STEVENS CHAPTER 15: AUTOIMMUNITY Flashcards
(174 cards)
1
Q
phenomenon that describes where the immune system could attack the very host it was intended to protect
A
horror autotoxicus
2
Q
horror autotoxicus is aka
A
fear of self-poisoning
3
Q
who described horror autotoxicus , as well as the year
A
Paul Erlich, early 1900s
3
Q
describe autoimmune diseases
A
disorders in which immune responses are targeted toward self-antigens and result in damage to organs and tissues
4
Q
cause of autoimmune diseases
A
T-cell-mediated immune responses
5
Q
T-cell-mediated immune responses are aka
A
autoantibodies
6
Q
the autoantibodies are directed against what
A
host antigens
7
Q
how many autoimmue diseases have been discovered
A
> 100
8
Q
T or F:
Autoimmune diseases are the second leading cause of chronic illness and death
A
F
first leading cause
9
Q
how many percent of the world’s population has an autommine disease
A
5%
10
Q
how many people in the US have autoimmune diseases
A
50 million
11
Q
under normal circumstances, the immune system should be able to differentiate what
A
self from nonself/foreign
12
Q
the ability of the immune system to accept self-antigens and not initiate a response agianst them
A
self-tolerance
13
Q
loss of self-tolerance can lead to
A
autoimmune diseases
14
Q
self-tolerance is a type of what tolerance
A
immunologic tolerance
15
Q
describe immunologic tolerance
A
state of immue unresponsiveness that is directed against a specific antigen
16
Q
how is self-tolerance developed
A
lymphocytes must be “educated” to distingusig self-antigens from foreign
17
Q
two levels of educating lymphocytes
A
central and peripheral
18
Q
where does central tolerance occur
A
central or primary lymphoid organs
19
Q
central or primary lymphoid organs
A
thymus, bone marrow
20
Q
part of the thymus where T cells encounter self-antigens
A
surface of the thymic epithelial cells
21
Q
what happens to T cells that express T-cell receptors (TCR) with strong affinity for self-antigens
A
deleted by apopotosis
22
Q
process where T-cells with strong affinity to self-antigens are apoptized
A
negative selection
23
Q
negative selection occurs with what cells
CD markers
A
1) double-positive CD4+/CD8+ cells
2) single-positive CD4+ or CD8+ cells
24
where are double-positive CD4+/CD8+ cells found
cortex
25
where are single-positive CD4+ or CD8+ cells found
medulla
26
T or F:
double-positive cells are less mature than single-positive cells
T
27
T or F:
some self-reactive CD4+ T cells are not deleted
T
28
happens to CD4+ cells that were not apoptized
differentiate into T regulatory (Treg) cells
29
function of Tregs
specifically inhibit immune responses to self-antigens
30
what happens to self-reactive B cells
stimulated to rearrange their immunoglobulin genes rather than being deleted
31
process where self-reactive B cells are induced to downregulate the expression of their receptors
receptor editing
32
what does B cells that undergo self-editing develop
state of unresponsiveness to antigens
33
the state of unresponsiveness to antigen is referred to as
anergy
34
T or F:
some self-reactive lymphocytes can escape to the secondary lymphoid organs
T
35
level of tolerance where lymphocytes that recognize self-antigens in the secondary lymphoid organs are incapable of reacting with those antigens
peripheral tolerance
35
peripheral tolerance resulted from anergy is caused by
1) the absence of costimulatory signal from an APC
2) binding of inhibitory receptors suc as CTLA-4
36
what does CTLA-4 do
prevents T-cell activation
37
aside from anergy, peripheral T-cell tolerance can be resulted from:
1) inhibition by Tregs
2) death by apoptosis
38
3 fates of self-reactive B-c-ells
1) deleted by apoptosis
2) anergic after repeated stimulation with self-antigens
3) receive inhibitory signals
39
self-reactive B-cells receive inhibitory signals through what receptor
CD22
40
what happens if self-tolerance fail even after peripheral tolerance
autoimmunity
41
developmetn of autoimmune disease is throught to be caused by what fators:
1) genetics
2) environmental factors
3) defects in immune regulation
42
T or F:
autoimmune diseases are more prevalent among family members than among related individuals
T
43
T or F:
autoimmune diseases are more prevalent among dizygotic twins that monozygotic twins
F
more prevalent among monozygotic twins
44
its presence is associated with the risk of developing an autoimmune disorder
