Autoimmunity

Question 1

When are self reactive lymphocytes normally eliminated from the body

Answer 1

central tolerance (neg selection)- in thymus if t or b cells bind to strongly

peripheral tolerance-removal of self reactive lymphocyte in periphery (anergy, deletion, suppression)

Question 2

monogenic autoimmune disorders= target gene and pathogenesis (3)

Answer 2

1. autoimmune regulator- impaired self antigen expression
2. FOXP3- decreased number of natural tregs
3. FAS, FASL- failure to perform activation induced death

Question 3

Which alleles are strongly associated with autoimmunity in males and femals

Answer 3

HLA genes

MHC b27- males
MHC DR genes- females

Question 4

What percentage of those with an autoimmunity are women

Answer 4

75%

Question 5

What is molecular mimicry and result of it

Answer 5

pathogens may express antigens that resemble host self molecules
–> immune system targets body tissues thinking its the microbe

Question 6

What occurs in graves disease and what type of hypersensitivity is it

Answer 6

Type II hypersensitivity

IgG autoantibodies bind to TSH causing overlord of thyroid horomones

Question 7

What occurs in hashimotos thryroditis and what type of hypersensitivity is it

Answer 7

Type II/IV hypersensitivity

directed against thyroid gland (mc middle aged women)

Question 8

Pathogenesis of hashimotos thyroids and s/s

Answer 8

• autoantibodies (b) attack thyroid cells and fix complement
• autoreactive CTLs induce apoptosis

:thryroid tissue destroyed causing decline in thyroid hormone causing dry skin, brittle hair etc

Question 9

What occurs in systemic lupus erythematosus and type of hypersensitivity

Answer 9

Type3hypersensitivity
IgG autoantibodies for immune complexes and deposits into tissues causing painful/swolen its, fever, chest pain, hair loss etc

Question 10

What are the specific antinuclear antibodies that cause systemic lupus erythmatosus

Answer 10

Anti-dsDNA
Anti-histone
Anti-centromeres

Question 11

Risk factors of developing Systemic lupus erythmatosus

Answer 11

female sex
vit d
female sex horomones
cigs
fam hx

Question 12

What is rheumatoid arthritis + type of hypersensitivity

Answer 12

type 3 hypersensitivity

-chronic inflammation of synovial jts

Question 13

1st stage of rheumatoid arthritis, what does it generate

Answer 13

Non specific inflammation and generation of disease encouraging antibodies

-generation of rheumatoid factor (causes IgG antibodies to stick together) + antibodies to citrullinated peptides (ACPs)

Question 14

2nd stage of rheumatoid arthritis

Answer 14

• amplification in synovium
• -RF and ACPs can aggravate macrophages and fix complement in tissue
• -Intense synovial inflammation (IL1, TNF A, IL6)
• -CD4 and CD8 T cells recruited to lesion

Question 15

3rd stage of rheumatoid arthritis

Answer 15

chronic inflammation

• -Pannus invades the space within its (granulation)
• -Enzymes released by inflammatory cells cause tissue damage

Question 16

risk factors of rheumatoid arthritis

Answer 16

Family hx
HLA DRB1 aleles
smoking
female
age onset 40-50

Question 17

s/s rheumatoid arthritis

Answer 17

inflammation of small its of hands + feet
Fatigue
low grad efever
loss of appetite

Question 18

What is psoriasis and why type of hypersensitivity is it

Answer 18

type 4 hypersensitivity

autoimmune disease of the skin causing red, itchy patches that may become scaly/white

Question 19

pathogenesis of psoriasis

Answer 19

auto reactive th17 cells in skin become activated and produce il17
-IL17 activate keratinocytes promoting proliferation and secretion of chemokine that recruits inflammatory innate cells

Question 20

What occurs in 30% of psoriasis cases and tx

Answer 20

psoriatic arthritis

tx: steroid creams, UV light, monoclonal antibodies

Question 21

What is MS and what type of hypersensitivity is it

Answer 21

type 4 hypersensitivity

-demylenation of myelin sheath surrounding nerve axons in the CNS (white/grey matter lesions in brain and spinal cord)

Question 22

pathogenesis of MS

Answer 22

Damage to BBB increases the trans endothelial migration of activated T cells/ B cells/ Macrophages into CNS

• Peripheral immune cells and CNS resident cells (microglia) secrete range of inflammatory mediators that demylenates neurone
• autoreactive t cells against myelin antigens

Question 23

Onset of MS and risk factors

Answer 23

20-50 onset, mc in women

• EBV in adolescence and early adulthood
• HLADRb1 alleles
• smoking
• lack of sun exposure/low vit d
• obesity during adolescence

Question 24

Types of MS and mc one

Answer 24

relapsing remitting (85%)
secondary progressive
primary progessive
progressive relapsing ms

Question 25

What is type I diabetes and what type of hypersensitivity is it

Answer 25

Chronic inflammatory destruction of the insulin producing b cells in the islets of langerhans of pancreas

Type 4 hypersensitivity

Question 26

What immune cells are responsible for type 1 diabetes

Answer 26

CD8 CTLs Primaily

CD4 t cells/macrophages as well

Question 27

What does type 1 diabetes have a strong genetic link to

Answer 27

HLA DRB1 alles

prior viral infection

Question 28

What is used to treat autoimmunity

Answer 28

• Corticosteroids
• NSAIDs
• Cytotoxic drugs (interfere w DNA synthesis in rapidly replicating cells)
• Disease modifying agents