Unit 4: hypersensitivity Flashcards
Hypersensitivity reactions are___ immune reactions that cause tissue damage.
adaptive
Hypersensitivity Reactions: A state of excessive antigen driven adaptive immune reactivity with a ___ rather than a ___ outcome. Leads to inflammation & tissue damage
deleterious
protective
Ab dependent effector mechanism for ___ reaction
1,2,3
Ab independent effector reaction for ___ reaction
4
hypersensitivity reaction can be categorized as:
Effector mechanism - Ab dependent (I, II, III) vs. Ab
independent (IV)
Time of onset - Immediate to days
Isotype involved - IgE vs. IgG
Is antibody bound to cell surfaces or. soluble antigens
T cells are primary mediators (Type IV)
atopic dermatitis is what type of hypersensitivity
Type 1
bee sting is a ___
type 1 hypersensitivity
arthus reaction
type III hypersensitivity
poison ivy
type 4 hypersensitivity
type 1 mechanism, onset and antigen
type 2 mechanism, antigen, onset
type 3 mechanism, antigen, onset
type 4 mechanism, antigen onset
Anaphylaxis, Atopic disease
type 1
immediate hypersensitivity are referred to as ___
allergies
type 1 hypersensitivity
___ are substances that so NOT cause any harm or trigger an immune response in 80% of the pop. These are IgE mediated
allergens
___ are substances that trigger an immune response in 100% of the population
antigens
type 1 HS reaction can cause what localized reactions:
Allergic conjunctivitis
allergic rhinitis (seasonal/hay fever). Airway obstruction in horses,
summer snuffles in Guernsey/Jersey cattle.
chronic allergic rhinitis. Dogs - (seasonal or year-round)
**allergic bronchiolitis**. Cats – low grade cough, wheezing, dyspnea – peribronchiolar density (rads).
allergic asthma. Cats, signs similar to humans. Transient and mild
reactions (wheezing, cough) develop in summer. Can be protracted and severe (exp. dyspnea, cyanosis, lung hyperinflation).
Intestinal/food allergies. Dogs/cats – vomiting 1-2 hr after eating
atopic dermatitis – dog and others. >10% of dogs affected (terriers,
dalmations, retrievers). Often triggered by inhaled antigens. In cats,
commonly due to food allergens.
type 1 HS can cause what systemic reactions
A. Anaphylactic shock.
B. Urticarial reactions (hives).
C. Milk allergy.
Type 1 : systemic reaction: anaphylactic shock;
After exposure to certain vaccines, drugs, food, insects
bites. Response takes seconds to minutes.
**Lungs are primary targets** in domestic species, but also portal mesenteric vasculature (except dogs are reverse).
Local or systemic (restlessness, excitement, pruritis, facial edema,
lacrimation, vomiting, diarrhea, dyspnea, cyanosis, shock, collapse,
convulsions, death.
Dogs: Liver is major target, portal hypertension, visceral blood pooling -GI vs respiratory.
in dogs what does anaphylactic shock look like?
Anaphylactic shock. After exposure to certain vaccines, drugs, food, insects bites. Response takes seconds to minutes.
Dogs: Liver is major target, portal hypertension, visceral blood pooling - GI vs respiratory.
Urticarial reactions
systemic reaction to type 1 HS
Edematous plaques in skin, lips, conjunctiva, facial skin (more severe) due to vaccines, drugs, foods, insect bites.
milk allergy
systemic reaction to Type 1 HS
Cows (+/- mares). Anti-milk casein IgE autoantibodies. Increased intramammary pressure pushes milk proteins into circulation (local or systemic, milking leads to recovery)
mechanism for type 1 HS
Sensitization phase: TH2 cell secrete IL4 and IL13 that turn B cell from IgM to IgE memory and plasma cells. Plasma cells produce allergen specific IgE
Activation phase allergen specific IgE will bind to mast cells at Fc receptor,
Effector phase: allergen binds to IgE on mast cell surface. this will cause release of granules that leads to anaphylactic response- (histamine, heparin and protease release)
what are some common IgE mediated allergic reactions
___: Antigens capable of stimulating Type I reactions. In industrialized countries, IgE responses to ___ predominate
innocuous antigen
The majority of humans mount significant IgE responses only
to ___
parasitic infection.
Most allergic IgE responses occur on mucous membrane
surfaces in response to allergens that enter the body by
___
inhalation or ingestion.
Atopic allergy
atopy
pertains to (inherited) clinical manifestations of type I IgE-mediated hypersensitivity to common environmental allergens
20%
runs in families- genetic link?
