Make practice questions usign these notes: 
Hypersensitivity is an exaggerated normal adaptive immune response
Can cause damage/ fatal responses in response to antigens that stimulate these responses
		Exaggerated response to foreign antigens 
		Inappropriate response to self-antigens 
ABCD → Allergies B-antiBodies C- immune Complexes D- Delayed T cell
Type I- IgE mediated hypersensitivity also called immediate hypersensitivity
	Cell surface-bound antibody bridged by binding antigen
Type II- antibody-mediated hypersensitivity
	Antibody-antigen mediated cytotoxicity 
	Ab binds inappropriately to ag on cell surface and activates complement 
Type III- immune complex-mediated hypersensitivity 
Antibody-antigen complex in the endothelium
ICs accumulate in circulation or on tissue and active complement 
Type IV- T cell-mediated hypersensitivity also called delayed-type hypersensitivity 

Type I
	Response- localized (atopic) and systemic (anaphylactic)
	IgE mediated- IgE is mostly found in tissues not circulation
	Allergen- antigen that induces an allergic response 
	People predisposed to develop IgE antibodies to harmless antigens are called atopic
		Can be due to genetics and environmental factors 
First exposure makes IgE and the person gets sensitized to the antigen/allergen
Second exposure is when hypersensitivity occurs

Main effector cells for IgE response are mast cells
Mast cells are in blood vessels in connective tissue and lining of gut and lungs
Crosslinking of two IgE molecules induces degranulation and is immediate, this also causes all mast cells in the area to degranulate. These mediators also recruit other immune cells to the site of mast cells.

Inflammatory mediators released by mast cells are what cause the symptoms.
	Preformed mediators- stored in granules and immediately released 
		Histamine- increases vascular permeability
		TNF-α- promotes inflammation; preformed and newly synthesized 
		Enzymes such as tryptase and chymase that remodel matrix 
Newly synthesized mediators- chemokines and cytokines that amplify the response and are made after activation
		Eicanosanoids -lipid mediators
Leukotrienes- like histamine but more potent. Histamine starts reaction but leukotrienes responsible for inflammation, smooth muscle contraction, airway constriction, mucus secretion  
		Prostaglandins
Platelet aggregating factor- induces shock-like symptoms; augments mast cell activity 
Histamine and leukotrienes leads to bronchoconstriction and vasodilation 	

Eosinophils- migrate to tissues in response to chemokines and the chemokines/cytokines at the site of inflammation induce expression of eosinophil FcεlRI. KNOW eosinophils are highly toxic  
IgE binds eosinophil and preformed compounds are expressed first
Synthesis of cytokines, leukotrienes, PGD amplify response
Major basic protein (MBP)- poisons parasites and host cells, induces mast cells to release histamine 
	
	Allergic reactions- 
		Wheal and flare
		Anaphylaxis
		Allergic rhinitis/ asthma
		Hives/Eczema
		Food allergies 
	Allergens- exposed by injection, inhalation, contact, ingestion 
		Are small soluble proteins present in dried-up particles
Good allergens are: proteins, low molecular weight, high solubility, stable, and low dose, often proteases 
Early and late response=
	In sensitized people:
Exposure to allergen causes immediate degranulation of mast cells
Early reaction is due to preformed and newly made mediators (seconds to minutes)
Results in Wheal and Flare Reaction
Wheal is histamine → rapid increase in vascular permeability allowing fluid to leak out of vessels causing local swelling
Flare is local redding due to increased blood flow 
Late reaction is result of continued synthesis and release of mediators by mast cells
Swelling due to leukotrienes, chemokines, and cytokines 
Depends on allergen dose
Increased edema that peaks 3-9 hours and can last 24 hours
The second exposure location will determine the outcome of the IgE reaction 
Localized reaction- 
Only mast cells at the site of allergen 
			Inhaled or ingested- mucosal mast cells
			Penetrated- connective tissue mast cells
		Anatomy determines how long the reaction lasts
			Airborne- respiratory tract
			Food- GI tract
			Bites/stings/wounds- blood and CT
The strength of reaction depends on number of IgE present 

Treatments for Type I
	Omalizumab- anti-IgE Fc antibodies
	Block IL4/R or IL5/R
	Corticosteroids- antiinflammatory 

Type II

Antibody-mediated by IgG or IgM
Binding of antibody directly to antigen on cell or tissue surface
	Reactions:
Complement- lysis or opsonization with C3b and antibodies and destruction by macrophages or neutrophils. Ex- wrong blood type transfusion
Antibody-mediated phagocytosis
Antibody-mediated cellular dysfunction- antibodies block a receptor and prevent its function. Ex- Myasthenia gravis inhibits the receptor for Ach.  

Type III
Systemic reaction, unlike Type II which is local or tissue specific. 
Caused by Deposition of antigen-antibody complexes
	Examples-
Subcutaneous type III- Arthus reaction 
		Deposition of immune complexes 
	Systemic Type III- Serum sickness
		Vasculitis, nephritis, arthritis, glomerulonephritis 

Type IV
T cell-mediated and delayed 
Causes- tuberculin, insect venom, metals, and plant toxins 
Two types:
Damage due to inflammation response and tissue destruction due to TH1 and macrophages
	Damage due to direct cytotoxic activity of CD8+ T cells