immune & inflammatory responses that are harmful to the host. The concept that the immune system is required for defending the host against infections has been emphasized throughout this book. How-ever, immune responses are themselves capable of causing tissue injury and disease. Injurious, or pathologic, immune reactions are called hyper-sensitivity reactions. An immune response to an antigen may result in sensitivity to challenge with that antigen, and therefore hypersensitivity is a reflection of excessive or aberrant immune responses. Hypersensitivity reactions may occur in two situations. First, responses to foreign anti-gens (microbes and noninfectious environmen-tal antigens) may cause tissue injury, especially if the reactions are repetitious or poorly con-trolled. Second, the immune responses may be directed against self (autologous) antigens, as a result of the failure of self-tolerance (see Chap-ter 9). Responses against self antigens are termed autoimmunity, and disorders caused by such responses are called autoimmune diseases.

1. Hypersensitivity
AMIR RAJAEY
Hypersensitivity

2. Hypersensitivity is a condition in
which an exaggerated or augmented
immune response occurs that is
harmful to the host. Hypersensitivity
requires a presensitized state. For
example, in a given individual, such
reactions typically occur after the
second encounter with that specific
antigen (allergen).

3. Types of hypersensitivity reactions
Immediate Hypersensitivity ( Type I)
Antibody-Mediated (Type II)
Immune complex-Mediated (Type III)
T cell- mediated (Type IV)

4. Type I hypersensitivity manifests itself in tissue reactions
occurring within seconds after the antigen combines with
specific IgE antibody. Its symptoms may manifest as a sys-temic
anaphylaxis (eg, after intravenous administration of
heterologous proteins) or as a local reaction (eg, an atopic
allergy involving rhinitis such as occurs with hay fever).
The general mechanism of immediate hypersensitivity involves
a series of steps. An antigen induces the formation of IgE
antibody, which binds firmly by its Fc portion to high-affinity IgE
receptors on mast cells, basophils, and possibly eosinophils.
Some time later, an individual experiences a sec-ond exposure
to same antigen. This second exposure results in the cross-
linking of the cell bound IgE molecules and the release of
pharmacologically active mediators. Cyclic nucleo-tides and
calcium are essential in the release of mediators.
Type I: Immediate Hypersensitivity
(Allergy) (ITH)

5. Type II: Hypersensitivity
Type II hypersensitivity involves the binding of IgG antibodies to
cell surface antigens or extracellular matrix molecules.
Antibody directed at cell surface antigens can activate
complement to damage the cells. The result may be
complement-mediated lysis, which occurs in hemolytic anemia,
ABO transfusion reactions, and Rh hemolytic disease. Drugs
such as penicillin can attach to surface proteins on red blood
cells and initiate antibody formation. Such autoimmune
antibodies may then combine with the cell surface, and cause
hemolysis. In Goodpasture syndrome, antibody is generated to
the basement membranes of the kidney and lung. This results
in complement activation, leukocyte chemotaxis, and severe
membrane damage. In some cases, antibodies to cell surface
receptors alter cell function without cell injury (eg, in Graves
disease, an autoantibody binds to the thyroid-stimulating
hormone receptor, which generates stimulation of the thyroid,
and hyperthyroidism).

6. Type III: Immune Complex Hypersensitivity
When antibody combines with its specific antigen, immune
complexes are formed. Normally, these immune complexes are
promptly removed, but occasionally, they persist and are
deposited in tissues. In persistent microbial or viral infections,
immune complexes may be deposited in organs (eg, the
kidneys), resulting in tissue and organ dysfunction. In
autoimmune disorders, “self” antigens may elicit antibodies
that bind to organ antigens or are deposited in organs and
tissues as complexes, especially in the joints (arthritis), kidneys
(nephritis), and blood vessels (vasculitis). Finally, environmental
antigens such as fungal spores and certain drugs can cause
immune complex formation with similar tissue and organ
damage.

7. Type IV: Cell-Mediated (Delayed
type) Hypersensitivity (DTH)
Cell-mediated hypersensitivity is a T cell–
mediated response. The interaction of an
antigen with specifically sensitized T cells
results in T cell proliferation, release of potent
inflammatory cytokines (IFN-γ and IL-2), and
activation of macrophages. This inflammatory
response most often begins 2 or 3 days after
contact with the antigen and typically lasts for
several days.

8. Type IV hypersensitivity: delayed-type hypersensitivity (DTH) mediated by CD4 T cells (TH1). In this case, chemically
modified self-proteins are processed, and peptides are presented to CD4 memory T cells cycling through the skin,
which release cytokines (including interferon-γ [IFN-γ]) that promote inflammation. Other examples of DTH are the
tuberculin response (purified protein derivative test) and reaction to metals such as nickel. APC, Antigen-presenting
cell; TCR, T-cell receptor.

9. Hypersensitivity Reactions