Hypersensitvity

Question 1

What is hypersensitivity?

Answer 1

over-reaction of the immune system to harmless environmental antigens

Question 2

What are the four types of hypersensitivity (I-IV)? What determines the four types of hypersensitvity?

Answer 2

Immediate, antibody mediated (cytotoxic) hypersensivity, immune complex-mediated, delayed (cell-mediated) hypersensitivity

based on location of the target antigen and whether the immune response is based on antibodies or immune cells

Question 3

It is possible to compare the effector mechanisms of immune response to

Answer 3

humoral and cell-mediated immunity against foreign antigens

Question 4

Describe Type 1or immediate hypersenstivity.

Answer 4

allergies or atopic disoders

atopic individuals are 10-40% of population and have higher levels of IgE and eosinophils

Question 5

Clinical manifestations of Type I hypersensitivity are called _____. They depend on____ and ____?

Answer 5

anaphylatic reactions; route of entry of the antigen and location of responding cells

Question 6

What are some common sources of antigens?

Answer 6

inhaled (pollen, dander, mold), injected: insect venom, vaccines, drugs, therapeutic proteins; ingested (food, orally administered drugs); contacted material (plant leaves industrial products made from plants)

Question 7

What are the requirements for allergens?

Answer 7

low molecular weight, highly soluble and stable
contain peptides that can be presented MHC class 2
activated TH2 cytokine, esp. IL 4
stimulate IgE repsonse

Question 8

What do type I responses require? How does this occur?

Answer 8

Initial sensitization to allergen;

first exp to antigen
antigen activation of TH2 cells–> IgE class switchign
production of IgE
binding of IgE to FceRI on mast cells

Question 9

What are some of the other mechanisms to mast cell degranulation?

Answer 9

IgG cross-linking and C5a binding to complement receptors

Question 10

What causes mast cell degranulation?

Answer 10

Subsequent exposures to allergen leads to mast cell degranulation

Question 11

Describe the reaction

Answer 11

reaction has 2 stages: immediate, withinin minutes- wheal (swelling from leakage-histamine effect) and flare (engorged with RBCs)

late phase: more widespread swelling, inflammation

Question 12

What do mast cell granules contain?

Answer 12

enzymes like tryptase which contribute to tissue remodeling

toxic mediators like histamine. which increase vascular permeability and cause smooth muscle contractions

cytokines especially TNF alpha, promotes inflammation and stimulates other cytokine production

chemokines and lipid activators

Question 13

What is the role of CCL3?

Answer 13

a chemokine that promotes the influx of monocytes, macrophages, and neutrophils

Question 14

What are leukotrienes?

Answer 14

cause smooth muscle contraction, increase vascular permeability, and are involved in smooth muscle contraction

Question 15

Is there a genetic component to developing allergies?

Answer 15

yes, possibly genes involved include MHC and non-MHC (IL-4, IL-4 receptor, IgE receptor)

Question 16

What is the hygiene hypothesis?

Answer 16

Suggests that the incidence of allergies has doubled over the past 10-15 years, possibly due to better and increased hygiene which has resulted in less exposure to pathogens, skewing to TH2 rather than TH1

Question 17

What are the treatments of allergies?

Answer 17

avoidance of allergen, use of drugs that reduce the symptoms, desensitization to allergen, allergenic peptide vaccination

Question 18

Describe Type II: antibody mediated (cytotoxic) hypersensitivity.

Answer 18

reactions occur after antibody is bound to cellular proteins; antibodies are produced because cell proteins have been altered and antibodies initiate the inflammatory response in the tissue

Question 19

Give an example of Type II hypersensitivity?

Answer 19

hemolytic anemia where production of anti-RBC antibodies results in the destruction of RBCs involved, can be a result of a mishandled blood transfusion

Question 20

What are some possible autoimmune diseases that result from Type II sensitivity?

Answer 20

when antibodies target cell surface receptors: myasthenia gravis, Grave’s disease, Hashimoto’s throiditis (hypothyroidism), insulin resistant diabetes

Question 21

Describe Type III hypersensitivity, what is another name for it?

Answer 21

Immune complex mediated hypersensitivity; caused by the deposition of persistent immune complexes of IgG and soluble antigens that are complement fixing, initiates tissue damaging inflammatory responses

Question 22

name the qualities of the immune complex that determine their pathogenicity

Answer 22

size, isotype, valency, charge, and ability to fix the complement

Question 23

In immune complex mediated hypersentivity, what determines the clinical manifestation?

Answer 23

site of deposition

Question 24

What are some sites of deposition for ICs?

Answer 24

Intravenous: vasculitis in blood vessels, nephritis in kidneys, and arthithritis in joints

subcutaneous: arthus reaction in perivascular area
inhaled: farmer’s lung in alveolar/capillary interface

Question 25

What are some examples of IC mediated hypersensitivity reactions?

Answer 25

arthus reaction, serum sickness, post-streptococcal glomerulonephritis

Question 26

What is arthus reaction?

Answer 26

localized injected antigen binds to IgG, activates complement, results in localized inflammatory response with increased fluid, protein and cells

Question 27

What is serum sickness?

Answer 27

response occurs after development of antibodies to a large amount of foreign protein such as anti-venom, mouse monoclonal antibody therapeutics, and streptokinase

Question 28

What is post-streptococcal glomerulonephritis?

Answer 28

occurs several weeks after group A beta-hemolytic streptococcal infection

Question 29

Describe Type IV hypersensitivity. What’s another name for it?

Answer 29

Delayed (cell-mediated) hypersensitivity; reactions are mediated by antigen specific effector TH1 cells, initiate inflammatory reactions via the production of cytokines (chemokines, IFN-gamma, TNF-alpha, IL-3, GM-CSF) in response to anigen

Question 30

When does Type IV hypersensitivity usually occur?

Answer 30

1-3 days after contact with antigen

Question 31

Gives 3 examples of delayed hypersensitivity

Answer 31

delayed-type hypersensitivity: TB reaction localized swelling, erythema, and cellular infiltrate, in response to tuberculin at site of injection

contact hypersensitivity: poison ivy, includes localized epidermal reaction with erythrema, cellular infiltrate, vesicles, and intraepidermal abscesses

celiac disease: gluten allergy, manifests as villous atrophy in the small bowel due to T cell responses to gliadin

Question 32

What are the treatments for Types II, III, IV hypersensitivities

Answer 32

avoidance of antigen

reduction of the imoact of the immune response to antigen with SAIDs and NSAIDs

reduction of the immune response in general or specifically

induction of regulation of the response- Regulatory T cells

blocking the effector mechanisms of allergic response- cytokines, costimulatory molecules

Question 33

How would you reduce the immune response in general? specifically?

Answer 33

steroids, cytoxan; targeting pathogenic B and T cells

Question 34

Type I is mediated by

Answer 34

IgE

Question 35

Type II is mediated by

Answer 35

IgG: either cell or matrix associated, or cell surface receptor

Question 36

Type III is mediated by

Answer 36

IgG

Question 37

Type IV is mediated by

Answer 37

TH1 cells, TH2 cells, CTL