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Block 6 Week 2 > AutoImmune Diseases- Hypersensitivity types II, III, IV > Flashcards

AutoImmune Diseases- Hypersensitivity types II, III, IV Flashcards

1
Q

What do you need to have autoimmunity?

A

T cells with receptors for self
susceptibility genes like MHC that allow self peptides to be presented
A trigger that upregulates co-stimulatory molecules on the APC (infection or tissue damage)

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2
Q

What 2 costimulatory moecules are needed to make a T cell reaction?

A

B7 and CD28

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3
Q

What is molecular mimicry?

A

when a microbe resembles a self antigen and thus you get a self-reactive T cell

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4
Q 
Which MHC class defect will cause suscpetiblity to:
 ankylosing spondylitits or acute anterior uveitis?
A

MHC 1

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5
Q 
Which MHC class defect will cause suscpetibility to:
good pasture's syndrome
MS
Graves' disease
Myasthenia Gravs
Systemic lupus erythematosus
Type I insulin-dependent diabetes mellitus
Rheumatoid arthritis
pemphigus vulgaris
hashimotos thryoiditis
A

MHC II

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6
Q

What kind of hypersensitivity reaction is this:

autoantibodies against surface antigens on blood cells

A

Autoimmune Type II hypersensitvity disease

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7
Q

What diseases are associated with autoantibodies aginst surface antigens on blood cells?

A

autoimmune hemolytic anemia

autoimmune (idiopathic) thrombocytopenic purpura

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8
Q

What kind of hypersensitivity reaction is this:

autoantibodies against cell surface antigens on fixed tissues

A

autoimmune type II hypersensitivity diseases

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9
Q

What diseases are associated with autoantibodies against cell surface antigens on fixed tissues?

A

good pasture syndrome
acute rheumatic fever
pemphigus vulgaris

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10
Q

What kind of hypersensitivity reaction is this:

autoantibodies against cellular receptors?

A

autoimmune type II hypersensitivity diseases

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11
Q

What diseases are associated with autoantibodies against cellular receptors?

A

myasthenia gravis

graves’ disease (hyperthyroidism)

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12
Q

In autoimmune thrombocytopenia, autoantibodies are formed against the (blank), a plasma membrane integrin

A

gpIIb:iiia

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13
Q

In thrombocytopenia, autoantibodies are formed against the gpIIb:IIIa, a platelet plasma membrane integrin
Antibody-coated platelets are destroyed by phagocytic cells in the (blank) and (blank).
How do you treat this?

A

liver and spleen

corticosteroids

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14
Q

WHat is this:
biopsy of early skin lesions show epidermal disruption and blister formation. There are deposits of IgG4 and antibodies to desmoglein 3.

A

Pemphigus vulgaris

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15
Q

How do you treat pemphigus vulgaris?

A

prednisone and cyclophosphamide

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16
Q

What antibodies do you find in good pasture syndrome?

A

alpha 3 chain of type IV collagen found in the glomerulus and alveolar basement membranes

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17
Q

What does good pasture syndrome cause?

A

causes a proliferative, rapidly progressive glomerulonephritis and a necrotizing hemorrhagic interstitial pneumonitis

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18
Q

How do you treate good pastures syndrome?

A

plasmapheresis (removes pathogenic circulating antibodies)

and immune suppression

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19
Q

How does graves’ disease work?

A

Antibodys mimic TSH and bind to TSH receptor to induce hyperthyroidism and thus pathophysiology

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20
Q

How does myasthenia gravis work?

A

antibodies bind to ACh receptors and inhibits acetycholine binding resulting in paralysis

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21
Q

(blank) is rare autoimmune disease that is usually associated with antagonistic autoantibodies directed against acetylcholine receptors

A

myasthenia gravis

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22
Q

How do you treat myasthenia gravis?

A

acetylcholinesterase inhibitors
and
plasmapheresis, immunosuppressants

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23
Q

Who are affected more with graves disease, men or women?

A

women

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24
Q

Graves hyperthyroidism has been linked to polymorphisms in immune-function genes like (blank) and (blank) alleles.

