Hypersensitivity

Question 1

Allergen

Answer 1

innocuous antigen that does not normally cause disease

Question 2

common sources of allergens

Answer 2

inhaled, injected, ingested, and contacted

Question 3

Type 1 hypersensitivity

Answer 3

immediate type hypersensitivity is mediated by igE and mast cells

Question 4

3 phases of type 1 hypersensitivity

Answer 4

sensitization, immediate response, and late phase response

Question 5

sensitization

Answer 5

APC presents antigen to MHC II–> MHC II presents to a naive CD4+ t cell–> this differntiates into th2 because of th2 bias–> th2 produces IL-4, IL-5, IL-13

Question 6

purpose IL-4 (and IL-13)

Answer 6

class switching igE

Question 7

purpose of IL-5 (IL-3)

Answer 7

eosinophil maturation/activation

Question 8

sensitization steps after th2 produces IL-4, IL-5, IL-13

Answer 8

th2 cells help B cells differentiate into IgE producing B cells–> IgE unload onto FcE receptors on mast cells–>mast cell becomes pre-armed

Question 9

atopy

Answer 9

exaggerated tendency to mount an IgE response to allergens; an atopic patient will have elevated serum IgE and eosinophils

Question 10

causes of atopy

Answer 10

genetic–> IgE binding and th2 bias increase atopic tendency; pollution; hygiene hypothesis

Question 11

second- immediate phase

Answer 11

crosslinking of IgE by the antigen which causes mast cell activation and degranulation within seconds (explosive degranulation of mast cells)

Question 12

primary mediators of immediate phase

Answer 12

histamines and proteases (like tryptase and chymase)

Question 13

effect of primary mediators (minutes)

Answer 13

vasodilation (permeability), smooth muscle spasm, and mucus secretion with tissue damage

Question 14

secondary mediator 1 = things cleaved from membrane phospholipids (eicosanoids) (15 min- hours)

Answer 14

leukotrienes, prostaglandins, and platelet activating factor (which is a chemotactic agent that brings in eosinophils, basophils, and neutrophils)

Question 15

effect of secondary mediators 1

Answer 15

vasodilation and permeability; smooth muscle spasm; chemotaxis of neutro, baso and eosinophil

Question 16

secondary mediators 2= cytokines (hours)

Answer 16

not preformed; have to be transcribed into mRNA and made into proteins and then secreted by the mast cells;
help prolonged activation
IL-4 and IL-5 help in maturation of eosinophils and MIP1 alpha and beta are involved in recruitment of macrophages

Question 17

Phase 3- late response

Answer 17

mediated by eosinophils that are circulating in the blood and must be recruited to the site of infection by factors of macrophages

Question 18

eosinophils are recruited by

Answer 18

eotaxin (lung epithelium, fibroblasts, smooth muscle) and leukotriene B4 (mast cells)

Question 19

eosinophils are activated by

Answer 19

IL-5

Question 20

eosinophils can ________ inflammation in ___________ of antigen

Answer 20

sustain; in the absence of …..whereas mast cells are only activated in the presence of antigen

Question 21

four sites of mast cells aka first line of defense

Answer 21

eye, nose; lung; gi; and skin—-skin and mucosal surfaces

Question 22

disease symptoms are determined by

Answer 22

the route of allergen entry and the site of activation of the tissue resident mast cells

Question 23

actute urticaria

Answer 23

route: skin or systemic; mast cell activation in upper dermis; and disease = increase vascular permeability, edema, and inflammation

Question 24

angioedema

Answer 24

route: mucosal surfaces or systemic; mast cell activation in the dermis, subcutaneous tissue and/or mucosa; disease = edema and inflammation …. this is what is dangerous in vocal cords or upper airways

Question 25

allergic asthma cause

Answer 25

elevateed IgE levels, eosinophil mast cell activation in the lung triggered by specific allergens

Question 26

anaphylaxis

Answer 26

route: systemic; anaphylactic shock = systemic vasodilation, BP drop, arrythemia, brady or tachycardia, cardiac arrest

