Exam 3: Immediate Hypersensitivity; Allergies

Question 1

Type 1 hypersensitivity mediated by

Answer 1

IgE

Question 2

Type 2 hypersensitivity mediated by

Answer 2

IgG or IgM

Question 3

Type 3 hypersensitivity mediated by

Answer 3

Immune Complex

Question 4

Type 4 hypersensitivity mediated by

Answer 4

Cell (TH1 response)

Question 5

Manifestations of Type 1 include

Answer 5

systemic anaphylaxis, localized anaphylaxis (hay fever), asthma, hives, food allergies, eczema
ALLERGIC RXNS

Question 6

Manifestations of Type 2 include

Answer 6

blood transfusion reactions, ERYTHROBLASTOSIS FETALIS, autoimmune hemolytic anemia

Question 7

Manifestations of Type 3 include

Answer 7

SERUM SICKNESS

Question 8

Manifestations of Type 4 include

Answer 8

Graft rejection, dermatitis, tubercular lesions

Question 9

Describe mechanism of Type 1 Hypersensitivity (TH2 Response)

Answer 9

Allergen cross links IgE receptors
step by step
First exposure:
1. Antigen activation of TH2 cells- antigen binds membrane-bound IgE on B cell and is recognised by TH2 cell (CD4). Therefore, allergen activates T cell after allergen is taken up by B cell and broken into a peptide that is presenting via MHC Class II (CD4) T cell. TH2 releases IL-4 as a result.
2. IL-4 binds to IL-4R on B cell and induces B cell to class switch and release IgE antibodies in the plasma (free IgE antibodies circulate in plasma)
3. Free IgE antibodies bind to Fc receptor for IgE (high affinity) on Mast cells to produce a sensitized mast cell.
NOTHING HAPPENS UPON FIRST EXPOSURE
SECOND EXPOSURE: EFFECTS SEEN
1. Antigen cross links IgE/FcR
2. Allergen binding induces degranulation of mast cells –> induce allergic reaction (histamine/lipid mediators –> IMMEDIATE REACTION revolves around vascular/smooth muscle response, other inflammatory molecules such as cytokines –> LATE PHASE REACTION via inflammation)

Question 10

What is unique about an allergen?

Answer 10

Allergen uniquely instructs TH2 cells to produce IL-4.

Question 11

List common allergens

Answer 11

Plant pollens: Ragweed, Rye grass
Drugs: Penicillin, Sulfonamides
Foods: nuts, Seafood, eggs
Insect products: Dust mites (fecal matter containing Der p1, a protease), bee venom, wasp venom
Latex

Question 12

Evidence that the claim of TH2 cells being inflammatory is wrong

Answer 12

Type 1 Immediate Hypersensitivity;

TH2 Granuloma

Question 13

How is allergen cross-linkage of antibody different than phagocytic macrophage cross-linkage of antibody?

Answer 13

In phagocytic macrophage cross-linkage: IgG binds to antigen allows low affinity Fc receptors to bind Ag-Ab complex (normally Fc receptors on macrophage cannot bind free Ab)
In allergen cross-linkage:
Fc-epsilon receptors on Mast cells have higher affinity, thus can bind cytophilic antibody IgE.

Question 14

What concentration of IgE in plasma is needed for 50% of Fc epsilon receptor to be saturated?

Answer 14

1x10^-9 M
Most ppl have 1x10^-10 M IgE concentration, so mast cells aren’t sensitized. Those with allergies have IgE concentration close to 1x10^-9 M

Question 15

Signal Transduction Pathway Steps 1-3TYPE 1 HYPERSENSITIVITY

Answer 15

Upon cross-linkage binding of allergen to Ige/FcR complex….

1. Activation of phospholipase C–> production of diacylglycerol (DAG) and IP3
2. DAG and IP3 activate Protein Kinase C (PKC); PKC induces movement of granules to surface.
3. PhosphoMethyltransferases (PMT1 and PMT2) activation by taking phosphatidylserine (PS)(plasma membrane phospholipid) and converts PS to phosphatidylcholine (PC); PC is necessary to increase fluidity of membrane to allow degranulation to occur

Question 16

Steps 4-8 Type 1 Hypersensitivity

Answer 16

4. Degranulation out of membrane
5. Leukotriene secreted
   6.Cytokine secreted
   *7. Adenylate cyclase induces production of cAMP. cAMP necessary for degranulation. Peak in cAMP needed, but transient downregulation actually triggers degranulation.
6. Whole pathway happens within minutes.

Question 17

Type 1 hypersensitivity mediators

Answer 17

1. Histamine –> increased vascular permeability; smooth muscle contraction
2. Serotonin (rodents) –> Increased vascular permeability; smooth muscle contraction.
3. Leukotrienes (slow reactive substance of anaphylaxis) –> increased vascular permeability; contraction of pulmonary smooth muscles.
4. IL-4/IL-13 –> Increased IgE production

Question 18

Biological effects of Type 1 Immediate Hypersensitivity

Answer 18

1. Vascular leakage causing swelling
2. Bronchoconstriction making it hard to breath
3. Intestinal hypermotility causing diarrhea.

Question 19

Why do we have a TH2 response if the effects make us miserable?

Answer 19

We have TH2 response primarily for killing parasites and worms. Presence of eosinophils indicates parasitic or worm infection.

Question 20

Describe wheel and flare rxn.

Answer 20

Flare: Red vasodilation ring
Wheel: White circular inflammation from fluids in middle of red ring

Question 21

How are wheel and flare rxns used in clinical allergy diagnosis

Answer 21

Inject skin with various allergens. Loof for observations of wheel and flare rxn.