A

CTLA4 and HLA-DR3 allele

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25
What is this: Thyroid-stimulating IgG autoantibody binds to the TSH receptor and mimics the action of TSH (agonist), stimulating the release of thyroid hormones; no feedback inhibition to the pituitary.
Graves disease
26
What is this: | Pathology includes diffuse hyperplasia of the thyroid, ophthalmopathy (exophthalmos), and dermopathy.
graves disease
27
What are the lab findings in graves disease?
elevated free T4 and T3, depressed TSH levels
28
What is scary about have an autoantibody disease when pregnant?
the autoantibodies can cross the placent and cause disease in the fetus and newborn infant
29
What is the symptom of myasthenia gravis?
muscle weakness
30
What is the symptom of graves' disease?
hyperthyroidism
31
What is the symptom of thrombocytopenic purpura?
bruising and hemorrhage
32
What is the symptom of neonatal lupus rash and/or congenital heart block?
photosensitive rash and/or bradycardia
33
What is the symptom of pemphigus vulgaris?
blistering rash
34
How long do autoimmune type III immune complex diseases usually last?
they persist for life
35
How prevalent is systemic lupus erythematosis (SLE)?
1 in 200 with a predilection for females of childbearing age
36
Is there a genetic component associated with SLE?
yes HLA-DR3
37
What system does SLE attack?
all of them
38
What are the clinical findings of SLE?
photosensitive rash, polyarthritis, serositis, fatigue
39
What usually leads to death in SLE?
lupus nephritis and CNS involvement
40
What laboratory finding can you find in systemic lupus and how?
presence of ANA via anti-double-strandd DNA and anti-Smith ribonucleoprotein
41
(blank) deficiency is an important risk factor for SLE
complement (hypocomplementemia may occur during flares)
42
explain how one gets systemic lupus erythematosis (SLE)
-something caues apoptosis of cells and inflammation -nuclei of cells are inadequately cleared and large amount of nuclear antigens are around -linked recognition causes self-reactive T and B cells to interact and make nuclear antibodies -complexes of the antigens and antibodies bind to Fc receptors on B cells and dendritic cells and are endocytosed - endosomal TLR stimulate B cells to produce more antibodies and activate dendritic cells to produce interferons and cytokines which further enhances immune response and causes more apoptosis. Net results in a cycle of antigen release and immune activation resulting in production of high affinity autoantibodies
43
anti-DNA antibodies are generated by (blank)
linked recognition
44
Explain linked recognition
T and B cells specifc for histone proteins are floating aroun. B cell internalizes some self DNA pieces (histones) and then acts as an APC to T cells which will bind to it and become stimulated and release cytokines and CD40L to bind to CD40 on B cells and activate more B cells
45
Which organ systems are most affected by systemic lupus erythematosus?
- consititutional symptoms (fatigue, fever, weight loss) - mucocutaneous involvement (malar rash, alopecia, mucosal ulcers, discoid lesions) - musculoskeletal involvement - serositis - glomerulonephritis - neuropsychiatric involvement - autoimmne cytopenia
46
Why are peope that have SLE so at risk to have renal failure?
because there DNA immune complexes get stuck in the kidneys and cant be removed and make sort of a clot that results in renal failure.
47
How can you tell whether you have drug induced LE or SLE?
drug induced has high amount of antihistone and SLE has high amounts of anti-double stranded DNA and anti-SM and nuclear RNP
48
What does sjogren syndrom have high levesl of ?
RNP
49
What does scleroderma have high levels of?
centromeric proteins
50
WHat does systemic sclerosis have high levels of?
DNA topoisomerase
51
What does inflammatory myopathy have high levels of?
histidyl-tRNA synthetase
52
Type IV hypersensitivity is mediated by (blank)
T cells
53
What are the 2 ways you can get Type IV hypersensitivity via T cells?
Cytokine-mediatd inflammation which is where APC connect with CD4 T ells to release cytokines and infammation OR T Cell-mediated cytolysis which is where APC connect with CD8 and these cells kill tissue
54
What are 2 organ-specific autoimmune diseases mediated by T cells?
Multiple sclerosis and hashimoto thyroiditis
55
What are 2 systemic autoimmune diseases mediated by T cells?
systemic sclerosis | sjogren syndrome
56
How do you get MS?