Hygiene hypothesis
Less hygienic environments help to protect against atopy (developing allergy)
air pollution and low fiber diets lead to ____
increased allergies
predisposition to develop allergies
TSLP
Produced by epithelial cells, especially in the lung in
response the certain allergens such as mite proteases
Produced by basophils and mast cells
Production can be upregulated by IL-4
Prompts dendritic cells to activate Th2 type responses → type 1 HS response
Allergen induced TSLP production by epithelial cells, mast cells, or basophils promotes DC maturation & ___
Th2 responses (type 1 HS response)
Basophils (IL-4 and TSLP producers) act as ___ to promote Th2 responses
APCs
Th2→ type 1 HS response
certain allergens directly cross link FcR on mast cells leading to __ release
IL-4
Will switch immature B to mature B
TSLP will cause ___ to help with the class switch of B cells with the help of ___ made by ___ cells
DC cells
IL4, TH2
(type 1 HS- will produce IgE cells)
mast cells release:
preformed/primary mediators: histamine, proteases, chemotactic factor (ECF, NCF)
newly synthesized/ secondary mediators: PAF, leukotrienes (B4, C4, D4) and prostaglandin (D2)
immediate vs late phase reaction of Type 1 HS reaction
antigen binds to TH2 which will release IL-4 and cause B cell switch to IgE B cell will produce IgE antibody which bind to Fc receptor on Mast cell
new antigen will bind to the IgE Fc recptor on the mast cell and cause release of primary and secondary mediators
Eosinophils
Express a low affinity receptor for IgE, as well as Fc receptors
for IgG. Therefore, both IgE and IgG bound antigen can bind
to eosinophils leading to their activation.
Activated by:
• Leukotrienes • Platelet-Activating Factor • Major Basic Protein (MBP) • Eosinophil cationic protein
example of type 2 HS
immune mediated disease
Antibody and Complement-dependent responses
Type 2 HS response → killing normal tissue
a. Antibody binds to target cell Ag, triggers classical C activation and
formation of a membrane attack complex (MAC) and cell lysis.
b. Antibody opsonizes(surrounds) the target cell and triggers phagocytosis by macrophages.
Examples: AIHA, Erythoblastosis fetalis, Goodpasture’s disease, transfusion reactions
Rh reaction
mom is RH-, fetus in +
mom gives antibodies to child by colostrum or placenta, which include anti RH
this will cause fetus to attack itself
prevent by giving rhogam
(hemolytic disease- erythroblastosis fetalis)
type 2 HS response
How to test for Type 2 HS
look for antibodies to normal tissues
detection of circulating antibody against the tissues involved, presence of antibody and complement in the lesion (biopsy) by IF. The staining pattern is normally smooth and linear, such as that seen below in a case of Goodpasture’s* nephritis (renal and lung basement membrane).
Goodpasture’s: anti-glomerular basement membrane antibody disease
___: anti-glomerular basement membrane antibody disease
Goodpasture’s (type 2 HS)
Antibody-dependent cell mediated cytotoxicity
(Type 2 HS response)
Ab bound cells are targeted through Fc receptors on:
Macrophages • NK cells • Eosinophils • Neutrophils
Examples:
- Drug induced hemolytic anemia
- Drug induced thrombocytopenia
- Drug induced neutropenia
- Transplant rejection
myasthenia gravis
type 2 HS → cause target cell dysfunction
AcH Receptor destruction → disrupts neural transmission → flaccid muscles
arthus reaction
type 3 HS
- Involves the in situ formation of antigen/antibody complexes after the
intradermal injection of an antigen. - Animal/patient has to be previously sensitized (has circulating Ab),
- Manifests as local vasculitis due to deposition of IgG-based immune
complexes in dermal blood vessels. - Activation of complement primarily results in cleavage of soluble
complement proteins forming C5a and C3a - C3a and C5a recruit PMNs and trigger local mast cell degranulation
(requiring the binding of the immune complex onto FcγRIII), resulting
in an inflammatory response)
Snake venom-producing farm
Technician bit by a Egyptian cobra
Rushed to ER: IV anti-venom serum given.
Patient left the hospital 7 days later
10 days discharge, patient developed joint pain, fever, recurrent itchy hives.
what is the diagnosis?
serum sickness
systemic type 3 response
how does poison ivy work
type 4 HS
TH1, TH17, & CD8+ T lymphocytes in contact dermatitis
Molecules such as pentadecacatechol (Urushiol) complex with skin proteins. This complex is internalized by APCs, processed and presented by MHC II to activate TH1 cells. Urushiol also haptenizes proteins in skin cells and is presented on MHC I to activate CD8+ lymphocytes.
Subsequent exposure to pentadecacatechol will activate these TH1 and cells & induce cytokine production and CTL mediated cytotoxicity
Macrophages also accumulate and release lytic enzymes
Together these actions lead to inflammation, cell damage, and blister formation
