The Autoimmune Disease Flashcards Preview

Sem 4: TI2 > The Autoimmune Disease > Flashcards

Flashcards in The Autoimmune Disease Deck (10):
1

Outline the processes that enable central and peripheral immune tolerance.

  • Self-reactive T or B cells are destroyed. 
  • Central tolerance - destroy self-reactive T or B cells before they enter the circulation. 
  • Peripheral tolerance - destroy or control any self-readctive T or B cells which do enter the circulation. 

2

Outline how T cells are selected in the thymus. 

  • T cells don't bind MHC - death by neglect - apoptosis. 
  • T cells bind MHC too strongly - apoptosis - negative selection. 
  • T cells bind self-MHC weakly - positive selection - signal to survive. 

3

Explain the 3 different mechanisms of peripheral tolerance. 

Ignorance:

  • Antigen present in too low a concentration to reach the threshold for T cell receptor triggering. 
  • Immunologically privileged sites - eye, brain. 

Anergy:

  • Naive T cells need costimulatory signals in order to become activated. 
  • Most cells lack costimulatory proteins + MHC class II. 
  • Naive T cells become anergic when they encounter MHC/peptide without costimulatory protein. 

Regulation:

  • A subset of helper T cells - Treg (T regulatory cells) - inhibit other T cells. 

4

Outline 4 therapeutic strategies used in autoimmune disease. 

  1. Anti-inflammatories - NSAID, corticosteroids. 
  2. T + B cell depletion. 
  3. Therapeutic antibodies - block adhesion. 
  4. Antigen-specific therapies in development - e.g. glatiramer acetate - increases Treg. 

5

Autoimmune diseases mediated by which Ig can cross the placenta? Name 2 examples. 

  • IgG - small enough to cross the placenta. 
  • Myasthenia gravis, Graves' disease. 

6

Outline the pathophysiology of Graves' disease. 

  • Autoantibodies bind to TSH receptor. 
  • This stimulates excessive TSH production. 
  • Results in hyperthyroidism. 
  • Disease can be transferred with IgG antibodies. 

7

Give 4 reasons why self tolerance might break down?

  1. Loss of/problem with regulatory cells. 
  2. Release of sequestered antigen. 
  3. Modification of self - e.g. citrullination. 
  4. Molecular mimicry - e.g. rheumatic fever - antibodies against streptococcus pyogenes cross-react with cardiac muscle. 

8

Outline the involvement of MHC in autoimmune disease. 

  • MHC is associated with more disease than any other region of the genome. 
  • Each copy of chromosome 6 carries 3 different MHC class I and 3 MHC class II genes. 
  • High levels of genetic variation - polymorphism. 

9

Name 2 examples of organ-specific and systemic autoimmune diseases. 

  • Organ-specific - Grave's disease, T1DM.
  • Systemic - systemic lupus erythematosus (SLE), rheumatoid arthritis. 

10

Outline the mechanisms of T cell damage in autoimmune pathology and give 2 examples of conditions where T cells are implicated. 

  • Direct killing by CD8+ cytotoxic T lymphocytes. 
  • Self-destruction induced by cytokines e.g. TNF-α. 
  • Activation of macrophages - bystander tissue destruction. 
  • Multiple sclerosis, T1DM.