Lec 01: Hypersensitivity and Allergic History, Physical Examination and Diagnostics

Question 1

What is autoimmunity?

Answer 1

failure of normal mechanisms or self-tolerance resulting to reactions against one’s cell or tissues

Question 2

Approximately what percentage of the population is abnormally responsive to environmental antigens?

Answer 2

20%

Question 3

What are allergens?

Answer 3

antigens that elicit immediate hypersensitivity (ex. animal hair, dust mites, pollen)

Question 4

What type of antibody mediates type 1 hypersensitivity?

Answer 4

IgE

Question 5

(T/F) A type 1 reaction is always local in nature.

Answer 5

F (may occur as a systemic or local reaction)

Question 6

How long does it take for an allergen to trigger immediate hypersensitivity?

Answer 6

occurs within minutes after the combination of an antigen with antibody bound to mast cells in individuals previously sensitized to the antigen

Question 7

What is the sequence of events in immediate hypersensitivity?

Answer 7

1. On first exposure, TH2 cells are activated, stimulating B cells to produce IgE antibodies.
2. IgE binds to Fc receptors on mast cells
3. On subsequent exposure to an allergen, the allergen crosslinks to IgE receptors on mast cells.
4. Activated mast cells release the mediators (vasoactive amines and lipid mediators) leading to immediate hypersensitivity

Question 8

How long does it take for a late-phase reaction to occur?

Answer 8

2-24 hours after repeat exposure to allergen

Question 9

What are the biologic effects of biogenic amines and lipid mediators (trigger immediate reaction)?

Answer 9

vascular leak, bronchoconstriction, instestinal hypermobility

Question 10

What are the biologic effects of cytokines and lipid mediators (trigger late-phase reaction)?

Answer 10

inflammation

Question 11

What are the characteristics of an immediate reaction?

Answer 11

1. wheal and flare reactions (urticarial)
2. vasodilation, vascular leakage, and smooth muscle spasms or glandular secretions depending on the location
3. changes usually become evident 5-30 minutes after initial exposure and tend to subside in 60 minutes

Question 12

What are the characteristics of a late-phase reaction?

Answer 12

1. mainly inflammation and edema
2. occurs in allergic rhinitis and bronchial asthma
3. occurs 2-24 hours later without additional exposure to antigen and may last for several days
4. infiltration of tissues with basophils, eosinophils, neutrophils, monocytes, and CD4+ T cells as well as tissue destruction (usually mucosal epithelial damage)

Question 13

What are the diseases associated with immediate hypersensitivity?

Answer 13

1. anaphylaxis
2. allergic rhinitis
3. atopic dermatitis (early phase)
4. bronchial asthma
5. urticaria

Question 14

What are the advantages of in vivo skin tests?

Answer 14

1. high sensitivity
2. results available in minutes
3. greater selection of allergen
4. cheaper than in vitro tests
5. minimal equipment needed

Question 15

What are the advantages of in vitro tests?

Answer 15

1. no risk of anaphylaxis
2. medications do not affect results
3. not dependent on skin condition
4. convenient for patients afraid of needles
5. perceived by patients as more scientific

Question 16

What are the indications for an in vivo allergy skin test?

Answer 16

allergic sensitivity to specific allergens in patients with: asthma, rhinitis, eczema, urticaria

Question 17

What are the characteristics of in vivo testing of serum IgE?

Answer 17

1. identify persons with high likelihood of atopy
2. should not be used as a diagnostic or screening test on its own
3. measures total circulating IgE and not amount of IgE responsible for clinical symptoms
4. there are variations of IgE levels with age
5. there is a considerable overlap between normal and abnormal values

Question 18

What is the drug of choice for anaphylaxis?

Answer 18

Epinephrine IM
Adults: 0.5mg maximum
Children: 0.3 mg maximum

Question 19

What drugs are used in the management of type 1 hypersensitivity?

Answer 19

antihistamines - biogenic amines
bronchodilators (B2 agonist) - bronchoconstriction
steroids - inflammation

Question 20

What is the definitive management for type 1 hypersensitivity?

Answer 20

allergen avoidance

Question 21

What is the goal of immunotherapy or desensitization?

Answer 21

administration of increasing doses of the allergen to induce a shift from TH2 to TH1

Question 22

What are the characteristics of type II hypersensitivity?

Answer 22

1. produced by antibodies that react with antigens present on cell surfaces or in the extracellular matrix
2. antigenic determinants may be intrinsic to the cell membrane or an exogenous antigen
3. usually localized

Question 23

What are the three mechanisms of antibody-mediated diseases?

Answer 23

1. opsonization and phagocytosis
2. complement and Fc receptor-mediated inflammation
3. abnormal physiologic responses without cell/tissue injury

Question 24

What type of antibody is mostly present during opsonization and phagocytosis?

Answer 24

IgG and IgM

Question 25

Antibody-mediated glomerulonephritis is an example of which mechanism

Answer 25

complement and Fc receptor-mediated inflammation

Question 26

What are the possible self-antigens in autoimmune urticaria?

Answer 26

IgG, alpha subunit of high-affinity IgE, complex formed by anti-IgE

Question 27

What test is used to determine whether there is autoimmune urticaria?

Answer 27

plasma-serum skin test

Question 28

What are the characteristics of type III hypersensitivity?

Answer 28

1. antigen-antibody complexes produce tissue damage by eliciting inflammation at the sites of deposition 2. can be systemic or localized 3. immune complexes may contain either self-antigens or foreign antigens

Question 29

What are the 3 phases of normal antigen-antibody complex formation?

Answer 29

1. zone of antigen excess - patient is exposed to antigen 2. zone of equivalence - antigen-antibody complexes are formed 3. zone of antibody excess

Question 30

When do antigen-antibody complexes cause disease?

Answer 30

1. produced in excessive amounts 2. not efficiently cleared 3. deposited in tissues

Question 31

What is an Arthus reaction (Janeway lesion)?

Answer 31

It is a localized inflammatory response characterized by increased fluid and protein release, phagocytosis, and blood vessel occlusion. It is produced when a locally produced antigen-antibody complexes activate a complement cascade.

Question 32

Give examples of systemic immune complex diseases.

Answer 32

acute serum sickness, SLE, post-streptococcal glomerulonephritis, polyarteritis nodosa in chronic hepatitis

Question 33

What are the characteristics of type IV hypersensitivity?

Answer 33

T lymphocytes sensitized after previous contact with a specific antigen, are activated by reexposure to the antigen; tissue is damaged by direct toxic effects or through release of cytokines