Autoimmunity I

Question 1

road to autoimmunity

Answer 1

Genetic factors + infection and environemntal exposure ..

immune regulation –> autoimmunity

Question 2

AIRE deficiency

Answer 2

incomplete deletion of T cells in the thymus

Question 3

CTLA4 deficiency

Answer 3

insufficient control of costimulation

Question 4

FoxP3 deficiency

Answer 4

Treg cell dysfunction

Question 5

eyes

Answer 5

immune priviledged site

Question 6

autoimmunity results when tolerance fails

Question 7

central tolerance

Answer 7

happens primarily during selection in primary lymphoid organs

Recognition of self antigen
- apoptosis (deletion)
- change in receptors (receptor editing by B cells)
- Development of regulatory T lymphocytes (CD4+ T cells only)

Question 8

if an autoreactive cell escapes the central tolerance, the cell goes into

Answer 8

peripheral tolerance
- anergy
- apoptosis (deletion)
- suppression

Question 9

AIRE promotes

Answer 9

central tolerance in the thymus

AIRE present
- negative selection of self reactive T cells: deletion

AIRE absent
- failure of negative selection , T cell would move into the periphery and react to self antigens - Autoimmunity

Question 10

what is AIRE?

Answer 10

transcription factor found in medullary thymic epithelial cell

Question 11

AIRE stands for

Answer 11

auto immune regulator, that is a transcriptional factor involved in transcriptional activation

Question 12

mutations in AIRE

Answer 12

results in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED OR APS1) a syndrome charaterized by autoantibodies to multiple self antigens and lymphocytic infiltration of exocrine glands.

Question 13

AIRE drives transcription of

Answer 13

some, but not all peripheral antigens in medullary thymic epithelal cells (mTECs)

Question 14

AIRE may have other roles in negative selection

Answer 14

AIRE deficient mice develop autoimmune responses against antigens AIRE doesn’t regulate. Several genes associated with chemokine expression and antigen presentation are also downregulated in these animals

Question 14

AIRE may have other roles in negative selection

Answer 14

AIRE deficient mice develop autoimmune responses against antigens AIRE doesn’t regulate. Several genes associated with chemokine expression and antigen presentation are also downregulated in these animals

Question 15

if T cell recieves signal 1, without signal 2

Answer 15

signaling block –> unresponsive T cell (anergic T cell)

Question 16

CTLA-4 structure

Answer 16

similar to CD28

upregulated on activated T cells

Question 17

CTLA4 binds B7

Answer 17

with 20x the affinity of CD28

CTLA4 antagonizes the actvity of CD28

Question 18

CTLA4 effect on T cell

Answer 18

dampens T cell responses on reduces their proliferation

• deficiency in CTLA4, causes widespread autoimmunity

Question 19

CTLA4 and CD28 binding on T cell

Answer 19

signal block - inactivation of T cell activation

Question 20

Blocking and removing b7 on APC

Answer 20

Reduced B7 costimulation - inhibition of T cell activation

Question 21

core regulator of Treg cells

Answer 21

FoxP3

Question 22

FoxP3 deficiency in humans

Answer 22

IPEX

present early in life, treated by bone marrow transplant

Question 23

Fas-FasL

Answer 23

• First apoptosis signal receptor
• Cells that express Fas are susceptible to death
• Cells that express FasL are capable of inducing death of cells expressing Fas
• Many T cells upregulate Fas expression after activation as part of the contraction phase.

Question 24

caspase 3 and caspace 9

Answer 24

induce apoptosis

Question 25

immunologically priviliged sites

Answer 25

• brain
• eye
• testis
• uterus (fetus)
• hamster cheek pouch

Question 26

Damage to a privilieged site result sin sympathetic opthalmia

Answer 26

• Trauma to one eye results in the release of sequestered intraocular protein antigens
• Released intraocular antigen is carried to lymph nodes and activates T cells
• Effector T cells return via bloodstream and encounter antigen in both eyes

Question 27

molecular mimicry

Answer 27

• the same MHC molecule presents both a pathogen peptide and a self made peptide that mimics it
• Naive T cells is activated by the pathogen peptide presented by the particular MHC molecule
• Effector Th1 cell responds to the self-peptide mimic and activates the macrophage, causing inflammation.

Question 28

influence of genetics on autoimmunity - monozygotic twins

Answer 28

Strong, but not complete. In SLE monozygotic twins 25% of both twins develop disease.

Question 29

MHC on autoimmunity

Answer 29

DR3/4 correlated with diabetes

Question 30

DR2

Answer 30

low representation in diabetic community

Question 31

chronic nature of autoimmune disease

Answer 31

• normally during an acute immune responswe the antigen is cleared
• in autoimmune syndromes, for most part, antigen persists and the disease enters a chronic phase.
• during this time due to inflammation and tissue damage, more self antigens are exposed to the immune system leading to amplification of the response

Question 32

in absence of AIRE patient would develop

Answer 32

APECED