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Immunopath Doc - Nichols Flashcards

- Definitions of Hypersensitivity I, II, III, IV - Know most common serological tests in rheumatology and their respective diseases - Know most common therapeutic agents for immunopathologic diseases and the MOA (mechanism of action). - Know systemic approach for Systemic Lupus Erythematosus, Sjogren Syndrome, systemic Sclerosis - Understand difficulty of dx and tx transplant rejection - know features of graft vs. host disease - Know features of common congenital immunodef. diseases - Kn

1
Q

A rapid immunological reaction within minutes after presentation of antigen bound to mast cells is what type of hypersensitivity?

A

Type 1

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2
Q

What are the clinical features /characteristics of anaphylaxis?

A

Shock, edema, bronchoconstriction

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3
Q

Type 2 hypersensitivity is what?

A

IIa: Antibody-dependent
Complement-mediated
Cytotoxicity or

IIb: Antibody-dependent
Cell-mediated
Cytotoxicity

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4
Q

Immune complex-mediated hypersensitivity is what type?

  • where is it most damaging?
A

Type 3

  • Blood vessels and glomeruli
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5
Q

Cell-mediated hypersensitivity is an immunological reaction caused by

A

sensitized CD-4 T cells, sometime triggering macrophages response.

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6
Q

Anti-cyclic citrullinated peptide (anti-CCP)

A

R.Arthritis

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7
Q

Anti-centromere

A

CREST syndrome

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8
Q

Anti-Jo-1 (one type of anti synthetase)

A

Polymyositis / dermatomyositis

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9
Q

Anti-Scl70 (anti-DNA topoisomerase)

A

Systemic sclerosis, diffuse

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10
Q

Anti-RNA polymerase (anti-U3 RNP)

A

systemic sclerosis

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11
Q

Anti-U1 RNP (anti-RNP)

A

mixed connective tissue diseases

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12
Q

Anti-Smith (anti-Sm)

A

Lupus

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13
Q

Anti-dsDNA

A

Lupus

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14
Q

Anti-nuclear (ANA)

A

Lupus and other rheumatic diseases

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15
Q

Anti-SSA (anti-Ro)

A

Sjogren syndrome, neonatal lupus, subQ lupus

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16
Q

Anti-SSB (anti-La)

A

Sjogren syndrome, neonatal lupus, subQ lupus

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17
Q

Anti-MPO (myeloperoxidase)

A

microscopic polyangiitis, eosinophilic granulomatosis w/ polyangiitis (Churg Strauss)

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18
Q

Anti-proteinase3

A

granulomatosis w/ polyangiitis

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19
Q

What are some immunosuppressive drugs that are used for treating cancer that could be used as immunosuppressive therapy?

A
  • methotrexate

- cyclophosphamide

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20
Q

What are the names of 2 drugs that Nichols mentioned in his word doc that are given to transplant patients to prevent or treat transplant rejections?

  • What are their MAO?
A

Cyclosporine
- tacrolimus

  • calcineurin inhibitors
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21
Q

What does calcineurin do?

A
  • phosphatase, remove phosphate from the nuclear reg. protein in lymphocytes.
  • thus promoting translocation of protein to nucleus to act as TF for lymphocyte activation, TNF, INF-G, IL-2, IL-4.
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22
Q

About how much of calcineurin activity does Cyclosporine and Tacroliumus block at therapeutic level?

A

about half of the activity

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23
Q

What is needed for F/U when prescribing Cyclosporin and Tacroliumus?

A
  • regular blood testing
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24
Q

What does mycophenolate mofetil do?

