Flashcards in Hypersensitivity Deck (53):
What are 3 other names for type 1 hypersensitivity reactions?
immediate, anaphylatic, atopic
What is type I hypersensitivity mediated by?
What are individuals who are genetically susceptible and have higher levels of IgE and eosinophils called?
What do clinical manifestations of type I hypersensitivity depend on?
route of entry of allergen, location of responding cells
What kind of immune response is activated by allergens? What cytokines produced?
Th2 response, IL-4
What happens upon initial sensitization to allergen?
Ag activates Th2 cells to cause IgE class switching in B cells, production of IgE, and binding of IgE to FcRe receptors on mast cells
What happens upon second exposure to allergen?
IgE bound to surface of mast cells, basophils and eosinophils is crosslinked, resulting in degranulation and release of inflammatory mediators
What are other mechanisms of mast cell degranulation besides IgE crosslinking?
IgG crosslinking, C5a binding complement receptors, TLR
What do mast cell granules contain?
enzymes for tissue remodeling (tryptase), toxic mediators that increase vascular permeability and cause smooth muscle contractions (histamine), cytokines that promote inflammation and cytokine production (TNFa), chemokines that promote influx of macrophages/monocytes/neutrophils (CCL3), lipid activators that cause smooth muscle contraction and increase vascular permeability (leukotrienes)
What mast cell mediators cause immediate hypersensitivity reaction?
vasoactive amines, lipid mediators
What mast cell mediators cause late-phase reaction?
What is a wheal and flare reaction?
Wheal and flare is the immediate hypersensitivity reaction.
Wheal- swelling from leakage-histamine effect
flare- engorged with RBCs
What is the late phase hypersensitivity reaction?
more widespread swelling, inflammation from cytokines
What is SRS-A?
Slow releasing substance of anaphylaxis
How does serotonin released from mast cells affect the response?
affects vascular permeability
When are eosinophils found in hypersensitivity reactions?
late phase reactions
What cytokines increase basophil influx? What is their action on eosinophils?
TGFb, IL-3, decrease eosinophil influx
What cytokines increase eosinophil influx? What is their action on basophils?
IL-5, GM-CSF, decrease basophil influx
How do granulocytes promote expulsion of parasites?
increased peristalsis and mucus
What are the responses to subcutaneous antigen?
urticaria (hives), angiodema (more diffuse swelling), eczema
What is the mechanism used in skin testing for allergies?
response to subcutaneous allergen
What is allergic rhinitis?
response to inhaled antigen
How does inhaled allergen elicit a hypersensitivity response?
Peptide derived from pollen presented by APCs to activate Ag-specific T cells, which secrete IL-4 causing class switch to IgE
What are the two clinical manifestations of inhaled allergens?
How is chronic asthma different from acute asthma?
can occur in absence of allergen, hypersensitive to other irritants like cigarette smoke, tissue remodeling from cellular infiltrate and inflammation
What is the reaction to food allergies?
Activated mast cells release histamine which acts on epithelium, blood vessels, and smooth muscle causing urticaria from Ag diffusion into blood vessels and vomiting and diarrhea from smooth muscle contraction
What is the most severe type of type I reaction? Where is the allergen?
systemic anaphylaxis, allergen in bloodstream
How do you treat systemic anaphylaxis?
epinephrine to promote tight junction formation, relax bronchial smooth muscle and stimulate the heart
What genes can contribute to genetic predisposition to allergies?
MHC class II genes and non-MHC genes (TCR, IL-4, IL-4 receptor, IgE receptor)
What is the hygiene hypothesis?
incidence of allergies has increased due to better hygiene that resulted in less exposure to pathogens, skewing to Th2 response rather than Th1
What is the counter-regulation hypothesis?
infections lead to production of IL-10 and TGFb which downregulate both Th1 and Th2 responses to lower hypersensitivity
How do you treat Type 1 hypersensitivity reactions? (6)
1. avoid the allergen
2. treat symptoms (antihistamine, corticosteroids, epinephrine, etc)
3. desensitization to allergen
4. allergenic peptide vaccination to anergize allergen-specific T cells
5. use humanized anti-IgE
6. block effector mechanisms (anticytokines)
How do you desensitize yourself to an allergen?
controlled exposure to increased dose of antigen over time leads to IgA and IgG Ab production which blocks binding of IgE to mast cells
What are two other names for type II hypersensitivity?
What are type II hypersensitivity responses mediated by?
IgG, Ab bind to cell-associated Ag or cell surface receptor and fix complement
How does penicillin initiate a type II hypersensitivity reaction?
penicillin modifies protein on RBCs, creating new epitopes that IgG is produced against, Ab binding leads to lysis of RBCs (hemolytic anemia)
How do mismatched blood transfusions initiate a type II hypersensitivity reaction?
not tolerized to Ags of non-host RBCS, production of anti-RBC Ab results in destruction of RBCs
What mediates the type III hypersensitivity response?
large and latticed immune complexes formed by soluble antigens and Ab
Why are latticed immune complexes pathogenic?
capable of depositing systemically in any tissue sites resulting in downstream cellular damage from tissue-damaging inflammatory response
What determines immune complex pathogenicity?
isotype, valency, charge, ability to fix complement, site of deposition
What are the clinical manifestations of type III hypersensitivity responses to the following sites: blood vessels, renal glomeruli, joints, perivascular area/subcutaneous, alveolar/capillary interface for inhaled
perivascular area- arthus reaction
alveolar/capillary- farmer's lung
What is Arthus reaction?
type III reaction to localized injected Ag that binds IgG, seen if a tetanus booster given < 5 years
Is serum sickness a result of localized or diffuse immune complex deposition?
What are 2 other names for type IV hypersensitivity reaction?
What mediates type IV hypersensitivity reactions? How?
antigen-specific effector Th1 cells, initiates inflammatory reactions via production of cytokines (chemokines, IFNgamma, TNFa, IL-3, GM-CSF) in response to Ag
Which requires greater amounts of allergens: Ig-mediated hypersensitivity or cell-mediated hypersensitivity?
cell-mediated hypersensitivity requires 100-1000x more allergen
What are the 3 types of type IV hypersensitivity reactions?
delayed-type, contact, gluten-sensitive (celiac disease)
What is an example of delayed type hypersensitivity?
TB reaction, Th1 effector cell recognizes Ag on APC and releases cytokines
What is an example of contact hypersensitivity?
poison ivy (pentadecatechol=Ag), nickel, latex, CD4+ T cells activate other immune cells while CTL kills chemical-reacted cells displaying foreign Ag
What type of Th cell is more important in type IV reaction?
What do T cells respond to in celiac disease? What is the result?
gliadin, villous atrophy in small bowel, malabsorption
What antigen stimulates CTL in a hypersensitivity reaction? What type of reaction is this? What is an example?
cell-associated antigen, type IV, contact dermatitis