Immunity and inflammation

At low concentrations, TNF-a activates a range of leukocytes that mediate selected elements of both specific and non-specific immunity. These TNF-a actions include  

In addition, TNF-a influences immunity indirectly by promoting synthesis and release of a variety of additional cytokines, including interferons, IL-1, IL-6, IL-8 and some CSFs. 

TNF-a also plays a prominent role in mediating the inflammatory response indeed, this may be its major normal physiological role. It promotes inflammation by a number of means, including  

Displays chemotactic effects, especially for monocytes and polymorphonuclear leukocytes. 

therefore, promotes various aspects of immunity and inflammation. Blockage of its activity, e.g. by administration of anti-TNF-a antibodies, has been shown to compromise the body s ability to contain and destroy pathogens. 

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Complement is not a single protein but comprises a group of functionally linked proteins that interact with each other to provide mar of the effector functions of humoral immunity and inflammation. Most of the components of the system are present in the serum as proenzymes, i.e. enzyme precursors. Activation of a complement molecule occurs as a result of proteolytic cleavage of the molecule, which in itself confers proteolytic activity on the molecule. Thus, many components of the system serve as the substrate of a prior component and, in turn, activate a subsequent component. This pattern of sequential activation results in the system being called the complement cascade. ... 

Many cytokines play a regulatory role in processes other that immunity and inflammation. Neurotrophic factors, such as NGF and BDNF, regulate growth, development and maintenance of various neural populations in the central and peripheral nervous system. EPO stimulates the production of red blood cells from erythroid precursors in the bone marrow. 

Interleukins Various, mainly cells mediating immunity and inflammation... 

Institute of Infection Immunity and Inflammation, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, United Kingdom s.r.chhabra nottingham.ac.uk... 

Cytokines are produced mainly by the leukocytes (white blood cells). They are potent polypeptide molecules that regulate the immune and inflammation functions, as well as hematopoiesis (production of blood cells) and wound healing. There are two major classes of cytokines (1) lymphokines and monokines and (2) growth factors. 

Theoretically, this appears to be a htting solution to gene problems. However, there are problems, such as immune and inflammation responses, toxicity, and means to target the intended cells. Non viral vectors may overcome the problems with viral delivery agents. Lipids, in the form of liposomes and other lipid complexes, are being studied. Injection of DNA directly into a patient s muscle cells is another avenue being researched. 

V. Chitu and E. R. Stanley, Colony-stimulating factor-1 in immunity and inflammation, Curr. Opin. Immunol. 18(1), 39-48 (2006). 

SECs, like the vascular endothehum, play an active part in the control of leucocyte recruitment in cases of acute and chronic inflammatory conditions. Eeucocyte recruitment from the blood compartment is a crucial determinant for the induction of immunity and inflammation. SECs control this process by producing cytokines that activate leucocytes and by expressing adhesion molecules. Under inflammatory conditions upregulation of intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was found [35 36], as well as expression of E-selectin and P-selectin [37]. Together with the expression of CD4 on SECs it has been postulated that these adhesion molecules might also be involved in the adhesion of KC cells to the sinusoidal wall [20]. 

After damage or infection, monocytes and KCs in the area detect the damaged cells or infectious agent and respond with release of primary mediators such as TNFa, IL-1 and some IL-6. These cytokines activate the surrounding cells, that respond with a secondary, amplified release of cytokines. This second wave includes large amounts of IL-6, which induce the synthesis of acute phase proteins in hepatocytes and chemoattractants such as IL-8 and MCP-1. These events will then lead to the typical inflammatory reactions. Both IL-1 and TNFa activate the central regulatory protein of many reactions involved in immunity and inflammation, nuclear factor kappa B (NFkB). These cytokines cause dissociation of NFkB from its inhibitor IkB, which makes translocation of NFkB to the nucleus possible. In the nucleus active NFkB induces the transcription of the second wave cytokines (see also Chapter 7 for the molecular mechanisms of cytokine-mediated cell activation). 

Dana MR, Hamrah P. Role of immunity and inflammation in corneal and ocular surface disease associated with dry eye. Adv Exp Med Biol 2002 506 729-738. 

Cytokines are small proteins synthesized de novo. They mediate and regulate functions such as immunity and inflammation. Cytokines bind to specific membrane receptors, signaling the cell via second messengers (often tyrosine kinases) to alter gene expression. Ty pical effects of cytokines include altered expression of membrane proteins (including cytokine receptors), proliferation, and secretion of effector molecules. 

Monteleone, G., Fina, D., Caruso, R., Pallone, F. New mediators of immunity and inflammation in inflammatory bowel disease. Curr. Opin. Gastroenterol., 22(4), 361-364 (2006). 

Cell-mediated immunity, also known as cellular immunity, uses T-leukocytes (referred to as natural killer cells or NK cells) to attack non-self cells. Cell-mediated immunity also causes the body to release cytokines, which regulate the activities of antibody-mediated immunity and inflammation. 

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