Lecture 17: Autoimmunity Flashcards
1
Q
What transcription factor is responsible for the tissue-specific proteins in the thymus (that contribute to self-tolerance)?
A
AIRE
2
Q
What do Treg cells do?
A
Shut down the immune response once a pathogen in cleared (they also play a role in autoimmunity)
3
Q
How is type II autoimmunity similar to type II hypersensitivity?
A
- mediated by Ab
2. specific for cell surface and extracellular matrix
4
Q
How is type III autoimmunity similar to type III hypersensitivity?
A
- mediated by Ab
2. caused by immune complexes deposited in tissues
5
Q
How is type IV autoimmunity similar to type IV hypersensitivity?
A
Mediated by T cells
6
Q
T/F: IgE is the most common mediator of autoimmune diseases
A
F: IgE mediates NO autoimmune diseases
7
Q
What is autoimmunity?
A
Adaptive immunity specific for self-determinants
8
Q
What are the 5 main tolerance mechanisms?
A
- negative selection (within the bone marrow and thymus)
- Expression of tissue specific proteins in the thymus for negative selection (driven by the transcription factor AIRE, which induces expression of proteins that are not normally expressed in the thymus)
- Lymphocytes do NOT have access to certain tissues
- T reg cells suppress autoimmune responses
- Anergy is induced in autoreactive B/T cells (“peripheral” tolerance; no 2nd signal)
9
Q
Autoimmune Hemolytic Anemia is a type ____ autoimmune disease because:
A
II; it is IgG and IgM mediated
10
Q
Autoimmune Hemolytic Anemia is caused by:
A
An antibody (IgG and IgM) specific for surface antigens of erythrocytes
This can result in activation of the classical complement pathway (thus RBC are opsonized and taken up by phagocytes with Fc receptors OR killed by MAC)
11
Q
Autoimmune Hemolytic Anemia is detected by what test?
A
Direct Coomb’s hemagglutination assays
- -Patient’s washed RBCs are combined with reagent
- -Antihuman Ab in the reagent binds to human Ab on RBCs, which link them together
- -Positive test = clump of RBC
12
Q
This enzyme links platelets and blood vessels with clots:
A
von Willdebrand Factor
13
Q
Autoimmune Thrombocytopenic Purpura is a type ____ autoimmune disease because:
A
II; it is IgG mediated
14
Q
Autoimmune Thrombocytopenic Purpura is caused by:
A
IgG-mediated inhibition of an enzyme responsible for cleavage of von Willdebrand factor (vWF)
**According to robbins, the IgG is against GpIIb/IIIa
15
Q
Autoimmune Thrombocytopenic Purpura is characterized clinically by:
A
1) Low platelet count
2) Bruising
3) Neuro symptoms
4) Microangioplastic hemolytic anemia–RBC are damaged as they are pushed through microscopic clots
16
Q
What is a schistocyte?
A
Broken RBC (can be visualized in a blood smear)
17
Q
Treatment for Autoimmune Thrombocytopenic Purpura (one common and 5 uncommon)
A
Plasmapheresis (exchange transfusion with plasma from healthy donors)
“Unusual Treatments”
- -Rutiximab (CD20-specific humanized monoclonal on the surface of all B cells; this trx will deplete B cells)
- -RhoGam (only works in RhD positive patients)
- -Steroids
- -Splenectomy (since this is the site where most platelets are taken up and removed)
- -Gamma Globulin
18
Q
Good Pasture syndrome is caused by:
A
An Ab specific for type-IV collagen
which lines basement membranes throughout the body
19
Q
Good Pasture syndrome is characterized by:
A
Inflammatory responses (initiated by the Ab)
- -Kidney damage (reduced function)
- -Pulmonary hemorrhage
20
Q
Good Pasture syndrome is a type _____ autoimmune disease.
