Introduction to Autoimmunity and Autoimmune Diseases Flashcards Preview

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Flashcards in Introduction to Autoimmunity and Autoimmune Diseases Deck (154)
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1
Q

autoimmune disease is a breakdown in

A

immunological tolerance

2
Q

most mechanisms of peripheral tolerance focus on

A

t cells

3
Q

all antibody responses are ___ dependent

A

t cell

4
Q

if you silence t cells you also take care of

A

autoreactive b cells

5
Q

breakdown in self tolerance is

A

autoimmune disease

6
Q

immunopathologies

A

diseases where pathology is mediated by the immune response

7
Q

ex of immunopathologies

A

HSR and autoimmunity

8
Q

all autoimmune diseases are

A

chronic

9
Q

autoimmune diseases are chronic b/c they are driven by

A

antigen

10
Q

define chronic autoimmune disease

A

Chronic diseases with evidence of active immune responses but no active infection

11
Q

you can never get rid of antigen in autoimmune disease b/c

A

it is part of yourself

12
Q

autoimmunity is a problem of self vs.

A

non self discrimination

13
Q

autoimmunity is caused by ____ ___ ______ processes that normally protect the host from the action of self-reactive lymphocytes

A

failure of tolerance

14
Q

two different kinds of tolerance

A

central or peripheral

15
Q

just b/c you detect autoantibodyt does not mean that antibody plays role in

A

pathology

16
Q

autoantibodies can be

A

diagnostic or pathogenic, they don’t have to all be both

17
Q

how can antibodies not necesarilly be pathology

A

autoimmune disease causes destruction of cell - so there are antibodies against the inside of cell proteins but the intracellular cells are not what is causing the pathology

18
Q

what happens regarding selection of b cell in bone marrow

A

clonal deletion of b cells in bone marrow

19
Q

expression of tissue-specific proteins in the thymus so that they participate in negative selection of t cells is made possibel by

A

Aire

20
Q

what kind of selection of t cells in thymus

A

negative

21
Q

central tolerance

A

mechanisms that happen in central or primary lymphoid orangism

22
Q

peripheral tolerance

A

mechanisms outside of central lymphoid organs

23
Q

what tissues are immune privileged sites

A

brain, eye, testis

24
Q

exclusion of lymphocytes from certain peripheral tissue is known as

A

peripheral ignorance

25
Q

anergy can happen where

A

peripheral circulation & bone marrow

26
Q

when is anergy likely to happen in bone marrow

A

immature b cell recognizes soluble antigen

27
Q

suppression of autoimmune responses by

A

regulatory t cells

28
Q

regulatory t cells are generated

A

in thymus and outside of thymus

29
Q

what is needed for t reg

A

Foxp3

30
Q

AIRE does what

A

allows deletion of autoreactive thymocytes - what is normally not expressed in thymus can now be exprssed, so can show proteins from around the body

31
Q

review pg 8

A

pg 8

32
Q

AIRE allows for

A

negative selection of thymocytes

33
Q

selection and deletion in thymus is governed by

A

how MHC binds self peptie

34
Q

if t cell binds to MHC with low affinity what happens

A

differentates to CD4+ or CD8+

35
Q

if MHC binds self peptide with high affinity what happens

A

apoptosis

36
Q

if MHC binds self peptide with intermediate affinity what happens

A

Treg

37
Q

what is Treg positive for

A

CD4, CD25, Foxp3

38
Q

aire deficiency results in

A

multi-system autoimmune diseases

39
Q

not all self reactive cells are deleted in the

A

thymus

40
Q

how do we silence reactive cells outside of the thymus

A

peripheral tolerance

41
Q

peripheral tolerance:

A

Prevent autoreactive cells that have escaped deletion from causing pathology

42
Q

mechanisms of peripheral tolerance:

A

Inactivated (anergy)
Suppressed by regulatory T cells (Tregs)
Kept immunologically ignorant

43
Q

naive t cell requires ___ signals to be activated

A

2

44
Q

what are the two signals to activate naive t cell

A

TCR CD3

CD28 CD80

45
Q

in absence of signal 2, naive t cell will

A

become anergic - shut down permanently

46
Q

where are Treg cells generated

A

thymus and periphery

47
Q

in absence of Foxp3+ what happens

A

autoimmune disease - don’t get Treg

48
Q

cytokines secreted by Treg:

A

TGF beta and IL-10

49
Q

TGF beta direct affect on

A

T cell proliferation and differentiation

50
Q

IL-10 does what to APC

A

makes them incapable of delivering signal 2

51
Q

Foxp3 is encoded where

A

x chromosome

52
Q

IPEX syndrome is result of

A

inactivating mutation or deletion of FRoxp3

53
Q

what does IPEX syndrome stand for

A

Immune dysregulation, Polyendocrinopathy (diseases affecting multiple endocrine glands), Enteropathy (disorder of the intestines), X-linked syndrome

54
Q

treatment of IPEX

A

Hematopoietic stem cell transplantation within the first year of life.

