Hypersensitivity

Front 1

1. To list the distinguishing features of Types I, II, III & IV hypersensitivity.

Back 1

Type 1 -mast cell activation to soluble antigen
Type 2 - antibody reacts to something on cell surface/matrix
Type 3 - antibody + soluble antigen forms immune complexes
Type 4 - T cell mediated

Front 2

What are the steps of type I hypersensitivity?

Back 2

1) soluble antigen present in serum
2) APC binds antigen
3) APC presents antigen to TH2 cell
4) TH2 secretes IL-4
5) TH2 cell activates B cell
6) B Cell secretes IL 4
7) B cell secretes IgE
8) IgE binds Fcε receptor
9) mast cell degranulates

Front 3

What is the name of the IgE receptor?

Back 3

FcεRI

Front 4

How does IgE work at the FcεRI receptor?

Back 4

via crosslinking of the repetitive epitopes on the FcεRI receptor

Front 5

What are the main hypersensitivity mediators of the Type 1 response?

Back 5

1) Tryptase, chymase, cathepsin G, carboxypeptidase
2) Histamine, Heparin
3) TNF-α
4) IL3&IL4
5) CCL
6) Leukotrienes, prostaglandins
7) platelet activating factor

Front 6

What is the difference between the IgE activation in mast cells in connective tissue vs mast cells in the mucosa?

Back 6

mucosal mast cells: tryptase
CT mast cells: chymotryptase

Front 7

What does the tryptase and chymotryptase enzymes do?

Back 7

remodel connective tissue matrix

Front 8

What does histamine and heparin do? (3)

Back 8

increase vascular permeability
cause smooth muscle contraction
mucus production
parasite toxicity

Front 9

What does Il-4 and IL-13 do in the Type 1 hypersensitivity response?

Back 9

promote inflammation
stimulate cytokines
production of many cell types
activates endothelium

Front 10

What does IL-3 and IL-5 do?

Back 10

stimulate and amplify TH2 resposne

Front 11

What does the chemokine CCL3 do?

Back 11

chemotaxis for monocyte, macrophages and neutrophils

Front 12

What do leukotrienes do?

Back 12

increase vascular permeability
cause mucus secretion

Front 13

What does patlet activating facotr do?

Back 13

activates cell mediators
chemotactic for leukocytes

Front 14

What enzyme produces histamine from what molecule?

Back 14

histidine decarboxylase from histidine

Front 15

What are the functions of the prostaglandins and luekotrienes? (2)

Back 15

blood vasodilation
PMN attraction (effector lymphocytes)

Front 16

what stimulates eosinophils?

Back 16

IL-5

Front 17

What attracts eosinophils?

Back 17

CCL11

Front 18

What does MC and TH2 activation cause to happen to eosinophils?

Back 18

accumulation of eosinophils at site
activation of FcεRI receptor on eosinophil

Front 19

What are the eosinophil mediators do?

Back 19

trigger release of histamine from mast cells
toxic to all cells

Front 20

What is the importance of basophils in the type I allergic response?

Back 20

initiate TH2/IgE by producing IL-4 and IL-13

Front 21

What are the important characteristics of allergens? (7)

Back 21

1) protein
2) proteases
3) low dose favors IL-4 producing CD4 cells
4) low molecular weight so it can diffuse into mucus
5) high solubility - allergen can get out of particle
6) allergen can survive in dessicated particle
7) contains peptides that bind MHC class II required for T cell priming

Front 22

What cell provides the first burst of IL-4 that primes the B cells to make IgE?

Back 22

basophils

Front 23

What happens during the late phase vs immediate phase reaction?

Back 23

Immediate: allergen-IgE induced MC degranulation
Late phase - prostglandins, chemokines, cytokines after MC activation

Front 24

What influences the severity of allargic symptoms?

Back 24

site of mast cell activation

Front 25

What happens when mast cells are degranualted in gastrointestinal tract?

