Hypersensitivity -Thrush Flashcards
What are the phases of a Type I Hypersensitivity reaction?
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
What happens within the mast cell when IgE’s cross link? (5)
- activation of protein tyrosine kinases
- second messengers produced
- Ca 2+ mobilization/influx stimulates the breakdown of arachidonic acids into prostaglandins and leukotrienes
- microtubule assembly to move granules to the cell surface
- cAMP levels rise then fall –> then get degranulation
What two medications can alter cAMP levels in the cell to prevent allergic responses? How do these work?
epinephrine and theophylline keep cAMP levels high, preventing the release of chemical mediators
What is an important early mediator of the allergic response? What does it do?
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
What enzyme can be measured to determine whether a person has experienced an allergic response?
What are the limitations of this test?
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
What is referred to as the slow-reactive substance of anaphylaxis (SRS-A)? What is its function?
leukotrienes
leukotrienes function similar to histamine (increase vascular permeability and contraction of pulmonary smooth muscles) but are 1000x more potent than histamine
What are the functions of platelet activating factor (2)?
platelet aggregation; contraction of pulmonary smooth muscles
what are the functions of prostaglandin D2?
vasodilation; contraction of smooth muscles
What are the 2 roles of cytokines in allergic reactions?
chemotactic and inflammation
What are the potential symptoms of an allergy? (4)
due to the inflammatory response
- wheal-and-flare reaction–>pruritus and erythema on the skin (site of exposure) due to degranulation of mast cells
- bronchoconstriction
- mucous secretion
- vasodilation (shock)
What happens if the allergen is introduced to the respiratory system?
What if the allergen is systemic?
smooth muscle contractions and mucous secretion
severe vasodilation and potentially shock can occur
What are three treatments of allergies?
- anti-histamines that block the binding of histamine to target cells
- desensitization: stimulate the immune system to produce IgG instead of IgE
- Anti-IgE therapy: add anti-IgE antibodies that will bind the CH3 domain of IgE and prevent its binding to Fc regions
What are the prolonged effects of allergy-induced asthma?
chronic inflammation and changes in the basement membrane of the airways and increased mucous production
How are allergies diagnosed?
- skin test for atopic allergens (could cause severe reaction)
- radioimmunoassays: detect specific IgE against a particular allergen. (need purified allergens)
What is type II hypersensitivity?
Antibody mediated cytotoxicity.
Abs bind to cell surface, activate complement and ADCC and then the cell lyses
Normally occurs AFTER the first exposure
What are the two most common Type II hypersensitivity reactions?
- 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)
- 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.
What is Type III hypersensitivity?
“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)
What is an example of a localized Type III reaction?
Where Ag is deposited, can get IC formation and local inflammation–> Arthus reaction
ex: insect bites or inhaling spores/dust causing respiratory inflammation
- What is serum sickness?
2. What is a common cause of serum sickness?
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
Can a type III hypersensitivity occur after the first exposure to an antigen?
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
What is type IV hypersensitivity?
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)
What type of hypersensitivity is a TB PPD test?
type IV hypersensitivity
indicates memory Tdth cells were activated during a previous exposure–> local inflammation
What can be used to monitor the immune status of AIDS patients?
DTH
inject an antigen that a patient was known to have been previously exposed to under the skin and monitor the response
What can induce a DTH response?
intracellular bacteria, intracellular fungi, intracellular parasites, viruses, and even contact antigens (poison ivy and poison oak)
How do non-protein molecules stimulate a DTH response?
Bind to a protein in a hapten carrier reaction
