hypersensitivity I

Question 1

describe the stages leading to a type I hypersensitivity reaction (5)

Answer 1

• first exposure to antigen
• activation of TH2 cells that cause IgE class switching in B cells
• production of IgE
• binding of IgE to FceRI receptors on mast cells
• repeat exposure to antigen = mast cell degranulation

Question 2

what stimulates mast cell degranulation specifically?

Answer 2

antigen binds to IgE (bound already to FceRI), this causes ITAM phosphorylation in the mast cell that triggers signaling cascade

Question 3

3 consequences of ITAM phosphorylation in mast cells

Answer 3

1- granule exocytosis (vasoactive amines, proteases)
2- formation of lipid mediators through modification of arachidonic acid (PG, LT)
3- transcriptional activation of cytokine genes

Question 4

what is a “unique” feature about IgE in type I hypersensitivity?

Answer 4

IgE will bind to FceRI before it binds to antigen

Question 5

route of entry for systemic anaphylaxis, sx

Answer 5

intravenous (directly or via gut absorption)

laryngeal edema, circ collapse, death

Question 6

route of entry for acute urticaria, sx

Answer 6

systemic through skin

localized increase in blood flow/swelling

Question 7

route of entry for hay fever, sx

Answer 7

contact with conjunctiva of eyes, nose

edema of nose/eyes

Question 8

route of entry for asthma, sx

Answer 8

inhalation into lower airways

airway inflammation, broncho-constriction, inc mucus

Question 9

route of entry for food allergies, sx

Answer 9

oral

vomiting, diarrhea, itching, hives (rarely anaphylaxis)

Question 10

common household cause of asthma

Answer 10

D. pteronyssimus and fecal particles due to Der p1 (cysteine protease)

Question 11

how does Der p1 enter tissues?

Answer 11

cleaves occluding tight junctions to gain access to tissue, then it is recognized as foreign by dendritic cells

Question 12

which IL are involved in allergic responses?
what type of cell will induce B cell class switching to IgE?

Answer 12

IL-4, 5, 9, 13

TH2

Question 13

knock outs of what 4 substances will inhibit allergic reactions?

Answer 13

IL-4, IL-13, CD40, STAT6

Question 14

what are the “preformed” substances in mast cell granules? (2)

Answer 14

histamine

enzymes to activate MMP to break down ECM

Question 15

what are the “newly synthesized” substances by mast cells? (4)

Answer 15

chemokines, lipid mediators, cytokines, TNF

Question 16

what 2 substances are toxic to parasites?

Answer 16

histamine, heparin

Question 17

what chemokine attracts monocytes/macrophages and neutrophils?

Answer 17

CCL3

Question 18

ow do mast cells (and basophils) amplify the IgE response?

Answer 18

release IL-4 and express CD-40L to stimulates additional IgE production by plasma cells

Question 19

which antibodies are bound by eosinophils?

Answer 19

IgA and IgG

Question 20

what stimulates the production of eosinophils?

Answer 20

IL-5

Question 21

what are the 3 levels of control for eosinophils?

Answer 21

1- small output from bone marrow, production increased only in response to IL-5 and TH2 cells
2- penetration of tissues by eosinophils requires specific cytokines
3- high affinity FceR1 not expressed until activated by cytokines/chemokines

Question 22

___ are responsible for immediate run vs. ____ for late-phase reaction

Answer 22

preformed (histamine, others)
newly synthesized (lipids, peptides, VEGF, cytokines)

Question 23

what 2 IL cause the transformation of epithelial cells to goblet cells?

Answer 23

IL-9 and IL-13

Question 24

acute airway response vs. chronic airway response when exposed to allergen

Answer 24

acute- increased mucus, bronchi-constriction

chronic- cytokines and eosinophils lead to airway remodeling

Question 25

“hallmark of asthma”

Answer 25

increased airway reactivity

Question 26

MOA of LT antagonists in asthma

Answer 26

relax smooth mm, reduce inflammation

Question 27

MOA of PDE inhibitors in asthma

Answer 27

relax smooth mm

Question 28

MOA of cromolyn

Answer 28

inhibit mast cell degranulation