Hypersensitivity

Question 1

Name the 4 types of HS

Answer 1

Anaphylaxis
Antibody-mediated cytotoxicity
Immune complex disease
Delayed Hypersensitivity

Question 2

What is atopy?

Answer 2

Tendency to develop allergies

Question 3

Low doses of antigen favors which pathway?

Answer 3

Th2

Question 4

Which cells are involved in T1HS?

Answer 4

Basophils and mast cells; eosinophils can also participate
IgE binds to Fc receptor on these cells

Subsequent exposure to Ag cross-links with IgE, releases granules

Question 5

What do the granules of basophils and mast cells do?

Answer 5

Vasoactive compounds

Edema
Smooth muscle contraction

Question 6

What happens after initial response of T1HS?

Answer 6

Late phase response
Brought about by prostaglandins, leukotrienes, chemokines, and cytokines of mast cells

2nd phase of smooth muscle contraction, sustained edema, recruitment of eosinophils and Th2 to site, possible remodeling (hypertrophy/hyperplasia)

Question 7

Late phase response of T1HS associated with what?

Answer 7

Chronic asthma, associated airway hyperreactivity

Question 8

What is in the granules of T1HS cells?

Answer 8

Histamine! - smooth muscle contraction, increased vascular permeability

Proteases - activate matrix metalloproteinases

TNF-alpha

Eosinophil chemotactic factor - attracts more eosinophils

Question 9

What are the main substances causing smooth muscle contraction/vascular permeability in the late phase response?

Answer 9

Leukotrienes C4, D4, and E4

(LTC, LTD, LTE)4

Most potent substances known that cause those effects

Question 10

Action of epinephrine

Answer 10

Increases cAMP
Tightens cell junctions
Relaxes bronchiole smooth muscles

ONLY treatment for reversing anaphylaxis

Question 11

Action of antihistamines, cromolyn sodium, and theophylline

Answer 11

Antihistamine - blocks histamine receptors, prevents histamine binding

Cromolyn sodium - blocks degranulation
Theophylline - blocks degranulation

Question 12

What are the types of T2HS?

Answer 12

Complement-mediated reactions
ADCC
Hemolytic disease of the newborn (Rh factor)
Non-cytotoxic reaction with cell receptors

Question 13

What are non-cytotoxic reactions with cell receptors?

Answer 13

One of the T2HS reaction mechanisms

Grave’s Disease - Ab to thyroid-stimulating hormone receptors cause overproduction of T3/T4, resulting in hyperthyroidism

Myasthenia Gravis - Ab bind to Ach receptor at neuromuscular junction, prevent transmission to muscles

Question 14

What is T3HS? Pathogenesis?

Answer 14

Immune Complex Disease

Caused by autoimmune diseases, drug reactions, infectious disease, ihnaled allergens

Complex lodges in kidney/skin
Activates Complement - C5a
Neutrophils accumulate
Lysosomal enzymes degrade tissue

Complex and Ag must be in the “goldilocks zone”

Question 15

Serum sickness?

Answer 15

T3HS

Form complexes with Ag from animal serum antivenom

Question 16

What normally happens to avoid T3HS?

Answer 16

RBC’s express CR1 protein, which binds C3b and C4b

Shuttled to liver and spleen, immune complexes removed from RBC by macrophages

But, in T3HS, system overwhelmed, causes problems in kidneys

Question 17

Contact Dermatitis?

Answer 17

Requires prior sensitization - memory response

Complex with skin proteins, expressed on MHC II

(Poison ivy lipid soluble - crosses membrane and expressed on MHC I)

Cytotoxic T cells then kill everything

Question 18

TB Skin Test - 3 steps in mechanism

Answer 18

Purified protein derivative injected - macrophages present to memory T cells

Endothelial cells upregulate VCAM-1 (vascular call adhesion molecule) to bind memory T helper cell-expressed VLA-4

T cells migrate to skin

Part 2:
Memory T cells secrete INF-gamma
- increases amount of MHC II on macrophages, becomes cycle

Part 3:
Lots of macrophages activated
Tissue damage, redness, hardness (fibrin deposition)

Remember - memory responses require smaller doses of Ag

Question 19

What happens when there is a TB infection?

Answer 19

Same thing as happens during TB skin test

Recruit lots of macrophages, which then form granuloma (compromises lung tissue)

AIDS patients don’t form granuloma - no CD4+ T cells! So, massive systemic infection results

Question 20

Which cytokine is released with T3HS?

Answer 20

C5a