Tolerance and Immunity

Question 1

Autoimmunity

Answer 1

results from a disruption in, or failure of, the host’s immune system to protect self structures

Question 2

Tolerance

Answer 2

prevention of an immune response against self structures

Question 3

Central tolerance

Answer 3

deletion of lymphocytes before they mature

Question 4

Where does central tolerance happen?

Answer 4

primary lymphoid tissue

Question 5

Peripheral tolerance

Answer 5

either renders self-reactive lymphocytes non responsive or actively generates inhibiting lymphocytes

Question 6

Where does peripheral tolerance happen?

Answer 6

peripheral system

• lymphoid tissue
• peripheral tissue
• regulatory tissue

Question 7

Antigen sequestration (evasion)

Answer 7

• protects tissue-specific antigens from exposure to the immune system

Question 8

Central tolerance (elimination)

Answer 8

limits development of auto-reactive T and B cells

Question 9

Peripheral tolerance (engagement)

Answer 9

regulates auto reactive cells in the circulation

• Treg
• Regulatory CD8+ T cells
• Regulatory B cells
• Myeloid-derived suppressor cells

Question 10

Regulatory CD4+ T cells (Treg)

Answer 10

down regulate immune responses upon TCR/ag-MHCII engagement

Question 11

Diabetes Mellitus

Answer 11

• autoimmune attack against insulin-producing beta cells in pancreas
• CTLs infiltrate the pancreas and activate macrophages
• This is followed. by cytokine release and production autoantibodies, which may activate complement or ADCC
• eventually DTH response
• Type 4

Question 12

Myasthenia Gravis

Answer 12

• Autoantibodies produced that bind acetylcholine receptors on motor end plates of muscle
• Block the normal binding of acetyl choline, induce complement- mediated lysis
• Progressive weakening of muscles
• treatments are aimed at increasing acetyl choline levels, decreasing Ab production, and or removing Ab

Question 13

Systemic Lupus erythematosus

Answer 13

• Auto-ab against DNA, histones, other self structures
• Symptoms result from specificity of Ab produced
• Type III hypersensitivity reactions often induce damage

Question 14

Multiple sclerosis

Answer 14

auto-reactive T cells form inflammatory lesions along myelin sheaths around nerve fibers in the brain and spinal cord

Question 15

Rheumatoid arthritis

Answer 15

• Auto-Ab reactive with determinants in the Fc region of IgG

- Form immune complexes and activate complement cascades

Question 16

Autoimmunity- Systemic

Answer 16

• due to disruption in immune regulation

Question 17

Autoimmune polyendocrine syndrome type-1

Answer 17

mutations in the AIRE gene

Question 18

IPEX syndrome

Answer 18

In mutations in the FoxP3 gene

Question 19

Genetics factors in susceptibility to autoimmunity

Answer 19

• Certain MHC genes linked to specific autoimmune disorders such as HLA-B27 expression
• Mutations in AIRE and FoxP3 genes result in particular immunodeficiencies that affect central and peripheral tolerance
• Genes that encode cytokines connected to Th17 function

Question 20

Environmental Factors in susceptibility to autoimmunity

Answer 20

• diet differences may lead to gut microflora differences
• different geographic areas may have different endemic disease
• inducement may be multifactorial

Question 21

Multifactorial

Answer 21

• combining a series of triggering events that cross an individuals systems of tolerance over a threshold
• infections and molecular mimicry
• infections that induce genetic changes
• Damages/stress events that expose sequestered Ag
• Foods that alter gut microbial balance, promoting chromic inflammation and hypersensitivity reactions