

The cellular immune system or cell-mediated immunity involves different cell types which also synthesize and release a number of soluble factors or mediators (cytokines). It is further subdivided into two components  

The major part of this section will deal with humoral immunity, which is mediated by the release of antibodies, and the response of the complement system. In the following section, attention will be focused on the role and structure of the different types of antibodies. 

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A recent report has demonstrated that the proteolytic activity of NS3 plays an additional role in viral infection, beyond polyprotein processing. An important mediator of the cellular immune response is the transcription factor interferon regulatory factor 3 (IRF-3), which becomes activated on infection and then stimulates production of type-1 interferon and other antiviral genes [46]. It was found that expression of heterodimeric NS3/4A... 

Details on the cellular immune responses occurring following the recognition of xenobiotic haptens as antigens by the immune system are described in chapters 33-35 of this volume. Ultimately, a certain combination of mediators is selectively activated and subsequently helps determine and differentiate the characteristic immune response (e.g., Thl vs. Th2). For example, dermal sensitizing chemicals (e.g., oxazolone and dinitrochlorobenzene) elicit a higher proportion of Thl cytokines such as IFNy and... 

The studies on stress-associated immunoregulation reviewed here are of great interest to both basic scientists and clinicians. Whereas these results implicate stress in the dys-regulation of the cellular immune response in healthy individuals, of greater importance... 

The serum immunoglobulins, in particular the IgM concentrations, are depressed in patients with Burkitt s lymphoma. All patients with central nervous system (CNS) involvement had IgM in their CSF, and subunits of IgM were detected in the urines of some Burkitt s lymphoma patients. The cellular immune responses were reported to be intact, but the humoral immunity was depressed in most patients with Burkitt s lymphoma. 

Observations regarding the cellular immune response in PTSD are also consistent with enhanced GR responsiveness in the periphery. In one study, beclomethasone-induced vasoconstriction was increased in women PTSD subjects compared to healthy, non-trauma-exposed comparison subjects (Coupland et al. 2003). Similarly, an enhanced delayed-type hypersensitivity of skin test responses was observed in women who survived childhood sexual abuse vs those who did not (Altemus et al. 2003). Because immune responses, like endocrine ones, can be multiply regulated, these studies provide only indirect evidence of GR responsiveness. However, when considered in the context of the observation that PTSD patients showed increased expression of the re-... 

Clinical pharmacology Basiliximab is a chimeric (mouse/human) interleukin-2 receptor antagonist. It is directed against the interleukin-2 receptor-alpha chain (CD25) on activated T-lymphocytes, and is a potent inhibitor of interleukin-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection. Another anti-CD25 monoclonal antibody, dacUzumab (Zenapax), has the same indication as basiliximab. 

Drug interactions Specific drug interaction studies have not been conducted with Enbrel. Although no data are available regarding the effects of vaccination in patients receiving etanercept therapy, vaccination with live vaccines is not recommended. The possibility exists for etanercept to affect host defenses against infections since the cellular immune response may be altered. 

An additional line of defense is provided by natural killer cells (NK cells), a type of circulating lymphoid cell able to kill cancer cells, to participate in antiviral defenses, and to help control immune responses.273 -276 NK cells, which utilize their own signaling pathways, are also able to use MHC class I molecules to recognize and to spare the lives of normal, healthy cells.277/277a b Partial deprivation of a night s sleep can reduce NK cell activity, damaging the cellular immune response.278... 

After tissue transplantation, the severity and the period of rejection depend on the tissue type, and this process involves the specificity and memory components of the immune response. Avrion Mitchison in the 1950s observed that allograft immunity could be transferred by the components of the cellular immune response, and antibodies present in the serum that were part of the humoral response were not associated with this process. Future studies delineated the role of T lymphocytes in the allograft rejection process, and the role of both CD4+ and CD8+ cells was established. 

Bispecific monoclonal antibodies are artificially developed antibodies with antigenbinding sites physically linked to different specificities. It is thought that bispecific monoclonal antibodies activate the cellular immune response by crosslinking immune cells to tumor cells, thus circumventing the proper structures for tumor cell-immune cell interactions (Koelemij et al., 1999). These antibodies are effective in low concentrations in vivo. For example, Kufer et al. (1996) have combined the anti-CD3 specificity directed against T cells in a bispecific monoclonal antibody, with the specificity against the tumor-associated 17-1A antigen. This antibody could be a major improvement, for example, in the therapy for disseminated micrometastatic tumor cells. 

The cellular immune response is mediated by T lymphocytes, so called because their maturation from stem cells occurs in the thymus. In cellular immunity it is the intact T lymphocytes themselves that are responsible for the recognition and killing of foreign invaders. These cells are the cytotoxic T lymphocytes (CTL), also called killer T cells. Other T lymphocytes have another role they provide essential help for B lymphocytes to produce antibodies and so are called helper T cells. 

