Hypersensitivity

Question 1

▪ X-linked Hyper-IgM Syndrome

Answer 1

Defective isotype switching and
cell-mediated immunity
• Mutation in CD40 ligand (CD40L) (costimulatory)
• Highly susceptible to Pneumocystis jirovecii (intracellular fungus

Question 2

What is hypersensitivity

Answer 2

exaggerated or inappropriate immune response that causes tissue damage
• Includes chronic reactions, allergies and autoimmunity
-sensitized individuals
-Antigen is a protein or is capable of complexing with protein (hapten)

Question 3

Why does hypersensitivity occur

Answer 3

• An infection that can not be cleared (e.g.,
tuberculosis)
• A normally harmless exogenous substance (e.g., pollen)
• An auto-antigen (e.g., DNA in systemic lupus erythematosus)

Question 4

• Immediate hypersensitivity

Answer 4

– Anaphylactic
– Antibody-antigen complexes
– Manifests in minutes

Question 5

Delayed-type hypersensitivity

Answer 5

– May occur in days

Question 6

Type I Hypersensitivity (allergy)

Answer 6

-immediate
-mediated by IgE
-IgE binds to high-affinity Fc-e receptors on mast cells and
basophils
-Upon subsequent exposures, cross-linking of membrane- bound IgE induces release of mast cell granules
-localized (allergies ,asthma ,food allergies ,wheals ) or systemic (anaphylaxis)

Question 7

Mast Cell Degranulation-primary mediators

Answer 7

Made before and stored in
granules
– Histamine, proteases, eosinophil chemotactic factor, heparin

Question 8

Mast Cell Degranulation-secondary mediators

Answer 8

after immediate response)

– Platelet-activating factor, leukotrienes, prostaglandins, bradykinins, some cytokines and chemokines

Question 9

Atopy

Answer 9

genetic predisposition to produce IgE in response to many common, naturally occurring allergens

Question 10

Positive skin prick test

Answer 10

IgE reaction

Question 11

Desensitization: The blocking antibody theory

Answer 11

• Th2 to Th1
• IgG blocking antibodies
• IgE with no degranulation

Question 12

Type II Hypersensitivity

Answer 12

Involves IgG or IgM induced damage to cell surface or matrix antigen
Cytotoxic or non cytotoxic

Question 13

Cytotoxic process -type 2 hypersensitivity

Answer 13

• Classical Complement
Pathway
• Phagocytosis via FcR and complement receptor
• ADCC via NK cells or eosinophil

Question 14

Cytotoxic Examples-Transfusion Reactions

Answer 14

Antibody attaches to RBC and initiates the complement system to lyse RBC
After lysis:
○ Hemoglobin detected in plasma, starts to filter through
kidneys and found in urine (hemoglobinuria)
○ Hemoglobin converted to bilirubin – toxic at high levels

Question 15

Cytotoxic examples

-Hemolytic disease of newborn:

Answer 15

Erythroblastosis fetalis
Rh+ fetus, Rh- mother
IgG antibodies cross placenta

Question 16

RhoGAM shot

Answer 16

✓ Given to mother
✓ Anti-Rh antibodies bind to fetal cells that might have entered mother’s system during birthing process, facilitates clearing before there is a B cell response

Question 17

Type II Hypersensitivity (non-cytotoxic)- Graves’ disease

Answer 17

stimulating antibodies are directed against the receptor for thyroid-stimulating hormone (over reactive thyroid

Question 18

Type II Hypersensitivity (non-cytotoxic)-Myasthenia Gravis

Answer 18

blocking antibodies are directed against the acetylcholine receptor

Question 19

Type III Hypersensitivity

Answer 19

This is immune-complex mediated hypersensitivity
▪ Antibody combines with soluble antigen
▪ The resulting complex is usually phagocytoses

Question 20

Where can the type 3 immune complexes be deposited

Answer 20

• deposited in tissue near the site of antigen entry (localized Type III reaction)
• blood vessels /kidneys /joints - serum sickness

Question 21

What can we use monoclonal antibodies

Answer 21

-cancer treatment

Question 22

Type IV Hypersensitivity

Answer 22

• subsequent encounter with the antigen, sensitized Th cells secrete cytokines. This attract and activate macrophages
• The reaction peaks at 48-72 hrs after contact with the antigen (delayed-type hypersensitivity

Question 23

Prolonged DTH can lead to

Answer 23

• granuloma

- Tuberculosis test is done this way

Question 24

Rheumatoid arthritis can be found in which types

Answer 24

Type 3 and 4