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30 Cards in this Set
- Front
- Back
Summary of CMI response:
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Which form of IgM is a pentamer?
Which is a monomer? |
Membrane-bound form is a monomer.
Secreted IgM in serum is a pentamer. |
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Summary of the humoral immune response:
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What is immunological tolerance?
two levels? describe them. |
-UNRESPONSIVENESS TO SELF ANTIGENS
1. Central Tolerance: serves to delete self-reactive clones of lymphocytes before the cells are allowed to mature if they possess receptors that recognize self antigens with high affinity. 2. Peripheral Tolerance: inactivates or regulates self-reactive lymphocytes that survive the initial screening process, complete their maturation and enter peripheral tissues. |
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3 MECHANISMS OF TOLERANCE INDUCTION (peripheral):
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Clonal Deletion
Clonal Anergy Suppression |
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Describe the process of central tolerance in T cells:
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What determines if a developing thymocyte will become a nTreg cell?
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-Must have intermediate affinity for self antigen
-FoxP3 |
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Why do we need Peripheral Tolerance processes?
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-Central tolerance is not a foolproof process; 100% of possible self-reactive T cells are not deleted.
-Peripheral tolerance prevents T cell responses to self antigens in peripheral tissues. |
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3 steps in the activation of T cells:
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How is clonal anergy promoted?
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When APCs are presenting self-antigen to a T cell, the costimulatory response occurs via the CTLA-4 receptor on the T cell interacting with the CTLA-4L receptor on the APC. This is an INHIBITORY interaction.
The T can't respond; it becomes "anergic" to the self-antigen. |
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IMMUNE SUPPRESSION BY REGULATORY T CELLS (Treg):
-where do they arise? -what important transcription factor is needed? -what cytokine is needed? |
-Most Treg cells are generated in the thymus, but may also arise after induction in the periphery, by self antigens.
-The development and function of these cells are dependent on the transcription factor Foxp3 (forkhead box P3) -Most are CD4+ and are dependent on the cytokine IL-2 for survival and function. |
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What are the steps in making Tregs?
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How do Tregs function in peripheral tolerance? 4
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*Tregs have high expression of IL-2Rs
*More of low-affinity alpha chain of IL-2R 1) Denies other T cells IL-2, thus inhibiting their function against self-antigen. 2) They secrete inhibitory cytokines like TGF-ß. 3) Interfere with APC function (unknown mechanism) 4) Can directly kill T cells if needed. |
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CLONAL DELETION BY ACTIVATION INDUCED CELL DEATH (AICD):
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-T cells in the periphery can be triggered to die by apoptosis in response to recognition of self antigens. This mechanism is called AICD.
*Fas/FasL are key in this process. *There's a lack of IL-2 in AICD. |
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Describe CENTRAL TOLERANCE IN B CELLS: 2
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When immature B cells strongly interact with self antigens in the bone marrow, the B cells either change their receptor specificity (receptor editing) or die by clonal deletion (negative selection).
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Describe peripheral anergy induction in B cells:
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-B and T cells require cooperation in the lymph nodes to keep each other stimulated.
-A mature B cell that recognizes a self antigen without T cell help is functionally inactivated (anergic). |
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What happens when central and peripheral tolerance fails?
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Autoimmunity
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What is autoimmunity?
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-Autoimmunity is an immune response against autologous or self antigens.
-It results when central and peripheral tolerance mechanisms fail! -Autoimmune disease arises when autoimmunity causes clinical damage or destruction of self proteins, cells, and organs by the activation and effector functions of autoreactive T and B cells. |
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What events are required for autoimmune disease? 4
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2 key factors in development of autoimmunity:
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The principal factors in the development of autoimmunity are the inheritance of susceptibility genes and environmental triggers, such as infections, inflammation, or injury.
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Most important genes in autoimmunity?
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The most important genes conferring predisposition to autoimmunity are the MHC (HLA) genes.
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One example of genetic involvement in developing an autoimmune disorder?
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Ankylosing spondylitis has a really high identified risk with the B27 HLA allele.
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Non-HLA genes involved in autoimmunity? 5
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AIRE
Fas/FasL Foxp3 IL-2 IL-2R alpha/ß *Failure of peripheral tolerance is the key level in developing autoimmunity. |
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Discuss influence of external factors in developing autoimmunity:
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-inflammation, infection, etc.
-molecular mimicry |
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2 main mechanisms by which external factors promote autoimmunity:
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Mechanisms by which pathogens may promote autoimmunity include:
1. Inflammation 2. Molecular mimicry Infections may activate self-reactive lymphocytes, thereby triggering the development of autoimmune diseases. |
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How does inflammation promote autoimmunity?
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The inflammatory microenvironment induced by infection “breaks” peripheral tolerance and promotes activation of self-reactive lymphocytes.
-xs cytokines --> xs activation of APCs |
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How does molecular mimicry promote autoimmunity?
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Occurs when microbial antigenic determinants cross-react with host self antigens.
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Good example of molecular mimicry in autoimmunity?
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Infection by Streptococcus pyogenes and development of Rheumatic fever.
-M PRO similar to cardiac tissue PROs -It's suspected this is happening with MS/EBV. |
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Two broad classes of autoimmune disease based on the clinical manifestations of the disease:
2 examples of each |
1) Organ-specific autoimmunity
Hashimoto thyroiditis Myasthenia gravis 2) Systemic autoimmunity Ankylosing spondylitis Systemic lupus erythematosus |
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Briefly list the pathologies that can be results of autoimmune disorders:
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Self-reactive antibodies, leading to type II and type III hypersensitivity responses.
Cell-mediated injury (type IV hypersensitivity). These may include cytotoxic T cell responses or macrophages driven by DTH responses. May result from both humoral and cell-mediated injury. |