Micro U2 L8. Flashcards
MHC class II genes - how can it cause allergy?
enhanced presentation of particular allergen-derived peptides
T-cell receptor alpha locus - how can it cause allergy?
enhanced T-cell recognition of certain allergen derived peptides
TIM gene family - how can it cause allergy?
regulation of the Th1/Th2 balance
IL-4 - how can it cause allergy?
(causes differentiation of Th2) - variation in expression
IL-4R - how can it cause allergy?
increased signaling in response to IL-4
High-affinity IgE receptor Beta chain - how can it cause allergy?
variation in consequences of IgE ligation by antigen
ALOX5 - how can it cause allergy?
variation in leukotriene production
Beta2Adrenergic receptor — how can it cause allergy?
increased bronchial hyper-reactivity
ADAM33 - how can it cause allergy?
variation in airway remodeling
What supports the hygiene hypothesis?
incidence of allergies has doubled over the past 10-15 years possibly due to better and increased hygiene
How do parasite-infested populations differ from parasite-free populations?
no parasites - immune system does not develop in the presence of parasites and parasite-specific IgE - lose balance of tolerance/resistance causing an increased tendency for the generation of inflammatory IgE-mediated immune responses against environmental shit
hypersensitivity reaction
occur after subsequent exposure to an antigen due to its interaction with previously formed antibodies or as a consequence of the activation of antigen-specific memory Tcells
Type I hypersensitivity
IgE binding to its FcR on mast cells leading to their activation - immediate due to pre-formed mediators (also have late phase involving cellular infiltration)
Type II hypersensitivity
IgG binding to FcR on phagocytes, NK cells, followed by complement activation or binding of IgG to a cell-surface receptor leading to altered signaling (antibody binds to proteins on human cells)
Type III hypersensitivity
formation of immune complexes which bind to FcR and fix complement
Type IV hypersensitivity
mediated by antigen-specific effector T cells (usually CD4 mediated that are presented by MHC class II) - 1-3 days after contact
Examples of Type I hypersensitivity
allergic rhinitis, asthma, systemic anaphylaxis
Examples of Type II hypersensitivity
drug allergies (esp penicillin), hemolytic anemia (destruction RBCs), thrombocytopenia (destruction of platelets), mismatched blood transfusions, autoimmune diseases including myasthenia gravis, Grave’s disease, Hashimoto’s thyroiditis, insulin-resistant diabetes
Examples of Type III hypersensitivity
serum sickness, vasculitis (if in blood vessels), nephritis (renal glomeruli), arthritis (joints)
Examples of Type IV hypersensitivity
contact dermatitis, chronic asthma, chronic allergic rhinitis, poison ivy, celiac disease (gluten)
What is important in the production of Type I hypersensitivity
IL-4 (Th2 environment favors the development of allergies)
What do mast cell granules contain?
enzymes like tryptase, toxic mediators like histamine, cytokines like TNF alpha, chemokine like CCL3, lipid activators like leukotrienes
tryptase
contribute to tissue remodeling
histamine
increases vascular permeability and cause smooth muscle contractions
TNF alpha
promotes inflammation and stimulates other cytokine production
CCL3
promotes influx of monocytes, macrophages, and neutrophils
leukotrienes
cause smooth muscle contraction and increases vascular permeability
Treatment of Type I hypersensitivity
- avoidance of allergen 2. use of drugs to reduce symptoms (anti-histamines, corticosteroids, epinephrine) 3. desensitization to allergen 4. targeting effector cells and mechanisms 5. allergen peptide vaccination
What cytokines are important for the initiation of type IV hypersensitivity
chemokines, IFN-gamma, TNF-alpha, IL-3, GM-CSF
Treatment for types II, III, IV hypersensitivities
- avoidance of allergen 2, reduction of the impact of immune response 3. reduce the immune response in general (steroids) 4. induce regulation of response - Treg 5. block the effector mechanisms