55
Q

B cells can be anergized if they id to

A

monivalent or soluble self antigen in bone marrow

56
Q

if b cell bind to self surface antigen

A

cross link BCR

57
Q

default pathway if immature b cell binds to self

A

editing

58
Q

what is re-expressed to edit B cell

A

RAG 1 and RAG2

59
Q

what is edited in b cell if it binds to self surface antigen

A

replace light chain with alternative light chain

60
Q

rearrangement of light chains in B cells, what genes are rearranged

A

V,J

61
Q

if B cells cannot edit to make a non-self reactive what happens

A

apoptosis

62
Q

immature b cell vs. mature b cell

A

mature b ells express IgM and IgD as BCR, only constant region of heavy chain will be different b/w the two

63
Q

most people have autoreactive

A

b cell

64
Q

without help from ___ there will not be an issue with autoreactive be cell

A

t cell

65
Q

as we age we lost t cell mediated regulation and have increased chance of

A

autoantibodies

66
Q

majority of autoimmune diseases are more prevelant in

A

females than males

67
Q

most autoimmune diseases have association with particular

A

class I or II alleles (HLA)

68
Q

disease associated alleles differ in non disease associated only in

A

amino acid residues that line the peptide binding groove

69
Q

ankylosing spondylitis 95% of ppl with it express what HLA

A

B27

70
Q

what diseases are associated with HLA: B27

A

PAIR: Psoriatic arthritis, ankylosing spondylitis, ifnlammatory bowel dise, reiter’s dsyndrome

71
Q

B27 is highly associated with

A

anklyosing spondylitis

72
Q

they don’t flly understand how B27 is associated with ankylosing spondyitis

A

:(

73
Q

what disease has high incidence of DQ2 and DQ8 HLA?

A

celiac disease & Type 1 diabetes

74
Q

why is there higher association with heterozygous DQ2 and DQ8 for celiac and type 1 diabetes

A

MHC II can mix and match their alpha and beta chain - good evidence that the susceptibility allele is not DQ2 or DQ8 but a hybrid of alpha chain of DQ8 with beta of DQ2

75
Q

autoimmune disease needs 3 components:

A

MHC molecules which are able to efficiently present self antigens
A failure to delete or functionally inactivate self-reactive lymphocytes
Breakdown in Immunological Tolerance

76
Q

review pg 25

A

25

77
Q

disruptino of tissue or cell barrier by infection or traumatic injury allows the release of

A

previously unseen antigens

78
Q

the release of antigens can go to t cells via injury can result in what disease

A

sympathetic opthalmia

79
Q

sympathetic ophthalmia is usually due to

A

eye injury

80
Q

one eye is damaged and causes sympathetic opthalamia, and eventually

A

the other eye is attacked

81
Q

if somebody gets traumatic eye injury they are put on what immediately

A

immunosuppressants

82
Q

what enviornmental factors have been associated with autoimmunity

A

infectious agents

83
Q

group A streptococcus can give rise to

A

rheumatic fever

84
Q

coxsackie virus and rubella can give rise to what autoimmune disase

A

type 1 diabetes

85
Q

how can previous infections give rise to autoimmune disease? describe molecular mimicry hypothesis

A

Immunological crossreactivity between epitope on pathogen and self antigen

86
Q

disease with strong evidence for pre-existing infection giving rise to autoimmune disease is

A

rheumatic fever

87
Q

how infections agents might break self tolerance (like rheumatic fever causing autoimmune disease)

A

t cells are cross reactive with t cells

activated effector cells secreting antibody

88
Q

molecular mimicry mediated by t cells

A

pathogen peptide that resembles self peptide
generate effector t cells that react against bacterial peptide presented on MHC
once bacteria cleared, left with activated effector cells cross reactive against self antigen

89
Q

why wouldn’t t cells be activated by the self peptide, why does the virus or bacteria cause the activation

A

naive t cells require higher level of antigen to become activated

90
Q

Ab mediated molecular mimicry

A

genrate antibody against surface antigens on bacteria, they cross creact witha ntigen expressed in our tissue

91
Q

in vast majority of cases, for autoimmune diseases, we really don’t know what antigen is that triggers

A

autoimmune disease

92
Q

by the time autoimmune disease presents, body has gone on to

A

recognize many antigens

93
Q

the autoantibodies you detect during autoimmune disease may not be

A

pathogenic - may just be diagnostic

94
Q

epitope spreading, what is it

A

immune response recognizes different antigens later on in immune response than it did earlier (the immune response is spreading, not the epitope).
this is normal phenomenom in immune response

95
Q

immune resopnse can spread so that different

A

epitopes are reocgnized at different stages of disease

96
Q

intermolecular epitope spreading:

A

Response spreads to epitopes on different antigens

97
Q

intramolecular epitope spreading:

A

Response spreads to different epitopes on the same antigen

98
Q

intermolecular epitope spreading, why does it happen

A

death of cells, so get other antigens released from those dead cells

99
Q

intramolecular epitope spreading, how does it happen

A

early on in disease process, get autoantibodies (not pathogenic)
later on get autoantibodies against membrane distal epitopes to it that you give rise to, for example, blistering skin disease

pg 38

100
Q

intramolecular epitope spreading is a feature of what disease

A

pemphigus

101
Q

why would resposne spread on an epitope

A

exhaustion or deletion of t cells reactive against dominant epitope early in disease
or autoantibody generated early on proximal domain block the membrane proximal domain and can no longer get stimulation of b cells specific for AKA binding of autoantibodies masks epitope allowing production of Abs against other epitopes

