Activation of Innate Flashcards
TNF
From: Macrophages, T cells, Mast cells targets | effects: endothelial cells | activation (inflammation, coag) Neutrophils | activation Hypothalamus | fever Liver | APP production Muscle | Fat catabolism and apoptosis in other cell types
IL-1
From: Macrophages, DCs, Endothelial, some epithelial, mast
Targets | effects:
Endothelial cells | activation (coag, inflammation)
Hypothalamus | fever
Liver | APP production
T cells | Th17 differentiation
Chemokines
From Macrophages, DCs, endothelial, T cells, fibroblasts, platelets
Targets | effects
leukocytes | increase integrity affinity - chemotaxis, activation
IL-12
From: DCs, Macrophages
Targets | Effects
NK cells and T cells | IFN-gamma production, increase cytotoxic ability
T cells | Th1 differentiation
IFN-gamma
From: NK cells, T lymphocytes
Targets | Effects
Macrophages | activation
Type 1 IFNs
From: DCs, Macrophages (alpha), fibroblasts (beta)
Targets | Effects
all cells | antiviral state, increase class I MHC expression
NK cells | activation
IL-10
From: Macrophages, DC, T cells
Targets | Effects
macrophages, DCs | inhibition of cytokine production and chemokine production, reduced expression of costimulators and class II MHC
IL-6
From Macrophages, endothelial, T cells
Targets | effects
Liver | APP production
B cells | proliferation of Ab producing cells
IL-15
From: Macrophages, others (???)
Target | Effects
NK, T cells | proliferation
IL-18
From Macrophages
Target | Effects
NK, T cells | IFN-gamma synthesis
TGF-beta
from many cell types
inhibits inflammation
T cells | differentation of TH17 regulatory T cells
Involved in contraction of immune response
TGF-Beta from many cell types
IL-10 from macrophages, DCs, Tregs
Effects of endogenous pyrogens (5 systems)
Liver - APP production
Bone-marrow endothelium - mobilize neutrophils
Hypothalamus - increase body temp
Fat, muscle - mobilize protein/fat to generate increase body temp
DCs - migration to lymph nodes and maturation to initiate adaptive immune response
stimulates DC migration to lymph nodes and maturation
TNF-alpha
cytokines induce the hypothalamus to produce heat because
bacterial/viral replication is decreased at higher temperature
+ Ag processing
+ adaptive immunity
human cells become more resistant to the negative effect of TNF
Hepatocytes produce what in response to IL-6
acute phase proteins
c-reactive protein, fibrinogen, mannose binding lectin
diagnostic marker of acute inflammation
levels of acute phase proteins in serum can be used to follow disease progression and treatment due to their characteristic of increasing rapidly due to infection, injury, inflammation, trauma
functions of complement
stimulates infection, facilitates antigen phagocytosis and can lyse some cells directly
primary opsonization complement fragment
C3b
anaphyalotoxins
C3a, C4a, C5a - increase vascular permeability to get stuff in and out of damaged/infected tissue by inducing smooth muscle contraction and degranulation of mast cells/ basophils
P and E selectin
expression on endothelium increased by IL-1 and TNF
binds rolling leukocytes for extravasation
neutrophil homing signal
LFA1-ICAM1, IL-8, IL-8L
Macrophage homing signal
VLA-4 - VCAM1, CCR2 - CCL2
processes of acute inflammatory response
vasodilation
increased vascular permeability
emigration of leukocytes from blood into damaged area
proteins of inflammatory exudate
clotting proteins
complement proteins
kinin cascade (vasodilation)
fibrinolytic (to degrade clot when wound has healed)
LAD
leukocyte adhesion deficiency
leukocytes cannot leave vasculature to migrate into tissue because defective beta2 chain of integrins (CD18)
defects in CD18 lead to low/no surface expression of CD11a, b, c
delayed separation of umbilical cord/omphalitis - recurrent bacterial infections of skin and mucosal, leukocytosis, periodontitis, impaired wound healing, absent pus formation
