Autoimmunity

Question 1

Mechanisms of tolerance

Answer 1

• Clonal deletion
• Clonal anergy
• Clonal ignorance
• Regulation

Question 2

Clonal deletion

Answer 2

• Deletion of self reactive lymphocytes

- Apoptosis

Question 3

Clonal anergy

Answer 3

• Silencing of self reactive lymphocytes
• Clone present but unable to respond
• Because, no co-stimulatory molecules, or a lower binding specificity- doesn’t bind properly

Question 4

Clonal ignorance

Answer 4

• Self reactive lymphocytes don;t have the opportunity to see/respond to antigen
• Antigen segregation
• eg, we may have T cell receptors for brain antigens, but its on an issue because immune cells don’t go into the brain unless there’s an injury

Question 5

Regulation

Answer 5

-Active suppression of antigen-specific lymphocytes

Question 6

Genes that predispose to autoimmunity- affect immune regulation and self tolerance

Answer 6

• Autoantigen availability and clearance
• Apoptosis (if we expose antigens that are usually inside the cells)
• Control of lymphocyte activation
• AIRE (autoimmune regulator), responsible for presentation of peripheral tissue antigens in the thymus
• Some associated with HLA locus

Question 7

General features of autoimmune diseases

Answer 7

• Tend to be chronic- relapses and remissions, damage often progressive. Intrinsic amplificatoin loops- when directed against self tissues, they exacerbate and prolong the injury or epitope spreading- immune response against one self antigen causes tissue damage
• Clinical and pathology determined by nature of the underlying immune response

Question 8

Organ specific autoimmune disease

Answer 8

Confined to particular organs or cell types
-Thyroid
Ovary
-Islet cells (T1 diabetes)
-Gastric parietal cell
-Neurologicakk

Question 9

Systemic autoimmune disease

Answer 9

-Multiple organs and systems

Question 10

Pathogenic autoantibodies

Answer 10

• Key autoantibodies assocaiated with autoimmune diseases
• Non-organ specific
• Ani-DNA antibodies: SLE
• Anti-cytoskeleton antibodies
• Organ-specific
• Anti-glomerular basement membrane: SLE, Goodpasture’s syndrome
• Anti-thyroglobulin antibodies: thyoiditis
• Anti-myelin basic protein: MS
• Anti-mitochondrial antibodies: primary biliary cirrhosis
• anti- beta cell molecules: type 1 diabetes

Question 11

Pathogenic autoantibodies

Answer 11

• Key autoantibodies assocaiated with autoimmune diseases
• Non-organ specific
• Ani-DNA antibodies: SLE
• Anti-cytoskeleton antibodies
• Organ-specific
• Anti-glomerular basement membrane: SLE, Goodpasture’s syndrome
• Anti-thyroglobulin antibodies: thyoiditis
• Anti-myelin basic protein: MS
• Anti-mitochondrial antibodies: primary biliary cirrhosis
• anti- beta cell molecules: type 1 diabetes