A
II
21
Q
Good Pasture syndrome is treated by:
A
- Plasma exchange (plasmapheresis)
2. Anti-inflammatory drugs
22
Q
Scleroderma is a type _____ autoimmune disease because:
A
II, mediated by IgG
23
Q
Scleroderma is caused by:
A
inflammatory destruction of:
–vascular endothelial cells of arterioles
–smooth muscle cells
These cells are replaced with collagen and other fibrous materials
24
Q
Scleroderma is characterized by:
A
- -localized or systemic symmetrical skin thickening
- -hard, smooth, ivory colored areas of hardened skin
- -neurological symptoms (because the brain is affected by inflammation/replacement)
- -sometimes rheumatoid factor (involved in nonspecific production of Ab that have specificity for Fc of other Ab)
25
Scleroderma is diagnosed via the presence of:
1) anti-nuclear Abs
2) anti-topoisomerase Abs
3) anti-centromere Abs (IgGs)
26
Scleroderma is treated by:
Increasing blood flow to the extremities (which will be on a patient-bypatient basis; there is no standard treatment)
27
Acute Rheumatic Fever is a type _____ autoimmune disease because:
II; mediated by IgM or IgG
28
Acute Rheumatic Fever is caused by:
antibodies that are produced during response to bacterial infection (Group A Streptococcus pyogenes)
29
Acute Rheumatic Fever is involved in molecular mimicry because:
Some streptococcal cell-wall carbohydrate components are very similar to determinants expressed in heart tissue
After an infection occurs, the bacteria specific Ab cross-react with the heart tissue determinants, causing inflammation
30
Acute Rheumatic Fever is characterized by:
```
Inflammation of heart tissue, causing:
1. Heart valve scarring
2. Myocarditis
3. Chest pain
(symptoms occur after 1 mo)
```
31
Pemphigus vulgaris is a type _____ autoimmune disease because:
II; IgG4 mediated
32
Pemphigus vulgaris is caused by:
Loss of cohesion in keratinocytes
in the epidermis
Due to IgG-mediated autoimmunity against 2 proteins: desmoglein 1 and 3
33
Pemphigus vulgaris is characterized by:
(Painful) chronic skin blistering
34
Pemphigus vulgaris is diagnosed by:
Punch biopsy of lesion
Immunofluorescent Staining
*IgG4 Ab is considered pathologic
35
Pemphigus vulgaris is treated with:
1. Corticosteroids
2. Anti-Inflammatory drugs
3. Rituximab (CD20-specific monoclonal Ab; B cell surface marker)
36
Autoimmune diseases affecting the thyroid:
1. Hashimoto's thyroiditis
2. Graves'
3. Subacute thyroiditis
4. Idiopathic hypothyroidism
37
Autoimmune diseases affecting the pancreas (islets of langerhans)
Type I DM
| Type 2 DM
38
Autoimmune disease affecting the adrenal glands
Addison's
39
Grave's disease is caused by:
Ab that bind to TSH receptor (mimics the binding of TSH to TSH receptor results in overproduction of thyroid hormone)
40
Symptoms of Graves':
```
heat intolerance
nervousness/irritability
warm/moist skin
weight loss
enlargement of the thyroid
bulging eye syndrome
characteristic stare (eye muscle inflammation)
```
41
What determines whether or not an autoimmune condition will be able to affect a developing fetus?
If it is IgG-mediated or not (because they cross into fetal circulation via the Brambell receptor
42
Myasthenia gravis is caused by:
antibodies specific for acetylcholine receptors on muscle
cells:
--Ab binds to ACh receptors, which are then endocytosed and degraded
--example of an antagonist autoantibody
43
Myasthenia gravis is characterized by:
Muscles that less sensitive to neuronal stimulation (due to loss of receptors)
Weakness progresses, starting with facial muscles
44
Myasthenia gravis is treated with (2):
1. anti-inflammatory drugs
2. Pyridostigmine, which inhibits acetyl cholinesterase (longer ACh half-life results in better competition for receptor binding)
45
Myasthenia gravis is a type _____ autoimmune disease
II
46
Grave's disease is a type _____ autoimmune disease
II
47
Subacute bacterial endocarditis is a type _____ autoimmune disease
III
48
Subacute bacterial endocarditis is caused by:
IgG-mediated Ab that bind to microorganisms colonizing damaged valves
49
Subacute bacterial endocarditis is associated with what bacteria?
Streptococcus viridans
50
Typically, patients only develop subacute bacterial endocarditis if...
already suffered damage to their heart valves
51
The actual inflammation in subacute bacterial endocarditis is caused by:
1. cytokines produced by phagocytes (which recognize the opsonized bacteria)
2. anaphylatoxins produced during the complement cascade
52
Mixed Essential Cryoglobulinemia is a type _____ autoimmune disease
III
53
Mixed Essential Cryoglobulinemia is caused by:
Cryoglobulins are produced and bind to the Fc regions of Ab (causing immune complex disorder)
*act similarly to rheumatoid factor
54
Mixed Essential Cryoglobulinemia is often seen in patients with:
B cell proliferative disorder
55
Mixed Essential Cryoglobulinemia often follows what infection?
