AUTOIMMUNITY When the Good Turns Bad A Guide for Teachers

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AUTOIMMUNITYWhen the Good Turns Bad - A Guide
for Teachers -

• Prepared by Johanna Mancini for Immunology
  Montreal
• August 2008

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What is autoimmunity?

• When the immune system is activated by
  self-antigens
• When the immune system no longer recognizes
  itself
• Generally is prevented by self-tolerance, where
  self-reactive antigens are eliminated
• But, the body cannot eliminate all self-reactive
  antigens because some help protect against
  foreign antigens!
• This means that everyone has some self-reactive
  antigens, only, they have not activated our
  antibodiesyet

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What is autoimmunity?

• When body mounts immune response against self, it
  is impossible for immune mechanism to eliminate
  antigen completely
• Result a sustained response, chronic
  inflammation, tissue damage and sometimes death!

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Tolerance
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Mechanisms of Self-Tolerance

• Receptor Editing
• In receptor editing, the B
• cell will stop in maturation
• and rearrange to make a
• light chain with a different
• specificity. If, again, they
• recognizes a self-antigen,
• they will undergo apoptosis.
• If they dont, the B cell will
• mature and go to the
• periphery.

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Mechanisms of Self-Tolerance

• If the B-cells are recognizing soluble antigens
  with high affinity, they will go to the periphery
  and become anergic, i.e. they will become
  inactive

• Low affinity B-cells will also go to the
  periphery but be kept clonally ignorant, meaning
  that when they encounter self-antigen they will
  not become activated
• Finally,if the B-cell does not recognize
  self-antigen, they will grow and mature, then
  migrate to the periphery and be functional

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Peripheral Tolerance

• Once the cells have moved into the periphery,
  there are still more mechanisms in place to
  eliminate self-antigens
• Ignorance
• Anergy
• Phenotypic skewing
• Apoptosis
• Antigen sequestration

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Peripheral Tolerance

• Ignorance
• An important mechanism
• Lymphocytes with low affinity for self-antigen,
  can go
• to the periphery and encounter the self-antigen
  but
• can avoid becoming activated by
• They remain ignorant, of self but functional
• to foreign agents
• Unfortunately, ignorance can be overcome by
  strong
• stimulus like major infection or tissue damage
  and
• can lead to autoimmune reactions

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Peripheral Tolerance

• Anergy
• B-cells recognize
• soluble antigen with
• high affinity and go to
• periphery, where
• they become inactive

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Peripheral Tolerance

• Phenotypic Skewing
• Some auto-reactive T-
• cells secrete cytokines
• that will fail to cause
• auto-immune tissue
• damage

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Peripheral Tolerance

• Apoptosis
• B-cells increase their affinity for a
• specific antigen when they
• encounter an antigen in the
• periphery. However, some B-cells
• that become activated by self
• antigens are removed by apoptosis
• (programmed cell death)

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Peripheral Tolerance

• Antigen Sequestration

• Immunological privileged
• sites where self-antigens are
• sequestered, such as the
• brain, eye, testis, uterus, etc.
• normally, have no T cell
• activation. However, if there
• is a trauma, there is a
• release of self-antigens
• which can activate auto-
• reactive T-cells.
• Autoimmunity will occur in
• the traumatized privileged
• organ since the T-cells are
• no longer ignorant

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Types of Autoimmune Disease

• Autoimmune disease is generally classified into
  systemic or organ specific diseases
• Diabetes involves antibodies against the insulin
  receptor in the pancreas, causing hyperglycemia
• Graves Disease involves antibodies against the
  thyroid stimulating receptor, causing
  hyperthyroidism
• Multiple Sclerosis involved antibodies that
  react against the central nervous system

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Types of Autoimmune Disease

• However, in some cases, the self-antigen is found
  everywhere in the body
• Systemic Lupus chronic inflammation of the
  connective tissue, characterized by red scaly
  skin lesions
• Rheumatoid Arthritis chronic inflammation of the
  joints
• Myasthenia Gravis caused by antibodies against
  acetylcholine receptor

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Factors Affecting Autoimmunity

• Familial studies suggest clear association
  between genetics and autoimmune disease
• Also found to be more prevalent in women
• However, studies between identical twins show
  that despite identical genetic background,
  cellular processes and environment also play a
  role

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Vocabulary

• anergy a state of non-responsiveness to antigen
• antibody an antigen-binding immunoglobulin,
  produced by B-ells, that functions as the
  effector of an immune response
• antigen a foreign molecule that does not belong
  to the host organism and that elicits an immune
  response
• B-cell a type of lymphocyte that develops in the
  bone marrow and later produces antibodies, which
  mediate humoral immunity
• central tolerance when auto-reactive B-cell in
  the bone marrow and auto-reactive T-cells in the
  thymus are eliminated
• humoral immunity the type of immunity that
  fights bacteria and viruses in the body fluids
  with antibodies that circulate in blood plasma
  and lymph
• immune system is the name used to describe the
  totality of the host defence mechanism
• lymphocyte a class of white blood cells two
  main classes B-cells and T-cells, which mediate
  humoral and cell-mediated immunity, respectively.
  
• peripheral tolerance is tolerance acquired by
  mature lymphocytes in the peripheral tissue
• plasma cell a derivative of B-cells that
  secretes antibodies, i.e. antibody factory
• T-cell a type of lymphocyte that develops in the
  thymus

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References

• 1) Janeway, Charles A. et al. Immunobiology,
  6th edition. Garland Science, 2005.
• 2) Wikipedia Autoimmunity. Accessed August
  2007. http//en.wikipedia.org/wiki/Autoimmune
• 3) Campbell, Neil A., Jane B. Reece, Lawrence G.
  Mitchell. Biology, 7th edition. Pearson
  Education, Inc. 2002.

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