T3 O 0 03

inflammation is a defense reaction of the organism and its tissues to injurious stimuli. The aim is to repair the damage or at least to limit it, and also to remove the cause, for example, bacteria or foreign bodies.

Causes of an inflammation can be:

♦ Microorganisms A), such as bacteria, viruses, fungi, or parasites;

♦ Foreign bodies (foreign protein, e.g., pollen; asbestos or silicon crystals); or

♦ Tissue destruction with formation of tissue debris, for example, through mechanical damage such as cuts, stabs, scratches or foreign bodies, chemical compounds such as acids or alkalis, physical influences such as cold, heat, radiation (UV, X-rays, radioactivity), and endogenous causes such as disintegrating tumor cells, extravascular blood, autoimmune reactions (^ p. 56), or crystals of substances precipitated in the body (uric acid, calcium oxa-late, calcium phosphate, and cholesterol).

An acute inflammation expresses itself as a local reaction associated with the symptoms, known since antiquity, of pain (dolor), swelling (tumor), reddening (rubor), and warmth (calor). in addition, there are general inflammatory reactions (acute-phase response; see below).

Rapid activation of mast cells (in tissue) or their counterparts in blood, the basophil leukocytes, or basophils, is an example of the occurrence of a very strong acute inflammatory reaction (^ A) on which especially type i hypersensitivity reactions are based (^ p. 52). if the body has previously been in contact with an antigen (= allergen in cases of hypersensitivity), for example, with bee-poison protein, B cells will have been sensitized as a reaction to it (cooperation with TH2 cells; ^ p. 47, B4). The ensuing plasma cells produce IgE that binds to the Fcs receptors of the mast cells. On renewed contact with the antigen this is now bound to the antigen-specific Fab-ends of IgE. it seems to be important for further reactions of the mast cells that the allergen is bound to several igE molecules (antibody cross-linking); large antigens that can repeatedly act antigenically with different molecular parts (polyvalence) are especially effective (e.g., parasites with several bound haptens).

Cross-linking of the antibodies by the antigen sets free second messengers in the mast cell (cGMP, inositol phosphate, Ca2+) that trigger a rapid degranulation of the mast cells, i.e., exocytosis of the inflammation mediators and chemokines stored within the granules (histamine, interleukin 8[IL-8], eotaxin, neutrophilic chemotactic factor [NCF], etc.). Ca2+ also activates phospholipase A2 that splits off arachi-donic acid from the phospholipids in the cell membrane. This is the starting substance for other important inflammation mediators, namely prostaglandins (E2 etc.) and leuko-trienes (C4, D4 and E4; together also called slow reacting substance of anaphylaxis [SRS-A], as well as B4). The ether phospholipid platelet activating factor (PAF), another important inflammation and hemostatic mediator, is liberated from the cell membrane of mast cells.

In the further course of inflammatory reaction leukotrienes and PAF (platelet-activating factor) are also released from eosinophils and neutrophils, from macrophages as well as PAF from thrombocytes. This contributes significantly to strengthening the reaction and to the inclusion of the hemostatic system. These cells are attracted by chemotaxis. Eotaxin, PAF, and leukotriene B4 act chemotactically on eosinophils (and TH2 cells). As PAF also activates the mast cells, the two cell types cooperate. Neutrophils and monocytes are attracted by leukotriene B4, C5 a (see below), NCF, tumor necrosis factor (TNF-a), 1L-1,1L-4, and several chemokines, such as 1L-8 (^ A).

Histamine, PAF, and the leukotrienes C4, D4, and E4 act together with other mediators (prostaglandin E2, bradykinin) to cause: 1) va-sodilation, 2) an increased paracellular permeability of the endothelium, and 3) stimulation of nociceptors (^ A).

Vasodilation is the cause of the reddening and warming at the site of inflammation (see above) and of reduced blood flow velocity which makes it possible for the chemotactical-ly attracted leukocytes to swim to endothe-lium-near regions. Endothelium that has been activated in the inflammatory area by, among others, 1L-4 (from TH2-lymphocytes) pushes se-lectins out into the lumen. These selectins, in

- A. Acute Inflammation-

Mast cell Previous antigen contact -

Mast cell Previous antigen contact -


TH2 cells IL-4

0 0

Post a comment