17: Hypersensitivity

Question 1

Type I hypersensitivity: primary exposure to allergen: 5 Steps

Answer 1

1. Th2 cell activation (via IL-4)
2. B cell activation
3. IgE production
4. IgE binds FCER (CD23) on mast cells
5. Pt now sensitized to allergen

Question 2

Type I hypersensitivity: subsequent allergen exposures: 2 Steps

Answer 2

1. Ag cross-linking of IgE on mast cells -> mast cell activation
2. Mast cells release inflammatory mediators

Question 3

Atopy

Answer 3

Genetic tendency to develop allergic disease

Question 4

Five inflammatory mediators released by mast cells

Answer 4

Cytokines, histamine, proteases, prostaglandins, leukotrienes

Question 5

Immediate vs late phase reaction of type I hypersensitivity

Answer 5

Immediate: within minutes - vasodilation and edema

Late phase: 2-24hrs later - inflammatory infiltrate rich in eosiniohils, neutrophils, and T cells

Question 6

Three examples of type I hypersensitivities

Answer 6

1. Allergies
2. Asthma
3. Anaphylaxis

Question 7

Three major mediators of asthma

Answer 7

Mast cells, prostaglandins, leukotrienes

Question 8

Asthma vs anaphylaxis

Answer 8

Asthma: local reaction
Anaphylaxis: systemic

Question 9

Two cell types involved in anaphylaxis

Answer 9

Mast cells, basophils

Question 10

3 goals of allergen-SIT

Answer 10

1. Induce peripheral T cell tolerance by generating Tregs
2. Increase threshold for mast cell and basophil activation by allergens
3. Decrease IgE-mediated histamine release

Question 11

Type II hypersensitivity

Answer 11

Abs bind tissue Ags -> cause complement dependent tissue injury

Question 12

What cells release inflammatory mediators in type II hypersensitivity

Answer 12

Neutrophils and macrophages

Question 13

11 Examples of Type II Hypersensitivity

Answer 13

1. ABO blood transfusion reaction
2. Hemolytic disease of Newborn
3. Drug-induced hemolytic anemia
4. Autoimmune hemolytic anemia
5. Autoimmune thrombocytopenic purpura
6. Goodpastures syndrome
7. Graves’ disease
8. Myasthenia gravis
9. Pemphigus vulgaris
10. Pernicious anemia
11. Rheumatic fever

Question 14

How do we form Abs against blood group Ags that we dont have?

Answer 14

There are sugars that are identical (or v similar) to blood group Ags in foods or microbes, which we form reactions to to produce Abs

Question 15

Hemolytic disease of newborn

Answer 15

The Rh thing

Question 16

Three types of drug-induced hemolytic anemia and treatment used

Answer 16

1. Penicillin: no tx needed
2. Quinidine: immunosuppression/plasmapheresis
3. Methyldopa: same as quinidine

Question 17

What is targeted in autoimmune thrombocytopenic purpura?

Answer 17

Platelet membrane proteins

Question 18

What is targeted in goodpastures syndrome?

Answer 18

Proteins in kidney glomeruli and lung alveoli

Question 19

Grave’s disease

Answer 19

Ab-mediated stimulation of TSH receptors

Question 20

Myasthenia gravis

Answer 20

Ab inhibits Ach receptor, causing muscle weakness, paralysis, and ptosis

Question 21

Pemphigus vulgaris

Answer 21

Abs target intercellular epidermal junctions -> vesicles on skin

Question 22

Pernicious anemia

Answer 22

Ab neutralizes intrinsic factor -> decreased vitamin B12 absorption

Question 23

Rheumatic fever

Answer 23

Ab targets strep cell wall, which cross-reacts with myocardial Ags

Question 24

Type III hypersensitivity

Answer 24

Circulating/soluble ICs form -> deposit in vessels -> complement activation

Question 25

Five examples of type III hypersensitivity

Answer 25

1. SLE 2. Polyarteritis nodosa 3. Post-strep glomerulonephritis 4. Serum sickness 5. Arthus reaction

Question 26

SLE Ab specificity

Answer 26

Ab specific for DNA or nucleoproteins

Question 27

Polyarteritis nodosa

Answer 27

Ab specific for microbial agents -> vasculitis

Question 28

Post strep glomerulonephritis

Answer 28

Ab specific for strep cell wall Ag -> nephritis

Question 29

Serum sickness and arthus reaction specificity

Answer 29

Ab specific for various protein Ags

Question 30

Serum sickness vs arthus reaction

Answer 30

Serum sickness: systemic + clinical or experimental | Arthus: local + experimental

Question 31

Serum sickness

Answer 31

Antiserum injected into blood -> Fc receptors on endothelium bind antitoxin Ab that has reacted with toxoid -> complement activation

Question 32

Arthus reaction

Answer 32

SubQ administration of protein Ag to a previously immunized animal -> IC formation at injection site -> vasculitis and complement cascade

Question 33

When do type IV hypersensitivities develop?

Answer 33

24-48 hours after Ag exposure

Question 34

Four major cell players in type IV hypersensitivity

Answer 34

Th1, Th17, CTLs, macrophages

Question 35

Six examples of type IV hypersensitivity

Answer 35

1. MS 2. RA 3. DM I 4. IBD / Crohn’s 5. Chronic infection 6. Contact dermatitis / sensitivity

Question 36

MS

Answer 36

T cells target myelin proteins -> demyelination in CNS

Question 37

RA

Answer 37

T cells target Ags in joints

Question 38

DM I

Answer 38

T cells target pancreatic islet Ags

Question 39

Crohn’s and IBD

Answer 39

T cells target unknown Ag linked to intestinal microbes

Question 40

Chronic infection

Answer 40

T cells target microbial infection -> chronic inflammation

Question 41

Contact sensitivity / dermatitis

Answer 41

T cells target modified skin proteins

Question 42

Most common contact allergen

Answer 42

Metals

Question 43

PPD

Answer 43

Purified protein derivative: protein Ag of mycobacterium tuberculosis that elicits a DTH reaction called tuberculin reaction in previously infected individuals