Allergies and hypersensitivities Flashcards
Allergy
a damaging immune response by the body to a substance, e.g., food pollen, fur dust, to which it has become hypersensitive.
anaphylaxis
• Anaphylaxis is a system-wide response that occurs if the same antigens are more widely disseminated e.g, injected intravenously. Anaphylactic shock can be fatal within 2-4 minutes of exposure to the antigen
examples of allergies
Asthma, atopic dermatitis and food allergies are examples of local allergic responses: the symptoms are restricted to the site where antigen interacts with the body e.g., lung, skin, GI tract.
mechanism of action of allergy
Allergy triggers unecessary increases in vascular permeability and inflammation that lead to tissue damage with little benefit.
hypersensitivity
an immune disorder caused by an inappropriate response to antigens that are not necessarily pathogens. Results from inappropriately vigorous innate/adaptive immune responses to antigens that often pose little to no threat. some antigens that cause hypersensitivity seems to cause intrinsic protease activity.
type I hypersensitivity mechanism of action
cross-linking of Fcer1 receptors by allergen-IgE complexes initiates multiple signalling cascades that resemble those initiated by antigen receptors. Signalling results in mast cell degranulation which releases histamine and other inflammatory mediators-> leukotrines, prostaglandins, ECF.A, etc which causes mucous productions, bronchoconstriction, bronchospasm, attraction of eosinophils due to epithelial damage, etc.
Examples of type I hypersensitivity
Urticaria, eczema, angioedema, hay fever, asthma
Primary sensitisation in Type I hypersensitivity
APC detects antigen and presents antigen -> Th2 cell recognises antigen and primes it-> Th2 releases IL-4 which causes the B cells to switch prod of IgM to IgE (antigen-specific) ->B cells also activate memory cells and IL-21 creates plasma cells that produce IgE-> IgE binds to Mast cells and basophils-> sensitises them to the antigen
Early response in type I hypersensitivity
Re-exposure to the antigen-> antigen cross links IgE bound to the sensitised basophils and mast cell -> (mast cell degranulation) -> releases mediators (histamine, leukotrienes, prostaglandins) -> vasodilation, bronchoconstriction, increased vascular permeability, mucous secretion
Late phase of Type I hypersensitivity
Lasts for hours
Mast cell degranulation-> Further synthesis and release of other/ more mediators -> TNF-a, PAF, IL-51, NCF/more Leukotrienes, Prostaglandins, ECF-A-> cytokines released from mast cells increase the expression of adhesion molecules on endothelial cells, and this facilitates the influx of neutrophils, basophils and Th2 cells.
Leukotrienes and Prostaglandins -> Bronchospasm (thickened basement membrane)
ECF.A (eosinophilic chemotactic factor anaphylaxis -> attracts eosinophils to tissues (epithelial injury)
Leukotrienes
Biologically active compound isolated from leukocytes and are metabolites of arachidonic acid, containing 3 conjugated double bonds, and are mediators of inflammation.
Prostaglandins
Group of hormone-like substances that participate in a wide range of body functions such as contraction/ relaxation of smooth muscle, vasodilation/constriction, BP control, inflammation modulation.
What enables an allergen in type I hypersensitivity to cross-link
The allergen needs to be multitalented ( have many epitopes) in order to cause cross-linking e.g., pollen.
Atrophy
Genetic predisposition to develop an allergic reaction and produce elevated levels of IgE in response to an environmental antigen that is inhaled or ingested
Type I hypersensitivity response in asthmatic response
- Initial contraction of bronchial and tracheal smooth muscles is mediated by histamine, typically within minutes of release as a result of mast cell degranulation.
- histamine + h1 receptor -> vascular permeability + mucous secretion
- phospholipase released by degranulation and it initiates the enzymatic breakdown of phospholipids in the plasma membrane that releases leukotrienes and prostaglandins which are 1000x more active than histamine
- 30 to 60secs- further bronchoconstriction and further vascular permeability + mucous secretion
- leukotrienes contribute significantly to the prolonged bronchospasm + mucous build up seen in asthmatics
- Curschmann’s spirals are spiral-shaped mucous plugs formed in asthmatics
The hygiene hypothesis
Hygiene hypothesis states that exposure of children to a farm environment pre-or postnatally are less likely to suffer from T1 hypersensitivity later in life as there is an early exposure to some pathogens/allergens and establishes a healthy balance of T cell subset activities (incl. development of reg T cells) so no one response dominates.
Type II hypersensitivity define
Cytotoxic: antibody mediated destruction of cells by antibody classes other than IgE
3 mechanisms that can trigger cell destruction in type II hypersensitivity
- Activation of complement cascade
- ADCC (antibody dependent cell mediated cytotoxicity
- Ab bound to target cells that kill by opsonisation
Activation of complement cascade in type II hypersensitivity
IgM and IgG possess the stalk of the Y shaped molecule in their Fc domain that initiates the complement cascade-> MAC complex which kills the cell bound by the antibody
ADCC in cytotoxicity
Antibody attaches to the antigens on a target cell via the variable domain whilst the Fc region binds to the FceR1 on cytotoxic cells;the antibody acts as a bridge and destroys the target cell.
Ab bound to target cells that kill by opsonisation in Type II hypersensitivity
Ab bound to target cells can act as an ‘opsonin’ enabling phagocytes cells with Fc or C3b receptors to bind and phagocytise the ab-coated cell.
Transfusion reactions in Type II hypersensitivity
A, B and H antigens (carbs) on transfused blood cells generate antibodies in people with a different blood group lacking the antigen, resulting in intravascular haemolysis.
Haemolytic disease of the newborn in Type II hypersensitivity
Maternal IgG specific for fetal Rhesus (Rh) antigens cross the placenta and destroy fetal red blood cells if mother is Rh- and father is Rh+
Malaria in Type II hypersensitivity
Red blood cells pick up antigens from the P.falciparum parasite and antibodies trigger haemolysis.
