Topic 12 Cyokines
Introduction
A cell can communicate with another
cell in one of two ways. It can either
contact the other cell and send a signal directly via cell-surface molecules,
or it can entrust the message to a water soluble molecule and dispatch this
messenger to seek out the recipient cell.
The cells of the immune system use both forms of communication, the
latter form being the subject of this lesson.
We should remember from previous
lessons that the activation of immune cells requires several signals, some of
which are provided by soluble substances released by a variety of cells. These substances are collectively referred
to as cytokines. Cytokines
released by monocytes are referred to as monokines, and when released by
lymphocytes they are called lymphokines. Those cytokines which participate in the cellular “communication”
between leukocytes are referred to as interleukins. Cytokines have several features in
common. They are antigen-nonspecific
glycoproteins, synthesized and generally rapidly secreted in response to a
stimulus, they are not stored within the cell that makes them. Cytokines are believed to act over a short
range and to have very short half-lives.
This topic is devoted to the review
of the biological activity and structure of cytokines, the structure of and
signal transduction by cytokine receptors, the role of cytokine abnormalities
in the pathogenesis of certain diseases, and possible therapeutic uses of
cytokines or their receptors.
Objectives
On completion of this section and
the required reading, you should be able to:
n describe the role of cytokines in the
development of immunity;
n construct a table of the major
interleukins and their functions;
n discuss the role of IL-2 in immune
regulation classify the major families
of cytokines;
n describe the positive and negative
regulatory roles of transforming growth factor Beta;
n discuss Tumor Necrosis Factors (TNF).
Required Reading
Please refer to the textbook key for
specific readings for this section.
P Key Words
|
• autocrine
• chemokine
• colony
stimulating factors (CSF) • granulocyte
CSF • cytokines
• Interferons |
• interleukin
IL-1 through IL-15 • lymphokines • monokines
• paracrine
• tumor
necrosis factor (TNF) |
P Key Concepts
n Various soluble substances collectively
referred to as cytokines serve as mediators in cell-cell “communication” and
function as signals for cell activation.
Cytokines are proteins or glycoproteins, and share certain structural
features that define the hematopoietin family of proteins.
n An important way in which the activity of
cytokines is directed toward specific cells is by regulation of the expression
of their receptors.
n One cytokine may affect the action of
another, which may lead to either an additive or an antagonistic effects on the
target cell.
DID YOU KNOW?
Superantigens Are Bad for You!
Toxic shock syndrom is a disease that usually affects menstruating
women. It is characterized by
development of a fever, low blood pressure leading to vascular collapse, the
development of a skin rash resembling scarlet fever, conjunctivitis and damage
to organs such as the kidney, liver, and intestine.
The disease is associated with the use of vaginal tampons that
permit overgrowth of certain strains of Staphylococcus aureus. These bacteria grow in the tampon and
produce a toxin called TSST-1. TSST-1
is a potent superantigen binding specifically to the V 2 regions on the
TCR. As a result it acts as a T cell
mitogen and as many as 20% normal T cells in human blood may respond to
it. In order to act as a superantigen
and stimulate these T cells, TSST must first bind to MHC class II molecules on
antigen presenting cells such as macrophages.
The toxin-MHC class II complex then binds to the V 2 positive T cell and
stimulates it to respond.
The clinical signs of toxic shock syndrome are therefore a result of
the massive release of cytokines, especially TNF- and IL-1, by stimulated T cells or by macrophages activated by
these T cells.
Review Questions
1. Textbook Study Questions
Review questions at the end of the
Chapter 13. The answers with
explanations are available at the end of the textbook.
2. Multiple Choice Questions
1. The CD45 molecule is a
A) tyrosine kinase
B) serine kinase
C) phosphotyrosine phosphatase
D) complement receptor
E) Fc receptor
2. Interferon-gamma
enhances
A) ADCC
B) NK cell activity
C) Macrophage activity
D) T-cell mediated cytotoxicity
E) all of the above
3. Which of these is not a
lymphokine?
A) interferon
B) histamine
C) lymphotoxin
D) tumour necrosis factor
E) transforming growth factor
4. To induce an immune
response, antigen-presenting cells must also secrete
A) IL-6
B) IL-2
C) TNF-alpha
D) IL-1
E) IFN-gamma
3. Definitions/Short Answer Questions.
1. Differentiate the following
terms: cytokines , lymphokines,
monokines, interleukins.
2. The difficulty in
characterizing IL-1 is caused by the fact that it seems to be made by every
cell and seems to be able to affect every cell. Explain.
3. What is Il-1’s primary
function in immune cell interactions?
4. Distinguish between
IL-1alpha and IL-1-beta.
5. Briefly discuss some
important immune functions of IL-2.
6. IL-2 is an autocrine T-cell
growth factor. Explain.
7. Briefly, discuss the
significance of the three forms of the IL-2 receptor.
8. What is the connection
between IL-2 production and IFN-gamma production?
9. Compare and contrast
TNF-beta and TNF-alpha.
10. Briefly describe the
CSFs. Why do you think IFN-gamma was considered to be a “magic bullet”?
11. Explain how some cancer cells that can make TGF-beta are
immunosuppressive.
12. Helper T cells can be divided into two subsets based on their
lympokine secretion profile. Explain.
Where to Go from Here
Once you have completed the review,
take some time and complete the objectives. If you are having trouble with any
of the concepts, contact your instructor.
Remember to regularly check your
Instructor and Assignment Information for assignments and due dates for
completing them.
When you are confident that you can
complete the objectives, proceed to the next topic.