Hypersensitivities

Question 1

Type I hypersensitivity

Answer 1

IgE causes release of mediators from mast cells leading to hypersensitivity.

Question 2

Type II hypersensitivity

Answer 2

Mediated by Abs that binds tissue Ags and cause complement-dependent tissue injury and disease.

Question 3

Type III hypersensitivity

Answer 3

Mediated by Abs that bind circulating Ags to form immune complexes that deposit in vessels and cause complement-dependent injury to vessel wall (vasculitis). Can have ischemic affects.

Question 4

Type IV hypersensitivity (AKA delayed type hypersensitivity)

Answer 4

Mediated by T cells and results from inflammation caused from cytokines produces by Th1 and Th17 cells OR killing of host cells by CD8+ cells.

Question 5

Atopy

Answer 5

Genetic tendency to develop allergic diseases.

Question 6

“Most important mediators of Type I hypersensitivity” (4)

Answer 6

Vasoactive amines (His)
Proteases
PGs
LKs

Question 7

Histamine causes:

Answer 7

Dilation of small BVs and increases vascular permeability.

Question 8

Proteases cause:

Answer 8

Damage to local tissues.

Question 9

Prostaglandins cause:

Answer 9

Vascular dilation.

Question 10

Leukotrienes cause:

Answer 10

Smooth muscle contraction.

Question 11

Cytokines cause:

Answer 11

Local inflammation (late phase reaction).

Question 12

Sequence of type I hypersensitivity (3)

Answer 12

1. Production of IgE after activation of Th2 cells by primary exposure to Ag.
2. Binding of IgE to Fc receptors of mast cells.
3. Release of mediators by mast cells after secondary exposure to Ag and cross-linking of membrane-bound IgE by Ags.

Question 13

Immediate reaction in type I hypersensitivity

Answer 13

Vascular and smooth muscle reaction to allergen that develops within minutes.

Question 14

Late phase reaction in type II hypersensitivity

Answer 14

Inflammation infiltrate with lots of eosinophils, neutrophils and T cells. Develops 2-24 hrs after.

Question 15

Allergen testing

Answer 15

Assess type I.
Inject allergens into ventral arm in dermis.
Positive reaction is redness and swelling within 20-30 min.

Question 16

Allergen-SIT

Answer 16

Performed by giving increasing doses of allergen to induce T cell tolerance, increase threshold for mast cells and basophil reaction and decrease IgE mediated His release.
Treg cells have an important role in successful allergen-SIT.

Question 17

Sequence of type II hypersensitivity

Answer 17

1. Ab-Ag deposits in tissues.
2. IgG and IgM activates classical pathway which recruits WBCs and causes inflammation.
3. IgG binds to neutrophils and Mo FcRs and activate a proinflammatory response.
4. ROS and lysosomal enzymes released cause damage to tissues.

Question 18

Which complement byproducts recruit leukocytes in an effector mechanism of type II?

Answer 18

C3a and C5a.

Question 19

Mechanism of Graves’ disease

Answer 19

Abs specific for cell receptors for hormones or NTs stimulate activity of TSH receptors EVEN in the absence of TSH causing hyperthyroidism (type II).

Question 20

Mechanism of Myasthenia Gravis

Answer 20

Abs specific for cell receptors for NTs inhibit binding of Ach to AchR (type II).

Question 21

Major mechanism of type II hypersensitivity

Answer 21

Classical pathway activation and recruitment of leukocytes.

Question 22

In all of type II disorders, injury is caused by:

Answer 22

Complement-mediated and Fc-receptor-mediated inflammation.

Question 23

Arthus reaction

Answer 23

Induced by subcutaneous administration of protein Ag to a previously immunized animal. It results in immune complexes at site of Ag injection and local vasculitis (type III).

Question 24

Autoimmune diseases mediated by type IV hypersensitivity (3)

Answer 24

MS
RA
Type I DM

Question 25

Crohn’s disease

Answer 25

Inflammatory disease w/ microbial component. Has an autoimmunity component and is likely caused by abherrant reactions to microflora.

Question 26

PPD is what? And causes what?

Answer 26

Protein Ag of tuberculosis.

Elicits a DTH reaction called “tuberculin reaction).

Question 27

Allergic contact dermatitis (ACD)

Answer 27

Caused by environmental exposure to external agents in contact with skin.
Type of type IV.
Most commonly from metals.
Can occur at any age.

Question 28

TB granulomas contain (3)

Answer 28

Activated Mo.
Multinucleated giant cells.
Lymphocytes (primarilty T cells).
In some, there may be a central area of necrosis.

Question 29

Formation of a granuloma

Answer 29

1. T cells home to the tissues.
2. Th1 cells and activated Mo lead to production of TGF.
3. IFN-y and TNF further stimulate Mo.
   4 Over the course of several days to weeks a mature granulama is formed.

Question 30

SLE overview

Answer 30

Type III.
Presents with rashes, arthritis, glomerulonephritis.
Auto-Abs are found (mostly anti-DNA Abs), creating immune complexes and cause the symptoms.

Question 31

RA overview

Answer 31

Type II/III
Inflammation of synovium and destruction of joint cartilage and bone.
Cells involved: Th1, Th17, activated B cells, plasma cells, Mo.
Pts often have circulating IgM/IgG that react with Fc of own IgG (auto-Abs).

Question 32

Principles of Immunotherapy (6)

Answer 32

Anti-inflammatory agents (steroids)
Depletion of cells and Abs 
Anti-cytokine therapy
Inhibit cell-cell interaction and leukocyte migration.
IV IgG
Treg cell-based therapies