hypersensitivity

Dr. Ahmed Adil Immunology 3rd class-college of Medicine
1
Hypersensitivity : An exaggerated or inappropriate immune response that results in reactions
harmful to the host.
Hypersensitivity reactions can be subdivided into four main types. Types I, II, and III are
antibody-mediated, whereas type IV is cell-mediated.
Type I: Immediate (Anaphylactic) Hypersensitivity
The process begins when an antigen (Allergen) induces the formation of IgE antibody which
binds firmly by its Fc portion to receptors on the surface of basophils and mast cells.
Re-exposure to the same antigen results in cross-linking of the cell-bound IgE, degranulation,
and release of pharmacologically active mediators within minutes (Immediate phase).
Immediate(Anaphylactic) hypersensitivity
Symptoms such as edema and erythema ("wheal and flare") and itching appear rapidly because
these mediators are pre-formed in mast cell, e.g., Histamine, and Serotonin .
Histamine release causes vasodilation, increased capillary permeability, and smooth-muscle
contraction.
The (late phase) of IgE-mediated inflammation occurs approximately 6 hours after exposure to
the antigen and is due to mediators, e.g., leukotrienes (SRS-A) & prostaglandin that are
synthesized after the cell degranulates. These mediators cause an influx of inflammatory cells,
such as Neutrophils and Eosinophils, and symptoms such as erythema and induration occur.
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
2
Prostaglandins and leukotrienes cause dilation and increased permeability of capillaries and
bronchoconstriction.
Complement is not involved with either the immediate or late reactions because IgE does not
activate complement, but complement factors C3a and C5a (anaphylatoxin) can cause
vasodilation and increasing capillary permeability.
The allergens involved in hypersensitivity reactions are substances, such as pollens, animal
danders , foods (nuts, shellfish), and various drugs, to which most people do not exhibit clinical
symptoms. However, allergic individuals respond to those substances by producing large
amounts of IgE and, as a result, manifest various allergic symptoms. Non-allergic individuals
respond to the same antigen by producing IgG, which does not cause the release of mediators
from mast cells and basophils because there are no receptors for IgG on those cells.
Clinical manifestation:
Atopy is the term can include the clinical manifestations of type I hypersensitivity which can
appear in various forms, e.g., Urticaria (also known as hives), eczema, angioedema, rhinitis
and conjunctivitis (also known as hay fever), and asthma. Which clinical manifestation occurs
depends in large part on the route of entry of the allergen and on the location of the mast cells
bearing the IgE specific for the allergen.
The most severe form of type I hypersensitivity is Systemic anaphylaxis, in which severe
bronchoconstriction and hypotension (shock) can be life-threatening. The most common causes
of anaphylaxis are foods, such as peanuts and shellfish, bee venom, and drugs.
Anaphylactoid : …………???????????????
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
3
Drug Hypersensitivity:
Drugs, particularly antimicrobial agents such as penicillin, are now among the most common
causes of hypersensitivity reactions. Usually it is not the intact drug that induces antibody
formation. Rather, a metabolic product of the drug, which acts as a hapten and binds to a body
protein. The resulting antibody can react with the hapten or the intact drug to give rise to type I
hypersensitivity.
When re-exposed to the drug, the person may exhibit rashes, fevers, local or systemic
anaphylaxis of variable severity.
Drug hypersensitivity (Hapten)
Treatment
Treatment of anaphylactic reactions includes drugs to counteract the action of mediators,
maintenance of an airway, and support of respiratory and cardiac function. Epinephrine,
antihistamines, corticosteroids and cromolyn sodium, either singly or in combination, should
be given.
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
4
Antihistamine drugs block histamine receptor sites and can be relatively effective in allergic
rhinitis but not in asthma.
Inhaled B-adrenergic bronchodilators, such as albuterol, are commonly used. Corticosteroids,
such as prednisone, are also effective. Aminophylline, a bronchodilator, is effective too. A
monoclonal anti-IgE antibody (omalizumab, Xolair) is indicated for patients with severe
asthma whose symptoms are not controlled by corticosteroids. For the prevention of asthma,
leukotriene receptor inhibitors, such as Singulair, and cromolyn sodium are effective.
Type II: Cytotoxic Hypersensitivity:
Cytotoxic hypersensitivity occurs when antibody directed at antigens of the cell membrane
(Self) activates complement . This generates a membrane attack complex(MAC), which
damages the cell membrane. The antibody (IgG or IgM) attaches to the antigen (Self) via its
Fab region and acts as a bridge to complement via its Fc region. As a result, there is
complement-mediated lysis as in hemolytic anemia, ABO transfusion reactions, or Rh
hemolytic disease. In addition to causing lysis, complement activation attracts phagocytes to
the site, with consequent release of enzymes that damage cell membranes. Severe damage to
the membranes is caused by proteases released from leukocytes attracted to the site by
complement component C5a.
