Lecture 6: Hypersensitivy reactions Flashcards
what are the hypersensitivity reactions?
A group of conditions in which the immune system, which normally serves a protective role, has a harmful effect. Hypersensitivity reactions are commonly classified into four different types: Type I hypersensitivity reactions are immediate allergic reactions (e.g., food, pollen, asthma), type II are cytotoxic, type III are immune complex-mediated, and type IV are delayed and cell-mediated.
what is the classification of hypersensitivity reactions?
Type I Immediate hypersensitivity (IgE)
Type II Antibody-mediated cytotoxicity
Type III Immune complex deposition
Type IV Delayed hypersensitivity (cellular)
what are the examples of type 1 hypersensitivity (IgE mediated)
- Rhinitis
- Asthma
- Urticaria
- Angioedema
- Anaphylaxis
- (Eczema)
what is the allergen?
An antigen that elicits an IgE-mediated, type I hypersensitivity response in individuals with an allergy to the substance containing the particular antigen.
give examples of common allergens
- -Pollen – various foods (e.g., apple, hazelnut, carrot, kiwi, apricots, peaches)
- -Mites – crustaceans
- -Latex – exotic fruits (e.g., banana, avocado, kiwi)
- -Bird dander – egg yolk
- -Cat dander – pork
what are the phases of IgE mediated response?
- Sensitisation
- Early/ acute phase of response
- Late phase of response
what is the sensitization to an allergen?
IgE is formed as a result of prior sensitization (i.e., previous contact with the antigen) and coats mast cells and basophils.
• Sensitisation can occur on first or subsequent exposure
• Some patients tolerate penicillin for decades, and then develop allergy in old age
• You can be sensitised by the substance itself, or something which crossreacts with it (eg: Pholcodine & rocuronium)
what is the early, acute phase response of type I hypersensitivity reaction
Subsequent encounter with antigen results in an IgE-mediated reaction by preformed IgE antibodies: Free antigen binds to two adjacent IgE antibodies (crosslinking) → degranulation of cells. his reaction is rapid because the antibodies involved have been preformed.
- -Release of histamine and other mediators (e.g., prostaglandin, platelet-activating factor, leukotrienes, heparin, tryptase) →
- -Increased smooth muscle contraction + peripheral vasodilation + increased vascular permeability → bronchospasm, abdominal cramping, and rhinitis → hypovolemia, hypoxia
- -Extravasation of capillary blood → erythema
- -Fluid shift into the interstitial space → edema, pulmonary edema
- -Pruritus
what are the cells of the late-phase reaction of type 1 hypersensitivity reaction?
Eosinophil and neutrophil chemotaxis induced by basophil and mast cell mediators → eosinophilia
These cells cause the late-phase reaction that may occur after the acute phase has subsided (erythema, rhinorrhea, sneezing, coughing, wheezing)
what is the cross-reactivity in type I hypersensitivity reaction
–Individuals with allergies may also react to substances that contain particles that are similar to the main antigen.
–Examples (primary allergen – cross-reactant allergen)
1)Pollen – various foods (e.g., apple, hazelnut, carrot, kiwi, apricots, peaches)
2)Mites – crustaceans
3Latex – exotic fruits (e.g., banana, avocado, kiwi)
4)Bird dander – egg yolk
5)Cat dander – pork
Clinical findings
what are the clinical features of the type 1 hypersensitivity reaction?
1) Course
- -Immediate reaction: allergic reaction within minutes of contact with the antigen
- -Late-phase reaction: occurs hours after immediate reaction for a duration of 24–72 hours
2) Main symptoms: pruritus, edema, rash, rhinitis, bronchospasm, and abdominal cramping
what are the specific manifestations of type 1 hypersensitivity reaction
1) Allergic conjunctivitis
2) Allergic rhinitis
3) Allergic asthma
4) Atopy: genetic predisposition to producing IgE antibodies against certain harmless environmental allergens (e.g., pollen, mites, molds, certain foods)
- Associated conditions: asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, food allergies
5) Urticaria (hives): well-circumscribed, raised, pruritic, and erythematous plaques with a round, oval, or serpiginous shape; up to several centimeters in diameter (wheals); caused by mast cell activation in the superficial dermis
6) Angioedema: due to mast cell activation in the dermis and/or subcutaneous tissue
7) Anaphylaxis
what is the type II HSR?
An IgG or IgM antibody-mediated hypersensitivity reaction. Antibodies bound to their targets induce antibody-dependent cellular cytotoxicity (e.g., immune thrombocytopenia, acute hemolytic transfusion reactions), complement-mediated inflammation (e.g., Goodpasture syndrome), or cell surface receptor interactions (e.g., myasthenia gravis, Graves disease).
what is the mechanism of tissue injury in type 2 HSR?
• Type II Hypersensitivity
Antibody mediated cytotoxicity
• Antibody binds to tissue component
• Complement is activated
• Influx of inflammatory cells lead to tissue damage
• Autoimmune cytopenias, anti-GBM disease
–IgM and IgG bind to antigens on cells in the body mistakenly detected as foreign and cause:
1)Complement activation and Fc-mediated immune cell activation (in hemolytic disease of the newborn and transfusion reactions)
2)Cellular lysis or phagocytosis ( rheumatic fever.)
–Opsonization → phagocytosis and/or complement activation
–Complement-mediated lysis
–Antibody-dependent cell-mediated cytotoxicity (NK cells or macrophages)
3)Inhibition or activation of the downstream signaling pathways (n myasthenia gravis and Graves disease)
what are the autoantibodies?
group of antibodies that react with self-antigens. Can be seen in healthy individuals and in several autoimmune disorders (e.g., antithryoid antibodies in Hashimoto thyroiditis and Graves disease).
