Specific, acquired immunity

Vergote D, Butler GS, Ooms M, Cox JH, Silva C, Hollenberg MD, Jhamandas JH, Overall CM, Power C (2006) Proteolytic processing of SDF-lalpha reveals a change in receptor specificity mediating HIV-associated neurodegeneration. Proc Nad Acad Sci USA 103(50) 19182-19187 von Giesen HJ, Roller H, Theisen A, Arendt G (2002) Therapeutic effects of nonnucleoside reverse transcriptase inhibitors on the central nervous system in HlV-1-infected patients. J Acquir Immune Defic Syndr 29(4) 363-367... 

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

Although acquired immunity to some parasitic diseases may lower the level of infection, absolute immunity as seen in bacterial and viral infections is seldom seen in parasitic diseases. Since parasitic infections produce a wide variety of antigens because of the many life cycle phases, it is more difficult to identify a constant antigenic protein against which specific antibodies are protective. However, malaria remains a likely candidate for a vaccine and there are ongoing studies to develop one. 

Compounds that are not overtly myelotoxic may still selectively damage or destroy lymphocytes, which are the primary effectors and regulators of acquired immunity. This toxicity may result from the destruction of rapidly dividing cells by necrosis or apoptosis. A variety of methodologies are available for this purpose (e.g., colorimetric, flow cytometric assays). If the cells are viable (80% or greater), basic functionality could be determined by performing specific functional assays. 

The acquired immune system has probably received most of the attention in marine mammals, as has been the case in rodent and human immunology. Recent advances include the production of monoclonal [22-24] and polyclonal [25] antibodies to marine mammal immunoglobulins, enabling more precise, and often species-specific, reagents for the detection and quantification of antigen-specific antibodies. 

Lymphocytes, the effector cells of the acquired immune system, include morphologically indistinguishable T and B cells, the former divided into CD4+ T helper cells and CD8+ cytotoxic T cells. Since the functions of those cell subsets differ so drastically, it became important to develop tools to distinguish them from each other. Efforts to identify cell subsets according to their expression of different surface antigens have been successful, including various Cluster of Determination (CD) markers (Table 23.1). In addition, cross-reactive monoclonal antibodies, and subsequently developed species-specific polyclonal and monoclonal antibodies towards the major histocompatibility complex (MHC) have been used to label cells in circulation and in tissue sections (Table 23.1). 

In addition to being able to recognize the different cells involved in the acquired immune system of marine mammals, it is important to assure that the cells perform their functions appropriately. The ability of lymphocytes to proliferate upon stimulation (usually with mitogens) has been studied for several decades [1,12,14,15, 32-35], Recent advances include the demonstration of a conserved specificity for standard mitogens used in beluga whales [32] and harbor seals [33], An assay to assess the expression of the receptor for interleukin-2 (IL-2), an early event in lymphocyte activation, was adapted in harbor seals [35], bottlenose dolphins [36], and sea otters [37], Molecular and biochemical mechanisms of activation of beluga T lymphocytes do not vary substantially from those in other mammals [38],... 

Three lipids A have been more intensively studied in animal models, all of them having indirect effects, mediated in vivo by the immune system. For two of them, DT-5461 and ONO-4007, TNF-a is an important mediator acting at the vascular level that provokes tumor necrosis. For the third one, OM-174, the treatment induces the accumulation of IFN-y and EL-1 P in tumors, which activate NOS II transcription in tumor cells that produce autotoxic NO, which then provokes the apoptosis of tumor cells. At the same time this treatment inhibits the production of TGF-pi by tumor cells which reduces the TGF-pi induced immunosuppression and enhances NO production. Acquired immune response, probably completes the tumor regression started by the apoptosis process and, most probably induces specific memory. 

One of the functions of the immune system is to protect the body from foreign invasion by dangerous pathogens (e.g., bacteria) recognized as not self." It does this by using a mixture of the innate immune and specific acquired immune systems. 

Miller, H.M. (1932) Acquired immunity against a metazoan parasite by use of non-specific worm material. Proceedings of the Society for Experimental Biology 29, 1125-1126. 

Figure 19.2 The acquired immune response. In response to a specific antigen there is clonal expansion of B cells and subsequent production of antibodies (Ig) specific for that antigen. Antigen presenting cells process and present antigen to T cells. Again there is clonal expansion of cells specific for that antigen.

Specific cellular immunity is a type of (more specialized) acquired immunity which is based primarily on T lymphocytes. Several subpopulations of T lymphocytes are differentiated in the thymus, where one subset has identical structures on the cell surface to recognize a specific set of antigen. Each subpopulation performs different effector functions. The dominant T-cell type involved is the so-called cytotoxic T lymphocyte. In addition, T-helper cells are important for enhancing the immune response. By synthesizing and secreting various cytokines such as interferon y (INF-y or interleukin 2 (IL-2), T-lymphocytes also have an important role in controlling other major parts of the immune system. 

Siglecs are expressed abundantly on many cells of the immune system and are therefore likely to be important in both innate and acquired immune responses. The development of siglec-specific agonists and antagonists may provide new approaches for the treatment of certain autoimmune and inflammatory conditions. Moreover, the... 

Acquired immunity is immunity that develops with exposme to antigens the immune system builds a defence that is specific to that antigen. B-ceU lymphocytes, produced in the stem cells of the bone marrow, synthesise and release antibody they oversee the humoral immune response. T-ceU lymphocytes, produced in the bone marrow but sensitised in the thymus, are the basis of the ceU-mediated immune response. 

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