L20: Hypersensitivity Flashcards
what are hypersensitivity diseases
diseases caused by the immune response
when responses are not adequately controlled or
targeting to ____ then the immune response
becomes ____
the wrong tissue, the cause of the disease
Type 1 mediated
IgE - allergy
Type II mediated
IgG - antibody mediated (cytotoxic)
Type III mediated
IgG - immune complex
Type IV mediated
TH cells
Why do we have IgE responses?
crucial in defence against parasite infection
Why IgE and not IgG/FcR mediated for T1HS
- Normal IgG/FcR-mediated activity not very effective in mobilising fast response
- The mast cell receptor affinity for IgE is high and the IgE/FcR response is immediate in the presence of pathogen
What is the action of IgE
causes mast cell degranulation by binding to FcER receptor and antigen crosslinking IgE
what happens when mast cells degranulate?
release of mediators
1. chemoattractants
2. activators (blood flow/dilation)
3. spasmogens (smooth muscle contraction, mucous secretions)
Mast cell mediators that are synthesised after activation
lipid mediatiors, cytokines
mast cell mediators pre-formed, what does this mean?
- biogenic amines (histamines), enzymes (tryptases)
- immediate release upon activation
action of histamines
vasodilation and vascular leak
action of enzymes
tissue damage
action of lipid mediators
bronchoconstriction, intestinal hypermotility, inflammation
action of cytokines
inflammation
common causes of allergies
rhinitis (hay fever), insect stings, food allergies, small molecules (morphine)
What is mast cell sensitization
The binding of IgE to its high-affinity IgE receptor on mast cell surfaces upon first exposure to allergen
What happens upon re-exposure when a mast cell has been sensitized?
mast cell preloaded with IgE - triggering a HS reaction
allergies treatment
- avoidance
- antihistamines (bind histamine receptor so histamine cant trigger symptoms)
- coritcosteroids
- epinephrine
- desensitisation (gradually increasing dose of allergen to insude high affinity IgG - competes with IgE = stops allergic reaction)
allergy testing
immunoassay (test for AB to allergen), skin prick
Explain the hygiene hypothesis in terms of T helper cells
Immune response to common allergens get polarised away from having a Treg/Th1 response to a Th2 IgE response
Explain what happens in T2 HS
- Antibodies (IgG/IgM) bind directly to antigens on the surface of cells and cause lysis
- can attack mobile cells (in blood stream), or antibodies bind fixed/solid tissue
what is hemolytic anemia
Individual makes
antibodies to their own red
blood cells (RBC)
Explain how hemolytic anemia occurs
- IgG coated RBC are cleared from circulation via uptake by Fc receptor bearing macrophages
- IgM coated RBC are fixed by complement and directly lysed (MAC complex formation)
What happens when AB bind to self antigen on tissue (T2 HS)
- ADCC - antibody dependent cellular cytotoxicity
- complement activation
- frustrated phagocytosis
what is an example of Anti-tissue antibodies
goodpastueres syndrome
explain how goodpastures syndrome occurs
- Antibodies against type IV collagen in glomerular basement membrane
- Affects the kidney glomeruli and the alveoli in the lungs
- Antibodies trigger complement activation that damages epithelial cells
- Patients present with transient kidney dysfunction and bleeding in the lungs
explain what happenscin T III HS
- Antibody complex is not cleared
- Complex becomes large, insoluble
- Complexes lodge in sites and provoke an immune response
give examples of T III HS
serum sickness, rheumatoid arthritis
What is Txpe IV HS
delayed-type hypersensitvity
Type IV HS is mediated by?
antigen specific T-cells
Explain how TIV HS is established
Antigen injected, process by local APC, Th1 effector response, recruitment of phagocytes, inflammation at site
What are examples of T IV HS
contact sensitivity eg jewellery
explain the process of contact sensitivity
- normal proteins act as carrier for small molecule
- transport to lymph
