Hypersensitivity (Bowden) Flashcards
What is the Type I hypsersensitivity
Immediate (IgE)
3 properties of IgE control in Type I immediate Hypersensitivity
changes half life of IgE (binding IgE to cell R)
control of IgG and IgE production by T cells
Cross linking of IgE on surface of mast and basophils
Describe how Type I hypersensitivity is T cell dependent
Supressive Th1
Promotes Th2
class switch IL-4
What causes type I reactions
Allergens. usually protein
How are allergens classified
source, route and nature of protein
What are the classical allergens
low doses: inhaled about 1mg/yr
high doses: food (egg milk, nuts, fish)
What happens during repeated exposure to allergen
Mast cells release mediators
Types of mediators and when they are released
Preformed(under 5min) Histamine, heparin, and tryptase Newly Generated(5-30 min) Leukotrience D4, Arachidonic Acid, Prostaglandin D2 Cytokines take hours. IL-4 and TNFa
What are the symptoms/signs of mediators effects
Vascular leak, broncho-constriciton, intestinal hypermotility, inflammation, tissue damage, killing of parasites and host cells
How do we test allergies
Wheal and Flare reaction.
The wheal is the extravasation of sera
The flare is the axon reflex
What is a Late Phase Reaction
4-6 hours after initial Type I reaction. lasts 1-2 days
Infiltration of PMNs, eosinophils, macrophages, lymphocytes and basophils
what causes the late phase reaction
MAst cells produce TNFa and IL-1 leading to expression of adhesion molecules. Mast cells produce chemotactic IL8 and there is onsite release of IL-3 IL-5 IL-8 and GM-CSF (hematopoietic)
What is the Type II hypersensitivity
Antibody Mediated
What are the necessary components in Type II hs
IgG IgM FcR on effector cells and C’ and the surfaces that have the Ab
What are the IgM and IgG Abs binding to in Type II hs
“fixed Ag”
What are more pathogenic: Ab against cell surface Ag or internal Ag
Ab against cell surface Ags are usually pathogenic
What components from activated C’ system cause chemotaxis of PMNs, basophils and eosinophils
C3a and C5a
How does the Fc R communicate with the bound Ab in type II hs
either binds the Fc or binds bound C’ components
What do the effectors do in type II hs
Cytokine and chemokine by activated Eos, Neutrohils, NKs, Macrophages which release TNFa and IL1
Describe frustrated phagocyte
unable to take in the Ag so releases all its contents to kill it
what hemolytic disease occurs by type II hs
Hemolytic disease of newborn (Rh factor) also happens for blood types- more rare
Describe transfusion reaction
Fever, hypotension, nausea/vomiting, back&chest pain. donated blood- not whole blood unless emergency
Abs (IgM) will cause agglutination, C’a ctivation and intravascular hemolysis
Describe warm/cold Abs and what they assoc with
Autoimmune hemolytic anemias, type II hs.
warm: different epitopes then when transfused.
cold: high titer IgM- usually old people in winter.
How can drugs cause autoimmune hemolytic anemias
drugs bind RBCs and Ab to drug. Drug-Ab- immune complex gets absorbed by RBCs and is activated by C’ to be lysed.
What disease has Ab to the acetylcholine R
Myasthenia Graves- extreme mm weakness.
IgG and C’
partial block of ACh, increases R turnover rate
What is type III hs
Immune complexes
What are the components of type III hs
IgG IgM FcR of effector cell, C’ and soluble Ag!!
Ab mediated
What makes up the immune complex
Ab/Ag/C’
What usually removes immune complexes from circulation
monophagocyte system. Normall IC binds C’ and removed by liver and spleen after binding CR1 on RBCs
Where are immune complexes in tissue
determined by localization of Ag in tissue, and size matters
3 groups of Immune complex hs
Persistent infection
autoimmune
inhalation of Ag
What is the function of immune complexes
when inflammed, they act on basophils and platelets to produce vasoactive amine release.
What amines are released by IC activation
histamine and tryptamine to cause endothelial cell retraction and increase vascular permeability
What is the net result of increased vascular permeability
leaky endothelium– complex deposition in some areas
What happens when IC are deposited in leaky endothlium
incudes platelet aggregation and C’ activation- Microthrombi form. Neutrophils are attracted by C’ products– leading to more damage
Increase BP and vascular turbulence in the area leading to increasing the complex deposition
Atrhrus Reaction
type III hs. Presensitization. Ag reaction with marked edema and hemorrhage 4-10 hours after exposure.
chronic allergy shots and allergic alveolitis (farmers lung)
What is serum sickeness
large injections of foreign antigen- causes deposition of IC in blood vessels. Leads to arthritis and glomerulunephritis
How are type II and III hs alike and different?
inflammatory pathways are identical.
Ags type II are fixed surfaces
Ags type III are soluble
Innapropriate activation of Ag in type II and III can lead to
Tissue damage, increase inflammation, and perpetuation of the disease.
Type IV hypersensitivity
delayed-type hypersensitivity- Ag specific T cells
Describe DTH
effector T cells activate macrophages
takes 24-72 hours post exposure
If Ag persists in DTH what can happen
granuloma formation
can lead to autoreactive T cells
Types of DTH
Contact- point of contact with allergen
Tuberculin- soluble Ag
Granulomatous- clinically most important
2 stages of contact sensitivity
Sensitization and Elicitation
Describe sensitization phase of contact allergen
10-14 days: epidermis
this is hapten driven- so like poison oak or ivy
protein/hapten taken up by langerhans
Class II HLA
Describe elicitation phase of contact allergen
recruitment of CD4+ T cells to contact site. monocytes, macrophages
mainly CD4, small CD8
What is the PPd test looking for
recall response to previous encounter with Ag
What happens during a + PPD test
infiltrate of neutrophils, monocytes, T cells
What does tuberculin tests measure generally
cell-mediated immunity
When do you usually see granulomatous DTH
chronic infections assoc with TH1-like responses
absence of infection. non-immune- foreign body
What characteristics of IC allow them to deposit easily
small, positively charged
Persistence of Ag in type Iv hs causes macrophages to change how?
differentiate into epithelioid cells. fusion to form giant cells
What cytokine is granuloma formation dependent on
TNF a because dependent on T cell activation of macrophages
