Chapter 13 Immunological Tolerance (3)

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Chapter 13 Immunological
Tolerance (3)

• I. Introduction
• Concept
• Natural tolerance
• Acquired tolerance
• II. Factors Affecting Tolerogenicing of
• Antigen
• III. Mechanisms of Tolerance Induction
• IV. Clinical significance of immunologic
  tolerance

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Concept

• Immunological tolerance is a state of
  unresponsiveness that is specific for a
  particular antigen it is induced by prior
  exposure to that antigen.

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II. Factors Affecting Tolerogenicing of Ag

• 1. The structure of antigen
• 2. The antigen dosage
• 3. The route of administration

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Low zone tolerance High zone
tolerance
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Experimental induction of tolerance at low and
high doses of antigen
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III. Mechanisms of Tolerance Induction

• 1. Clonal deletion therapy
• Central thymic tolerance to self
  Ags-positive and negative selection.
• 2. Clonal anergy
• a.  Lack of signal of activation can cause
  unresponsiveness
• b. The blocking of immunocompetent cells
• c. Lack of helper cells
• 3. The Suppressant effect of various cells

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Mechanisms of Tolerance Induction

• Clonal deletion physically deleting cells from
  the repertoire at come stage during their
  lifespan.
• Clonal anergy downregulating the intrinsic
  mechaism of the immune response.
• Suppression inhibiting cellular activity
  through interaction with other cells, such as
  those producing inhibitory cytokines or
  idiotype-specific lymphocytes which recognize the
  antigen receptor itself.

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Blocking of BCR
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IV. Clinical significance of
immunologic tolerance

• 1. The induction and maintenance of immunologic
  tolerance
• 2. The elimination of immunologic tolerance

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Chapter14 Regulation of the
Immune Response (4)

• Regulation by antigen
• Regulation by antibody
• Regulation by lymphocytes
• Idiotypic modulation of responses
• Neuroendocrine modulation of
• immune responses

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Regulation by antigen

• A decline in Ag levels ultimately
  results in diminished clonal proliferation and a
  decline in further homuoral or cell-mediated
  responses.

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Immune regulation by immune complexes
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Idiotypic modulation of responses

• According to the network theory, a
  series (or network) of anti-idiotype antibodies
  are induced during an immune response these
  anti--idiotype antibodies act to upregulate the
  immune response in some cases and to downregulate
  it in other cases.

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Neuroendocrine modulation of immune responses

• It has long been known that stressful
  conditions may lead to a suppression of immune
  functions, for example, reducing the ability to
  recover from infection. There is considerable
  evidence demonstrating that the nervous,
  endocrine and immune systems are interconnected.
  Broadly, there are two main routes.
• a.  Most lymphoid tissues receive direct
  sympathetic innervation, both to the blood
  vessels passing through the tissues, and directly
  to the lymphocytes themselves.
• b. The nervous system directly or indirectly
  controls the output of various hormones, in
  particular, corticosteroids, growth hormone,
  thyroxine and adrenaline.

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