Drugs (e.g., penicillins,) can attach to surface proteins on red blood cells and initiate antibody
formation (Hapten). Such autoimmune antibodies (IgG) then interact with the red blood cell
surface and result in hemolysis. The direct antiglobulin (Coombs) test is typically positive.
Other drugs (e.g., Quinine) can attach to platelets and induce autoantibodies that lyse the
platelets, producing thrombocytopenia and, as a consequence, a bleeding tendency.
Certain infections, e.g., Mycoplasma pneumoniae infection, can induce antibodies that crossreact
with red cell antigens, resulting in hemolytic anemia. In Rheumatic fever, antibodies
against the group A streptococci cross-react with cardiac tissue.
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
5
Cytotoxic hypersensitivity
Type III: Immune-Complex Hypersensitivity:
Occurs when antigen–antibody complexes induce an inflammatory response in tissues.
Normally, immune complexes are removed by the reticuloendothelial system, but occasionally
they persist and are deposited in tissues, resulting in several disorders. In persistent microbial
or viral infections, immune complexes may be deposited in organs, e.g., the kidneys, resulting
in damage. In autoimmune disorders, "self" antigens may elicit antibodies (autoantibodies) that
bind to organ antigens or deposit in organs as complexes, especially in joints (arthritis),
kidneys (nephritis), or blood vessels (vasculitis). Wherever immune complexes are deposited,
they activate the complement system. Polymorphonuclear cells are attracted to the site, and
inflammation and tissue injury occur. Two typical type III hypersensitivity reactions are the
Arthus reaction& serum sickness. Arthus Reaction inflammation caused by the deposition of
immune complexes at a localized site ,e.g., hypersensitivity pneumonitis. An Arthus reaction
can also occur at the site of tetanus immunizations if they are given at the same site with too
short an interval between immunizations (The minimum interval is usually 5 years). Serum
sickness is a systemic inflammatory response to the presence of immune complexes deposited
in many areas of the body. After the injection of foreign Ab (Passive immunization) (or, more
commonly these days, certain drugs).Most common immune complex disorders are Systemic
Lupus Erythematosus, Glomerulonephritis , Rheumatoid Arthritis &IgA nephropathy.
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
6
Immune- Complex Hypersensitivity
Type IV: Delayed (Cell-Mediated) Hypersensitivity:
Delayed hypersensitivity is a function of T lymphocytes, not antibody. The response is
"delayed"; i.e., it starts hours (or days) after contact with the antigen and often lasts for days.
Delayed (cell-mediated) hypersensitivity starts when the macrophage ingests the antigen,
processes it, and presents an epitope on its surface in association with class II MHC protein.
The helper T (Th-1) cell is activated and produces gamma interferon, which activates
macrophages. These two types of cells mediate delayed hypersensitivity.
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
7
Delayed (cell-mediated) hypersensitivity.
Clinically Important Delayed Hypersensitivity Reactions
1-Contact Hypersensitivity
Occurs after sensitization with simple chemicals (e.g., nickel, formaldehyde), plant materials
(e.g., poison ivy, poison oak), topically applied drugs (e.g., sulfonamides, neomycin).
The manifestations of pruritic, vesicular skin rash is caused by CD8-positive cytotoxic T cells
that attack skin cells that display the plant oil as a foreign antigen.
2-Tuberculin-Type Hypersensitivity (Mantoux test)
It is typified by the tuberculin reaction. When a patient previously exposed to Mycobacterium
tuberculosis is injected with a small amount of tuberculin Purified Protein Derivatives (PPD)
intradermally, there is little reaction in the first few hours. Gradually, induration and redness
develop and reach a peak in 48–72 hours. A positive skin test indicates that the person has
been infected with the agent, but it does not confirm the presence of current disease.
In an individual who has not had contact with mycobacteria, there is no reaction to PPD-S. An
individual who has had a primary infection with tubercle bacilli develops induration, edema,
erythema in 24–48 hours, and, with very intense reactions, even central necrosis. The skin test
should be read in 48 or 72 hours. It is considered positive if the injection of 5 TU is followed
by induration 10 mm or more in diameter.
After BCG vaccination, people convert to a positive tuberculin test, but this may last for only
3–7 years.