Hypersensitivity
CPMS
Hypersensitivity
• The immune response has been described as a defense mechanism by which
the body rids itself of potentially harmful antigens.
• In some cases, however, this process can end up causing damage to the host.
When this type of reaction occurs, it is termed hypersensitivity, which can
be defined as a heightened state of immune responsiveness.
• British immunologists P. G. H. Gell and R. R. A. Coombs devised a
classification system for such reactions based on four different categories.
Type I hypersensitivity
• Also called Immediate hypersensitivity
• The key reactant present in type I is IgE.
• The distinguishing feature of type I hypersensitivity is the short time lag,
usually seconds to minutes, between exposure to antigen and the onset of
clinical symptoms.
• Antigens that trigger formation of IgE are called atopic antigens, or
allergens. Atopy refers to an inherited tendency to respond to naturally
occurring inhaled and ingested allergens with continued production of IgE.
Type I hypersensitivity
• Carl Wilhelm Prausnitz and Heinz Küstner were the first researchers to show
that a serum factor was responsible for type I reactions. It was the first
observance of Passive cutaneous anaphylaxis.
• Passive cutaneous anaphylaxis occurs when serum is transferred from an
allergic individual to a nonallergic individual, and then the second individual
is challenged with specific antigen
Type I hypersensitivity
IgE attaches to the cell
membrane of mast cells or
basophils, and they become
the receptors for the
allergen.
After binding has occurred,
the cells elaborate the
substances (histamine) that
cause the allergic reaction.
Type I hypersensitivity
• Mast cells and Basophils
• Mast cells are the principle effector cells of immediate hypersensitivity, and they
are derived from precursors in the bone marrow that migrate to specific tissue
sites to mature.
• Typically have more histamine content than basophils.
• Basophils represent approximately 1 percent of the white blood cells in
peripheral blood. They have a half-life of about 3 days. They contain histaminerich granules and high-affinity receptors for IgE, just as in mast cells.
Type I hypersensitivity
Mediators released from granules
• Can be classified into two: Preformed or Newly synthesized
Mediator
Preformed Histamine
Action
Smooth muscle contraction, vasodilation, increased vascular
permeability
ECF-A
Chemotactic for eosinophils
Neutrophil
Chemotactic factor
Chemotactic for neutrophils
Proteases
Convert C3 to C3b, mucus production, activation of
cytokines
Type I hypersensitivity
Mediators released from granules
• Can be classified into two: Preformed or Newly synthesized
Mediator
Platelet activating
Newly
synthesized factor
Action
Platelet aggregation
Prostaglandin
Vasodilation; increased vascular permeability
Leukotrienes
Chemotactic for neutrophils, eosinophils
Type I hypersensitivity
• Anaphylaxis is the most severe type of allergic response, because it is an
acute reaction that simultaneously involves multiple organs.
• Anaphylactic reactions are typically triggered by glycoproteins or large
polypeptides. Typical agents that induce anaphylaxis include venom from
bees, wasps, and hornets; drugs such as penicillin; and foods such as
shellfish, peanuts, or dairy products.
• Clinical signs of anaphylaxis begin within minutes after antigenic challenge
and may include bronchospasm and laryngeal edema, vascular congestion,
skin manifestations such as urticaria (hives) and angioedema, diarrhea or
vomiting, and intractable shock because of the effect on blood vessels and
smooth muscle of the circulatory system.
Type I hypersensitivity
Common Examples:
• Anaphylaxis
• Hay Fever
• Food Allergies
• Asthma
• Bee stings
Special Tests for Type I hypersensitivity
• Competitive Radioimmunosorbent Test (RIST)
• Non-competitive RIST
• Non-competitive Radioallergosorbent test (RAST)
Type II hypersensitivity
• The reactants responsible for type II hypersensitivity, or cytotoxic
hypersensitivity, are IgG and IgM.
• They are triggered by antigens found on cell surfaces. These antigens
may be altered self-antigens or heteroantigens.
• Best example: Transfusion reactions
Type II hypersensitivity
• Transfusion reactions happen when incompatible RBCs are given to
the patient, resulting in an immune response.
• Can be classified as either acute (patient has preformed antibodies)
or delayed (patient has not yet encountered the antigen)
• Most acute hemolytic transfusion reactions produce intravascular
hemolysis while delayed reactions produce extravascular hemolysis
Type II hypersensitivity
• Other examples of type II hypersensitivity
• Hemolytic Disease f the Fetus and Newborn
• Autoimmune hemolytic anemia
• Organ specific autoimmune diseases such as Goodpasture syndrome
Type III hypersensitivity
• Type III hypersensitivity reactions are similar to type II reactions in
that IgG or IgM is involved and destruction is complement mediated.
However, in the case of type III diseases, the antigen is soluble. When
soluble antigen combines with antibody, complexes are formed that
precipitate out of the serum
• Example:
• Arthus reaction
• Serum sickness
• Autoimmune diseases (SLE, RA)
Arthus reaction
A localized type III
reaction that is rare in
humans.
Type IV hypersensitivity
• Type IV hypersensitivity differs from the other three types of
hypersensitivity in that sensitized T cells, usually a subpopulation of
Th1 cells, play the major role in its manifestations. Antibody and
complement are not directly involved.
• Best example:
• Contact Dermatitis
• Pneumonitis
• Tuberculin test
Type V hypersensitivity?
• This is an additional type that is sometimes (often in the UK) used as
a distinction from type 2.
• Instead of binding cell surface components, the antibodies recognise
and bind to cell surface receptors, which either prevents the intended
ligand from binding with the receptor or mimics the effects of the
ligand, thus impairing cell signaling.
• Examples
• Graves’ disease
• Myasthenia gravis
END