Hypersensitivity

Question 1

describe type 1 hypersensitivity

Answer 1

allergic reactions. IgE is created in response to a innocuous antigen. they attach to Fc receptors on mast cells and are ready to react with a subsequent exposure.

mast cells produce degranulation (histamine), eosinophil, neutrophil, lymphocyte, and macrophage recruitment, smooth muscle contraction, and increased vascular permeability.

reactions only occur after prior sensitization but occur immediately after secondary exposure.

Question 2

what are the 4 ways you can come into contact with an allergen?

Answer 2

1. injestion
2. inhalation
3. contact
4. injection

Question 3

what are some systemic symptoms seen with type 1 hypersensitivity

Answer 3

skin: pruritis (itching), edema (swelling), urticaria (hives)
pulmonary: bronchospasms, mucosal edema w/ airway obstruction, laryngeal edema
CV: hypotension, arrhythmias,
GI: cramps, vomiting, diarrhea

Question 4

what are the Fc receptors on mast cells that bind IgE

Answer 4

Fc3RI

Question 5

what is the difference between mast cells and basophils

Answer 5

both respond to IgE, but mast cells are found in the connective tissue and mucosa near blood vessels whereas basophils circulate

Question 6

how are mast cells activated?

Answer 6

cross-linking of bound IgE

Question 7

describe the effects of histamine

Answer 7

H1 receptor: contracts smooth muscle, increases vascular permeability, increases mucous secretion

H2 receptor: increases gastric secretion, decreases mediator release by basophils/mast cells

Question 8

describe the effects of prostaglandin D

Answer 8

vasodilation and edema, bronchoconstriction, muscus secretion, itching

Question 9

describe the effects of SRS-A (LTC, LTD, LTE)

Answer 9

derived from arachidonic acid, bronchoconstrictors, increased dilation and permeability of microvessls, edema, coronary and cerebral vasoconstriction, increased mucous, decreased contractility, and increased gastric acidity

Question 10

describe the effects of leukotriene B

Answer 10

neutrophil, macrophage, and eosinphil attractant, edema (increased permeability)

Question 11

describe the effects of platelet activating factor

Answer 11

vasodialator, bronchoconstrictor, increased permeability, chemotaxis and degranulation

Question 12

describe the effects of proteases

Answer 12

activate kinins, complement, and endothelial cells which increase permeability, decrease BP, vasoconstriction

Question 13

what are anaphhylatoxins

Answer 13

C3a, 4a, 5a- chemoattractants of the complement system that also cause vasoconstriction

Question 14

what mediators can cause tissue destruction?

Answer 14

toxic oxygen radicals (from phagocytes) and acid hydrolases and neutral proteases (mast cell granules)

Question 15

/what are some non-immunological mechanisms that can lead to anaphylaxis?

Answer 15

NSAIDs
cold
exercise

Question 16

how can drugs be used to treat type 1 rxns

Answer 16

inhibit mediator action:
histamine antagonists: sneezing, runny nose, itchy eyes
leukotriene antagonists: asthma, anaphylaxis
steroids
epinephrine- low bp, brochospasm

inhibit mediator production
glucocorticoids
IgE antibodies
leukotriene synthesis inhibitors

Question 17

subcutaneous immunotherapy

Answer 17

hyposensitization- slowly increasing the dose of subQ allergen injection. allergen specific t-regs are activated, increasing levels of IgG and IgA for allergen removal, which does not use mediators like the IgE.

Question 18

describe type 2 hypersensitivity reactions

Answer 18

IgG or IgM bind to host cells, causing destruction via complement or cytolytic cells

Question 19

how are ABO blood types different?

Answer 19

a different terminal sugar residue on the backbone of a glycoprotein

Question 20

describe the following type 2 conditions:
transfusion reaction
hemolytic disease of the newborn
autoimmune blood dyscrasias
hyperacute graft rejection
transfusion related acute lung injury

Answer 20

transfusion reaction: recipient reacts against foriegn donor blood sugars

hemolytic diease of the newborn- newborn has RhD+ and mom is -. during first birth mom is exposed to D+, placing second child at risk if they are also D+

dyscrasias- autoantibodies recognize ones own blood cells

graft- hyperacute rejection occurs when a recipient is already sensitized to antigens found in the donor. this only occurs in grafts that are revascularized directly during transplantation (kidney)

TRALI- abs in donated plasma induce serious rxns

Question 21

what are the treatment options for type 2 rxns?

Answer 21

transfusion
plasma exchange
glucocorticoids
cytotoxic drugs/anti-b cell drugs
splenectomy
IVIG
drugs to stimulate RBC/platelet production

Question 22

what is type 3 hypersensitivity?