T cells with receptors for many neuroantigens dont get destroyed in the thymus, an unknown trigger causes inflammation n the CNS and ten you get diruption of BBB that allows these neuroantigen specific T ells into the CNS and microglial cells activate these T cells to release mediators and demyelinate axons
57
What are the 3 mediators in MS that promote demyleination?
CF ROS IL-1beta
58
What are 2 frequent presentations of symptoms in MS?
visual compromise and stiffness/weakness
59
What do oligoclonal bands of IgG in the CSF indicate?
clonal expansion of B-cell clones
60
HOw do you typically treat MS acutely? what about chronically?
IV corticosteroids | Alpha and Beta interferons and glatiramer acetate
61
What is the prevalence of MS, and what gender do you find it in most? is there a genetic component?
females (10x more likely) | yes HLA DR2
62
What do CD8 cells need to mess up tissues?
FASL and FAS
63
What is the prevalence of hashimoto thyroiditis?
1 in 200
64
How does hashimoto thyroiditis work?
make autoantibodies agaoins thyroglobulin and thyroid peroxidase
65
In Hashmimoto thyroidits, what will you see in a thyroid?
infiltration of parenchyma by a mononuclear inflammatory infiltrate contain small lymphocytes, plasma cells and well-deveoped germinal centers
66
What are the lab values of hashimoto thyroiditis?
low T3 and T4 levels and high levels of TSH
67
Hashimoto thyroiditis increases the risk for what other disease?
B cell non-hodgkin lymphomas
68
(blank) is characterized by excessive fibrosis in a variety of tissues from collagen deposition by activated fibroblasts.
Systemic sclerosis (SS)
69
What is the benign form of systemic sclerosis?
limitd scleroderma OR | CREST syndrome
70
How can you tell if you have limited scerleroderma or CREST syndrome?
via the presence of anti-centrome antibody
71
What does CREST stand for?
C = Calcinosis in skin and elsewhere R = Raynaud's phenomenon, sensitivity to cold E = Esophageal dysmotility from submucosal fibrosis S = Sclerodactyly from dermal fibrosis T = Telangiectasias
72
What is diffuse scleroderma? How do you diagnosis this?
the worst form of SS | anti-DNA topoisomerase I antibody (Scl-70)
73
(blank) presents with CREST findings and arterial intimal thickening and proliferation (hyperplastic arteriosclerosis "onion skin" lesion) leading to malignant hypertension with arterial fibrinoid necrosis, thrombosis, and renal infarction.
Diffuse scleroderma
74
What do half of Systemic Sclerosis patients die of?
renal disease
75
What is the mechanism behind systemic sclerosis (scleroderma)?
CD4 t cells respond to an antigen that accumulates in the tissues and release cytokines that activate inflammatory cells and fibroblasts
76
Systemic sclerosis is a rare disorder with a female-to-male ratio of (blank) to (blank)
3:1
77
What age do most people get systemic sclerosis?
50 to 60 years old
78
What is raynauds phenomenon?
episodic vasoconstriction of the arteries and arterioles of the extremities. (it is seen in al patient and preceds other symptoms in 70% of patients)
79
How often do you see dysphagia in SS patients?
50% of the time
80
What is this disease: | decrease in tears and saliva (sicca syndrome)
sjogren syndrome
81
Why do you get decrease in tears and saliva in sjogren syndrome?
you get lymphocytic infiltration and fibrosis of lacrimal and salivary glands
82
What is the mechanism of action behind sjogren syndrome?
an initial trigger-> local cell death-> release of self-antigens-> CD4 cell and B cells react-> inflammation, tissue damage, fibrosis-> antibodies come -> rheumatoid factor, 2 antibodies which are SS-A(Ro) and SS-B(La)
83
What are the 2 antibodies found in sjogren syndrome?
SS-A(Ro) and SS-B (La)
84
What is the prevalence of sjogren syndrome? Female to male ratio?
1 in 300 | 9:1
85
What age is sjogren syndrome most prevalent?
40-60 year old females
86
What is the dry eyes and dry mouth sjorgen syndrome caused by
T cell-mediated destruction of lacrimal and salivary glands
87
What is found in 70% of cases of sjogren syndrome?
rheumatoid factor
88
What are diagnostic for sjogren syndrome?
SS-A(Ro) and SS-B(La)
89
What is a schirmer test?
measures quantity of tears secreted
90
What will a lip biospy show us if someone has sjogren syndrome?
lymphoid foci
91
WHat drugs will you use to relieve symptoms?
pilocarpine (relieves dryness) an artificial tears

Block 6 Week 2 (7 decks)

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