Transcript Cytokines

Cytokines
Cytokines and their Receptors in
Inter-Cellular Communication
Cytokines-Based Diseases
and Cytokine Therapy
Updated: November 28, 2011
Folder title: Cytokine
Key Hematopoietic Growth Factors and
Their Targets
Relatively Multi-Specific:
Granulocyte-Macrophage Colony-Stimulating Factor
GMCSF
Interleukin III - IL3
Relatively Mono-Specific:
Granulocyte Colony Stimulating Factor - GCSF
Macrophage Colony Stimulating Factor - MCSF
Erythropoietin - EPO
GrowFact
Cytokine Table
Macrophage to T-Helper
Inter-Leukins and IL-Receptors
Interleukin Actions
Gamma Interferon
Pleiotropic
activity of
Interferon
Gamma.
Immunology,
5th Edition,
Figure 15-15,
p. 355
Table of Redundancy and
Pleiotropy
See Table 15-3,
Immunology, 5th Edition,
p. 350
Blocked
TH1 and TH2 in Disease
Blocked
Roles of TH1 and TH2
Cytokines and TH1 and TH2
See Table 12-4,
p. 315,
Immunology, 6th
Edition
Functions of TH1 and TH2
TH1 and TH2 Helper Cell Subsets in the Pathology and Progression of Infection
with Mycobacterium leprae
Tuberculoid (Cell-mediated) and Lepromatous (Humoral response) Leprosy
(Figure 12-14, Immunology, 6th Edition, p. 318)
Leprosy
Discovery of IL1
In this graphic, PHA (phytohemagglutinin) is a non-specific mitogen that stimulates
T-cell proliferation measured by labeled thymidine incorporation into the cell culture.
Why use PHA? Why not use a specific T-cell antigen?
Response Grid
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The Specific Cytokines that are present, and their
concentrations matter in how the immune response
reacts.
The presence and structure of cytokines receptors
matter just as much as the cytokines themselves.
IL2 Receptor Family
Figure 12-7 (c)
Kuby, 6th Ed.,
p. 309
IL2RFam
Cytokines, Cytokine Receptors, and Human Disease
(Part 1)
Bacterial Septic Shock:
Bacterial Cell-wall Endotoxins
Macrophage Overproduction if IL-1 and
TNF-alpha
Bacterial Toxic Shock
Polyclonal activation of T-cells by Super-Antigens
Over-production of IL-1, TNF, other cytokines
Cutaneous T-Cell Lymphoma
Inappropriate Expression of IL-2 and IL-2R
Chagas Disease
Blocked Expression of IL-2R Alpha Subunit
CytoSick
Cytokines, Cytokine Receptors,
and Human Disease (Part 2)
X-Linked Severe Combined Immune-Deficiency
(X-SCID)
Boy-in-the Bubble Syndrome
Failure to Express IL-2R Gamma Subunit
May Also Affect IL4R and IL7R
Produces Broad-ranging Immune Unresponsiveness
Anti-inflammatory and Immunosuppressive Viral
Products as Mimics of Cytokines and Cytokine Receptors
XSCID
Gamma C Subunit Shared
Severe Combined Immune Deficiency or “Boy-in-a-bubble Syndrome”
arises because of
1.
2.
3.
4.
5.
6.
A congenital abnormality
affecting cytokine synthesis
A severe viral infection
A congenital abnormality
affecting the coding of cytokine
receptor subunit
A metabolic defect that
generates an inhibitor of a
cytokine receptor
A bacterial endotoxin
An autoimmune antibody attack
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Immunosuppression and
Anti-inflammatory
Effects of Viral Mimics
of Cytokines and of
Cytokine Receptors.
(Kuby, 6th Ed., p. 314)
Viral Mimics of Cytokines and
Receptors
For information on chemokines,
See Table 13-2, p. 330,
and footnotes to Table 13-2,
Kuby, 6th Edition.
Not part of BIO 447 Exams
or Quizzes.
Viral Mimics
(This is a fill-in-the-blank question)
Several viruses are known to produce soluble
interferon-γ receptors (INFγR).
Why would producing a soluble INFγR be
something the virus “wants” to do? Why does
that help the virus?
(You can use INF to abbreviate interferon-γ)
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Other Sources of Cytokines used in Host Response to
Pathogens:
e.g. Mediators in Type I Immediate Hypersensitivity
Overview of Mast Cell Mediated Type I Immediate
Hypersensitivity: Triggering of Sensitized Cells and Release of
Early and Late Mediators:
How Do We Treat This???
IgEOView
Cytokines in Therapy of Diseases
Since cytokines have potent activities at low
concentrations in controlling responses of host cells to
normal and pathological events,
can we use Cytokines deliberately in therapy?
Tumor Necrosis Factor and
Melanocytes
Tumor Necrosis Factor in Vivo
Tumor Necrosis Factor and
Weight Loss
Cytokine Therapies in the Clinic
LAK Cells
TIL Cells
On a scale of -2 to +2 rate:
1 = -2 = I’m totally lost; 2 = -1 = I’m having a hard time but I get some of it
3 = 0 = I’m doing OK. I get a lot of it. I’ll figure the rest out later
4 = +1 = I’m doing fine. I get most of it; 5 = +2 = This is no problem. Please
get moving before I get totally bored
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Duration: 0 Seconds
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33%
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33%
Y
1. Yes
2. No
3. Not sure
es
I am here!
mat
opoi
esis
Hematopoietic
Cytokines and
Hematopoiesis:
Immunology, 5th
Edition, Figure 12-16,
p. 297
IL1, Tumor Necrosis Factor (TNFά) and IL6 all promote fever responses
These three cytokines are ___________________ in this effect.
Antagonistic
Pleiotropic
Redundant
Synergistic
Independent
Mutually exclusive
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IL4 and IL10 inhibit activation of Th1 cells and enhance activation of Th2
cells. Interferon Gamma inhibits the activation of Th2 cells and stimulates
the activation of Th1 cells. That means that IL4 and IL10 on the one hand
and Interferon gamma on the other hand
are ___________________ .
1.
2.
3.
4.
5.
6.
Antagonistic
Pleiotropic
Redundant
Synergistic
Independent
Mutually exclusive
Response Grid
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