Innate immunity: Inflammatory Cytokines Flashcards
What are cytokines
Small = ~25kD
Heterogeneous glycoproteins= made up by diff components
Are cytokines soluble
Mostly soluble
Some have membrane bound forms
Describe cytokine production
Tightly regulated = post transcriptional and translational mods - polish cytokines before secreted
What do cytokines provide
Cellular communication
What do cytokines effect behaviour of
The producing cell = autocrine
Adjacent cells= paracrine, directional release
Distant cells = endocrine mechanism
Describe autocrine mechanism of cytokines
Cytokines secreted bind receptor on cell that produced it
Describe paracrine mechanism of cytokines
On nearby cell
Describe endocrine mechanism of cytokines
Goes into circulation
Binds receptors on distant cell
Why are cytokines produced
Due to inducing stimulus = triggered
What can cytokines have
Numerous biological functions
= activation, proliferation (produce multiple copies of each cell), differentiation (naive—>mature), survival or death of target cells
Describe ex of cytokine functions = adhesion molecules
Change expression of adhesion meolcuels on chemokine receptors on target membranes
Can lead to migration
Describe ex of cytokine functions = enzymes
Increase or decrease activity of particular enzymes = change transcriptional program (modulate its effector functions) = type 1 interferon
Describe ex of cytokine functions = activation
Active and differentiation of b and T cells
Describe ex of cytokine functions = cascade induction
Action of one cytokine on one target cell induces that cell to produce one or more additional cytokines
How many groups of cytokines
5 major groups
Name and describe all cytokines groups
Interleukins = il, 1-37
Interferons = ifn, alpha beta (type 1) and gamma (type 2)
Tumour necrosis factor = tnf, alpha and beta
Hematopeoitins or growth factors = gm-car, g-csf
Chemokines = for migration
Cytokines in bone marrow = make more of these cells
What is pleiotropism
One cytokine may be produced by many diff cell types and have effects on many diff cell types
One cytokine produces multiple effects
What is redundancy
Diff cytokines - more than one induces same effect
What is synergy
2 or more cytokines work together to induce an effect
What is antagonism
One cytokine can Inactivate effect of another
= inhibit effect of other
Describe complex network of cytokines
Same cytokine produced by multiple cells
Each cell type can produce multiple cytokines
Network of complex interactions
Specific cytokines are produced at diff times in diff locations
*once dendritic cells goes to lymph node = will produce diff cytokines than when at site of infection
What can cytokines do - response
Imprint adaptive response
Descrie cytokine profiles
Fate specifying cytokines for T cells
Cytokine secreted by dendritic cell = determines type of T cell it will differentiate into = all have diff roles
Cytokine secreted depends on subset T cel
Diff cytokines can induce differentiation of diff cell types
Diff cell types then produce diff cytokines too
What do cytokines impact
Impact differentiation of T cells (signal 3, fate specifying cytokines affect)
Then differentiated T cells produce diff cytokines
What does cytokine environment do
Imprints adaptive immune responses
Is only humoral or cell mediated responses activated by cytokines
NORMALLY= mix of both
But one response can dominate
Cytokines can determine type = which will dominate
What is cell mediated immunity mostly directed to
Viral infections
Intracellular pathogens
Some Extracellular pathogens
What is cell mediated immunity characterized by
T helper cells —> innate immunity cell activation
Cytotoxic T lymphocyte (ctl) activation
What is humoral immunity mostly directed to
Extracellular bacteria/pathogens
What is hum oral immunity characterized by
B cell activation
Antibody production
What is a cytokine involved in inflammation
TNF-alpha= pro inflammatory cytokine
What is tnf-alpha secreted by
Macrophages
Also other cells too
Describe what tnf-alpha stimulates
Migration of innate cells
Dilates blood vessels (vasodilation), increases clotting (prevents pathogen from entering blood stream)
What if tnf-alpha involved in
Many autoimmune diseases =
Therapies targeting tnf-alpha or recpetor for it used to treate rheumatoid arthritis and Crohn’s disease
Describe local vs systemic effects
Local infection usually
But if systemic = bad, lose fluid and blood and multiple organ failure, collapse of vessels
With certain pathogens = if enters blood stream or if multiple organs infected
Local tnf-alpha —> local inflammation
Systemic tnf-alpha —>systemic effects
What is sepsis
Systemic infection and inflammation
What is acute phase response
Change in proteins present in the blood that occurs during early phases of infection
What is actuate phase response induced by
Pro ifnlammtory cytokines = Il 1, beta, tnf-alpha, Il-6
What does acute phase response involve
Increased synthesis/secretion of antimicrobial proteins form liver = acute phase proteins
Help innate immune response
Name and describe some acute phase proteins
Mannose binding lectins
Complement proteins (main help for innate)
C reactive protein = can opsonize bacteria and trigger classical complement Cascade by binding to c1q
Describe liver acute phase proteins
Activate other processes that help eliminate pathogens
Name key pro inflammatory cytokines
Il-1beta, Il-6, tnf-alpha
What are the effects of inflammatory cytokines
Acute phase response
Mobilizing cells
Fever
Contributes to response against pathogen
What is fever caused by
Il-1beta, Il-6, tnf-alpha = which signal to induce a cascade that leads to a signal to hypothalamus = increase body temp
Describe effects of inflammatory cytokines on liver
Acute phase proteins = c reactive, Mbl = activation of complement and opsonziation.
Describe effects of inflammatory cytokines on bone marrow epithelium
Neutrophil mobilization —> phagocytosis
Describe effects of inflammatory cytokines On hypothalamus
Increase body temp —> decreased viral and bacterial replication, increased antigen processing, increased specific immune response (*these same effects produced by fat/muscle effect = protein and energy mobilization to allow increased body temp = leads to same downstream effects)
