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aspirin sensitivity reaction 80 atherosclerosis, MCP-1 in
reactions such as asthma and rhinitis due to intolerance and
idiosyncratic reactivity against the drug.
aspirin sensitivity reaction
A hypersensitivity response to aspirin (acetylsalicylic acid,
ASA) as a manifestation of allergy and asthma. This allergic
reaction may be manifested as either urticaria and angioedema
or rhinoconjunctivitis with bronchospasm. Aspirin
sensitivity is sometimes termed a pseudoallergic reaction.
Possible mechanisms include cyclooxygenase blockade
resulting in an altered ratio of PGE 2 (bronchodilator) to
PHF 2 (bronchoconstrictor), a shunting of arachidonate from
the cyclooxygenase to the 5-lipoxygenase pathway with
eosinophilia, and viral infection in which altered prostaglandin
regulation of cytotoxic lymphocytes is postulated. Mast
cells and eosinophils in the nasal mucosa and periphery
point to a possible role of these cells in aspirin hypersensitivity.
Patients with this type of allergic reaction present
clinically with such features as rhinitis, nasal polyps,
eosinophilia in nasal smears, abnormal sinus, radiographs,
and chronic asthma. ASA sensitivity is associated with various
nonsteroidal anti-inflammatory drugs (NSAIDs).
association constant (KA)
A mathematical measurement of the reversible interaction
between two molecular forms at equilibrium. The AB
complex, free A and B concentrations at equilibrium, are
expressed in K A liters per mole by [AB], [A], and [B]. The
s (molecules of substance A) interact reversibly with the t
(molecules of substance B); i.e., sA + tB1 A sB t, the association
constant is [A sB t]/[A] s [B] t . Molar concentrations at
equilibrium are indicated by the symbols in brackets.
asthma
Inflammation of the bronchi in the lungs characterized by
reversible airway obstruction (in most cases). Inflammation
of the airway is characterized by prominent eosinophil
participation, and there is increased responsiveness by the
airway to various stimuli. Bronchospasm is associated with
recurrent paroxysmal dyspnea and wheezing. Some cases
of asthma are allergic (i.e., bronchial allergy), mediated by
immunoglobulin E (IgE) antibody to environmental allergens.
Other cases are provoked by nonallergic factors that
are not discussed here.
ataxia telangiectasia
A disorder characterized by cerebellar ataxia, oculocutaneous
telangiectasis, variable immunodeficiency that affects both T
and B cell limbs of the immune response, the development of
lymphoid malignancies, and recurrent sinopulmonary infections.
A consequence of a mutation of the tumor suppressor
gene ATM associated with the nonhomologous end joining
(NHEJ) pathway of DNA repair. Clinical features may appear
by 2 years of age. Forty percent of patients have selective
IgE
Ag
Mast cell
Histamine (+ other mediators)
release
Increased
vascular
permeability/
edema
Asthma.
immunoglobulin A (IgA) deficiency. The disease has an autosomal
recessive mode of inheritance. There may be lymphopenia,
normal or decreased T lymphocyte numbers, and normal
or diminished lymphocyte responses to PHA and allogeneic
cells. The delayed-type hypersensitivity skin test may not
stimulate any response. Some individuals may have an IgG 2,
IgG 4, or IgA 2 subclass deficiency. Other patients may reveal
no IgE antibody levels. Antibody responsiveness to selected
antigens is diminished. B cell numbers are usually normal, and
natural killer (NK) cell function is within physiologic limits.
The level of T cell deficiency varies. Defects in DNA repair
mechanisms lead to multiple breaks, inversions, and translocations
within chromosomes, rendering them highly susceptible
to the injurious actions of ionizing radiation and radiomimetic
chemicals. The chromosomal breaks are especially apparent
on chromosomes 7 and 14 in the regions that encode immunoglobulin
genes and T cell receptor genes. The multiple chromosomal
breaks are believed to be linked to the high incidence
of lymphomas in these patients. α-Fetoprotein is also elevated.
Endocrine abnormalities associated with the disease include
glucose intolerance associated with anti-insulin-receptor antibodies
and hypogonadism in males. Patients may experience
retarded growth and hepatic dysfunction. Death may occur in
many of the patients related to recurrent respiratory tract infections
or lymphoid malignancies.
ATG
Abbreviation for antithymocyte globulin.
atherosclerosis, MCP-1 in
Chemokines are involved in the pathogenesis of atherosclerosis
by promoting directed migration of inflammatory
cells. Monocyte chemoattractant protein-1 (MCP-1), a CC
chemokine, has been detected in atherosclerotic lesions by
anti-MCP-1 antibody detection and in situ hybridization.
MCP-1 mRNA expression has been detected in endothelial
cells, macrophages, and vascular smooth muscle cells
in atherosclerotic arteries of patients undergoing bypass
revascularization. MCP-1 functions in the development of
atherosclerosis by recruiting monocytes into the subendothelial
cell layer. MCP-1 is critical for the initiation and
development of atherosclerotic lesions. During the progression
of atherosclerosis, there is an accumulation of low density
lipoprotein (LDL) within macrophages and monocytes
present in the intimal layer. Deposition of lipids within
these cells leads to the formation and eventual enlargement
of atherosclerotic lesions. Studies suggest a noncholesterolmediated
effect of MCP-1 in the development of atherosclerotic
lesions. MCP-1 plays a crucial role in initiating
atherosclerosis by recruiting macrophages and monocytes
to the vessel wall.
Recruitment of
basophils and
eosinophils to
tissue
Bronchospasm/
smooth muscle
constriction