Hypersensitivity Flashcards
What is hypersensitivity
An exaggerated or inappropriate immune response to environmental antigens which do not normally cause tissue damage. The exaggerated response ratehr than the antigen itself is responsible for the tissue damage which results.
Type 1 hypersensitivity
IgE mediated response resulting in an immediate reaction to an antigen.
Allergen exposure results in mast cell responding to IgE. There is then degranulation (release of mediators like histamine, heparin, tryptase, chymase, ECF, NCF) and synthesis of new mediators (prostaglandins and leukotrienes)
These all result in mucosal oedema, capillary leakage, secretions, smooth muscle contraction and vasodilation.
Sensitisation phase of type 1 hypersensitivity
Antigen-presenting cells see cell, go to lymph nodes, genetic predisposition (atopy) of the Th cell makes an exaggerated response
Th involved in type 1 hypersensitivity (sensitisation)
Th2 cell (releases interleukins) released
IL-4 which activated B cells (circulating antibodies made to protect against future). IgE. The antibody is specific to the dust. These activate mast cells (primed mast cells).
IL-5 activates eosinophils which degranulations which releases pro-inflammatory cytokines
Reaction phase type 1 hypersensitivity
The mast cell is already primed to the specific IgE of the allergen. It then degranulates releasing histamine (recruits more eosinophils and granular cells) which results in inflammation. EXAGGERATED RESPONSE.
Late reaction phase type 1 hypersensitivity
Recruits more eosinophils and recruitment of Th2 cells (recruits more B cells) and basophils
These release leukotrienes which result in further inflammation.
Treatment of Type 1 Hypersensitivity
Antihistamine (specific to histamine released from mast cells) Corticosteroids (anti-inflammatory) Adrenaline Allergen avoidance Leukotriene antagonists
Atopic
Genetic tendency to produce IgE to normally innocuous environmental allergens.
Triad of symptoms - eczema, asthma, allergic rhinitis.
Atopic dermatitis
Common in children
Occurs on exposed surfaces
Degranulation of basophils and mast cells in response to sensitized IgE
“Leaky” skin allows more allergen in and more water out
Type 2 Hypersensitivity (cytotoxic reaction)
IgG or IgM mediated autoimmune reaction to antigens found or the surface of cells or fixed within certain tissues.
Once the antibody has bound to the relevant antigen, damage arises through:
- complement activation
- Fc binding and stimulation of phagocytes (commonly neutrophils)
- antibody dependent stimulation of phagocytes
INAPPROPRIATE RESPONSE TO OWN CELLS.
Type 3 Hypersensitivity (Complex mediated reaction)
Also known as an autoimmune reaction.
Antibody-antigen immune complex formation.
These are deposed in tissues resulting in activating phagocytes and damage.
The complexes form from fragments but are too small for macrophages to sweep up. They deposit in tissues wherein complement is activated causing inflammation.
Type 4 Hypersensitivity Reaction (Delayed)
Repeated exposure causing an allergic response.
T cell-mediated (CD8+) and helper (CD4+)
T-helper cell 1 released interleukin 2 which recruits more TH1 cells which then release more IL-2 and interferon gamma (recruits macrophages)
Complement cascade to be activated (IL-6) increase in temperature (IL-1)
CD28/B7 ligand bonds
Contact dermatitis
Haptens cross stratum corneum. Langerhans cells present to TH1 cells. TNF alpha and IL-1,13,18. LC’s become differentiated Dendritic cells presenting allergenic epitope and multiply. More aggressive response 2nd time.
Late phase response Type 1 hypersensitivity
Newly synthesised mast cell mediators, Th2 cytokines, eosinophil mediators
Lab investigations of type 1 hypersensitivity
IgE levels RAST test)
