8 – Innate Immunity V Flashcards
Cytokines are …
Small (25kD)
Heterogenous glycoproteins
Mostly soluble
Cytokine production
= tightly regulated
Post-transcriptional/translational modifications
Cytokine provides…
Provide cellular communication
Cytokine affect behavior of (3)
Producing cell
Adjacent cells
Distant cells
how does Producing cell work
-Autocrine mechanism
-Secrete cytokine bind to its own receptor
how does Adjacent cells work
-Paracrine mechanism
-Cytokine secreted bind to nearby cells
-Directional release
how does Distant cells work
-Endocrine mechanism
-Cytokine secreted and in circulation bind to receptor on far/distant cells
pleiotropism:
1 cytokine may be produced by many different cell types & have effects on many different cell types
redundancy
Different cytokines may have same effect
Cytokine functions: (4)
Activation
proliferation (make copies)
differentiation (naive to effector)
survival/death of target cells
cytokine activation & differentiation example:
Activate & differentiation B & T cells
cytokine can change expression of
Change expression of adhesion molecules & chemokine receptors on target membranes
cytokine can increase/decrease activity of…
Increase/decrease activity of particular enzymes – change transcriptional program
Modulate its effector functions
(TYPE I IFN)
Cascade induction:
Action of one cytokine on one target cell induces that cell to produce one/more additional cytokines
5 major groups of cytokines:
-IL – interleukins (1-37)
-IFN - interferons
(Type I – IFN-α/β
Type II – IFN- γ )
-TNF – tumor necrosis factors
(α/β)
-Hematopeoitin/growth factor
(GM-CSF, G-CSF )
-Chemokines
(migration of cells to site of infection)
Cytokines can exert effect in different ways (4)
Pleiotropy
Redundancy
Synergy
Antagonism
Pleiotropy
1 cytokine produces multiple effects
Redundancy
More than 1 cytokine induce same effect
Synergy
2 or more cytokines work together to induce an effect
Antagonism
One cytokine can inactivate effect of another
Specific cytokines are produced at…
different times in different locations
Complex network of cytokines:
Same cytokine produced by
multiple cells
Complex network of cytokines:
Each cell type can produce
multiple cytokines
cytokines have a big influence on…
adaptive immune response
Different cytokines can induce…
-differentiation of different cell types
-Cytokines impact differentiation of T cells – signal 3 needed to activate it
Different cell types produce…
-different cytokines produced by differentiated T cells
what is 3rd signal to activate T cell?
Cytokines that can differentiate T cells
what happens when 3rd signal is given to T cell?
1.once T cells differentiated = effector T cells
2. they secrete cytokines
3. the cytokines have a specific effect
(they are different cytokines secreted depending on subset of T cells
cytokines can determine…
type of adpative immune response we can get
cytokines can influence who immuniy dominate more, what immunitites are we talking about?
Cell-mediated immunity
Humoral immunity
Cell-mediated immunity: Mostly directed to:
Viral infections
Intracellular pathogens
Some extracellular pathogens
Cell-mediated immunity:Characterized by:
T helper cells –> innate immune cell activation
Cytotoxic T lymphocyte (CTL) activation
Humoral immunity Mostly directed to:
Extracellular bacteria/pathogens
Humoral immunity Characterized by:
B cell activation
Antibody production
Proinflmmatory cytokine examples: (3)
IL-1β, TNF-α, IL-6
TNF-α secreted by: mainly by
macrophages
TNF-α stimulates:
-Migration of innate cells
To site of infection
-Dilate blood vessels
Vasodilation help migration
I-ncreases clotting (preventing pathogen from entering bloodstream)
TNF-α involved in …. disease
Involved in autoimmune diseases
Local TNF-α lead to
local inflammation
-in tissues
Systemic TNF-α lead to
systemic effects
-in bloodstream
-Sepsis: systemic infection & inflammation
what is Acute phase response
A change in proteins present in blood that occurs during early phase of infection Induced by proinflammatory cytokines
Acute phase response involves:
Increased synthesis/secretion of antimicrobial proteins from liver – acute phase proteins
acute phase proteins
-MBL – mannose-binding lectin
-Complement components
-C-reactive protein – can opsonize bacteria & trigger classical complement cascade by binding to C1q
Liver acute phase proteins help in… response
innate immune
-help by opsonization or trigger compliment system
Fever caused by IL-1β, TNF-α, IL-6 signals:
Signal to induce cascade leading to signal to hypothalamus –> increase body temperature
IL-1β, TNF-α, IL-6 have effect on..
different tissues/cell types
IL-1β, TNF-α, IL-6 can lead to…
-Acute-phase response
-Mobilizing cells
-Fever