Question 27

treatment of anaphylaxis

Answer 27

epinephrin for cardiovascular | b2 receptor agonist (salbutamol) for brochospasm

Question 28

type 2 hypersensitivity

Answer 28

antibodies mostly IgG bind either cells or ECM

Question 29

2 principle mechanisms that cause hypersensitivity type 2

Answer 29

binding to cells = phagocytosis or lysis and recruitment of neutrophils causing inflammation is if it binds to ECM

Question 30

mechanism behind type 2 hypersensitivity

Answer 30

RBC presents a non-self antigen that activates complement, which opsonized the RBC--> c3b receptor along with fcgamma receptor (antibody) on macrophage recognize the opsonized particle and phagocytose it this can cause anemia as well as low levels of circulating platelets

Question 31

type 2 hypersensitivity happens most commonly with

Answer 31

transfusion reactions and drug allergies

Question 32

2 other instances where type 2 hypersensitivity plays in:

Answer 32

eryhthroblastosis fetalis and drug allergies where some drugs alter the cell surface molecules that can then be targets for antibody responses

Question 33

explain mechanism of antibodies (IgG) having hypersensitivity type 2 to ECM

Answer 33

macrophages through Fcgamma receptor recognize antigen on the surface of a matrix and they bind to it, along with complement. c5a recruits neutrophils to the site. the neutrophils then release lysozymes and ROS

Question 34

best examples of type 2 hypersensitivity from ECM's

Answer 34

acute rheumatic fever (antibodies to the streptococcus pyogenes wall proteins that bind to cardiac glycoprotein) goodpasture syndrome- antibody to collagen of basement membrane in kidneys and lungs

Question 35

type 3 hypersensitivity reaction

Answer 35

immune complexes are formed between a soluble antigen and IgG antibody (the IC are then deposited on the wall of the blood vessel and cause inflammation- vasculitis)

Question 36

Phase 1 of hypersensitivity type 3

Answer 36

antigen--> recognized serum proteins by t cells--> stimulate b cells--> stimulate production of antibodies which are secreted (takes about a week)

Question 37

Phase 2 of hypersensitivity type 3

Answer 37

immune complexes form from the reaction of the antibodies and the serum proteins (which is what makes the serum proteins go down in the graph). IC deposition preferentially happens in kidney glomeruli, joints, skin, and serosal surfaces

Question 38

phase 3 of hypersensitivity type 3

Answer 38

IC deposited in blood vessel causes activation of complement activation, neutrophil recruitment, and neutrophil activation

Question 39

diseases of hypersensitivity type 3

Answer 39

serum sickness- systemic application of soluble proteins and depending on where IC deposits stick to determines clinical signs. this can look like type 1 but the difference is that it is delayed onset arthurs reaction- local immune complex activation (can happen with repeated exposure to a vaccine) arthurs is local as opposed to systemic hypersensitivity pneumonitis- farmer's lung- hay dust/ mold spores poststreproccocal glomerularnephritis; reactive arthritis (post infection) SLE (LUPUS) is the classic type 3 hs reaction

Question 40

type 4 hypersensitivity reactions

Answer 40

delayed hypersensitivity reaction mediated by t cells

Question 41

mechanism behind type 4 hypersensitivity reacion

Answer 41

antigen is taken up by APC, they present them to cd4+ t cells which differentiate into TH1 cells; th1 cells then secrete the th1 characteristic cytokines; cytokines and chemokines cause severe inflammation through recruitment and activation of macrophages along with lysozymes, radicals, and vasoactive mediators

Question 42

typical th1 cytokines

Answer 42

IFN gamma- activates macrophages, vascular adhesion molecules INF alpha- causes local tissue destruction chemokines (IL-8) recruits macrophages

Question 43

example of a DTH reaction

Answer 43

poison ivy or contact dermatitis from nickel

Question 44

2 ways that urushiol causes the poison ivy reaction we see

Answer 44

modification of extracellular proteins--> uptake by langerhans cells (DC) --> presentation via MHC class II --> activation of CD4+ Th1 cells uptake by epidermal cells and modification of intracellular proteins --> presentation via MHC class 1 --> activation of CD8+ T cells