What are the four types of hypersensitivity reactions?
The four types of hypersensitivity reactions are:
- Type I: Immediate (anaphylactic) hypersensitivity reaction
- Type II: Antibody-dependent cytotoxic hypersensitivity reaction
- Type III: Immune complex hypersensitivity reaction
- Type IV: Delayed (cell-mediated) hypersensitivity reaction
What is the mechanism of Type I hypersensitivity reaction?
In Type I hypersensitivity, the first contact with an antigen (allergen) induces the formation of IgE antibodies. The IgE binds firmly to receptors on the surface of basophils and mast cells through the Fc portion. Upon re-exposure to the same antigen, cross-linking of cell-bound IgE occurs, leading to degranulation and release of active mediators within minutes.
What are the two phases of Type I hypersensitivity reaction?
The two phases of Type I hypersensitivity reaction are:
- Immediate phase: Occurs within minutes due to the release of preformed active mediators, mainly histamine.
- Late phase: Occurs about 6 hours later due to the synthesis and release of mediators, mainly leukotrienes (Slow Releasing Substance of Anaphylaxis, SRS-A).
What are the clinical manifestations of Type I hypersensitivity?
The clinical manifestations of Type I hypersensitivity can be localized or generalized and appear in various forms depending on the route of entry of the allergen and the location of mast cells bound with specific IgE. Examples include:
- Lung: Asthma (wheezing, dyspnea)
- Nose & eye: Rhinitis, conjunctivitis (runny nose, redness, itchy eyes)
- Skin: Eczema, urticaria (pruritic lesions)
- Intestinal tract: Allergic gastroenteropathy (vomiting & diarrhea)
- Systemic: Anaphylaxis (shock, hypotension)
What are the main mediators involved in Type I hypersensitivity?
The main mediators involved in Type I hypersensitivity are:
- Histamine (vasodilation, increased permeability, smooth muscle contraction, bronchospasm)
- Slow-Releasing Substance of Anaphylaxis (SRS-A)
- Eosinophil Chemotactic Factor of Anaphylaxis (ECF-A)
- Serotonin
- Prostaglandins & thromboxanes
- Platelet-Activating Factor (PAF)
What is the mechanism of Type II hypersensitivity reaction?
Type II hypersensitivity occurs when antibodies (IgG or IgM) are directed toward antigens on the cell membrane, leading to activation of the complement system. This results in the formation of the membrane attack complex, which damages the cell membrane and causes cell lysis. Additionally, complement activation attracts phagocytes, which release enzymes that further damage tissues.
What are some examples of diseases caused by Type II hypersensitivity?
Examples of diseases caused by Type II hypersensitivity include:
- ABO transfusion reactions
- Hemolytic disease of the newborn
- Some autoimmune diseases (e.g., Graves’ disease, myasthenia gravis)
What is the mechanism of Type III hypersensitivity reaction?
Type III hypersensitivity occurs when antigen-antibody complexes form in the blood and deposit in tissues, leading to activation of the complement system. This attracts neutrophils to the site, inducing an inflammatory reaction that causes tissue injury. Normally, immune complexes are removed by the reticuloendothelial system, but in some cases, they persist and deposit in tissues, leading to disorders.
What are the clinical manifestations of systemic Type III hypersensitivity?
Systemic Type III hypersensitivity involves the deposition of immune complexes in many tissues, leading to a systemic inflammatory response. Clinical examples include:
- Serum sickness
- Poststreptococcal glomerulonephritis
- Rheumatoid arthritis
- Systemic lupus erythematosus
What is the mechanism of Type IV hypersensitivity reaction?
Type IV hypersensitivity is mediated by sensitized T-lymphocytes (CD4+ and CD8+ T-cells). Sensitized T-cells interact with specific antigens and activate macrophages, leading to tissue damage. Cytotoxic T-cells recognize target cells by interacting with antigens on the cell surface in association with MHC class I, leading to cell death through the release of toxic granules (perforin and granzyme). This reaction is delayed, typically peaking within 48-72 hours after contact with the antigen.
What are some clinical examples of Type IV hypersensitivity?
Clinical examples of Type IV hypersensitivity include:
- Tuberculin skin test
- Lepromin skin test
- Contact dermatitis (caused by chemicals like nickel, plant substances, or topical drugs)
What is the role of IgE in Type I hypersensitivity?
In Type I hypersensitivity, IgE antibodies are produced in response to an allergen. These IgE antibodies bind firmly to receptors on the surface of mast cells and basophils. Upon re-exposure to the same allergen, the allergen cross-links the cell-bound IgE, leading to degranulation and the release of active mediators such as histamine.
What is the Arthus reaction in Type III hypersensitivity?
The Arthus reaction is a localized inflammation caused by the deposition of immune complexes at a specific site. It occurs when there is a high level of pre-existing antibodies due to repeated exposure to antigens. Upon exposure to the antigen, immune complexes form, leading to complement activation, recruitment of neutrophils, and tissue damage. This reaction typically develops within 6 hours and resolves within a day.
What is the role of cytotoxic T-cells in Type IV hypersensitivity?
In Type IV hypersensitivity, cytotoxic T-cells (CD8+) recognize target cells by interacting with antigens on the cell surface in association with MHC class I. They kill the target cells by releasing toxic granules containing perforin and granzyme, leading to cell death.
What is the diagnostic method for Type I hypersensitivity?
The diagnostic methods for Type I hypersensitivity include:
- In vitro: Radioimmunoassay to measure total serum IgE and specific IgE.
- In vivo: Skin test, where a series of allergens are administered by scratching or intradermally, and the injection sites are examined within 15-20 minutes for the appearance of a wheal and flare.
