Hypersensitivities Flashcards
What are hypersensitivity reactions ?
Over the top reaction to a common and inoffensive antigen.
Type 1 hypersensitivity reactions are :
IgE mediated
in response to common environmental allergens
Ag induces cross-linking of IgE bound to mast cells and basophils with release of vasoactive mediators.
Food allergies, hives, hay fever, eczema & asthma are examples of :
Type 1 hypersensitivity reactions.
Ab directed against cell surface An mediates cell destruction via complement activation or ADCC ?
IgG-mediated cytotoxic hypersensitivity (type 2)
What kind of reaction is involved in type III hypersensitivity reactions?
Ag-AB complexes deposited in various tissues induce complement activation and inflammatory response mediated by massive infiltration of neutrophils
Serum sickness, lupus, RA and glomerulonephritis, vasculitis are examples of :
Type 3 hypersensitivities
Sensitized Th1 cells release cytokines that activate macrophages or Tc cells which mediate cellular damage :
E.g. contact dermatitis, tubercular lesions and graft rejections.
Type IV or cell-mediated hypersensitivity
Autoimmune hemolytic anemia, erythroblastosis fetalis and blood transfusion reactions are :
Type II hypersensitivity reactions
Low concentration in serum
Short half life
In response to Th2 cells, dependent on IL-4
IgE
Type I HSRs have a sensitization phase followed by an elicitation phase :
This means you need a first exposure which will not give you any reaction. The second exposure will elicit the reaction.
The IgE receptor bound with IgE and the antigen is what elicits the reaction, not the antigen itself.
Mast cell degranulation and phospholipid release leads to activation of what pathway ?
Arachidonic acid pathway
Where is the main site of allergy development ?
Mucosal surfaces
Th2 responses that lead to production of IgE are most common on mucosal surfaces.
Required for type 1 HSRs to occur ?
Must be recurrent, low dose exposures of B cells to an antigen.
Production of this enzyme results from long term mast cell activation and is used as a dx tool for anaphylactic shock :
Tryptase
You can have immediate and then a later reaction in type I HSRs. Why is that ?
- Mast cell degranulation causes sx (wheal and flare)
- Other cells respond to that degranulation approx 2-4h later (such as eosinophils & Th2 cells)
Max inflammation at about 24h ; usually subsides on its own after.
The reaction is immediate (within 15 min) & characterized by wheal and flare reaction:
Type I hypersensitivity reaction
Early or late phase reactions are characterized by accumulation of leukocytes ?
Late
Increased production of mucous in allergic rhinitis is mediated by what cytokine ?
IL-13
What is the difference between asthma and bronchial asthma ?
Bronchial asthma is a reversible airway obstruction ofen caused by the release of inflammatory mediators from mast cells upon encounter with allergen. The inflammatory mediators cause loosening of tight junctions in the bronchiolar epithelium, increased capillary permability and spasmotic contraction of smooth muscle surrounding the bronchi.
Basically its the normal inflammatory response you see in asthma, with the addition of a bronchospasm.
Bronchospasm can also be triggered by non immunologic stimuli such as :
(Intrinsic asthma)
Cold
Exercise
Viruses
Aspirin
NOT A TYPE 1 HSR
It has nothing to do with IgE, but still the Mast cells are triggered. We don’t really know why. All we know is that mast cells are easy to piss off.
What is extrinsic asthma ?
Inflammatory disease of the airway characterized by intermittent airway narrowing and variable symptoms of chest tightness, wheezing and SOB.
Is a type 1 hypersensitivity reaction
Common allergens : dust, pollen, food, molds..
Usually a family hx of allergies
Food allergies can result from all types of HSR. What is the most common one ?
Type I (IgE mediated)
Why is atopic dermatitis more severe than urticaria?
Both started as a Type 1 hypersensitivity reaction, inducing Th2 responses, but AD causes more swelling and inflammation, people tend to scratch more and introduce bacteria in there. Inflammation and bacteria, IL-12 drives Th1 response.
Chronic flares leads to fibrosis of the tissue.
Children with AD usually go on to develop asthma, hay fever and other allergies. Strong positive family history.
Gold standard for diagnosing type I HSRs ?
Skin testing
Positive if wheal and flare reaction
RAST test is another dx tool that detects allergen-specific IgE in the blood that can be used for dx of type I HSRs, but this is less sensitive.
If you have many tissue bound IgEs, plasma level may appear WNL.
Haptenized penicillin can cause what kind of hypersensitivity reaction ?
Type I
The beta-lactam ring structure can form a complex with proteins such as benzylpenicillin. The protein-polylysine-penicillin structure is big enough for the IgE to target it.
Most people’s MHC class II will not present the haptenized penicillin, so penicillin allergy will never develop.
What is Red Man syndrome ?
Reaction 4-10 min after rapid and high dose of vancomycin.
Results from mast cell degranulation, but is NOT IgE mediated.
Tryptases in the blood are not elevated!
What is allergic desensitization ?
The allergic pt receives progressively increasing doses of allergen, which results in increased IL-10, serum IgG (IgG4), decreased T cell response, decreased IgE response and late reactions in the skin. It can occur as early as 3 months after the process is initated, but may take 2 years to see max effects.
Myasthenia gravis and Graves diseases are what types of HSRs ?
Type II HSRs
Pemphigous vulgaris is what type of HSR ?
Type II
What type of HSR is Goodpasture syndrome ?
Type II
What is Arthus and what type of HSR is it ?
Arthus It is a localized immune complex reaction due to formation of Ab-An complexes near vessel walls. It produces a > 50 mm reaction with a less defined edge, 5-12h after exposure to An.
Type III HSR!
What is Steven Johnson syndrome ? What type of HSR ?
Drug-induced reaction (haptonized) involving cytotoxic T cells causing death of epithelial cells in the skin & mucosa.
Most commonly associated with sulfa atb, antiepileptics (carbamazepine) and HIV trx (Nevirapine).
Type IV HSR
Severe form - toxic epidermal necrolysis (TEN).
Difference between serum sickness and SJS ?
Serum sickness is a type III HSR. It involves joint pain, flank pain, full body rash and fever.
SJS is a type IV HSR in response to a drug also, but involve massive amount of skin falling off, not just a rash.
Granulomatous diseases in response to what types of HSRs ?
Type IV HSR
Sarcoidosis corresponds to what type of HSR ?
Type IV
What type of HSRs is extrinsinc allergic alveolitis and what causes it ?
Type III HSR
Can insect venom cause type IV HSR ?
Yes
What type of HSRs are Crohn’s and psoriasis ?
Type IV HSRs
What is DTH ?
Delayed type hypersensitivities
(Types II & III)
Classified as both type 2 and 4 HSR. Why is that ?
RA
Synthesized Th1 release cytokines that activate macrophages, that in turn mediate direct cellular damage in what type of HSR ?
Type IV HSRs
IgG & IgM mediated HSRs ?
Types II & III HSRs
HSRs involved with causing autoimmune diseases ?
Types II & III HSRs
Ab-An complexes deposited in tissues, complement activation, massive infiltration of neutrophils is associated with what HSR ?
Type III HSRs
