lecture 5 exam 2 Flashcards
CD4+ T cell details
very diverse
differnetiate from Th0 (naive) to Th1, 2, 17, follicular helper and tregs by DCs and their cytokines
th subsets are distinguished by unique transcription factor and effector cytokine expression
activation bw macrophage/DC and pathogen signals differentiation
Th1 function
killing cytosolic/vesicular intracellular pathogens
IFNgamma (activates CD8+ to become CTL, activate macrophages in classical/M1 macrophages, antiviral activity), TNFalpha (induces apoptosis), IL2
t cell responses
ex: mycobacterium tuberculosis
Th2 function
killing extracellular parasites/allergies
IL4 (activates b cell class switch, M2 macrophages, mast cell), 5 (eosinophil recruitment and activation), 9, 13 (activation of M2) b cell responses
ex: roundworm parasite
Th17 function
killing extracellular bacterial/fungal infections
numerous at mucosal borders
potent inducer of inflammation (IL17)
dysregulation activity can lead to chronic inflammation or autoimmune dz
down regulates th1 and th2 responses
IL17 (recruits neutrophil), 21, 22
increased inflammation
Tfh function
activates B cells in lymphoid follicles
CXCL13 expressed in follicles signals tfh cells to localize to lymph node follicles (CXCR5)
IL6, 21
Treg
regulation of immune responses bw peripheral tolerance
express FoxP3 transcription factor
express CTLA4
suppress autoreactive lymphocytes, dampen antigen specific immune responses to pathogens, tumors, and parasites
absence of tregs = uncontrolled inflammation or autoimmune dz
IL10, 35, TGFbeta
decreased inflammation
Th polarizing cytokines
mixtures of these induces differentiation of Th subtypes that then induce specific transcription factors in each population
TSLP
thymic stromal lymphopoietin
cytokine secreted by innate immune cells and epithelial cells
IFNgamma & TNFalpha activates
macrophages & CTLs to kill intracellular bacteria
Th1
IL4 activates
B cells to produce IgE for mast cells
activates M2 macrophages
activates mast cells
Th2
IL21 helps
B cells make high affinity antibodies
DC uses this to drive differentiation of tfh
Tfh
IL17 attracts
neutrophils (bacteria/fungi)
Th17
IL10 and TGFbeta inhibits
immune responses (decreases inflammation)
treg
DC1 releases IL12 & IFNgamma
Th0 -> Th1
important in activation of macrophages against intracellular/intravesicular pathogens (viruses, some bacteria)
activate CD8+ (CTL) NK and macrophages
DC2 releases IL4
Th0 -> Th2
important for activating B cells to make antibodies against extracellular parasites
DC2 releases IL23 & IL6
Th0 -> Th17
important for activating neutrophils
TNFalpha
induces apoptosis in infected cell
released by Th1
IFNgamma
activates CD8+ to become CTL
activates macrophage (classical/M1 macrophage)
antiviral activity
released by Th1
IL5 function
eosinophil recruitment and activation
released by Th2 cell
IL13 function
activates M2 macrophage
relesaed by Th2 cell
CTLA4 function
inhibits effector T cell by direct contact
expressed by treg
Th1 response to leishmania
C57BL/6 resistant to dz
Th1 repsonse leads to activated macrophages and CTLs
intracellular stage KILLED
Th2 repsonse to leishmania
Balb/c susceptible to dz
th2 response leads to vigorous antibody response (igG or IgE) driven by Th2 cells
organisms SPREAD dz and dz becomes strengthened
reduced tregs contributes to insect bite allergy in horses
allergic rxn to salivary proteins
prevalence of insect bite hypersensitivity (IBH) to culicoides increases after importation of icelandic horses to britain
excoriations, alopecia, yperkeratosis