human leukocyte antigen (HLA) types
45
HLA-527 allele is strongly associated with the development of what disease
ankylosing spondylitis
46
what is ankylosing spondylitis
inflammatory dse that affects the spine
47
chance of individuals with HLA-B27 in developing ankylosing spondylitis compared to individuals without the allele
100 times greater
48
how do differences in MHC genes influence the development of autoimmune disease
because the structure of MHC can determine whether or not a self-antigen can attach to the peptide-binding cleft of the molecule and be presented to T cells
49
non-MHC genes that can be associated with development of autoimmune disease
1) PTPN22
2) IL2RA
3) CTLA4
4) BLK
5) AIRE
50
role of PTPN22
T and B cell receptor signaling
51
role of IL2RA
T-cell activation and maintenance of Tregs
52
role of CTLA4
has an inhibitory effect on T-cell activation
53
role of BLK
B-cell activation and development
54
role of AIRE
promotes the development of T-cell tolerance in the thymus
55
endogenous and environmental factors
1) hormonal influence
2) tissue trauma and release of cryptic antigens
3) microbial infections
4) epigenetics and modification of self-antigens
5) interaction between factors
56
T or F:
women are 2.7 times more likely to acquire an autoimmune dse than men
T
57
why do women have higher risk of developing an autoimmune dse
higher absolute CD4+ cell counts and higher levels of circulating antibodies than men
58
what type of immune response estrogens promote
type 2 helper cell (Th2) immune response-> more B cell, more antibody
59
what type of immune response androgens promote
type 1 helper cell (Th1) immune response->activation of CD8+ T cells
60
what does prolactin do to the immune system
stimulate both humoral and cell-mediated immune responses
61
how does cryptic antigens associate with T and B lynphocytes
T and B cells will not be "educated" about them since they are sequestered-> no tolerance
62
how are cryptic antigens suddenly exposed to uneducated lymphocytes, triggering an immune response
1) inflammation
2) tissue trauma/tissue damage
63
the concept of uneducated lymphocyte being ignorant to cryptic antigens is called
immunologic ignorance
64
how can pathogens trigger an autoimmune response
1) molecular mimicry
2) bystander effect
3) superantigens
4) polyclonal B cell activation
5) microbiota
65
mechanism of bystander effect
pathogens induce a local inflammatory response that recruits leukocytes
66
recruitment of leukocytes in the bystander effect mechanism leads to
stimulation of APCs to release cytokines that nonspecifically activate T cells
67
how is the recruitment of T cell can induce autoimmunity
since some T cells are specific for self-antigens
68
the expansion of immune response to unrelated antigens is called
epitope spreading
69
describe superantigens
proteins produced by microbes that can bind to both class II MHC molecules and TCRs, regardless of antigen specificity
70
examples of superantigens
staphylococcal enterotoxin that can cause food poisoning and toxic shock syndrome
71
how can superantigens act as potent T-cell mitogens
by activating a large number of T cells with different antigen specificities
72
viruses that can cause polyclonal activation of B cells
1) EBV
2) CMV
73
how endogenous bacteria from the microbiota induce risk of autoimmune response
they stimulate innate immune responses
74
how does endogenous bacteria stimulate innate immune response
through the interaction with Toll-like receptors (TLRs)
75
how does the interaction of endogenous bacteria with TLRs risk autoimmune response
triggers cell signaling pathways->production of IFNα->stimulate adaptive system cells
76
decrease in number and function of Tregs can perpetuate the activity of what cells
autoreactive cytotoxic T cells and hyperactive B cells, which produce autoantibodies
77
what can activated lymphocytes through stimulation of adaptive immune response do
produce inflammatory cytokines that provide signals to stimulate the innate system cells
78
modifications in gene expression that are not caused by changes in the originaal DNA sequence
epigenetics
79
external factors can lead to epigenetic changes by
1) increasing or decreasinf methylation fo cytosine bases
2) modifying histones
3) abnormal regulation of microRNAs
80
How can epigenetic changes contribute to autoimmune disease?
By causing over- or underexpression of immune-related genes, leading to immune system imbalance.
