The Immune System Gone Wrong Flashcards
Two examples of when the immune system is doing its job but then matters get out of hand
- TB
- sepsis
TB causing a pathological condition
- macrophage infected with Mycobacterium tuberculosis
- no fusion with phagolysosome
- necrosis of lung tissue, leading to inflammation and hyperactivation of macrophages can lead to more tissue damage
life threatening effects of local defenses that go systemic
- sepsis
- invading organisms make it out into the bloodstream
- gram negs are worst offenders due to potent ‘danger’ signal that LPS represents
- TNF released from activated macs can cause blood vessels to leak = shock
Type I Hypersensitivity
- IgE-mediated
- allergy or atopy; tendency of some ppl to respond to certain antigens by producing IgE instead of IgG
hay fever vs. asthma
- both examples of allergies or atopy
- hay fever = typically triggered by environmental allergens
- asthma = typically triggered by household allergens
Two phases of atopy
immediate and delayed phase
immediate phase of atopy
- degranulation of mast cells can recruit basophil from the blood (immediate aspect)
- basophils can also bind IgE, get cross-linked and degranulate
delayed phase of atopy
- eosinophils can be recruited (delayed aspect) from bone marrow IL-5 secreted by Th cells in response to an allergic attack
- eosinophils contribute to chronic allergic diseases like asthma
T or F. People with atopy tend to have a bias for Th1 type T helper cells when they contact allergens for the first time
F! Th2 helper T cells
Explain the role of the placenta and fetal immunity in Th2 bias
- since a fetus is basically a ‘transplant’ due to non-maternal proteins contributed by the father, placenta has to suppress Th1 response (NK and CTLs to kill)
- placenta produces LARGE amounts of IL-4 to get Th0 to become Th2 instead
- microbial infections ealr on = helps switch to Th1 so can be a balance now
Genetics and Atopy
- allergy in one identical twin is found 50% of the time in the other twin
- certain MHC II genes are more commonly associated with allergy than others
- mutant IgE receptors that send stronger signals to mast cells?
- mutations that cause increased IL-4 production?
- activation of IL-4 producing immune cells by mutant thymic stromal lymphopoietin (TSLP) in inflamed lung epithelial cells are more common in asthma patients
Treatment therapies for atopy
- glucocorticoid steroids suppress cytokines produced by T cells that would activate B cells (not specific; generalized immunosuppression overtime?)
- Omalizumab (Ab therapy that binds IgE at its Fc region and prevents it from binding to mast cells); expensive!
- ‘specific immunotherapy’ involves immunizing with increasingly small doses of allergen to encourage an antibody switch from IgE to IgG (ex: iTregs and IL-10 production in beekeepers that are repeatedly stung + not allergic)
Type II Hypersensitivity
- erythroblastosis fetalis or hemolytic disease of the newborn
- treat with Rhogam or anti-Rh antibody
Type III Hypersensitivity
- localized
- not in tissues; blood!
- complement activation initiated by immune complexes produces complement intermediates that (1) mediate mast-cell degranulation -> chemotactically attract neutrophils -> stimulate release of lytic enzymes from neutrophils -> stimulate release of lytic enzymes from neutrophils trying to phagocytose C3b-coated immune complexes = leading to tissue damage
Genetic Autoimmune Diseases
- defects in Fas or FasL = undermine normal safety net of AICD for self-reactive lymphocytes
- autoimmune lymphoproliferative syndrome (ALPS, or Canale-Smith syndrome)