Hep C
56
The three symptoms of Mixed Essential Cryoglobulinemia:
Meltzer's triad:
purpura
arthralgia
myalgia
57
Systemic Lupus Erythmatosis is caused by:
autoantibodies specific for many self macromolecules (DNA, histones, ribosomes, ect.)
When cells die and release soluble macromolecules (normal process):
--immune complexes form
--deposited in vessels/kidneys/joints
leading to more inflammation
58
Systemic Lupus Erythmatosis is a type _____ autoimmune disease
III
59
Systemic Lupus Erythmatosis is characterized by:
"butterfly" facial rash
loss of kidney function:
--thickening of basement membrane
--infiltration of neutrophils
60
Why is Lupus a progressive disease?
Once inflammation occurs, it leads to further cell destruction and priming of immune responses
This leads to MORE inflammation, more cell destruction, etc etc etc
61
How are responses primed in lupus?
A CD4 T cell specific for self (e.g. histone protein) can provide stimulation for B cells that are also specific for other determinants in the complex
This B cell can then present to T cells specific for any proteins in the complex
(he was unclear on this process**)
62
What disease is caused by auto-Ab that serve as receptor antagonists?
Myasthenia gravis
63
Insulin dependent DM is a type _____ autoimmune disease
IV
64
Insulin dependent DM is caused by:
destruction of insulin producing β cells in Islets of Langerhan’s by CD8 CTLs
CD8's recognize beta-cell determinant
65
What is histologically different about the pancreas of IDDM patients?
Lymphocyte infiltration (primarily CD8 T cells)
66
Insulin dependent DM is treated by:
daily injections of pig/bovine insulin
67
What if IDDM patients make an immune response to non-human insulin?
an immune-complex hypersensitivity results
| and they get human recombinant insulin
68
RA is a type _____ autoimmune disease mediated by:
IV; TH1 cells
69
RA is caused by:
Autoreactive T cells that initiate inflammatory responses in the joints (damages cartilage and ligament tissue)
And B cells--evidenced by rituximad success
70
What is a common (but not required) immuno feature of RA?
Production of rheumatoid factor (IgG, IgM, and IgA) specific for Fc of other Ab
71
RA is treated with: (2)
1) TNF-alpha specific Ab (infliximab)
| 2) Use of ADCC to deplete B cells with anti-CD20 Ab (rituximab)
72
What does rituximab do?
Monoclonal Ab that targets B cells for destruction, mostly by NK cells
73
Sjögren’s Syndrome is a type _____ autoimmune disease mediated by:
IV; autoreactive T cells
74
Sjögren’s Syndrome is caused by:
autoreactive T cells initiate inflammatory destruction of exocrine glands (i.e. tears
and saliva production)
75
Sjögren’s Syndrome is characterized by:
dry eyes
dry mouth
(sometimes skin, nose and vaginal dryness)
76
Sjögren’s Syndrome is diagnosed via: (2)
1) Schirmer test to measure tear output (most important)
2) anti-nuclear Ab and rheumatoid factor tests
* rheumatoid factor will not necessarily be present
77
Sjögren’s Syndrome is treated with:
Treatment of symptoms (artificial tears, punctal plugs, goggles)
78
Multiple sclerosis is a type _____ autoimmune disease mediated by:
IV, TH1 CD4
79
Multiple sclerosis is caused by:
TH1 cells specific for myelin basic protein initiate immune response directed at myelin sheath of nerve cells (demyelination in CNS)
80
Multiple sclerosis is characterized by:
```
motor weakness
impaired vision
lack of coordination
spasticity
progressive, but very variable
```
81
Multiple sclerosis is treated by:
(Reduction of symptomatic attacks)
1) immunosuppressive drugs
2) IFN-β1
82
Multiple sclerosis is diagnosed by the presence of:
Very few specificities of (oligoclonal) IgG in CSF
83
T/F: There is no association between MHC and autoimmune disorders.
