Hypersensitivity types
- type 1: anaphylaxis
- type 2: Ab mediated within blood
- type 3: clumping of Ab/Ag
- type 4: cell-mediated, delayed hypersensitivity
Type 1 HSR,
mech,
timeline of events
- cross linking of IgE on mast cells by antigen causes release of histamine (immediate rxn)
- Delayed rxn: 6 hours later, continued swelling from leukotrienes, which cause acute inflammation (influx of neutrophils, etc)
Asthma airway hyperactivity is caused by what cytokine
-IL13
“hygiene” hypothesis of type I HSR prevalence
- IgE evolved to combat parasites, and in most of the world IgE is used up to fight them
- However, in the developed world, IgE is available to cause allergic reactions
What cytokine is increased in Type I HSR?
- IL4
- used to induce class switching of B Cells to IgE
Type I HSR: why treat by injecting antigen regularly?
- this allows the IgE to be used up gradually
- dangerous reactions occur because IgE builds up to high levels and is then used up
Type 2 HSR, mech
-Ab reacts with antigen, then recruits complement to attach cell
Type 3 HSR, mech
- Ab/Ag complexes are formed, which clump and be deposited in tissues, then recruit complement
- deposited esp in joints, kidney, and vessels
- Arthus reaction
- Serum sickness
Arthus reaction
- type 3 HSR
- inflammation caused by local deposition of Ab/Ag complexes
Serum sickness
-timeline
- type 3 HSR
- can occur with serum of other animals
- systemic inflammatory response to presence of immune complexes deposited in many areas of the body.
- occurs 7-10 days after antigen exposure because this is time for IgM to switch to IgG
- ex: penicillin allergy
Type 4 HSR, mech, examples
- T cell-mediated, delayed hypersensitivity
- can be CD8 cell mediated, or CD4/macrophage mediated.
- no Ab
- starts hours/days after contact with antigen, can last for days
- Ex: contact dermatitis from poison oak (CD8 cells)
- Ex: Tuberculin skin test (CD4/macrophages)
Tuberculin test
- type 4 HSR, delayed hypersensitivity
- rash caused by CD4, macrophages
What mediator is released within 15 minutes of anaphylaxis and is used to identify mast cell release?
Tryptase
Cytokine mediators released by mast cell in Type 1 hypersensitivity
- when released?
- list them
- 4-6 hours after degranulation
- IL4, IL13
- IL3, IL5, GM-CSF
- TNF
RANTES (CCL5), Eotaxin (CCL11)
chemokines released by mast cells, chemotactic for T cells and eosinophils
Why are steroids a tx for Type 1 hypersensivity?
- steroids induce apoptosis of eosinophils
- reduce IL5 production
IL5
- produced why who
- what does it do
- produced by Th2 cell
- prolongs survival of eosinophils
- enhances cytoxicity against parasites
why can’t you do a skin allergy test (type 1) immediately after an anaphylactic event?
-IgE all used up. wait 4-6 weeks, otherwise get false negative.
Farmer’s lung
type 3 HSD due to Ab against hay dust or mold spores
-affects alveolar wall
Type 4 HSD: how long does it take to occur?
24-72 hours to develop
