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Chapter 12
Cytokines
Cytokines:
- Any of numerous secreted, low-m-w proteins
(usually < 30 kDa) that regulate the intensity
and duration of the immune response by exerting
a variety of effects on lymphocytes and other
immune cells.
- Role in cell-to-cell communication
- Messengers of the immune system
Overview of the
Induction and
Function of
Cytokines
(Kd ~ 10-10 to 10-12)
Most Cytokines Exhibit Autocrine and/or Paracrine Action;
Fewer Exhibit Endocrine Action
Pleiotropy,
Redundancy,
Synergy,
Antagonism
of Cytokines
Cascade Induction
of Cytokines
Cytokines, Hormones, and Growth Factors
1. All three are secreted soluble factors that elicit their
biological effects at pM concentrations.
2. Growth factors tend to be produced constitutively,
whereas cytokine production is carefully regulated.
Cytokines are usually secreted after activation of a
particular cell, and secretion is short-lived, generally
ranging from a few hours to a few days.
3. Hormones generally act long range in an endocrine
fashion, most cytokines act over a short distance in an
autocrine or paracrine fashion.
Cytokines, Hormones, and Growth Factors
4. Most hormones are produced by specialized glands and
tend to have a unique action on one or a few types of
target cell. In contrast, cytokines are often produced by
a variety of cells and bind to receptors present on
numerous types of cells.
Functions of Cytokines
1.
2.
3.
4.
5.
Development of cellular and humoral immune responses
Induction of the inflammatory response
Regulation of hematopoiesis
Control of cellular proliferation and differentiation
Healing of wounds
* Although the immune response to a specific Ag
includes the production of cytokines, cytokines
act in an Ag-nonspecific manner.
(1)
(2)
(3)
(4)
- Most of the functions of cytokines have been
identified from analysis of the effects of
recombinant cytokines, often at nonphysiologic
concentrations, added individually to in vitro
system.
- In vivo, however, cytokines rarely, if ever, act
alone.
- Instead, a target cell is exposed to a milieu (環境)
containing a mixture of cytokines, whose
combined syneristic or antagonistic effects can
have very different consequences.
- Cytokines often induce the synthesis of other
cytokines, resulting in cascade of activity.
Cytokine Receptor Families
•
•
3.
4.
5.
Ig superfamily receptors
Class I cytokine receptor family (hematopoietin)
Class II cytokine receptor family (interferon)
Tumor necrosis factor (TNF) receptor family
Chemokine receptor family
3 Subfamilies of Class I Cytokine Receptors
CNTF: ciliary neurotrophic
factor
LIF: leukemia-inhibitory factor
OSM: oncostatin M
Interactions between Cytokine-specific Subunits
and a Common Signal-transducing Subunit of
Cytokine Receptors
Competition of Ligand-binding Chains of Different
Receptors for a Common Subunit Can Produce
Antagnistic Effects between Cytokines
3 Forms of the IL-2 Receptor
(CD25)
JAK-STAT Signal Transduction Pathways
of Cytokine Receptors
JAK: Janus kinases
Stat: signal tranducers and activators of transcription
(lymphotoxin, LT)
TH1 Response
- The TH1 subset is responsible for many cell-mediated
functions (e.g., delayed-type hypersensitivity and activation
of TC cells) and for the production of opsonizationpromoting IgG Abs (i.e., Abs that binds to the high-affinity
FcRs of phagocytes and interact with the C system, such as
IgG3, IgG1, IgG2). This subset is also associated with the
phenomenon of excessive inflammation and tissue injury.
- The production of IL-2, IFNg and TNFb makes the TH1
subset particularly suited to respond to viral infections and
intracellular pathogens. IFNg also inhibits the expansion of
the TH2 population.
TH2 Response
- The TH2 subset stimulates eosinophil activation and
differentiation; provides help to B cells, and promotes the
production of relatively large amounts of IgM, IgE, and
noncomplement-activating IgG isotypes, such as IgG4
in humans and IgG1 in mice. The TH2 subset also supports
allergic reactions. The production of Il-4, IL-5 and IL-10
promotes the function of IgE and eosinophils on the antihelminth (round worm) immunity.
The Regulation of TH Subsets by Cytokines
Correlation between Type of Leprosy (痲瘋)
and Relative TH1 or TH2 Activity