Final Exam (Lecture 18) - Hypersensitivities Flashcards
List the four types of hypersensitivity and the basic mechanism of each.
1) Type 1: Immediate tye
- mediated by IgE
- mast cell degranulate
- immediate clinical signs
2) Type 2: Cytotoxic type
- mediated by IgG or IgM
- complement activation/phagocytosis
3) Type 3: Immune-complex type
- mediated by accumulation of immune
complexes (IgG or soluble antigen) and
response to them
4) Type 4: Delayed type
- T-cell mediated (TH1 activation of macrophage)
- soluble antigen
Define sensitization.
An abnormal primary response to an antigen (sensitizing agent) such that, in a subsequent exposure, the individual mounts an excessive or abnormal secondary response that causes disease rather than immunity
Explain the important factors responsible for IgE production (e.g. type of antigen, location in the body, antigen-presenting cell, Th cells, B cells, and cytokines).
IgE production = for defense against helminthic parasites
- Type of antigen: allergens
- Location in body: mucosal surfaces
- APC: dendritic cells presenting on MHC II
(tells naive T helper 0 to become TH2 via IL-4)
- T helper cell: TH2
- B cell: undergoes class-switching and clonally
expand to switch from IgG to IgE via cytokine
signaling
- Cytokines: IL-4, IL-5, IL-10, and IL-13
List the cell responsible for the early phase immediate-type hypersensitivity reaction and special features of that cell (e.g. Fce receptors).
Mast cell
- FceR1 receptor; binds Fc portion of IgE even
when IgE has not bound its antigen
- Has preformed granules that cause clinical
signs upon degranulation
List the three waves of mediators released from mast cells during IgE-mediated degranulation, approximately when they are released, and give an example of a mediator from each wave, including function.
1) Seconds (immediate release)
- Preformed and stored in granules
(histamine, heparin, serotonin)
- Toxic to parasites
- Increase vascular permeability
- Increase vasodilation
- Bronchoconstriction
2) Minutes (products from membrane
phospholipids are generated)
- Arachidonic acid metabolites (leukotrienes);
same function as histamine
3) Hours
- Cytokines are synthesized (IL-4, IL-5, IL-13)
- IL-4, IL-13 stimulate and result in the production
of more TH2 (this adds to the allergy cycle; the
more TH2, the more IgE from B cells and the more
mast cells sensitized to degranulate)
Define hypersensitivity.
Adaptive immune response directed toward innocuous substances such as self or pollen that induce damage to the host. It is an immunologically mediated damaging inflammatory response to a normally innocuous antigen.
Define allergy.
Something triggers the immune system to respond to foods and other substances that wouldn’t normally cause an immune response and produce either TH2 and IgE or TH1 response and decreased Tregs.
Define atopy.
A genetic tendency to develop allergic diseases
Define anaphylaxis.
A rapid, generalized mast cell degranulation followed by eosinophil degranulation that can lead to shock.
Define allergen.
A type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body.
Explain the difference in a post-vaccination response of low-grade fever, lack of appetite, and lethargy the day after vaccination
vs.
An immediate-type hypersensitivity reaction.
Include timing and mechanism (important cells and molecules).
1) The day after:
- Due to proinflammatory cytokines secreted from
dendritic cells that bind PAMP to PRR
- Common and expected with young or first vaccine
- 12-24 hours post-vaccine
2) Immediate type:
- Occurs due to sensitization
- Swollen muzzle/ears
- Mast cell degranulation due to IgE binding antigen
- Occurs with booster vaccines (NOT first dose)
- 10-15 minutes post-vaccine
Draw and compare/contrast with words, IgE on a mast cell, IgE on a B cell that will produce IgE (BCR), and IgE binding a parasite it recognizes.
Look at slide
Explain the immunologic basis for the most likely reason why a puppy may develop a low-grade fever and be lethargic 12-24 hours after its first set of vaccinations.
PAMP from vaccine binds to PRR on sentinel cell
Sentinel cell > proinflammatory cytokine secretion > systemic sites of action > effects in 12-24 hours
Explain the immunologic basis for the most likely reason 15 minutes following a third vaccination booster, a puppy would develop swollen eyes and a swollen muzzle and begin to paw at its face.
This reaction was not observed after the first set of vaccinations. Please explain why.
Allergen cross-links IgE on mast cells > degranulation of mast cells > histamine release
Two dogs, Wrigley and Bush, are in for intradermal skin testing for allergies. Explain why Wrigley developed wheal and flare to ragweed and Bush did not and why they both developed wheal and flare to histamine.
1) Wrigley:
- Has IgE on mast cells that recognize ragweed and
on exposure mast cells degranulated
2) Bush:
- Had no IgE antibodies against ragweed so he didn’t
have a wheal and flare response
3) Both responded to histamine because it will always
produce a response because it is what is produced
when mast cells degranulate