Inhibits IL-2 mediated activation of lymphocytes, a critical pathway in the cellular immune response involved with allograft rejection... 

Differentiation of lymphocytes produces cells with different functions, such as B cells, and T helper and killer cells. The former produce and secrete antibodies, releasing them into Ijrmph and blood, the latter are responsible for the cellular immune response. The response of T cells is antigen-spedfic, just like the response of B cells. But, T cells interact with another cell in the body, the antigen-presenting cells (APCs), which have taken up and processed the foreign antigen. Helper T cells react with APCs and killer T cells... 

In the cellular immune response, cells called cytotoxic T lymphocytes (also commonly called killer T cells) kill cells that display foreign motifs on their surfaces. Another class of T cells called helper T lymphocytes contributes to both the humoral and the cellular immune responses by stimulating the differentiation and proliferation of appropriate B cells and cytotoxic T cells. The celluar immune response is mediated by specific receptors that are expressed on the surfaces of the T cells. 

Molholm, 1942). This finding could be replicated in unmecU-cated schizophrenic patients using a skin test of the cellular immune response (Riedel et al., 2007). 

Lepromatous leprosy occurs in people who exhibit an efficient antibody response to M. leprae but an inefficient cellular immune response. The antibody arm of the immune system is not useful in neutralizing intracellular pathogens such as M. leprae therefore, people who initially react to invasion by M. leprae by making antibodies may be at risk for developing more severe forms of leprosy. Researchers are not sure what determines whether a person will react with a cellular response or an antibody response current evidence suggests that the cellular immune response may be controlled by a special gene. If a person has this gene, he or she will probably develop the less severe tuberculoid leprosy if exposed to M. leprae. 

Azathoiprine is metabolised to 6-mercaptopurine (see p. 608), which is responsible for many, but not all, of its actions as an inhibitor of purine synthesis. The cellular immune response is impaired, notably the function of both B and T lymphocytes. As a result of a genetic polymorphism, approximately 1 in 300 Caucasian people have very low levels of thiopurine methyltransferase (TPMT) the enzyme that metabolises 6-mercaptopurine these individuals are at high risk of toxicity to normal doses of azathioprine. 

The humoral and cellular immune systems function jointly as an acquired defence against infection. Whether the humoral or the cellular defence system is predominantly used depends in the individual case on the nature of the pathogen or the foreign body, the reactivity of the organism and the mode of infection. The humoral immune response proceeds via the B-l)miphocytes and plasma cells, while the cellular immune response is mediated via the T-l)miphocytes. The haematopoetic stem cells mature into B-lympho-cytes. These are further transformed to plasma cells, which in turn synthesize IgM, but they can also switch to produce IgA and IgG. (99)... 

Cofactors Coinfections with HAV and HBV as well as with other viruses worsen the prognosis. By contrast, coinfections with HGV, GBV-C, SENV and TTV had no influence on the course of chronic hepatitis C. (115, 146) Alcohol influences the cellular immune response unfavourably and leads to an aggravation of pathological liver morphology. (85, 120, 128, 129, 144) Age and gender play a special role. Generally, older patients are... 

Inhibition of oxazolone-induced delayed-type hypersensitivity is used as an in vivo test for inhibition of the cellular immune response. The shaved abdominal surfaces of groups of mice are sensitized by topical application of 0.1ml of 5% oxazolone. The test drug is given intraperitoneally an hour later and then daily for five consecutive doses. After an additional 4 days, the animals are challenged by application of 0.5 ml oxazolone to one ear. Ear thickness is measured 24 h later. A decrease in ear thickness relative to untreated controls is an indication of immunosuppresion. 

Defective IL-12 production is associated with increased susceptibility to infection (e.g., familial disseminated Mycobacterium avium complex infection, T. cruzi infection, and human visceral leishmaniasis), a finding that supports the critical role of this cytokine in host defense and in the regulation of the cellular immune responsed The loss of immune function following infection with HIV may resrdt from altered production of immunoregulatory cytokines, such as IL-10 and IL-12. It was suggested that monocytes from HIV-positive individuals secrete decreased amounts of IL-12, which may lead to the development of Th2 type of responses characterized by high IL-10 secretion and immune dysfunction/ ... 

An early report of the therapeutic possibilities of chemical imrnuno-modulation of the cellular Immune response in toxoplasmosis utilizing levamisole is of interest. ... 

Tokuda, N. et al. (2000) Caldtriol therapy modulates the cellular immune responses in hemodialysis patients. American Journal of Nephrology, 20, 129-137. 

A major challenge for immunologists has been the development of vaccines designed to emphasize the cellular immune response and to generate high levels of T-cell memory. This is especially needed to prevent infectious diseases caused by viruses or intracellular pathogens [6]. Many vaccines, especially recombinant proteins, predominantly induce Tn2-based (humoral) immune responses, and therefore are not ideally qualified to prevent virus-mediated diseases. 

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