11. Hypersensitivity reactions Flashcards
(49 cards)
Sensitizing antigens
1) Environmental
2) Tissue/matrix (self)
3) Persistent microbes
* Can be foreign or self (!) materials
Types of hypersensitivity reactions
Type I: classic allergic reaction (IgE)
Type II: immobilized antigen (IgG)
- Immobilized=cell- or matrix associated, cell surface R
Type III: soluble circulating antigens (IgG)
- Immune complexes
Type IV:
- no antibodies
- Th1, Th2, CTL cells (Th for soluble Ag’s, CTL for cell-associated Ag’s)
**Bra tabell i pp!
Clinical expressions of hypersensitivity type I-IV, and times
I: “immediate”: allergy, anaphylaxis (minutes)
II: “cytotoxic” (4-6 hrs)
III: “immune complex mediated” (2-8 hrs)
IV: “delayed type” (2-3 days)
FcγRI (CD64)
- IgG
- High affinity
- Can bind monomeric IgG
- Cells: macroph, neutro and eos
- Function: phagocytosis, activation phagocytes
Type I hypersensitivity reaction
First encounter with allergen: symptom free
1) APC present antigen to T cell
2) Naive T cell -> Th2 cells
3) Th2 cell secrete IL-4 and IL-13 -> activate (class-switch) IgE secreting B cell
4) IgE bind naked to mast cell FcεRI
Second encounter:
5) Antigen bind in cross-link to IgE on FcεRI on mast cells -> mast cell activation (release mediators)
- ITAM motif on receptors!
Secretory granule content mast cells, early mediators
- Histamine
- Enzymes (tryptase, chimase, carboxypeptidase..)
- From preformed granules, immediate reaction
De novo synthesis products mast cells
- PAF
- PGD2
- LTC4 (+LTD4, LTE4)
*By PLA from arachidonic acid and phosphatidylcholine
+ 5-lipoxygenase and cycloxygenase
*From membrane
Immediate reaction
- Within 30 min due to histamine from mast cells
- Disappears after 1 hr
Late phase reaction
- Around 8 hrs
- Eosinophils (activated by IL-5 from Th2 and mast cells)
- Important to bring patients with severe allergic reaction to hospital even though immediate reaction was resolved!
- Se tegning i bok!
Inhaled antigen
- Mucosal mast cell
- Constrict SMC
- Dilate vessel + increase permeability
- Consequence: Hayfever and Allergic asthma
Ingested antigen
- Mucosal mast cell
- Constrict SMC
- Dilate vessel + increase permeability
- Consequence: food allergy (increased peristalsis-abdominal cramping)
Connective tissue mast cell
Intravenous or subcutaneous allergen
Syst anap++
Systemic anaphylaxis
- Ag directly to blood stream or absorbed rapidly to blood stream
- Induce connective tissue mast cell degranulation along the capillaries -> severe swelling
Atopy
Genetic predisposition to exaggerated IgE production (hyperallergic person)
Example type II hypersensitivity reaction
- Rh-incompatibility -> erythroblastosis fetalis (anti Rh Ab’s attack fetal RBCs in 2nd pregnancy)
- and drug (penicillin) hypersensitivty?
Type II autoimmune disease
- “Subtype of type II hypersensitivity”
- No inflammation!!
1) Basedow disease (Graves disease) - Antibody stimulates receptor w/o ligand
- Agonistic molecule
- Thyroxine overexpression
2) Myasthenia gravis - Antibody inhibits binding of ligand to receptor
- Antagonistic molecule
- Muscle weakness
Examples type III diseases
1) Local immune complex disease
- Arthus reaction
- Temporary, in tissues
2) Acute-systemic immune complex disease
- Acute serum disease (7-10 days)
- Temporary, in body fluid
3) Chronic immune complex disease
- SLE (systemic lupus erythematosus)
- Maintained
Example type IV
1) Poison ivy contact
- Cathechol molecules (haptens) combined w/ skin proteins -> immunogenic and present MHC I becausethe skin proteins contain self antigen
2) Ni-induced contact dermatitis
3) Coeliac disease
- Gliadin Ag (protein) enter if surface of gut damaged
- Gliadin only immunogenic if tissue transglutaminase changes conformation of it (deaminates)
- HLA-DQ2 (!) can present deaminated gliadin peptide -> patients with this MHC have coeliac disease
Activated Th1 cells secrete:
1) Chemokines
- Recruit macrophages
2) TNFα and TNFβ
- Local tissue damage, adhesion molecules on endothel
3) IFNγ
- Activation macrophages, release of proinflammatory mediators
4) IL-3/GMCSF (Granulocyte-macrophage colony-stimulating factor)
- Monocytes in bone marrow
IFNγ effect on epithelial + mesenchymal cells
MHC II expression: Makes them able to present antigens with MHC II to CD4 Th1 cells
Overfunction of immune system
- Hypersensitivity
- Autoimmunity
Underfunction of immune system
- Immunedeficiencies
- > Congenital (inherited)
- > Acquired
- > tumor
Immunmodulation
- Stimulation: vaccine
- Inhibition: transplantation
FcγRIIA (CD32)
- IgG
- Low affinity
- Cells: macroph, neutro, eos and platelets
- Function: phagocytosis and cell activation