81
chemical changes to proteins after they’re made (translated)
post-translational modifications
82
biochemical processes in post-translational modifications
1) acetylation
2) lipidation
3) citrullination
4) glycosylation
83
citrullination of collagen is associated with what autoimmune disorder
rheumatoid arthritis
84
glycosylation of myelin is associated wtih what autoimmune disorder
multiple sclerosis
85
2 classifications of autoimmune diseases
systemic and organ-specific
86
disease that targets joints, bone; tissues in some cases
rheumatoid arthritis
87
RA autoantibodies
1) Anti-CCP (cyclic citrulinated proteins)
2) rheumatoid factor
3) Antinuclear antibodies (ANAs)
88
disease that targets upper respiratory system, lungs, blood vessels
granulomatosis with polyangiitis (Wegener's granulomatosis)
89
associated autoantibodies of Wegener's granulomatosis
1) antineutrophil cytoplasmic antibodies (ANCA); c-ANCA pattern
2) Rheumatoid factor
3) ANAs
90
disease that targets multiple cells and organs throughout the body, including the skin, joints, kidneys, brain, heart, lungs
systemic lupus erythematosus (SLE)
91
SLE autoantibodies
1) antibodies to DNA and Sm (ANAs)
2) Phospholipid antibodies
3) Ab to RBCs
4) Ab to platelets
5) Ab to lymphocytes
6) Ab to ribosomal components
7) Ab to endothelium
8) RF
92
T or F:
SLE is a systemic disease
T
93
statistics of people affected by SLE
40->200 persons per 100,000
94
peak age of SLE onset
20-40 years
95
women to men affected by SLE ratio
9:1
96
ethnicity where SLE is more common
African Americans and Hispanics than Caucasians
97
5 year survival rate of SLE in 1950s
50%
98
5 year survival rate of SLE in the present time
90%
99
environmental factors that can cause SLE
1) UV lught
2) certain medications
3) infectious agents
100
why is exposure to sunlight a trigger for lupus px skin
because of their photosensitive rashes
101
medications that can induce lupus-like syndrome
1) procainabmide (arrythmia)
2) hydralazine (high BP)
3) isoniazid
4) chlorpromazine
5) isoniazid
6) quinidine
7) methyldopa
102
how many genetic loci is associated with lupus
20
103
HLA associated with increased risk of developing lupus
HLA-A1
B8
DR3
104
typical lupus px has autoantibodies with an average of
three
105
what play a central role in the pathologic mechanisms of lupus
B cells and autoantibodies they produce
106
in lupus, the presence of autoantibodies can precede the onset of disease by how many years
9-10 years
107
in lupus, abnormal apoptosis may cause the excess release of what cellular constituents
DNA and RNA
108
what antibodies are highly specific for lupus
antibodies to dsDNA
109
anti-dsDNA and complement proteins have been found in what organs in px with lupus
kidneys and skin
110
why is accumulation of IgG to dsDNA the most pathogenic
because it forms complexes of an intermediate size that become deposited in the glomerular basement membrane (GBM)
111
other possible deficiencies in lupus patients
defects in:
1) complement receptors on phagocytic cells
2) receptors for Fc portion of immunoglobulins
3) deficiencies of C1q, C2, C4
112
how does lupus cause tissue damage
immune complexes activate complement-> inflammatory response-> wbcs go to site of infx->cytokines release
113
what type of hypersensitivity causes hemolytic anemia and thrombocytopenia
antibody-mediated cytotoxic (type II) hypersensitivity
114
in lupus, vascular damage by antibodies to endothelial cells can cause what
vasculitis and neuropsychiatric symptoms
115
phospholipid antibodies in pregnant lupus px is associated with
increased miscarriage, stillbirth, and preterm delivery
116
percent of babies born with neonatal lupus from pregnant women with SLE
8%
117
neonatal lupus is associated with what nuclear antigens
SS-A/Ro
SS-B/La
118
T or F:
Symptoms of neonatal lupus are transient
T
when maternal Abs have cleared the infant's circulation
119
neonatal lupus resolves within how many months of age
6-8 months
120
in utero, what complication can occur to fetuses with mothers with SLE
heart block
121
what antibody do mothers with SLE have that can cause a heart block to fetuses
SS-A
122
first symptoms to appear in SLE
1) fatigue
2) weight loss
3) malaise
4) fever
5) anorexia
123
most frequently reported manifestation of px with lupus
joint involvement
124
why is joint pain the frequent complaint of lupus px
90% of them are subject to polyarthralgias (joint pain) or arthritis
125
second most common sign of lupus after joint involvement
skin manifestations
126
percent of lupus px with skin manifestations
80%
127
