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39 Cards in this Set

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Cytokines important points
-Important mediators of cell-cell communication
-generally, act locally
-paracrine and autocrine
-dependent on receptor expression
Cytokines definition
proteins secreted by cells of host defense that regulate the immune response
lymphokines
cytokines produced by lymphocytes
monokines
cytokines produced by monocytes/macrophages
e.g., IL-1, TNFa, IL-6
interleukins
cytokines produced by WBCs and act on WBCs
e.g.,IL-1 through IL-25 (more?)
chemokines
low molecular weight molecules important in the inflammatory response; chemotaxis
e.g., IL-8, RANTES, etc
A given cytokine can be
pleiotrophic -- give definition
different biological effects on different target cells
Cytokines can be redundant -meaning
multiple cytokines having a similar activity
Cytokines can be synergistic -meaning
cytokines that work together
Cytokines can be antagonistic-meaning
cytokines that work against each other
Th cells can be divided into two major subsets. Name them, the type of immunity they produce, and the cytokines associated with them
Th1 – CMI
IL-2, IFNg, TNFb

Th2 – Humoral
IL-4, IL-5, IL-10
What is the importance of Th subsets in leprosy
Th1 response with cell mediated immunity results in tuberculoid leporacy - you have granuloma, nervous and skin tissue damage but the patient usually survives.

Th2 ab response results in disseminated disease and a fatal outcome
mRNA levels for Th cell cytokines in patient with tuberculoid lepracy show high levels of mRNA for which cytokines
TNFbeta, IFNgamma, IL2
mRNA levels for Th cell cytokines in patient with full blown disseminated leprocy show high levels of mRNA for which cytokines
IL-4,IL-5,IL-10
Importance of Th subsets in HIV/AIDS
-CMI more effective
-progression to AIDS has been associated with Th1 to Th2 shift
Activity of cytokines

Cytokines must bind to a specific _________ after binding receptor, a _________ occurs within cell to exert a biological activity (changes in gene expression)
cytokine receptor/signaling cascade
Cytokines have a short in vivo half life therefore, they ________
act locally
Cytokine receptors often have at least TWO chains. What are they?
1)cytokine specific unit
2)signal transducing unit
cytokine receptors have a common _______ cytokine specific subunit
gamma
signalling chain is often the same within a
cytokine receptor family
Often get _____ binding when have two (or three)signalling chains
higher affinity
After cell activation, get ____________
increased cytokine receptor expression
X-linked SCID results from
defect in g chain gene
What are three ways microbe evasion of host response relating to cytokines
They act as cytokine antagonists --molecules that bind cytokine receptors but don’t send signal

they bind to cytokine--
prevent cytokine binding to receptor

They mimic cytokine receptor
Cytokine related diseases
Bacterial septic shock-LPS causes high levels of cytokine release

Toxic shock diseases-
superantigens

Lymphoid and myeloid cancers
e.g., Adult T cell leukemia – overproduction of IL-2
Therapeutic uses of cytokines
Graft survival
Lymphokine activated killer cells (LAK)
Tumor infiltrating lymphocytes (TILs)
Direct administration of cytokines
What do Th cytokines do
cells produce cytokines to regulate the immune response
What do Tdth (delayed type hypersensitive) do
cells produce cytokines to stimulate an inflammatory response
What do Tc (cytotoxic) cytokines do
cells produce cytokines that kill target cells
What do Tc (supressor) cytokines do
cells produce cytokines to turn off the immune response
CTLs
important in eliminating
-altered self cells
-virally infected cells
-tumor cells
foreign graft tissue
CTL - Cytotoxic response
Phase 1: generation of CTLs
-Naïve CTLs must be activated
-TCR : Ag/MHC interaction
-CD28 : B7 costimulation
-IL-2 stimulation (from Th cells)
Phase 2: destruction of target cells
-directional delivery of cytotoxic proteins
Describe CTL action on target cell
after CT; recognition of target cell: the GOLGI “moves” near cell membrane and releases cytotoxic mediators at the Tc:target cell interface
CTL cytotoxic proteins
PERFORIN
GRANZYMES
FASL
PERFORIN
pore forming
similar to C’ pore formation
GRANZYME
enter target cell through pores HAS enzymes that produce DNases within target cell resulting in cell apoptosis
FASL on CTL and FAS on target cell interaction
-Cascade of events yielding apoptosis
-TNFa binds to Fas (can kill tumor cells directly)
NK cell mediated cytotoxicity
-similar to CTL but no Ag specific recognition
-produce perforin and granzymes
-don’t need prior activation (constitutive expression of these molecules)
ADCC (antibody-dependent cell-mediated cytotoxicity)
the Ab is the signal to attract non-specific cells to the target cell.

Ab are bound to Ag on the target cell and Fc receptor on the NK cell, neutorphil, eosinophil, or macrophage.

The release of granules from the NK cell, the neutrophil, the eosinophil , or the macrophage results in dealth of the target cell.