Page 58 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Inflammation
Inflammation is a defense reaction of the or- Cross-linking of the antibodies by the anti-
ganism and its tissues to injurious stimuli. gen sets free second messengers in the mast
2+
The aim is to repair the damage or at least to cell (cGMP, inositol phosphate, Ca ) that trig-
limit it, and also to remove the cause, for ex- ger a rapid degranulation of the mast cells, i.e.,
ample, bacteria or foreign bodies. exocytosis of the inflammation mediators and
Causes of an inflammation can be: chemokines stored within the granules (hista-
! Microorganisms (→ A), such as bacteria, mine, interleukin 8[IL-8], eotaxin, neutrophilic
viruses, fungi, or parasites; chemotactic factor [NCF], etc.). Ca 2+ also acti-
! Foreign bodies (foreign protein, e.g., pollen; vates phospholipase A 2 that splits off arachi-
asbestos or silicon crystals); or donic acid from the phospholipids in the cell
! Tissue destruction with formation of tissue membrane. This is the starting substance for
debris, for example, through mechanical dam- other important inflammation mediators,
age such as cuts, stabs, scratches or foreign namely prostaglandins (E 2 etc.) and leuko-
bodies, chemical compounds such as acids or trienes (C4, D4 and E4; together also called
alkalis, physical influences such as cold, heat, slow reacting substance of anaphylaxis [SRS-
radiation (UV, X-rays, radioactivity), and en- A], as well as B4). The ether phospholipid
dogenous causes such as disintegrating tumor platelet activating factor (PAF), another impor-
cells, extravascular blood, autoimmune reac- tant inflammation and hemostatic mediator, is
Blood tions (→ p. 56), or crystals of substances pre- liberated from the cell membrane of mast
cells.
cipitated in the body (uric acid, calcium oxa-
3 late, calcium phosphate, and cholesterol). In the further course of inflammatory reac-
An acute inflammation expresses itself as a tion leukotrienes and PAF (platelet–activating
local reaction associated with the symptoms, factor) are also released from eosinophils and
known since antiquity, of pain (dolor), swelling neutrophils, from macrophages as well as PAF
(tumor), reddening (rubor), and warmth (ca- from thrombocytes. This contributes signifi-
lor). In addition, there are general inflamma- cantly to strengthening the reaction and to
tory reactions (acute-phase response; see be- the inclusion of the hemostatic system. These
low). cells are attracted by chemotaxis. Eotaxin,
Rapid activation of mast cells (in tissue) or PAF, and leukotriene B4 act chemotactically
their counterparts in blood, the basophil leuko- on eosinophils (and T H2 cells). As PAF also acti-
cytes, or basophils, is an example of the occur- vates the mast cells, the two cell types coop-
rence of a very strong acute inflammatory re- erate. Neutrophils and monocytes are attract-
action (→ A) on which especially type I hyper- ed by leukotriene B4, C5a (see below), NCF, tu-
sensitivity reactions are based (→ p. 52). If the mor necrosis factor (TNF-α), IL-1, IL-4, and sev-
body has previously been in contact with an eral chemokines, such as IL-8 (→ A).
antigen (= allergen in cases of hypersensitiv- Histamine, PAF, and the leukotrienes C4, D4,
ity), for example, with bee-poison protein, B and E4 act together with other mediators
cells will have been sensitized as a reaction to (prostaglandin E 2 , bradykinin) to cause: 1) va-
it (cooperation with T H2 cells; → p. 47 , B4). The sodilation, 2) an increased paracellular perme-
ensuing plasma cells produce IgE that binds to ability of the endothelium, and 3) stimulation
the Fc ε receptors of the mast cells. On renewed of nociceptors (→ A).
contact with the antigen this is now bound to Vasodilation is the cause of the reddening
the antigen-specific Fab-ends of IgE. It seems and warming at the site of inflammation (see
to be important for further reactions of the above) and of reduced blood flow velocity
mast cells that the allergen is bound to several which makes it possible for the chemotactical-
IgE molecules (antibody cross-linking); large ly attracted leukocytes to swim to endothe-
antigens that can repeatedly act antigenically lium-near regions. Endothelium that has been
with different molecular parts (polyvalence) activated in the inflammatory area by, among
48 are especially effective (e.g., parasites with others, IL-4 (from T H2 -lymphocytes) pushes se-
several bound haptens). lectins out into the lumen. These selectins, in
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Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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