F: Certain MHC I or II are associated with certain autoimmune diseases
84
Bacteria that is responsible for several autoimmune conditions through mimicry:
Campylobacter jejuni
85
How do reactions occur to immuno privileged sites?
1. Trauma to site (e.g. one eye) results in release of antigens that are otherwise sectioned off
2. Self antigens are carried to secondary lymph, where they activate T cells
3. Effector T cells return to attack site or both sites (e.g. placenta or testes)
86
Molecular mimicry of group A strep causes:
Rheumatic fever
87
How does MHC presentation cause molecular mimicry?
the same MHC presents a pathogen peptide AND a self peptide that mimics it
Once the T cell is activated by the pathogen (presented on MHC), it will respond to the self peptide on MHC as well
(This leads to macrophage activation, inflammation)
88
Guillain Barré Syndrome is a type _____ autoimmune disease mediated by:
II; IgG specific for gangliosides
89
Guillain Barré Syndrome is caused by:
Immune response made against pathogen (C. jejuni) cross-reacts with IgG specific for gangliosides--this results in demyelination
(gangliosides = common components of human nerve tissues)
90
Guillain Barré Syndrome is treated by: (2)
1) plasma exchange
| 2) immunosuppressive drug
91
Guillain Barré Syndrome is characterized by:
- -symmetrical weakness of lower limbs, which rapidly ascends to upper limbs
- -symmetrical weakness of face (difficulty swallowing and breathing; drooling)
- -partial paralysis often occurs
92
T/F: Typically, Guillain Barré patients fail to regain function of limbs.
F: Usually patients regain most motor function with appropriate and effective treatment
93
What often precedes Guillain Barré Syndrome?
Infection with Campylobacter jejuni
94
Wegener’s Granulomatosis is a type _____ autoimmune disease mediated by:
II; IgG produced following a bacterial or viral infection
95
Wegener’s Granulomatosis is treated by: (2)
1) plasma exchange
| 2) anti-inflammatory drug treatment
96
Wegener’s Granulomatosis is characterized by:
1) rhinitis (pain, stuffiness, nose bleeds) and conjuctivitis--usually first
2) lung infiltrates
3) glomerulonephritis (rapidly progressive)
4) granulomas (usually found in all affected tissues, but not always)
97
Wegener’s Granulomatosis is caused by:
anti-neutrophil cytoplasmic Ab bind to neutrophils, causing them to become activated
Neutrophils upregulate adhesin expression and bind to vascular endothelial cells
Neutrophils then degranulate causing damage to the vasculature (vasculitis)
98
Most common determinant involved in Wegener’s Granulomatosis?
proteinase-3
99
Three diseases associated with molecular mimicry:
Wegener’s Granulomatosis
Guillain Barré Syndrome
Acute rheumatic fever
100
In this disease, Ab cross react with cardiac tissue:
Acute rheumatic fever
101
In this disease, vWF cleavage is inhibited:
Thrombocytopenic Purpura
102
In this disease, Ig that become insoluble at lowered temperatures are produced:
Mixed Essential Cryoglobulinemia
103
These Ig behave similar to rheumatoid factor (i.e. they bind Fc of Ab regions)
Cryoglobulins (binding to Fc causes an immune complex disorder)
104
This disease is associated with inflammation that damages cartilage and ligament tissues:
Rheumatoid Arthritis
105
This disease is associated with loss of keratinocyte adhesion:
Pemphigus vulgaris
106
T/F: All autoimmune diseases involve a breach of T cell tolerance
T (I got this from the textbook)
107
Why are more genetic disorder linked to MHC II?
Because more autoimmune disorders are linked to CD4 (I got this from the textbook)
108
Little SusieJo Epstein noticed that walking on her hands (something she can usually do for 0.25 mile) was becoming increasingly difficult. When she complained of difficulty chewing gum and swallowing it, her auntie took her to the ER (where eye drooping was noted). Tests detected impaired nerve-muscle transmission, and she was treated with pyridostigmine. What Ab does her blood test show?
Anti-ACh receptor antibodies
109
T/F: Smokers with Good Pasture syndrome often have pulmonary hemorrhage.
T: Smoking damages alveoli basement membrane; due to this damage, anti-type-IV-collagen can get into the basement membranes and deposit/activate/rupture
(I got this from the textbook)
