Hypersensitivity Flashcards
Define hypersensitivity
A harmful immunologic reaction developing in response to an otherwise harmless specific trigger
What is an arthus reaction?
- Hypersensitivity type III reaction
- Skin reaction when sensitized individuals are re-exposed to a specific antigen (hemorrhage/edema within 4-10 hrs)
- Repeated injection of vaccines cause localized inflammation and necrosis (already high IgG titers from previous vaccination)
What is serum sickness?
- Type III hypersensitivity reaction
- Systemic reaction following large quantities of foreign protein:
- Humans immunized with serum of immunized horses triggers illness (flu like; joint pain, swelling, fever, malaise, rash) a week later
- Onset 7-10 days after initial exposure (IgM to IgG class switch)… subsequent exposures have a more rapid onset
Define atopy
The predisposition to develop allergies (used interchangeably with “allergic”)
Summarize the 4 Gell and Coombs classifications of hypersensitivity reactions
- Immediate Allergy (IdE mediated)
- Direct antiBody mediated (cytolytic)
- Immune Complex mediated
- Delayed type (T cell mediated)
What are the two stages of the mechanism of hypersensitivity?
- Sensitization stage
Development of the immune response (requires adaptive immunity, symptoms silent) - Effector stage
Elicitation of the secondary immune response (symptoms evident)
Describe type I hypersensitivity
“Immediate type” hypersensitivity
Mast cells and basophils mediate the initial phase of anaphylaxis (IgE crosslinking by antigen triggers degranulation)
What are the steps of the type I hypersensitivity sensitization phase?
- BCRs on naive B cell bind antigen
- Antigen is also processed and presented by APCs to CD4+ T cells
- Naive CD4+ T helper cell matures into a Th2 antigen specific cell
- Th2 cell produces cytokines to support B cell class switching to IgE
- B cell and plama cell produce IgE
- Circulating IgE binds long-term onto Fc£RI on mast cells/basophils “priming” them for future activation
What are the steps of the type I hypersensitivity effector phase?
- Repeated exposure to allergen
- Antigen crosslinks antigen-specific IgE already bound to Fc£RI on mast cells/basophils
- Crosslinking triggers rapid extracellular release of preformed mediators -> immediate symptoms of anaphylaxis
- Hours later delayed phase symptoms develop
What are the 3 types of mediators in a type I hypersensitivity reaction? Give examples and their effects
- Preformed mediators (released in sec-min)
E.g. Histamine -> vascular dilation, smooth muscle contr
Tryptase -> tissue damage - Rapidly produced mediators (released in min-hr)
*From modification of arachidonic acid!
E.g. Prostaglandins (PGD2) -> vascular dilation
Leukotrienes -> smooth muscle contraction - Slowly produced mediators (released hrs-days)
*Transcriptional activation of cytokine genes!
E.g. Cytokines -> inflammation/leukocyte recruitment
What are the physiologic changes obsered in a type I hypersensitivity reaction?
- Leaky/dilated blood vessels
- Low BP
- Shock
- Cardiac effects
- Myocardial depression
- Tachy/bradycardia
- Smooth muscle spasm
- Bronchospasm
- GI/GU tract spasm
- Coronary spasm
What are the two main histamine receptors (note: at least 4 total)?
- H1R
- Itching
- Increased vascular permeability; edema
- Smooth muscle contraction; bronchospasm/cramping
- H2R
- Gastric acid secretion
What are the main preformed mediators of a type I reaction?
-
Histamine
*short half-life in serum, gone withing minutes -
Tryptase (mast cells only, not basophils)
*Immature constitutively released, mature only released with degranulation
*Found in serum up to 4 hrs after release (best clinical marker of mast cell activation), leads to connective tissue remodeling - Proteases (degrade toxin, lead to connective tissue remodeling)
Describe the crystalloid granule (of eosinophil)
Oval granule with major basic protein
Describe the origin and importance of IL5 in type I hypersensitivity
**Produced by Th2 CD4+ lymphocytes
- In vitro
- enhances surivival, leukotriene synthesis and parasite cytotoxicity
- promotes adhesion and transendothelial migration
- In vivo
- T cell production can cause hypereosinophilic syndrome
- Levels increased in fluids from allergic late-phase reactions