how does erythematous rash appear in lupus px
when exposed to UV light
128
lupus in Latin means
"wolf-like"
129
describe the skin lesions in discoid lupus
have central atrophy and scarring
130
major cause of illness and death in lupus
nephritis
131
most dangerous type of lesion (kidney damage) in lupus
diffuse proliferative glomerulonephritis
132
diffuse proliferative glomerulonephritis is characterized by
cell proliferation in the glomeruli-> end stage renal dse
133
cardiac effects of lupus
1) pericarditis
2) tachycardia
3) ventricular enlargement
4) pleuritis with chest pain
134
neuropsychiatric effects of lupus
1) seizures
2) mild cognitive dysfunction
3) psychoses
4) depression
135
hematologic effects of lupus
1) anemia
2) leukopenia
3) thrombocytopenia
4) lymphopenia
136
11 clinical criteria of lupus
1) acute cutaneous lupus
2) chronic cutaneous lupus
3) oral ulcers
4) non-scarring alopecia
5) synovitis
6) serositis
7) renal involvement
8) neurological symptoms
9) hemolytic anemia
10) leukopenia
11) thrombocytopenia
137
6 immunologic criteria of lupus
1) elevated antinuclear antibody titer
2) elevated anti-dsDNA titer
3) presence of antibody to the Sm nuclear-antigen
4) antiphospholipid antibody
5) low complement levels
6) positive direct Coombs' test w/o hemolytic anemia
138
in most cases, a px must satisfy how many of 17 criteria of lupus
4 out of 17
139
T or F:
the 17 criteria of lupus is definitive for diagnosis
F
140
treatment for mild symptoms of lupus
high dose of aspirin or anti-inflammatory drugs
141
treatment for lupus skin manifestations
hydroxychloroquine or chloroquine (antimalarials)
142
antimalarial drugs are thought to inhibit the signaling of what TLRs
7, 8, 9
143
treatment used for acute fulminant lupus, lupus nephritis, or CNS complications
systemic corticosteroids
144
mechanism of systemic corticosteroids as lupus treatment
suppress the immune response and lower antibody titers
145
most common causes of death in lupus px
infection, heart dse, renal involvement
146
general laboratory tests used in initial evaluation of lupus
1) CBC w/ plt
2) urinalysis
147
T or F:
ESR can be elevated even though CRP tends to be low or normal
T
148
most commonly measured complement in lupus
C3
149
why is serum complement levels low during disease flares in lupus
result of complement consumption by immune complexes
150
first test typically done when SLE is suspected
screening test for antinuclear antibodies (ANA)
151
what are ANAs
autoantibodies directed against antigens in the nuclei of mammalian cells
152
T or F:
ANAs are specific for SLE
F
153
ANAs are present in what diseases
connective tissue diseases:
1) mixed connective tissue disease
2) Sjogren's syndrome
3) scleroderma
4) polymyosititis-dermatomyositis
5) RA
other conditions:
6) chronic infx
7) cancer
8) pregnancy
154
T or F:
healthy persons can be ANA-positive
T
5% of healthy persons, 30% of elderly
155
characteristics of ANA under immunofluorescence
homogenous
peripheral
speckled (most common)
nucleolar
156
most specific diagnostic for SLE especially if C3 levels are low
Anti-dsDNA
157
specific antibody of SLE, not found in other autoimmune dse
Anti-Sm (Smith)
158
antibody used for diagnosis of drug-induced SLE
anti-histone
159
antibody found in 20-30% of SLE px
anti-RNP
160
antibodies that may cross the placenta causing neonatal lupus with cardiac manifestations
Anti-SS-A/Ro
161
antibodies that may cross the placenta causing neonatal lupus with skin manifestations
Anti-SS-B/La
162
detection of these antibodies in lupus vis ELISA that correlates with prolonged PT and APTT
anti-phospholipid
163
nuclear antigens directed against ANAs
1) dsDNA
2) ssDNA
3) histones
4) nucleosomes
5) centromere proteins
6) extractable nuclear antigens (ENAs)
164
antigens that are ENAs
1) ribonucleoproteins (RNP)
2) Sm antigen
3) SS-A/Ro
4) SS-B/La
5) Scl-70
6) Jo-1
7) PM-1
165
5 major classes of histones
H1, H2A, H2B, H3, H4
166
what histone antibodies are present in drug-induced lupus
H2A and H2B
167
conditions with antihistone antibodies
1) RA
2) Felty's syndrome
3) Sjogren's syndrome
4) systemic sclerosis
5) primary biliary cirrhosis
168
antibody found in lupus that correlates with disease severity
nucleosome antibodies
169
In which autoimmune condition are Anti-RNP antibodies found at high titers?
Mixed Connective Tissue Disease (MCTD)
170
staining of the nucleolus in IIF is mainly caused by antibodies to one of three nucleolar components namely:
1) fibrillarin
2) RNA polymerase I
3) PM-1
171
antibody to fibrillarin is common in what disease
systemic sclerosis
172