102
Q

review pg 39

A

39

103
Q

for most autoimmune diseases, concordance is higher in

A

monozygotic twins vs. dizygotic twins

104
Q

for most autoimmune diseases, concordance is higher in, this means that

A

there is strong genetic component for many autoimmune diseases

105
Q

concordance rate for monozygotic twins are never

A

100%

106
Q

APCED what gene is inactivated

A

aire

107
Q

in IPEX what gene is inactivated

A

FOXP3

108
Q

inactivattion of CTLA4 can lead to

A

T cell anergy

109
Q

inactivation of Fas can lead to

A

no check on proliferation of autoreactive t cells - so autoreactive t cells accumulate

110
Q

ALPS is inactivation of

A

Fas

111
Q

usually a single gene mutation will not give rise to autoimmune diseases, most

A

autoimmune diseases do not have pin-poinaable gene, it is very complicated

112
Q

polymorphisms leading to overexpression of what in many autoimmune diseases

A

pro-inflammatory cytokines

113
Q

polymorphisms leading to underexpression fo anti-finfalmmatory cytokines leads to

A

many autoimmune diseases

114
Q

reivew pg 45

A

45

115
Q

how does gender predispose to autoimmune diseases

A

female more likely to get disease

116
Q

how is aging associated with autoimmune diseases

A

the older you get the more likely you are to have autoimmune disease

117
Q

why does aging increase autoimmunity

A

erosion of self-tolerance of t cells (thymic atrophy)
frequency 9of autoantibodies increases
altered t cell and b cell function in elderly - immune senescence

118
Q

what is immune senescence

A

Aging-associated increase in autoantibody production has been attributed to altered T cell and B cell function in the elderly

119
Q

by what age, most of thymus is replaced by fatty tissue

A

7 years

120
Q

what is thymic involution

A

it gets smaller and more fatty as you age

121
Q

thymic involution impairs

A

negative selection

122
Q

smoking can induce the production of what enzyme to increase autoimmunity

A

PAD

123
Q

what does PAD stand for

A

peptidyl arginine deiminase

124
Q

what does PAD do

A

converts Arg into citrulline

125
Q

what are first cell to infiltate site of acute inflammation

A

neutrophil

126
Q

when neutrophil exhausts itself what happens

A

it dies by apoptosis

127
Q

if you have chronic infection, how else can neutrophil die besides apoptosis

A

NETosis

128
Q

netosis

A

explosive material from neutrophils - looks like net

129
Q

when neutrophils die by netosis it basically

A

forms a trap - so it essentially explodes, extruding DNA, chromatin, all the proteins with it, and the net traps bacteria and makes it easier for monocytes and macrophages to deal with

130
Q

peptidyl arginine deiminase is released ruing

A

Netosis (death by neutrophil)

131
Q

peptidyl arginine deiminase what does it do when released via netosis

A

cittrilate proteins (like same way that cigarettes do)

132
Q

netosis shows that there may be link b/w autoimmune disease and infection, doesn’t have to be

A

specific infection

133
Q

NETs contain autoantigens that are reocnigzed in many

A

rheumatic autoimmune diseases

134
Q

once we have autoreactive t cells or b cells how does the rxn proceed

A

type II, III, or IV HSR

135
Q

most joint damage is mediated by what HSR in autoimmune disease

A

IV

136
Q

review pg 58

A

58

137
Q

most autoimmune diseases classified by:

A
organ specificity
and systemic (multiple organs targeted)
138
Q

type II and IV HSR determiend by

A

localization of auto-antigen

139
Q

type III HSR are what kind of autoimmune

A

systemic

140
Q

type III HSR not dependent on

A

anigen

141
Q

example organ specific autoimmune disease

A

Type 1 diabetes mellitus
goodpasture’s syndrome
Multiple sclerosis
grave’s disease

142
Q

type 1 diabetes mellitus is what classification of autoimmune disease

A

organ specific

143
Q

rheumatoid arthritis is what Classification of Autoimmune Disease

A

systemic

144
Q

systemic means

A

multiple organs affected

145
Q

will never get organ specific autoimmune disease mediated by

A

type III HSR

146
Q

fastest form of rejection is mediated by what/ and what type HSR?

A

pre-existing antibody

type II

147
Q

autoimmune hemolytic anemia is mediated by

A

IgG autoantibody that binds to surface or RBC

148
Q

autoimmune hemolytic anemia is what HSR

A

II

149
Q

systemic lupus erythematosus is mediated by

A

immune complexes

150
Q

systemic lupus erythematosus is what HSR

A

III

151
Q

type I diabetes is what HSR

A

IV

152
Q

REVIEW PG 62

A

62

153
Q

autoimmune diseases mediated by immune complex are what type HSR

A

III

154
Q

joint damage in RA is mediated by what HSR

A

type IV