PoD - Hypersensitivity

Question 1

what is an autoimmune disease?

Answer 1

• a failure or breakdown of immune system that maintains tolerance to self-tissues

Question 2

how does loss of tolerance occur?

Answer 2

• abnormal selection or lack of control of self-reactive lymphocytes (T & B)

Question 3

are there environmental or genetic risk factor for AI?

Answer 3

• susceptibility genes mutate leading to failure of self tolerance
• tissue injury and inflammation due to environmental factors leads to activation of self-reactive lymphocytes

Question 4

how do we treat AI disease?

Answer 4

• need to use a targeted selective approach

- target the offensive immune activation while leaving the rest of the immune system intact

Question 5

what is hypersensitivity?

Answer 5

• a harmful, over-exaggerated immune response that may produce tissue injury and cause serious disease

Question 6

what are the main categories of hypersensitivity?

Answer 6

• 4 categories
• Type I, II, II, IV
• type I, II and III are all antibody mediated
  type IV is T cell mediated

Question 7

describe type 1 hypersensitivity

Answer 7

• immediate hypersensitivity = allergy
• drives allergic response when in contact with a solute antigen
• IgE is the mediator
• stimulates T helper cell reactions and IgE production
• IgE sensitises mast cells and gets repeated exposure to the allergen
• activation of mast cells leads to release of mediators (cytokines/histamine)
• mediators impact vascular/smooth muscle response in immediate reaction (vasodilation, oedema, bronchoconstriction, tissue damage)

Question 8

describe differences between type 2 and 3 hypersensitivity

Answer 8

• both responses are mediated by IgG
• type 2 = deals with cell/matrix antigen/type 3 = is soluble antigen
• type 2 = antibodies bind specifically to tissue antigens, this recruits and activates inflammatory cells which causes tissue injury (glomerulonephritis/systemic lupus)
• type 3 = complexes of antibodies and antigens are formed in the circulation and deposited in blood vessels, induces vascular inflammation and ischemic damage to tissues

Question 9

what is a type 4 hypersensitivity response?

Answer 9

• T cell mediated immune diseases
• cytokine-mediated inflammation - antigen presenting cells present antigen to CD4/8 T cells which causes release of cytokines = inflammation
• T cell-mediated cytotoxicity - = CD8 cells involved leads to cell killing
  examples - type 1 diabetes, rheumatoid arthritis, MS

Question 10

what is immunological tolerance?

Answer 10

• state of indifference or non-reactivity towards a substance that would normally be expected to excite an immune response
• antigens can be self or foreign
• prevents adaptive responses that are damaging
• can be exploited by microbes/tumours

Question 11

what are the categories of AI disease?

Answer 11

• systemic - AI process is spread throughout body and affects multiple tissue/organs
• organ-specific - AI process directed against one organ specifically

Question 12

what are examples of AI disease?

Answer 12

• lupus - relapsing/remitting chronic systemic disease. Characteristic - lupus erythematous cell - macrophages engorged with apoptotic neutrophils. immune complex mediated damage of glomeruli leading to glomerulonephritis
• type 1 diabetes - destruction of the insulin-producing b cells of the islets of Langerhans in the pancreas. Insulin replacement is main therapy. Islet damage is mediated mainly by CD4+ T helper cells - reactive with islet auto antigens