Cytokines
Cytokines and their Receptors in
Inter-Cellular Communication
Cytokines-Based Diseases
and Cytokine Therapy
Updated: November 15, 2012
Folder title: Cytokine
(Presented in Part 2 under “Cells of the Immune Response”)
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
Cytokine Table
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Activities of Cytokines: What They Do
Cytokines in Hematopoiesis
Cytokines in Innate and Adaptive
immunity
mat
opoi
esis
Stem Cell Factor from Bone Marrow Stromal Cells
Lymphocytes
Hematopoietic
Cytokines and
Hematopoiesis:
Immunology, 5th
Edition, Figure 12-16,
p. 297
------------------Myelocytes------------------
Stem Cell Production
Myelocyte Production
Lymphocyte Production
The Complexity of Cytokine-Receptor Signaling and Effects
What cytokine is being made?
When is it being made?
At what concentration?
How long will it be around?
Is it being modified by other proteins?
Activated?
Degraded?
What other cytokines are being made?
Do they affect the first cytokine?
Do they activate or inhibit the first cytokine?
Is the cytokine receptor available on the target cell or cells?
Is the receptor being activated or inhibited?
Is the receptor defective?
Does the receptor have a high enough affinity for the cytokine?
Cytokines:
Where They Come From: The Discovery of IL1
How They Work
Macrophage to T-Helper
Discovery of IL1
PHA = phytohemagglutinin (poly-clonal t-cell mitogen from fungi
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
Cytokines and TH1 and TH2 Helper T-Cell Subsets:
Immunological and Pathobiological Effects
Blocked
TH1 and TH2 in Disease
Blocked
Dashed -------- arrow indicates blocking response
Roles of TH1 and TH2
Cytokines and TH1 and TH2
See Table 12-4,
p. 315,
Top Half
Immunology, 6th
Edition
Functions of TH1 and TH2
See Table 4-4, p. 96 for structures and functions of IgG subtypes
See Table 12-4, Bottom Half,
p315, 6th Edition
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)
M-RNA from Tuberculoid or lepromatous lesions analyzed for types of cytokines
being produced
Cytokine Receptors in Normal immune Response and
in Pathobiology
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.
Receptors for IL2
Gamma subunit is
used by other
cytokine receptors
(IL15, IL7, IL9, IL4)
General model of cytokine
receptors for interleukin and
interferon types of cytokines.
See figure 12-6 (b) and (c) p. 308,
for interleukin (“hematopoietin”)
and interferon class of cytokines
STAT = signal transducers
and activators of
transcription.
See Table 12-2, p. 313 for
STAT family of transcription
factors associated with
different cytokines of the
interleukin and interferon
series
IL2 Receptor Family
Figure 12-7 (c)
Kuby, 6th Ed.,
p. 309
IL2RFam
Cytokines, Cytokine Receptors, and Human Disease
(Part 1):
Over-production of Cytokines
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
Cytokines, Cytokine Receptors, and Human Disease
(Part 2)
Cytokine Receptor Miss-expression
Cutaneous T-Cell Lymphoma
Inappropriate Expression of IL-2 and IL-2R
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
Gamma C Subunit Shared
Cytokines, Cytokine Receptors, and Human Disease
(Part 3)
Cytokine Receptor Blocking
Chagas Disease (Trypanosoma Cruzi)
Severe Immunosuppression of Infectious Etiology
Blocked Expression of IL-2R Alpha Subunit
Cytokines, Cytokine Receptors,
and Human Disease (Part 4)
Cytokine Mimics
Anti-inflammatory and Immunosuppressive Viral Products as
Mimics of Cytokines and Cytokine Receptors
XSCID
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
Macrophage inflammatory
protein
Monocyte
chemoattractant
protein
For information on chemokines,
See Table 13-2, p. 330,
and footnotes to Table 13-2,
Kuby, 6th Edition.
Chemokines are small MW cytokines
that mostly regulate leukocyte trafficking
and adherence but also regulate
non-leukocyte cellular interactions.
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
Turning Down Helper T-Cell and Cytotoxic TCell Mediated Auto-immune Responses
Cytokine Activation of Leucocytes
in Anti-Leukemia Treatments
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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