Page 62 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Hypersensitivity Reactions (Allergies)
An allergy is a specific overreaction of the im- hypersecretion in the respiratory tract as well
mune system to a substance that is foreign to as any vomiting or diarrhea actually help to
the body but otherwise harmless, i.e., an an- remove the allergen. The skin reacts to aller-
tigen (→ p. 42), which now becomes an aller- gens (e.g., to bee-poison protein) with itching,
gen. By binding to small-molecule foreign swelling, urticaria, and atopic dermatitis. If the
substances (so-called haptens), endogenous allergen gains direct access into blood through
proteins can have the same effect as an aller- injection (e.g., serum or haptens such as pen-
gen. While normally the increased immune icillin), a immediate systemic reaction occurs
(secondary) reaction can act protectively on and the resulting liberation of vasoactive
repeated antigen contact (immunization; mediators can lead to a life-threatening drop
→ p. 42ff.), in an allergy it will lead to the de- in blood pressure (anaphylactic shock;
struction of intact tissue via immune mecha- → p. 230ff.). It may also occur, although slight-
nisms that are in principle quite similar. Thus, ly delayed, after strong gastrointestinal or re-
the primary contact will have initiated an al- spiratory exposure to allergens. Similarly, urti-
lergizing process. However, similar destruction caria may develop in cases of food allergy.
can also occur when the immune system fails In type II, or cytotoxic hypersensitivity
to recognize endogenous proteins as being en- (→ A), the focus is usually on antigen-effective
dogenous and autoantibodies are formed cells or extracellular matrix proteins, in that ei-
Blood (→ p. 54). In each case it is inflammatory reac- ther haptens (e.g., drugs) bind to endogenous
(blood) cells, or foreign blood cells enter the
tions (→ p. 48ff.) that do the damage.
3 Hypersensitivity reactions are divided into organism. After allergization on first contact
(sometimes overlapping) types I–IV. Type I with the allergen, subsequent antigen expo-
(immediate) reaction is common. It is preced- sure results in large amounts of allergen-spe-
ed by allergization: when B and T H2 cells coop- cific IgM and IgG being formed and being
erate, the allergen is presented, and, among densely bound (10 –10 per cell) to the aller-
5
4
others, IL-4 and IL-5 are liberated. Under the genic cell surface (opsonification; → A). In this
influence of IL-4, antigen-specific B cells pro- way the complement system is activated
liferate (→ IgE formation; → p. 47 B4), and eo- (→ p. 43, A1), and natural killer cells unfold
sinophils in bone marrow are stimulated by their cytotoxic action (antibody-dependent
IL-5 to differentiate and then enter the blood- cell-mediated cytotoxicity [ADDC]; → p. 43,
stream (→ p. 49, top). On second contact, im- A3). Both produce destruction of the allergenic
mediate reaction (anaphylaxis) occurs within cell within a few hours (cytolysis; → A). Hapten
seconds to minutes and may be followed in a binding to endogenous erythrocytes thus re-
few hours by a late reaction. The immediate re- sults in hemolytic anemia (→ p. 40), and hap-
action is based on rapid liberation and new ten binding to thrombocytes results in throm-
formation of vasoactive inflammation media- bocytopenia. (The two cell types are especially
tors from IgE-coupled mast cells, while the exposed to complement attack, because they
late reaction is mediated by attracted eosino- possess only a few complement-regulating
phil and neutrophils and IgG (→ p. 49, top). proteins; see also p. 40). Foreign erythrocytes
A type I (immediate) reaction can, depend- (e.g., in ABO incompatibility) are agglutinated,
ing on allergen exposure, be local or to a vari- i.e., they are bound together via IgM and are
able extent generalized. Allergens in the air quickly hemolyzed (acute transfusion acci-
(e.g., pollen, mite dust, animal hair) precipitate dent; → p. 41, B). In a basically similar (but not
reactions in the respiratory tract, where muco- as yet fully clarified) way, autoantibodies
sal edema with hypersecretion (e.g., hay fever) against the basement membrane lead to tissue
and bronchospasm (asthma) may occur, while destruction in the kidneys and lung (Goodpas-
food allergens (e.g., constituents of milk, fruit, ture’s syndrome). IgG is deposited along the
or fish) result, in the first instance, in gastroin- capillaries of the renal glomeruli, where they
52 testinal symptoms such as abdominal pain, cause a strong inflammatory reaction (rapidly
nausea, vomiting, and diarrhea. Nevertheless, progressive glomerulonephritis with impend-
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Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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