Hypersensitivity -Thrush

Question 1

What are the phases of a Type I Hypersensitivity reaction?

Answer 1

Sensitization phase (first exposure): exposure to allergen (antigen) and production of IgE –> binding to mast cels and basophils (via Fc region of these cells )

Effector phase (second + exposure): IgE binds to the allergen. cross linking of IgE of surfaces of mast cells/basophils results in degranulation and release of chemical mediators of the allergic reaction

Question 2

What happens within the mast cell when IgE’s cross link? (5)

Answer 2

1. activation of protein tyrosine kinases
2. second messengers produced
3. Ca 2+ mobilization/influx stimulates the breakdown of arachidonic acids into prostaglandins and leukotrienes
4. microtubule assembly to move granules to the cell surface
5. cAMP levels rise then fall –> then get degranulation

Question 3

What two medications can alter cAMP levels in the cell to prevent allergic responses? How do these work?

Answer 3

epinephrine and theophylline keep cAMP levels high, preventing the release of chemical mediators

Question 4

What is an important early mediator of the allergic response? What does it do?

Answer 4

Histimine is preformed inside the cell and is always ready to release upon cross linking of IgE on the cell surface

Histimine increases vascular permeability and smooth muscle contraction

Question 5

What enzyme can be measured to determine whether a person has experienced an allergic response?

What are the limitations of this test?

Answer 5

beta-tryptase is produced by mast cells and its levels in the blood will increase (>1 ng/mL) after an allergic reaction

beta-tryptase has a short half-life so blood samples must be taken soon after the anaphylactic reaction

Question 6

What is referred to as the slow-reactive substance of anaphylaxis (SRS-A)? What is its function?

Answer 6

leukotrienes

leukotrienes function similar to histamine (increase vascular permeability and contraction of pulmonary smooth muscles) but are 1000x more potent than histamine

Question 7

What are the functions of platelet activating factor (2)?

Answer 7

platelet aggregation; contraction of pulmonary smooth muscles

Question 8

what are the functions of prostaglandin D2?

Answer 8

vasodilation; contraction of smooth muscles

Question 9

What are the 2 roles of cytokines in allergic reactions?

Answer 9

chemotactic and inflammation

Question 10

What are the potential symptoms of an allergy? (4)

Answer 10

due to the inflammatory response

1. wheal-and-flare reaction–>pruritus and erythema on the skin (site of exposure) due to degranulation of mast cells
2. bronchoconstriction
3. mucous secretion
4. vasodilation (shock)

Question 11

What happens if the allergen is introduced to the respiratory system?

What if the allergen is systemic?

Answer 11

smooth muscle contractions and mucous secretion

severe vasodilation and potentially shock can occur

Question 12

What are three treatments of allergies?

Answer 12

1. anti-histamines that block the binding of histamine to target cells
2. desensitization: stimulate the immune system to produce IgG instead of IgE
3. Anti-IgE therapy: add anti-IgE antibodies that will bind the CH3 domain of IgE and prevent its binding to Fc regions

Question 13

What are the prolonged effects of allergy-induced asthma?

Answer 13

chronic inflammation and changes in the basement membrane of the airways and increased mucous production

Question 14

How are allergies diagnosed?

Answer 14

1. skin test for atopic allergens (could cause severe reaction)
2. radioimmunoassays: detect specific IgE against a particular allergen. (need purified allergens)

Question 15

What is type II hypersensitivity?

Answer 15

Antibody mediated cytotoxicity.
Abs bind to cell surface, activate complement and ADCC and then the cell lyses

Normally occurs AFTER the first exposure

Question 16

What are the two most common Type II hypersensitivity reactions?

Answer 16

1. Transfusion reactions: if a person is given the wrong blood type, they will likely have anti-blood group antibodies which will clump together leading to C’ activation and cell lysis. (blood is cross-matched before giving a transfusion detect presence of Abs in donor and/or recipient sera)
2. erythroblastosis fetalis: An Rh- mother who gives birth to an Rh+ child can develop antibodies against Rh. If she has a second Rh+ child, the fetus could be destroyed by these antibodies.
   the mother should be given RhoGAM to prevent the formation of anti-Rh antibodies in her first pregnancy and first delivery.

Question 17

What is Type III hypersensitivity?

Answer 17

“immune complex disease”

a soluble antigen associates with its antibody, forming an immune complex. Normally the immune complexes are taken up by macrophages and destroyed but in some cases, (ex: lupus) the ICs are not effectively destroyed and will localize in the body, activating complement and inflammation and leading to the damage of bystander cells (mostly endothelial cells of the blood vessels of the kidneys and lungs)

Question 18

What is an example of a localized Type III reaction?

Answer 18

Where Ag is deposited, can get IC formation and local inflammation–> Arthus reaction
ex: insect bites or inhaling spores/dust causing respiratory inflammation

Question 19

1. What is serum sickness?

2. What is a common cause of serum sickness?

Answer 19

serum sickness is a type III hypersensitivity reaction where a foreign serum (antiserum) is injected into humans. upon second injection, there will be a large immune complex formation and will see rash, arthritis, edema, glomerulonephritis, etc.

A commonly seen example is in a snakebite victim who receives anti-snake venom produced in horses. If the horse anti-venom is given a second time, the anti-horse antibodies that were produced after the first exposure will form an immune complex with the horse anti-venom leading to inflammation and vasculitis

Question 20

Can a type III hypersensitivity occur after the first exposure to an antigen?

Answer 20

yes. because passively administered antibodies can stay in the blood for a while, the hosts immune system can get activated. If by the time the antibodies are produced, the original antigen is still in the system, immune complexes can form leading to a type III hypersensitivity

Question 21

What is type IV hypersensitivity?

Answer 21

Delayed type hypersensitivity
CD4+ T cell (Tdth) – cytokines stimulate inflammation (Th1 type cytokines)
influx of inflammatory cells (especially Mf)
initial symptoms seen after ~24 hours and peeks between 48-72 hours
not always detrimental…can be useful to fight certain infections
especially intracellular pathogens (e.g. TB)

Question 22

What type of hypersensitivity is a TB PPD test?

Answer 22

type IV hypersensitivity

indicates memory Tdth cells were activated during a previous exposure–> local inflammation

Question 23

What can be used to monitor the immune status of AIDS patients?

Answer 23

DTH

inject an antigen that a patient was known to have been previously exposed to under the skin and monitor the response

Question 24

What can induce a DTH response?

Answer 24

intracellular bacteria, intracellular fungi, intracellular parasites, viruses, and even contact antigens (poison ivy and poison oak)

Question 25

How do non-protein molecules stimulate a DTH response?

Answer 25

Bind to a protein in a hapten carrier reaction