Mechanisms of Immune Injury (Hypersensitivity Reactions) Handout

Question 1

Type 1 Initiation

Answer 1

Production of IgE antibodies because CD4 cells of Th2 type favored over Th1….Th2 cells secrete IL-4 and turn on IgE producing B cells…IgE attaches to mast cells and basophils using Fc receptors to arm them

Question 2

Type 1 exposure second time

Answer 2

Binding and bridging of IgE antibodies causes release of primary and secondary meidators

Question 3

Type 1 primary mediators

Answer 3

Histamine (quick and short lived)

Question 4

Type 1 secondayr mediators

Answer 4

Leukotrienes (begins later and longer liver)

Question 5

What do type 1 mediators result in?

Answer 5

Cellular infiltration, vasodilation, increased permeability, and smooth muscle spasm

Question 6

Local reactions of Type 1

Answer 6

Allergic rhinitis
Uticaria
Angioedema
Asthma

Question 7

Systemic reaction of Type 1

Answer 7

Anaphylaxis…happens when gained access to vasculature…generalized itching to respiratory distress…can cause death

Question 8

Type 2 complement dependent

Answer 8

IgG or IgM attaches to cell surface and complement activated…MAC pokes holes…C3a and C5a recruit inflam cells…C3b opsonizes

Transfusion rxns, erythroblastosis fetalis, AI hemolytic anemai, Good pasture syndrome

Question 9

ADCC

Answer 9

Complement independent…effector cells posses Fc receptors that attach to target cells coated with IgG.

Tumor cell destruction and parasite destruction

Question 10

AB mediated cellular dysfunction

Answer 10

AB involved but no inflammation or destruction.
MG - antibodies block Ach receptors
Graves- AB stimulate TSHR

Question 11

Type 3 hypersensitivity

Answer 11

Immune complex related

SLE, glomerulonephritis, Serum sickness

Question 12

Immune complex tissue pathology determinants

Answer 12

Size - smaller are more phagocytic because they can survive
Mononuclear phagocytic system - dysfunction of these can reduce elimination
Valency/avidity of AB, affinity of antigen to tissue componendts, 3D strucutre of complex, hemodynamic factors

Question 13

Favored areas of immune complex formation

Answer 13

Filter barriers like glomerular basement membrane in kidney or synovial membranes in joints

Question 14

Tissue injury type 3 phase 1

Answer 14

Formation of Complex…about a week

Question 15

Tissue injury type 3 phase 2

Answer 15

Deposition of complex in tissues…facilitated by vascular permeability that comes about from cytokines being released after complex interacts with inflam cells

Question 16

Tiasue injury type 3 phase 3

Answer 16

Complement activation and inflam cell activation results in inflam reaction…coagulation cascade activation and platelet aggregation…about 10 days

Question 17

Local immune complex dz

Answer 17

Arthus rxn
Localized area of tissue necrosis from acute immune complex vasculitis
Typical reaction peaks 4-10 hours after injection…complexes formed at site of injection

Question 18

Type 4 rxns

Answer 18

DTH and T cell mediated cytotoxicity

Question 19

DTH

Answer 19

Must have been sensitized…reexposrue activates Th1 cells to secrete IL-12, TNFalpha, IL-2, IFNgamma…activated macrohpages attempt to remove agent…if they can’t granulomatous inflammation occurs

Examples in TB test, contact dermatitis

Question 20

DTH is important defense in

Answer 20

Intracellular pathogens like mycobacteriam fungi, and parasites

Question 21

T cell med cytotoxicity

Answer 21

CD8s kill antigen bearing target cells…primary allograft rejection mechanism
Granzyme induces apoptosis
Fas-fas ligand dependent killing can also cause apoptosis since FasL is on surface of CD8s