Immediate (type 1) hypersensitivity: Th2-mediated
diseases
These disorders are characterized by abnormally
strong Th2 responses against environmental
antigens that are essentially ignored by the
~75-80% of the population that does not suffer
from allergies.
All the clinical and pathologic manifestations
of allergy are the result of cytokines produced
by Th2 cells (Fig. 2).
IL-4 stimulates B cells specific for the antigens
to produce IgE antibody, which then binds
to mast cells.
When the antigen binds to this antibody, it
activates mast cells to release many mediators
(histamine, proteases,
cytokines) that cause the acute vascular and
smooth muscle reactions and inflammation that
are typical of allergies.
IL-5 made by Th2 cells activates eosinophils,
which can exacerbate tissue damage.
Th2 cells also secrete IL-13, which acts on
mucosal epithelial cells to stimulate secretion
of mucus.
Bronchial asthma is a Th2-mediated disease
about which you will hear more in the �Organs�
block.
The propensity to develop allergies is genetic,
but the actual genes that may be causative
have not been definitively identified.
How antibodies damage tissues: types 2 and
3 hypersensitivity
Antibodies other than IgE can cause severe
tissue injury.
In some cases, antibodies may be produced
against cell or tissue antigens and may deposit
on cells or in the tissues (antibody-mediated,
or type II, hypersensitivity).
Usually, these are autoantibodies, and their
production reflects a failure of self-tolerance.
In other cases, antibodies against self-antigens
or microbial antigens may form immune complexes
if the antigens are present in the circulation,
and these complexes may deposit in vascular
walls (immune complex-mediated, or type III,
hypersensitivity).
The �tail� of the antibody activates a
series of plasma proteins that make up the
are activated by microbes or by antibodies
bound to microbes and tissue antigens, and
are deposited on these surfaces.
Various products of complement bring in leukocytes
(inflammation); are recognized by phagocytes,
resulting in phagocytosis of coated cells;
and promote death of cells 
on which complement proteins are deposited.
The tail of the antibody (called the Fc piece
because this fragment has a propensity to
and neutrophils).
Once these pathways are activated, they cause
disease in several ways (see Fig. 4).
A. If the antibody is deposited on a cell
(e.g. erythrocyte or platelet), the combined
action of complement and Fc receptors results
in that cell being eaten and destroyed by
phagocytes.
(This is the basis of red blood cell and platelet
depletion in autoimmune hemolytic anemia and
thrombocytopenia, respectively.)
B.
If the antibody is deposited on a solid surface
the phagocytes may be activated 
and release toxic substances that induce inflammation
and damage the tissue (as in 
some forms of glomerulonephritis).
C. Less commonly, antibodies can cause disease
by interfering with normal molecules (such
as hormones and hormone receptors), without
any actual tissue injury; examples include
myasthenia gravis (BMB) and Graves� disease
(M&N).
F. How T lymphocytes damage tissues: type
4 hypersensitivity
T lymphocytes injure tissues by two principal
mechanisms (Fig. 4).
1.
CD4+ T lymphocytes of the Th1 subset produce
cytokines 
that activate macrophages (mainly IFN-?) and
recruit inflammatory cells (TNF).
Th17 cells secrete cytokines that also recruit
leukocytes, such as neutrophils, and 
may 
thus 
be major contributors to inflammation in T
cell-mediated hypersensitivity disorders.
These 
reactions 
are called Delayed type hypersensitivity,
because they take 24-48 hours t develop after
antigen challenge (the classical example is
a PPD skin test).
Th1 and/or Th17 reactions against self-antigens
or against persistent microbes are responsible
for many chronic disorders that you will hear
about (Crohn�s disease, type-1 diabetes,
multiple sclerosis, rheumatoid arthritis).
2.
CD8+ CTLs directly kill host cells, as 
in viral hepatitis (mentioned above).
CTL-mediated cell injury may also contribute
to 
some Th1-mediated disease such as 
type-1 diabetes.
