Immune response acute phase

Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., and Kohler, G. (1994). Impaired immune and acute phase responses in interleukin-6 deficient mice. Nature 368, 339-342. 

A number of chimerized, humanized, and one human mAb have now been approved for therapeutic use in humans in the treatment of autoimmunity, malignancy, infection and cardiovascular disease (Table 1). Some of the currently licensed mAb will be discussed here. A much larger number of mAb are currently being evaluated in Phase I, II and III trials. In general, chimeric, humanized and human mAb are very well tolerated with few side effects. Chimeric or humanized mAb still have the potential to evoke host immune response to the variable domains or CDRs of the antibody so-called HACA (human anti-chimeric antibody) or HAHA (human anti-human antibody) responses, although these responses are uncommon. Short-lived and occasionally severe infusion-related acute hypersensitivity reactions such as fever, skin itching, shivering, respiratory compromise and low blood pressure sometimes occur-. Such effects may... 

Family of transcription factors that modulate the expression of genes which control immune, inflammatory, and acute-phase responses, as well as cell growth, responses to stress, apoptosis, and oncogenesis. All members of this family have a Rel-homology domain that contains sequences responsible for dimerization and DNA binding. In vertebrates, this family includes NF-kB1 (also known as p50), NF-kB2 (also known as p52), Rel (also known as cRel), Rel-A (also known as p65), and Rel-B. 

L4. Le, J., and Vilcek, J., Interleukin 6, a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab. Invest. 61,588-602 (1989). 

These are generated by the liver during infections and other forms of inflammatory challenge, as part of the acute-phase response. This response to infection is characterised by fever, sleep, adrenotrophic hormone release, decreased plasma iron and zinc levels, elevated neutrophils in the bloodstream and enhanced cytokine production. These changes, part of the body s response to combat infection, occur within hours. The elevated temperatures may inhibit the replication of some bacteria and viruses and may also enhance the function of some immune cells. 

Figure 17.19 Sequence of events from phagocytosis by the APC, activation of the Th cell and subsequent immune response. Events in the infected tissues, in the Lymph node, in the plasma and in the whole body are summarised Peplides include acute phase proteins. For effects on the tissues in the whole body, see Chapter 18 Table 18.2.

In some cases, a slow rejection phase begins many months or even years after transplantation when acute rejection has subsided. The chronic rejection appears to be due to the slow buildup of antibodies against the graft antigens and/or due to cell-mediated immune responses by the recipient. It does not respond well to the immunosuppressive drugs, and a new transplant is needed following chronic rejection reaction. 

While cytokine release may be localized both in tissue distribution and in time, secondary measurements can reflect cytokine release or resulting immune cell activation at time points with other scheduled safety labs. One of the most useful, with a long history of clinical use, is C-reactive protein (CRP), for which EIA kits are available for species including rodents, rabbits, and dogs. CRP is a serum acute-phase reactant, and levels can increase by over 2 logs driven mainly by release of IL-1, IL-6, and TNF-alpha. The peak increase usually lags cytokine release by 24 to 48 hours and can remain above baseline for several days to a week once the acute phase response is stimulated. 

The effects of marijuana on immune function have been reviewed (122). The studies suggest that marijuana affects immune cell function of T and B lymphocytes, natural killer cells, and macrophages. In addition, cannabis appears to modulate host resistance, especially the secondary immune response to various infectious agents, both viral and bacterial. Lastly, marijuana may also affect the cytokine network, influencing the production and function of acute-phase and immune cytokines and modulating network cells, such as macrophages and T helper cells. Under some conditions, marijuana may be immunomodulatory and promote disease. 

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