  • what is it MOA?
  • what is it used for?
A
  • inhibits lymphocyte proliferation
  • reversible inhibitor of INP DH in purine (guanine) synthesis
  • tx autoimmune diseases, particular Lupus and preventing transplant rejection
25
What is azathioprine?
purine analogue | - tx Lupus, R.A, and other autoimmune disases
26
What is hydroxycholorquine?
- anti-malarial antibiotic w/ anti-inflammatory activities. - tx. Lupus, R.A - low toxicity
27
Define Systemic Lupus Erythematosus
- prototype multisystem autoimmune disease
28
SLE: epidemiology
Common, 13X more in women, 1/245 black women
29
SLE: pathogenesis
Failure of self-tolerance
30
SLE Gross Pathology:
non-erosive synovitis (inflammation of the synovial membrane) in 90%, 46% pleuritis 25% pericarditis peritonitis (basically, all fluid-filled cavities) - Libman-Sacks endocarditis: nonbacterial endocarditis formed by vegetation.
31
SLE micro path:
acute necrotizing vasculitis of small arteries and arterioles (fibrinoid deposit) - nephritis in 50% - cerebritis in 50%
32
SLE symptoms:
- joint pain - fever - fatigue - weight loss - pleuritic chest pain - photosensitivity - nephrotic syndrome - angina - alopecia - myalgias
33
SLE signs:
- skin rash over bridge of nose and check - edema: 1st in feet - hematuria - neuropsychiatric - oral ulcers - interarticular skin rashes - peri-ungual erythema around fingernails - alopecia
34
SLE dx:
ANA, present in 100% | also present in 15% of normal people
35
SLE tx:
corticosternoids | immunosuppressive meds
36
SLE prognosis:
90% 5 yr survival | 80% 10 yr ''''
37
Define Sjogren Syndrome
autoimmune chronic inflammatory diseases of lacrimal glands and salivary glands, causing dry eyes and dry mouth. - eye: kerato-conjunctivitis sicca - oral: xerostomia primary form: limited to eye and mouth --> sicca snydrome secondary form: associated with autoimmune disorders like R.A, lupus.
38
Sjogren Syndrome Epidemiology:
90% 35-45 y/o women | secondary form more common than primary form
39
Sjogren Syndrome: pathogenesis
T cell mediated immunological attack of self-Ag in ductal epithelial cells. - or viral infection that has tropism in cells of these glands
40
Sjogren Syndrome Gross Patho:
dry ocular and dry mouth | - enlarged salivary and lacrimal glands
41
Sjogren Syndrome Micro Path:
1) infiltration of CD4 T cells 2) destruction of gland architecture +/- plasma cells, +/- germinal centers Renal: interstitial nephritis rather than glomerulonephritis
42
Sjogren Syndrome Symptoms:
dry eyes, dry mouth
43
Sjogren Syndrome Signs:
dry mucous membrane of eyes and mouth - conjunctival ulcers - oral ulcers - enlarged salivary and lacrimal glands
44
Sjogren Syndrome Dx:
Anti-SSA, SSB.
45
Sjogren Syndrome Tx:
topical therapy - systemic cholinergic agents - hydroxychloroquine
46
Sjogren Syndrome prognosis:
notorious for developing lymphoma
47
Systemic Sclerosis definition:
chronic disease characterized by abnormal accumulation of fibrous tissue in skin and other organs Diffuse: widespread skin, early visceral limited: skin of fingers, forearms, face, late visceral involvement within context of CREST syndrome
48
Systemic Sclerosis epidemiology:
10-20 M / year F:M - 3:1 50-60 y/o most severe: black women
49
Systemic Sclerosis Pathogenesis
abnormal immune response and vascular damage leads to increase growth factors and fibrosis. CD4 T cells stimulate fibroblast to produce collagen Microvascular disease: intimal proliferation, capillary dilation, endothelial injury (increase vWF) + platelet activation --> fibrosis
50
Systemic Sclerosis gross path:
skin - areas initially edematous, ultimately fibrotic - begin in face and fingers - decrease motility leads to masklike face and clawlike hands GI involvement 90%
51
Systemic Sclerosis micro path:
dense collagen deposition in dermis - thinning of epidermis - thickening of capillary/ arterial basal lamina - vascular changes promote HTN and renal failure, in lung - pulmonary HTN and interstitial fibrosis.
52
Systemic Sclerosis symptoms:
Raynaud's phenomenon - numbness/tingling/ cyanosis of peripheral skin - jt pain
53
Systemic Sclerosis sign:
edema of hands and feet, most prominent in the morning later: thickened, hard / shiny skin -- long bones/ lower legs
54
Systemic Sclerosis Dx:
generalized cutaneous sclerosis, HTN, renal failure, pulmonary HTN and fibrosis.
55
Systemic Sclerosis Tx:
Exercise, splinting, avoid cold Pharm: antifibrotic Hemotopoietic stem cell transplantion
56
Systemic Sclerosis Prognosis:
Age, gender adjusted mortality rate increase 5-8 times.
57
Hyperacute Transplant Rejection:
Hypersensitivity Type 2 - vascular injury after attachment (kidney, heart) - ABO blood type - cytotoxic Ab against donor organs -
58
Acute Rejection
w/in 3 months ``` Cell mediated (most important): donor macrophage and host T cells ``` Antibody mediated: type 2 necrotizing vasculitis with vessel damage and thrombosis Tx: Cyclosporin A
59
GVH:
Donor lymphocytes produce IL-2, which activates NK cells (effectors of GVH injury) -

Common Mechanisms of Disease-2 (24 decks)

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