lecture 2b Flashcards
most TLRs
monocytes
TLR 9, 10
B cell
TLR 3
epithelial cells (lungs)
TLR 11
murine kidney, bladder, liver
TLR 7, 9, 10
eosinophil
most TLRs except TLR 11
spleen
-filters blood, place for B/T cell maturation, lymphoid organ
toll-like receptor
pathogen recognizing receptor on immune cell that initiates innate immune response to pathogen assoc. molecular protein
TLR 3 disease pathogenesis
WNV triggers a TLR3 dependent inflammation response which can breakdown the blood-brain barrier
dsRNA
TLR 9 disease pathogenesis
chromatin antibody complexes in lupus serum is internalized by dendritic cell and delivered to TLR9 - causing inflammation
bacterial DNA cause inflammation in lower respiratory tract
TLR2/4/9 disease pathogenesis
excessive signaling can lead to HIV replication -> which can lead to septic shock
excessive TLR signaling
contributes to pathogenesis of inflammatory diseases (rheumatoid arthritis, septic shock etc)
cytokines/chemokines
soluble mediators of innate and adaptive immunity
mechanism that leukocytes (WBC) communicate with one another and w other cells
stimulate diverse responses of cells involved in immunity and inflammation
generation of leukocytes
source of cytokine/chemokine
produced mainly by leukocytes in response to antigens
cytokines
systemic action (large scale!)
ex: TNF a -> fever (kills microbes by increased temperature)
mediators and regulators of innate immunity (1), adaptive immunity (2), and stimulators of hematopoesis
chemokines
localized action (small scale!)
ex: IL8 (CXCL8) -> attract neutrophils
cytokines as mediators and regulators of innate immunity
produced mainly by mononuclear phagocytes and NK cells in response to infection
stimulates early inflammation reactions to microbes in order to promote microbe elimination
cytokines as mediators and regulators of adaptive immunity
produced mainly by T cells in response to antigens
regulate the growth and differentiation of various lymphocytes
involved in activation of T cell dependent immune responses
other T cell derived cytokines recruit, activate and regulate effector functions of macrophages, neutrophils and eosinophils
cytokines as stimulators of hematopoiesis
produced by bone marrow stromal cells and leukocytes
stimulate the growth and differentiation of leukocytes (hematopoiesis)
properties of cytokines (4)
- pleiotropism
- redundancy
- synergy
- antagonism
pleiotropism
property of cytokine
one cytokine having multiple effects on diverse cell types
redundancy
property of cytokine
multiple cytokines having same or overlapping actions
in absence of one the other can take over and function will still occur
synergy
property of cytokine
two or more cytokines having greater than additive effects
antagonism
property of cytokine
one cytokine inhibiting the action of another
immune degradation control inflammation - depending on amount available
resistance to phagocytosis (how microbes evade innate immunity)
capsular polysaccharide around microbe is slippery and inhibits phagocytosis
pneumococcus
resistance to reactive oxygen intermediates in phagocytes (how microbes evade innate immunity)
production of catalase by microbe breaks down the ROS intermediates
staphylococci
resistance to complement activation (alternative pathway) (how microbes evade innate immunity)
sialic acid expression inhibits C3 and C5 convertases (neisseria meningitides)
M protein blocks C3 from binding to organism, C3b (larger) binding to complement receptors - inhibiting binding inhibits degradation (streptococcus)
resistance to antimicrobial peptide antibiotics (how microbes evade innate immunity)
synthesis of modified LPS that resists the action of peptide antibiotics
pseudomonas