Back 25

diarrhea, vomiting

Front 26

What happens when mast cells are degranulated in airway?

Back 26

increased mucus
decreased airway diameter

Front 27

What happens when mast cells are degranulated in blood vessels?

Back 27

edema
inflammation

Front 28

What causes anaphylaxis?

Back 28

antigen in blood stream enters tissue and activates mast cells throughout the body

Front 29

What occurs during allergic rhinitis?

Back 29

allergen crosses mucus membrane

Front 30

What happens in allergic asthma?

Back 30

submucosa has MC that degranulate upon seeing antigen

Front 31

What are ways to block Type I allergy? (5)

Back 31

1) block histamine or leukotrienes
2) epinephrine
3) block IgE binding to MC via Xolair
4) allergen shots
5) desensitization

Front 32

What is the mechanism of type II hypersensitivity?

Back 32

1) IgG or IgM is produced in response to exogenous or endogenous tissue that is modified
2) this leads to membrane attack complexes or ingestion by phagocytes

Front 33

What are the conditions associated with type II hypersensitivity? (5)

Back 33

1) Good pastures (anti kidney and lung)
2)autoimmune hemolytic anemia
3) pemphigus vulgaris
4) myasthenia gravis
5) graves

Front 34

What happens in pemphigus vulgaris?

Back 34

disrupt epidermis

Front 35

What happens in Graves disease?

Back 35

antibodies stimulate TSH receptor

Front 36

What happens in myasthenia gravis?

Back 36

antibodies block AcH signaling

Front 37

What is type III hypersensitivity caused by?

Back 37

immune complexes of IgG and soluble antigens circulating and can not be removed

Front 38

What is the arthus reaction? (6)

Back 38

1) antigen gets complexed with IgG antibody
2) immune complex activates complement
3) c5a binds mast cell
4) immune complex binds to mast cell FcγRI
5) degranulation
6) inflammation and occlusion of blood vessel
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Front 39

What determines the pathology of Type III immune response?

Back 39

where immune complex is deposited

Front 40

What is the pathway for the type III immune response?

Back 40

1) IgG/IgM bind soluble antigen
2) immune complex deposited on tissue
3) complement and neutrophils activated
4) pathology

Front 41

What are the conditions associated with type III immune response? (6)

Back 41

1) SLE
2) GN
3) dermatitis
4) Arthritis
5) Retinitis
6) Vasculitis

Front 42

What is the mediator of type IV hypersensitivity?

Back 42

antigen specific T effector cell

Front 43

What are the 3 main types of Type IV hypersensitivity?

Back 43

1) delayed type hypersensitivity
2) contact hypersensitivity
3) gluten sensitive enteropathy

Front 44

What is the antigen for delayed type insensitivity?

Back 44

proteins such as insect venous, mycobacterial proteins

Front 45

What is the consequence of delayed type hypersensitivity?

Back 45

dermatitis

Front 46

What is the mechanism for type IV hypersensitivity?

Back 46

1) antigen processed by tissue macrophages
2) TH1 cells are stimulated
3a) chemokines are secreted to recruit macrophages
3b) INF-γ is secreted to activate macrophage and so they release their inflammatory mediators
3c) TNF-α and LT - local tissue destruction, increase blood adhesion
3d) IL-3/GM-CSF- monocyte production by bone stem cells

Front 47

What is type course of Type IV hypersensitivity?

Back 47

24-72 hours

Front 48

What is poison ivy an example of?

Back 48

contact hypersensitivity

Front 49

What causes celiac disease?

Back 49

HLA-DQ2 or HLA-DQ8 MHC Class II

Front 50

What are some common drugs that cause severe hypersensitivity?

Back 50

1)carbamzepine
2) allopurinol
3) abacavir

Front 51

Why do some common drugs cause severe hypersensitivity?

Back 51

class I association indicates CTL reactivity towards drugs with modified proteins