IHL I - Cytokines/Chemokines of Innate Immunity Flashcards
adaptive immunity
highly specific defense
**failure of this system can result in autoimmune disease
innate immunity
protective barriers
cytotoxic molecules
phagocytic cells
cytokines
peptides
chemical signals responding to environmental signal
involved in immune response
general properties of cytokines?
rapid secretion
self-limited secretion
redundant
pleiotrophic
activate and influence eachother
receptor-specific activation
feedback inhibited
type I cytokine receptor
hemopoietin receptors (EPO and TPO)
jak-stat
type II cytokine receptors
Jak-stat
IL-1 family receptors
toll-like / IL-1 receptor
TNF receptors
may induce apoptosis
Seven transmembrane alpha-helical receptors
GPCRs
three categories of cytokines
mediators of innate immunity
mediators of adaptive immunity
mediators of hematopoiesis
TNF
tumor necrosis factor
acute inflammatory response to gram-negative bacteria
recruit neutrophils and monocytes
- induces expression of selectin and chemokines - stimulates mononuclear phagocytes to produce IL-1 - stimulates microbicidal action of neutrophils and macrophages
IL-1
secreted by mononuclear IL-1
induced by TNF
selectin
exposed on endothelial cells
E and P
L selectins - on leukocytes
diapedesis
aka extravasation
movement of leukocytes into the inflamed tissue
monocytes
excreted and circulate in blood stream
will mature to macrophages in the tissue
negative affect of TNF?
can cause systemic complications
-septic shock
if in large quantities in the blood stream
effect of TNF in hypothalamus?
stimulates endogenous pyrogen
induces fever
**stimulates prostaglandin synthesis - inhibited by aspirin
affect of TNF on liver?
acute-phase response
increased synthesis of serum proteins C-reactive protein which functions in opsonization
C-reaction protein
expressed in the hepatocytes
induced by TNF
result in opsonization
endotoxin shock
aka septic shock
TNF inhibits myocardial contractility and vascular smooth tone
-in high quantities
TNF also stimulates tissue factor and inhibits thrombomodulin
-increases coagulation (thrombosis)
results in low blood glucose
-inhibiting production in liver and overusing glucose in muscle
TNF pathway
produced by several cells
- mononuclear phagocytes - antigen-stimulated T cells - NK cells - mast cells
toll like receptors and TNF?
activated by LPS on gram negative bacteria
activation results in TNF secretion
**IFN-gamma also stimulates the release of TNF
TNF receptors
death like receptor
cytosolic domain - death domains
extracellular domain -
tumor necrosis factor alpha activity?
through NFkB
results in cytokine release
IL-1
mediates local inflammation
induces expression of integrin ligands
activated by Toll like receptors
synthesized by the inflammasome
can IL-1 induce septic shock?
nope
chemokines
important in migration of leukocytes
IL-12
interleukin 12
produced by activated dendritic cells and activated macrophages
increases the IFN-gamma synthesis
type I interferons
IFN alpha
IFN beta
response to viral infections
increase in antigen presentation on the cell
activated by viral nucleic acids - intracellular receptors
IFN-alpha
produced by immune cells
IFN-beta
produced by systemic cells
type I interferon activity
can mess with viral replication machinery
IL-10
inhibits the innate immune response
for macrophages and and dendritic cells
extracellular cytokines
TNF, IL-1, and chemokines
promote extravasation
responder: neutrophil
intracellular bacteria
IL-12 and INF-gamma
main responder is macrophages
viral innate reaction
type I IFNs and IL-12
inhibit viral replication
activate NK cells
symptoms of septic shock
hyperthermia tachycardia hypotension tachypnea acute hyperventilation mental status change
patient history of a new infection
basiliximab
prevents IL-2 binding
inhibit transplant rejection
IFN-gamma
used in TB diagnosis
TNF and IL-6
can be used to determine septic shock
IL-12
to boost immune response in cancer patient
IFN-beta
used to treat multiple sclerosis
IFN-alpha
used to treat chronic hepatitis and hematologic cancers
