Tolerance and Autoimmunity Flashcards Preview

MSS-IHL Final Exam > Tolerance and Autoimmunity > Flashcards

Flashcards in Tolerance and Autoimmunity Deck (69):
1

tolerance

unresponsiveness to self antigens

2

autoimmunity

results when immune system recognizes self antigens

3

anergy

functional unresponsiveness

4

central tolerance

takes place in central lymph organs
-B cells in bone marrow
-T cells in thymus

ex/ negative selection

5

peripheral tolerance

what mature lymphocytes undergo out in body
-lymph nodes and spleen

ex/ T reg function, anergy, cell death

6

T cell development?

positive and negative selection

ones that recognize MHC - selected for

central tolerance

negative selection if high affinity for MHC and self-antigens

7

Foxp3

transcription factor
signals to become a T reg cell

8

where are T reg cells formed?

thymus

9

when does selection for T reg cells occur?

intermediate affinity
-upregulate Foxp3

10

function of T reg cell

check on immune system to keep it from going out of control

also involved transplantation tolerance

11

peripheral T cell tolerance?

Regulatory T cells in the periphery

12

what do T reg cells express?

Foxp3 and CD25

13

CD25

on T reg cells
is the IL-2 receptor

14

what do T reg cells secrete?

IL-10 and TGF-beta

15

T reg cells depend on what for survival?

IL-2

16

T reg cells?

CD4+

17

anergy?

peripheral T cell tolerance
-occurs when T cells activated without co-stimulation**

18

what happens without co-stimulation in T cell activation?

leads to signaling block
-leads to anergy of T cell

19

what can lead to anergic T cell?

1 signal without co-stimulation
2 engagement of inhibitory receptors (CTLA-4)

20

co-stimulation in T cells?

B7:CD28 interaction

21

what could break anergy?

a very strong danger signal

22

cell death in T cells?

peripheral tolerance
-normally anti-apoptotic signals are higher
-absence of co-stimulation has more pro-apoptotic signals

23

Fas and FasL?

upregulated when T cell recognizes self antigen

results in apoptosis

24

what can mutations in Fas result in?

children with autoimmune diseases

25

tolerogenic antigens?

usually in generative organs
high concentrations

long-lived exposure (bc its self)

26

immunogenic antigens?

in blood and periphery

short lived

27

central B cell tolerance?

in bone marrow
if recognizes self antigen (T-independent antigen)
-can die (apoptosis)
-can undergo receptor editing

28

peripheral B cell tolerance

anergic
-if self antigen recognition without T cell help

apoptosis
-exclusion from the lymphoid follicle

29

immature B lymphocyte?

IgM+ and IgD-

30

tolerance-sensitive cell for T cells?

CD4+ CD8+ (double positive) T cells

31

effector mechanisms of autoimmunity?

circulating autoantibodies and autoreactive T lymphocytes

32

principle factors in development of autoimmunity?

susceptibility genes and environmental triggers

33

Type I diabetes

autoimmune destruction of beta cells in pancreas
-genetic predisposition - Dq8
-thought to be an environmental trigger

can predict the onset based on autoantibodies

goes through phases:
-genetic predisposition
-insulitis
-pre-diabetes (loss of first phase insulin response)
-diabetes

34

insulitis

beta cell death (type I diabetes)

35

types of autoimmune disease?

organ-specific and systemic

36

what sex has more autoimmune diseases?

female
-much more likely in women
-don't know why

37

factors contributing to autoimmunity

genes, infections, and environmental factors

38

HLA-B27

ankylosing spondylitis
autoimmune disorder

39

HLA-DR4

rheumatoid arthritis
autoimmune disorder

40

HLA-DR3/DR4

Type I diabetes mellitus

41

HLA-DR4

pemphigus vulgaris
autoimmune disorder

42

AIRE

gene that if we lose will result in autoimmune polyendocrine syndrome (APS-1)

responsible for expressing self antigens in the thymus (no negative selection)

43

Foxp3

defects in this gene lead to deficiency of regulatory T cells

can lead to X-linked polyendocrinopathy and enteropathy (IPEX)

44

Fas

defect leads to autoimmune hypoproliferative syndrome (ALPS)

defective apoptosis of self-reactive T and B cells in periphery

45

IPEX

from loss of Foxp3 gene

46

what would cue you to think a single gene defect?

multiple autoimmune disease at early age

47

action of IL-10

suppress IgE production

48

action of TGF-beta

inhibit IgE prduction

49

what do T reg cells secrete?

IL-10 and TGF-beta

50

how does IL-4 and IL-13 induce IgE formation?

activate STAT6 to induce isotype switching

51

how does TGF-beta induce IgE formation?

inhibit Id2-repressor of IgE isotype switching

52

treatment of IPEX

bone marrow transplant
-to restore Foxp3 expressing cells

poor prognosis for IPEX

53

triggers of autoimmunity?

presence of microbe induces co-stimulators on the APC presenting self antigen

molecular mimicry - microbe antigen resembles the self tissue

54

streptococcus pyogenes?

rheumatic fever

molecular mimicry for protein on heart muscle

activated T cells will attack cardiac muscle

55

what is pathogenic in lupus?

antibody

56

what is pathogenic in diabetes?

T cells

57

what is pathogenic in myasthenia gravis?

antibody

58

what is pathogenic in multiple sclerosis?

T cells

59

autoantibodies

can be stimulatory or blocking

60

stimulatory autoantibodies?

ex/ bind the TSH receptor and result in upregulation of thyroid hormones

Graves disease

61

inhibitory autoantibodies?

ex/ bind the acetylcholine receptor (without activation)
-prevent the muscle activity

myasthenia gravis

62

effect of corticosteroids?

immunosuppression

63

cyclophosphamide

immunosuppression

64

multiple sclerosis

Th1 cell response against mylein

more likely in women HLA-DR2

65

oligoclonal immunoglobulins in central nervous system for MS?

never been exposed to all these new self antigens!

66

treatment of multiple sclerosis?

corticosteroid, cyclophosphamide, IFN-beta

67

treatment of MS with IFN-gamma not favorable?

because promoting Th1 cytokines (don't want that)

68

why feed MBP (myelin basic protein) to mice to prevent EAE?

because this would place self-antigen in their bodies (induce peripheral tolerance)

69

can you induce EAE in CD28 knockout mice?

no because no co-stimulation

CTLA-4 mice would be really terrible EAE