Test 3: Immediate type hypersensitivity Flashcards
What are individuals called who have a response to allergens?
Atopic
Does immediate type hypersensitivity occur after first or second exposure?
Second (unlike serum sickness)
Put the sequence of events in order:
– Release of mast cell mediators
– Binding of IgE to Fcε receptors on mast cells or
basophils
– Production of IgE in response to an antigen
– Cross-linking of the bound IgE by “reintroduced”
antigen.
– Production of IgE in response to an antigen.
– Binding of IgE to Fcε receptors on mast cells or
basophils
– Cross-linking of the bound IgE by “reintroduced”
antigen.
– Release of mast cell mediators.
What are some features of allergens?
- low molecular weight proteins
- glycosylated
- highly soluble
- many are enzymes
How do most allergens enter the body?
skin/mucosa such as respiratory/GI tract
Is there a genetic predisposition for allergies?
Yes–genetics influences ability to make IgE
How much IgE is in serum and what is the half life?
1 microgram/mL; half life is 2-3 days (unless bound)
What are the major cytokines released by TH2 cells and what are their functions?
IL-4: isotype switching to IgE and eosinophil recruitment
IL-5: eosinophil activation
IL-13: same as 4 with regulation of inflammation
Where do mast cells come from and where do they mature?
Derived in bone marrow but travel to peripheral tissue and mature in situ
What are the two types of mast cells?
- Mucosal mast cells: Very little histamine
- CT Mast cells: large amounts of histamine
Where do basophils mature?
In bone marrow, <1% leukocytes
What part of the Fc epsilon RI receptor has a high affinity for IgE?
Alpha chain
What is sensitization?
Binding of IgE to the high affinity receptors on a mast cell in a non-specific manner
What causes activation of mast cells?
Binding of 2nd exposure antigens–>cross linking of receptors
What are the responses of the activated mast cells?
- Degranulation (primary mediator)
- Synthesis/secretion of lipid mediators (secondary)
- Synthesis/secretion of cytokines (secondary)
What else can activate mast cells/basophils?
-anaphylatoxins (C5a) and some drugs
When histamine is released and attaches to H1 receptors, what are the effects?
- endothelial cell constriction=capillary leakiness
- smooth muscle relaxants are produced=vasodilation/erythema
- bronchial smooth muscle constriction=bronchospasm and more mucous
- intestinal smooth muscle constriction=peristalsis
Which receptor effects can be inhibited by antihistamines?
H1
What are the effects of H2 receptors?
gastric acid and airway mucous secretion
What drugs inhibit H2 receptors?
-cimetidine(tagamet), ranitidine(zantac), famotidine(pepcid)
What are the 3 lipid mediators synthesized in mast cells (comes from arachidonate that is taken from cell membrane via phospholipase A2)
- Prostaglandin D2: COX pathway for vasodilation and bronchoconstriction
- Leukotriene C4: lipooxygenase pathway that does the same as histamine but lasts longer
- Platelet Activating Factor: bronchoconstriction and vascular permeability
What are some of the cytokines released from mast cells? (late-phase rxn)
IL-3, TNF-alpha; TH2 cytokines
What is the major cellular component in late phase reaction?
Eosinophils; effects from immediate response can return hours later, kills parasites and can damage tissue
What are the 3 phases from immediate hypersensitivity manifestations upon intradermal administration? (associated with histamine)
1: erythema
2: central area becomes edamatous and blanches (plasma leakage from post-cap venules)=WHEAL
3: marginal perimeter erythematous=FLARE
What is caused by increased permeability of vessels in the skin and subcutaneous tissues?
Urticaria (hives) and angioedema
What is the most common manifestation of immediate hypersensitivity?
Hay fever/allergic Rhinitis
What are some symptoms of hay fever?
- watery rhinorrhea, sneezing, pruritis of nose and palate, eye itching and redness and tearing
- associated with histamine release along with Leukotrines and PGD
What type of asthma is caused by immediate type hypersensitivity?
Extrinsic asthma
What mediates the asthma?
Leukotrines and prostaglandins (from mucosal mast cells–not a lot of histamine)
What are the cardio effects of anaphylactic shock?
- general arterial vasodilation and increased vascular permeability–>hypotension and shock
- cardiac ischemia from hypotension
What are the respiratory and GI effects of anaphylactic shock?
smooth muscle constriction–mucous plugging airways; cramping, nausea, vomiting
What is involved in desensitization?
- sterile aggregated antigens injected subcutaneously in increasing doses until a small local area of inflammation is reached
- this is a maintenance dose that is used for years
- shifts Ig production to IgG instead of IgE=blocking antibody
