Cytokines

Cytokines-Based Diseases and Cytokine Therapy

Cytokines and their Receptors in Inter-Cellular Communication

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

Pleiotropic activity of Interferon Gamma.

Immunology, 5th Edition, Figure 15-15, p. 355

Gamma Interferon

Table of Redundancy and Pleiotropy

See Table 15-3, Immunology, 5th Edition, p. 350

TH1 and TH2 in Disease

Blocked

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?

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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

IL2RFamFigure 12-7 (c)Kuby, 6th Ed.,p. 309

Cytokines, Cytokine Receptors, and Human Disease(Part 1)

Bacterial Septic Shock:Bacterial Cell-wall EndotoxinsMacrophage Overproduction if IL-1 and

TNF-alphaBacterial Toxic Shock

Polyclonal activation of T-cells by Super-AntigensOver-production of IL-1, TNF, other cytokines

Cutaneous T-Cell LymphomaInappropriate Expression of IL-2 and IL-2R

Chagas DiseaseBlocked 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. A congenital abnormality affecting cytokine synthesis

2. A severe viral infection3. A congenital abnormality

affecting the coding of cytokine receptor subunit

4. A metabolic defect that generates an inhibitor of a cytokine receptor

5. A bacterial endotoxin6. An autoimmune antibody attack

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Viral Mimics of Cytokines and Receptors

Immunosuppression and Anti-inflammatory Effects of Viral Mimics of Cytokines and of Cytokine Receptors.(Kuby, 6th Ed., p. 314)

Viral Mimics

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.

(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 ImmediateHypersensitivity: 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

-2

-1

0

1

2

Duration: 0 Seconds

I am here!

33% 33%33%

n

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1. Yes

2. No

3. Not sure

Hematopoietic Cytokines and Hematopoiesis:

Immunology, 5th Edition, Figure 12-16,

p. 297

Hematopoiesis

IL1, Tumor Necrosis Factor (TNFά) and IL6 all promote fever responses These three cytokines are ___________________ in this effect.

Ant

agon

istic

Plei

otro

pic

Red

undan

t

Syn

ergis

tic

Indep

enden

t

Mutu

ally

exclu

sive

0% 0% 0%0%0%0%

1. Antagonistic

2. Pleiotropic

3. Redundant

4. Synergistic

5. Independent

6. 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 handare ___________________ .

1. Antagonistic

2. Pleiotropic

3. Redundant

4. Synergistic

5. Independent

6. Mutually exclusive

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