Cell-mediated immunity macrophage activation

Cell-Mediated Immunity, Cytotoxic Activated Macrophages, and Cytokines 5... 

CELL-MEDIATED IMMUNITY, CYTOTOXIC ACTIVATED MACROPHAGES, AND CYTOKINES... 

Figure 9.3 Activation of T-cells by interaction with macrophage-displayed antigen. Activation results in IL-2 production, which acts in an autocrine manner to stimulate further T-cell growth and division. IL-2 thus represents the major regulatory molecule responsible for stimulation of cell-mediated immunity. Note that it was initially believed that binding of presented antigen alone was insufficient to trigger T-cell activation. It was thought that co-stimulation with IL-1 was reguired. However, the assay used to detect the co-stimulation was found not to be specific for IL-1 alone. The role of IL-1 as a co-stimulator of T-cell activation is now believed to be minimal at most...

Large numbers of activated macrophages surround the solid caseous (cheese-like) TB foci (the necrotic area) as a part of cell-mediated immunity. Delayed-type hypersensitivity also develops through activation and multiplication of T lymphocytes. Macrophages form granulomas to contain the organisms. 

Respiratory allergies and infections are the most common form of illness in the United States and Europe and account for more missed school and work days than any other disease [1], A substantial body of experimental work has clearly shown that airborne toxicants such as tobacco smoke, ozone, and other air pollutants can alter many aspects of the host defense network to either decrease resistance to infection, or exacerbate respiratory allergies and asthma [2], Exposure to air toxicants can suppress a number of key host defenses including mucociliary clearance in the airways, pulmonary macrophage function, and development of specific immune responses such as IgG antibody production and cell mediated immunity. In contrast, immune stimulation in the form of increased T cell activity and IgE antibody formation has also has been shown to occur under some circumstances, resulting in increased incidence or severity of allergic lung disease. 

Interferon-7 was the first secretory product of T cells to be discovered when it was found that supernatants derived from suspensions of T cells that had been treated with mitogenic agents could activate macrophages. This macrophage activating factor , subsequently found to interfere with the replication of viruses, was thus named interferon. The production of this compound, associated with delayed-type hypersensitivity and cell-mediated immunity, was termed immune interferon or type II interferon. With the discovery of other lymphokines with interferon-like activity (interferon-a and -j3), the compound was finally designated interferon-7. 

The two types of cell-mediated immunity involve basically different types of T cells. In the delayed-type hypersensitivity response, the T cell, TD, that reacts specifically with antigens secretes interleukins (see Box S3A) that attract and activate macrophages or other leukocytes, thereby causing a slowly developing inflammatory response. A second type of T cell, known as the T killer cell, TK, reacts specifically with antigen that is bound to target cells, causing their lysis. 

IFN-y also induces the costimulatory molecules on the macrophages, which increases cell-mediated immunity. As a consequence, there is activation and increase in the tumoricidal and antimicrobial activity of mononuclear phagocytes, granulocytes and NK cells. The activation of neutrophils by IFN-y includes an increase in their respiratory burst. IFN-y stimulates the cytolytic activity of NK cells. It is an activator of vascular endothelial cells, promoting CD4+ T lymphocyte adhesion and morphological alterations, which facilitates lymphocyte extravasation. IFN-y promotes opsonization by stimulating the production of IgG subclasses that activate the complement pathway. A summary of the characteristics of selected cytokines is shown in Table 2.3. 

About 10 days after transplantation, acute rejection of the graft begins as a result of cell-mediated immunity. Acute rejection is a result of infiltration of large numbers of macrophages and lymphocytes into the graft. Helper T-cell activation and proliferation play a major role in this process, and both complement-dependent cell-mediated cytotoxicity and ADCC are involved in the destruction of the graft. Acute rejection could be in the form of acute vascular rejection, acute cellular rejection or both. Acute vascular rejection involves the necrosis of the blood vessel cells of the graft... 

Two types of immunity may be induced in response to an antigen, namely humoral immunity mediated by antigen-specific antibodies produced by B lymphocytes, and cell-mediated immunity produced by activated macrophages and cytotoxic T lymphocytes. Antibodies may neutralize pathogens, whereas... 

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