Type 1 Diabetes

Question 1

Possible environmental factors

Answer 1

• Infection
• Of the beta cells
• molecular mimicry
• proinflammatory
• Hygiene hypothesis
• Microbiome
• Climate/nutrition (vitamin D)

Question 2

Development of T1D

Answer 2

• An immune response needs to be elcited against beta cel antignes
• The response needs to develop strong proinflammator characteristic
• Regulatory control of the autoimmune responses needs to be ineffective to allow the response to become chronic and destroy the beta cells

Question 3

Initiation of the immune response

Answer 3

• Cell death in the islets can occur both physiologically and as a result of infection
• Dendritic cells take up released beta cell antigen
• Release of proinflmmatory cytokines in response to infection/cell stress/ death
• Cytokines activate DCs and promote presentation of the beta cell antigens to T cells

Question 4

Effector mechanisms

Answer 4

• Activated CD4+ T-cells
• promote macrophage-mediated killing
• activate islet antige-specific B cells so that they differentiate into antibdy-producing plasma cells
• Antbodies can bind beta cells
• complement killing as well as binding to Fc receptors on macrophages
• Activated B cells can function as antigen-presenting cells, further enhancing the anti-beta-cell immune response
• Proinflammatory environment can licence the DCs to cross-present antigen to beta cell antigen-specific CD8+ T ells.
• Cytolytic CD8+ T cells can kill beta cells through release of cytolytic granules containing perforin and granzymes, as well as through Fas-FasL interaction

Question 5

Loss of regulatory control

Answer 5

Temered by regulatoy cell subsets

• NK T-cells
• Forkhead box regulatory (Treg) cells