Immune surveillance

T-Lymphocytes (4,5) and other cellular components of the immune system also have equally wide implications in regulation of the normal immune system. The T-lymphocytes play a central role in the body s response to harmful antigens and tumor—host interaction (4). Responses involve antigens derived from vimses, bacteria, parasites, and tumors. T-ceUs also participate in the immune surveillance response, where self-antigens are recognized, but usually sequestered within the cell and, when exposed, become markers of cellular damage. 

The pathogenesis of AIDS (10,12,13) following HIV infection may be separated into primary and secondary effects. The primary effects are (/) quantitative and quahtative decreases in infected cells, ie, the T-lymphocytes (2) impaked cellular immunity (J) impaked immune surveillance and... 

Gradual diminution of 004 T-lymphocytes from the peripheral blood is the most consistent feature observed in HIV infection. Because the majority of 004 cells are T-helper lymphocytes, removal leads to deficiency of cellular immunity, which depends on T-helper cells to initiate cytotoxic T-ceU killing of vims-infected cells of cancer. The loss of immune surveillance leads to the appearance of viraHy induced tumors from unopposed clonal expansion of viraHy transformed cells. Furthermore, depletion of cellular immunity leads to exaggerated viral, fungal, and proto2oal infections. 

Transforming growth factor-beta (TGF- 3) proteins are multifunctional morphogens that control cell proliferation, differentiation and apoptosis, as well as cell migration and immune surveillance. TGF-(3 acts as a tumor suppressor, but can also act as a tumor promoter in... 

Since the endogenous levels of inducible transcription factors like NF-kB and NFAT (Duh et al. 1989 Kinoshita et al. 1997) in these cells have been reported to be very low, HIV-1 promoter activation is inefficient resulting in non-expression of viral gene products (Figs. 5.1 and 5.2). Therefore, these cells can escape immune surveillance and act as passive carriers of HIV-1 for their natural lifespan. 

Naturally occurring tumours evoke little or no immune response in experimental animals. This is disappointing but it must be remembered that these cells have already escaped the normal immune surveillance. 

Moser B, Willimann K. Chemokines role in inflammation and immune surveillance. Ann Rheum Dis 2004 63(Suppl 2) ii84-ii9. 

There exists direct evidence that the immune system mounts an immune response against most cancer types. Virtually all transformed cells express (a) novel surface antigens not expressed by normal cells or (b) express, at greatly elevated levels, certain antigens present normally on the cell at extremely low levels. These normal expression levels may be so low that they have gone unnoticed by immune surveillance (and thus have not induced immunological tolerance). 

Although immune surveillance is certainly responsible for the detection and eradication of some transformed cells, the prevalence of cancer indicates that this surveillance is nowhere near 100 per cent effective. Some transformed cells obviously display characteristics that allow them to evade this immune surveillance. The exact molecular details of how such tumour escape is achieved remains to be confirmed, although several mechanisms have been implicated, including ... 

The major mode of action of such products appears to be depot formation at the site of injection. The antigen is only slowly released from the gel, ensuring its sustained exposure to immune surveillance. The aluminium compounds are also capable of activating complement. This can lead to a local inflammatory response, with consequent attraction of immunocompetent cells to the site of action. 

At least two specific properties make the immune system vulnerable to chemical or physical insults (1) the immune system develops rather late in life (thymus development lasts at least until puberty), and some bone marrow-dependent immune components are continuously renewed (i.e., granulocytes), and (2) each pathogen attack, as well as immune surveillance, demands a delicate control of the balance between activation, silencing, and regulation of immune reactivity. 

Blood is the transport medium of the body. Plasma, which accounts for approximately 60% of the total volume, carries a wide range of small and medium-sized metabolites some are simply dissolved in solution (93% of the plasma is water), others are carried by specific carrier proteins. The chemical composition of the plasma is complex and reflects the chemical composition inside cells, which is why blood tests are so commonly used in diagnosis to see the biochemical events occurring in tissues. The formed cellular elements of the blood perform several functions defence against blood loss from bleeding (platelets, also called thrombocytes), defence against infection and immune surveillance (white cells, leucocytes), and gas transport and pH buffering (red cells, erythrocytes). 

Kupper TS. Fuhlbrigge RC Immune surveillance in the skin mechanisms and clinical consequences. Nat Rev Immunol 2004 4 211-222. 

Ochsenbein AF, et al. Immune surveillance against a solid tumor fails because of immunological ignorance. Proc Natl Acad Sci USA 1999 96 2233. 

Garcia-Lora, A., Algarra, L, and Garrido, E., 2003, MHC class 1 antigens, immune surveillance, and tumor immune escape, J. of Cell. Physiol. 195 346-355. 

Johnsen, A., Templeton, D. J., Sy, M. S., and Harding, C. V., 1999, Deficiency of transporter for antigen presentation (TAP) in tumor cells allows evasion of immune surveillance and increases tumorigenesis, J. Immunol 163 4224-4231. 

The cells are called natural killer cells since they kill without a requirement for MHC class I or class II proteins. This characteristic is sometimes termed the MHC-independent immune response. Their principal role is in defence against virnses and other intracellular microorganisms that is, they kill host cells infected with a vims or other pathogen. They also kill tumour cells. Thus they have a role in the process of immune surveillance for tumour cells. 

There is evidence that stressful conditions decrease the effectiveness of the immune system the loss of a job, a divorce or a bereavement increases the risk of development of cancer. This is due to impairment of the process of immune surveillance carried out by the neutrophils and other immune cells. They kill tumour cells that are migrating from a primary tumour to establish another tumour in a different tissue. The impairment may be due to chronic activation of the sympathetic system, which increases the... 

Site of infection/latency Accessible to immune surveillance Infect cells in immunoprivileged sites... 

Herberman, R.B. (1984) Possible role of natural killer cells and other effector cells in immune surveillance against cancer, J. Invest. Dermatol, 83,1375. 

The resulting epitope density may depend on the number of lysine groups in the particular protein, and this will in turn affect the immunogenicity of the antigen. Trifluoroacyl adducts have been detected on the outer surface of hepatocytes, presumably as a result of the hapten-complex processing and delivery by MHC I, which is described above. The fact that the production of the trifluoroacetyl chloride is part of the major metabolic pathway and that the majority of patients produce trifluoroacylated proteins suggests that it is differences in the immune surveillance system or immune responsiveness, which determine which patients will succumb to the immunotoxic effect. 

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