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Immunoregulation: Dr. Safari Wahyu Jatmiko

The document discusses immune regulation and how a failure of control mechanisms can lead to immune-mediated inflammatory diseases. It explains that regulatory mechanisms act at all phases of the immune response, from antigen recognition through activation and effector function, to prevent excessive immune responses and maintain self-tolerance. Regulatory T cells play an important role in immune regulation through the secretion of cytokines and the inactivation of other immune cells.

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20 views13 pages

Immunoregulation: Dr. Safari Wahyu Jatmiko

The document discusses immune regulation and how a failure of control mechanisms can lead to immune-mediated inflammatory diseases. It explains that regulatory mechanisms act at all phases of the immune response, from antigen recognition through activation and effector function, to prevent excessive immune responses and maintain self-tolerance. Regulatory T cells play an important role in immune regulation through the secretion of cytokines and the inactivation of other immune cells.

Uploaded by

septin
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPTX, PDF, TXT or read online on Scribd
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IMMUNOREGULATION

Dr. SAFARI WAHYU JATMIKO


The importance of immune
regulation
• To avoid excessive lymphocyte activation and
tissue damage during normal protective responses
against infections

• To prevent inappropriate reactions against self


antigens (“self-tolerance”)

• Failure of control mechanisms is the underlying


cause of immune-mediated inflammatory diseases
Regulation of immune responses
• Magnitude of immune response determined by:
– Ag-driven activation of lymphocytes
– Negative regulatory influences that prevent or
dampen response
• Regulatory mechanisms act at all phases of
immune response
– Recognition
– Activation
– Effector function
Regulation in response
to Antigen
• Recognition:
– in absence of co-stimulation → anergy
(inability to respond)
• Activation:
– with CTLA-4 engagement of CD80/CD86 →
down regulation of Ts (dampens activation)
• Effector function:
– Too much Ag → tolerance (induced state of
unresponsiveness)
Summary: Lack of co-
stimulation can lead to
tolerance (anergy)
Normal
Response Proliferation &
differentiation

CD28 B7

Anergy

Antigen Recognition
without co-stimulation
Regulation by CTLA-4

CTLA4
CTLA4-B7 interaction

B7

Functionally
Activated T cell Unresponsive (Anergic) T cell
Regulatory T cells

From Abbas, Lichtman and Pillai. Cellular and Molecular Immunology 6th ed, 2007
Properties of regulatory T cells

• Phenotype: CD4, high IL-2 receptor


(CD25), low IL-7 receptor, Foxp3
transcription factor; other markers

• Mechanisms of action: multiple


– secretion of immune-suppressive
cytokines (TGF, IL-10, IL-35),
– inactivation of dendritic cells or
responding lymphocytes
Thymic (“natural”) regulatory T cells
(Treg)

• Development requires recognition of self


antigen during T cell maturation

• Reside in peripheral tissues to prevent


harmful reactions against self
Peripheral (adaptive, inducible)
regulatory T cells
• Develop from mature CD4 T cells that are
exposed to persistent antigen in the
periphery; no role for thymus
• May be generated in all immune responses,
to limit collateral damage
• Can be induced in vitro (stimulation of CD4
T-cells in presence of TGF + IL-2)

• What factors determine the balance of


effector cells and Treg?
CD4 T cell subsets: function
Th1 cells (IFN-g)
Host defense: many microbes
Systemic and organ-specific
autoimmune diseases
Th2 cells (IL-4, IL-5)
Host defense: helminths
Allergic diseases
Naïve CD4
T cell

Th17 cells (IL-17)

Host defense: fungi, bacteria


Organ-specific
autoimmune diseases

Regulatory T cells
CD4 subsets: generation and function
Th1 cells (IFN-g)
Host defense: many microbes
Systemic and organ-specific
autoimmune diseases
Th2 cells (IL-4, IL-5)
Host defense: helminths
Allergic diseases
Naïve CD4
T cell

Th17 cells (IL-17)

TGF-IL-2: Host defense: fungi, bacteria


Foxp3, Stat5 Organ-specific
autoimmune diseases

Regulatory T cells

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