Answer 22

the destructive inflammatory lesions that result from tissue deposition of complexes w/ antigen, ab, and complement

Question 23

serum sickness

Answer 23

animal serum was injected into humans and caused a type 3 rxn. human abs specific to animal abs form and result in the deposition of ab complexes in the tissue, causing damage by the mediator release and inflammation.

symptoms clear in acute cases (ie serum sickness) but chronic cases occur when the offensive ag is persistent (ie autoags, viruses).

Question 24

type 3 diseases are often identified by the site at which they occur: lymphadenitis, necrotising vasculitis, periarteritis nodosa, and arthritis

Answer 24

ok

Question 25

how do soluble complexes form?

Answer 25

they form when there is a moderate excess of ag (3ag/2ab). the size of the complex is an important determinant of its potential to do damage. some are the optimal size to escape phagocytosis but get stuck in blood vessels or between epithelia

Question 26

what happens to an immune complex when it is recognized?

Answer 26

IgG crosslinks with Fc receptors on neutrophils to produce leukotriene B4 and IL8, activating macrophages neutrophils and mast cells to produce leukotrienes C D and E. combined, these mediators cause increased vascular permeablity, which facilitates the movement of immune complexes to the basement membrane. simultaneously, complement is also activated by IgG and C3a and 5a act as chemoattractants for neutro and eosinophils

Question 27

arthus rxn

Answer 27

Ab is in gross excess and injected intradermally. forms a complex that precipitates within venules w/in 3-8 hours

Question 28

how are complexes cleared?

Answer 28

1. macrophages- via Fc receptors and C3b 2. erythrocytes- contain C3b receptors- bind to and carry complexes to the liver, where kupffer cells remove them 3. complement- alternate complement pathway facilitates destruction 4. neutrophils 5. any other cells with Fc or C3 receptors

Question 29

what factors are important in determining the behavior of the complex?

Answer 29

1. ab isotype 2. ag 3. complex size 4. ab/ag ratio 5. ability to fix complement 6. concentration of complex

Question 30

what assays can be used to detect immune complexes?

Answer 30

1. C1q- C1q binds the complex and then can be detected w/ a labeled ab 2. CH50- measure serum complement levels. activated complement will decrease the amount of soluble complement in the serum 3. immunohistology

Question 31

what are the treatment options for type 3 hypersensitivity

Answer 31

1. withdraw culprit ag 2. symptomatic- antihistamines, NSAIDS 3. glucocortidoids- for more severe cases

Question 32

what is type 4 hypersensitivity

Answer 32

delayed type hypersensitivity- t-cell mediated results from the reintroduction of an antigen that activates t-cell immunity. the DTH response results from the inflammatory mediators from th1 and th17 t cells or CTLs. major causes= autoimmunity (usually limited to one tissue; not systemic) and persistent responses to environmental antigens

Question 33

tuberculosis causes type 4 sensitivity and it is the basis of the PPD test

Answer 33

ok

Question 34

compare the onset, duration, ab class, ab quantity, primary mediators, key cells, and transfer mechanisms of type 1, 2/3, and 4 hypersensitivities

Answer 34

type 1- immediate onset, 1 hr duration, IgE ab, .01 ug quantity, mast cells factor mediators, mast cells, and can be transfered with serum or cells type 2- 2 hr delayed onset, 24 hr duration, IgD or IgM ab, 100 ug quantity, PMN mediators, transfered with serum or cells type 4- 15 hr onset, 5 day duration, no abs involved, t-cell mediated, only transfered with cells

Question 35

describe the 4 subtypes of type 4 sensitivity

Answer 35

4a- th1 mediated, IFN-y and TNF-a driven, macrophage effectors 4b- th2 mediated, IL-4, 5, 13 driven, eosinophilic inflammation 4c- CTL mediated, perforin/ granzyme/ FasL driven, CD8 killing 4d- T cell mediated, CXCL-8/GMCSF driven, t cells recruit PMNs

Question 36

tuberculin type hypersensitivity

Answer 36

the mantoux rxn is DTH rxn to tuberculin. after 12-24 hours, erythema and induration develop at the site on inoculation in pts previously exposed via TB infection or BCG vaccination

Question 37

contact hypersensitivity

Answer 37

small molecules (haptens) interact with self proteins and are taken up by DCs, stimulating t-cells. upon reintroduction of the antigen (posion ivy, certain metals) a t-cell mediated response occurs response is primarily driven by CD4, although CD8 does contribute

Question 38

granulomatous hypersensitivity

Answer 38

d/t persistent antigen presence, often because they are difficult to remove