Cytokines are cell signaling molecules that aid cell-to-cell communication in the immune system. They are proteins, peptides, or glycoproteins secreted by immune cells that mediate and regulate immunity, inflammation, and hematopoiesis. Cytokines bind to specific receptors on target cells and regulate the immune response by stimulating or inhibiting cell activation, proliferation, and differentiation. Abnormal cytokine production or receptor expression has been implicated in diseases like septic shock, toxic shock syndrome, and cancer.

1. Post graduate & Research Center- Department of Microbiology
2022-2024
2nd sem core: Immunology

2. INTRODUCTION
The term " Cytokines" is derived from a combination of two
greek words - "cyto" meaning cell & "kinos" meaning
movement.
Cytokines are cell signaling molecules that aid cell to cell
communication in immune responses & stimulate the
movement of cells towards sites of infection.
Cytokines are a large group of proteins, peptides or
glycoproteins that are secreted by specific cells of immune
system.
Cytokines are a category of signaling molecules that
mediates and regulates immunity, inflammation &
hematopoiesis.
Cytokines are produced throughout the body by cells of
diverse embryological origin.

3. PROPERTIES OF CYTOKINES
Cytokines bind to specific receptors on the membranes of
target cells, triggering, signal- transduction pathways that
ultimately alter gene expression in the target cells.
The cytokines and their receptors exhibit very high affinity
for each other, and can mediate biological effects at
picomolar concentration.
Cytokines regulate the intensity and duration of the
immune response by stimulating or inhibiting the
activation, proliferation, and/ or differentiation of various
cells and by regulating the secretion of antibodies or
other cytokines.

4. CYTOKINES EXHIBIT THE ATTRIBUTES OF:
Pleiotrophy
Redundancy
Synergy
Antagonism
Cascade Induction
which permit them to regulate cellular
activity in a coordinated, interactive way.

5. Pleiotrophy:
It is common for different cell types
to secrete the same cytokine or for a
single cytokine to act on several
different cell types

6. Cytokines are redundant in their activity, meaning
similar functions can be stimulated by different
cytokines.
Cytokines are often produced in a cascade, as one
cytokine stimulates its target cells to make
additional cytokines.
Cytokines can also act synergistically (two or
more cytokines acting together) or
antagonistically (cytokines causing opposing
activities).

7. NOMENCLATURE
Interleukins: That act as mediators between
leukocytes, the vast majority of these are produced by
T- Helper cells.
Lymphokines :produced by Lymphocytes.
Monokines: Produced exclusively by monocytes
Interferons: involved in antiviral response.
Colony Stimulating Factor: Supports the growth of
red blood cell.
Chemokines: mediate chemoattraction (chemotaxis)
between cells.

8. BIOLOGICAL FUNCTIONS OF
CYTOKINES
Although a variety and the
macrophage of cells can secrete
cytokines, the two principle
producers are the T- Helper cells
and the macrophage.
Cytokines released from these
two cell types activate an entire
network of interacting cells.

9. Among the numerous physiologic responses that require
cytokine involvement are development of cellular and
humoral immune responses, induction of the
inflammatory response, regulation of hematopoiesis,
control of cellular proliferation and differentiation, and
the healing of wounds
One way in which specificity is maintained is by careful
regulation of the expression of cytokine receptors on
cells. Often cytokine receptors are expressed on a cell
only after that cell has interacted with antigen. In this way
cytokine activation is limited to antigen-activated
lymphocytes

10. Cytokines secreted at the junction of
interacting cells reach high enough local
concentrations to affect the target APC but
not more distant cells.
In addition, the half-life of cytokines in the
bloodstream or other extracellular fluids into
which they are secreted is usually very short,
ensuring that they act for only a limited
period of time

12. CYTOKINE RECEPTOR
To exert their biological effects, cytokines must first
bind to specific receptors expressed on the
membrane of responsive target cells
Because these receptors are expressed by many
types of cells, the cytokines can affect a diverse array
of cells.
Biochemical characterization of cytokine receptors
initially progressed at a very slow pace because their
levels on the membrane of responsive cells is quite
low.

13. Cytokine Receptors Fall Within Five Families
Receptors for the various cytokines are quite diverse
structurally, but almost all belong to one of five
families of receptor proteins
Immunoglobulin superfamily receptors
Class | cytokine receptor family (also known as
hematopoietin receptor family)
Class II cytokine receptor family (also known as the
interferon receptor family)
TNF receptor family
Chemokine receptor family

16. Fig showing: General model of signal transduction
mediated by most class and class II cytokine receptors.

17. CYTOKINES IN HEMATOPOIESIS
Many cytokines have been shown to play essential roles in
hematopoiesis.
During hematopoiesis, cytokines act as developmental signals that
direct commitment of progenitor cells into and through particular
lineages.
A myeloid progenitor in the presence erythropoietin would proceed
down a pathway that leads to the production of erythrocytes;
suitable concentrations of a group of cytokines including IL-3, GM-
CSF, IL-1, and IL-6 will cause it to enter differentiation pathways
that lead to the generation of monocytes, neutrophils, and other
leukocytes of the myeloid group

18. Fig Showing: Hematopoietic cytokines and
Hematopoiesis

19. CYTOKINE RELATED DISEASES
Defects in the complex regulatory networks governing the expression of
cytokines and cytokine receptors have been implicated in a number of
diseases.
Several diseases resulting from over expression or under expression of
cytokines or cytokine receptors
The role of cytokine overproduction in pathogenesis can be
illustrated by bacterial septic shock
This condition may develop a few hours after infection by certain
gram-negative bacteria, including E. coli, Klebsiella pneumoniae.
Bacterial Septic Shock

20. The symptoms of bacterial septic shock, which is
often fatal, include a drop in blood pressure, fever,
diarrhea, and widespread blood clotting in various
organs
Bacterial septic shock apparently develops because
bacterial cell- wall endotoxins stimulate
macrophages to overproduce IL-1 and TNF-to levels
that cause septic shock.

21. A variety of microorganisms produce toxins that act as
superantigens.
Included among these bacterial superantigens are
several enterotoxins, exfoliating toxins, and toxic-shock
syndrome toxin (TSST1) from Staphylococcus aureus;
pyrogenic exotoxins from Streptococcus pyrogenes; and
Mycoplasma arthritidis supernatant (MAS).
The large number of T cells activated by these
superantigens results in excessive production of
cytokines. The toxic-shock syndrome toxin, for example,
has been shown to induce extremely high levels of TNF
and IL-1.
Bacterial Toxic Shock

22. Abnormalities in the production of
cytokines or their receptors have been
associated with some types of cancer.
For Example, abnormally high levels of IL-6
are secreted by cardiac myxoma cells (a
benign heart tumor), myeloma and
plasmacytoma cells, and cervical and
bladder cancer cells.
Cytokine Activity Is Implicated in Lymphoid
and Myeloid Cancers

23. The protozoan Trypanosoma cruzi is the causative
agent of Chagas' disease, which is characterized by
severe immune suppression.
Antigen, mitogen, or anti-CD3 monoclonal antibody
normally can activate peripheral T cells, but in the
presence of T. cruzi, T cells are not activated by any
of these agents. The defect in these lymphocytes
has been traced to a dramatic reduction in the
expression of the 55-kDa subunit of the IL-2
receptor.
Chagas' Disease

24. REFERENCES
Kuby-immunology-7th-edition
https://www.sciencedirect.com/topics/neuroscience/cy
tokines
https://www.verywellhealth.com
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC17666
76/pdf/v060piii4 3.pdf