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Common Mechanisms of Disease-2 > Immunopath Doc - Nichols > Flashcards

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
Q

What is azathioprine?

A

purine analogue

- tx Lupus, R.A, and other autoimmune disases

26
Q

What is hydroxycholorquine?

A
  • anti-malarial antibiotic w/ anti-inflammatory activities.
  • tx. Lupus, R.A
  • low toxicity
27
Q

Define Systemic Lupus Erythematosus

A
  • prototype multisystem autoimmune disease
28
Q

SLE: epidemiology

A

Common, 13X more in women, 1/245 black women

29
Q

SLE: pathogenesis

A

Failure of self-tolerance

30
Q

SLE Gross Pathology:

A

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
Q

SLE micro path:

A

acute necrotizing vasculitis of small arteries and arterioles (fibrinoid deposit)

  • nephritis in 50%
  • cerebritis in 50%
32
Q

SLE symptoms:

A
  • joint pain
  • fever
  • fatigue
  • weight loss
  • pleuritic chest pain
  • photosensitivity
  • nephrotic syndrome
  • angina
  • alopecia
  • myalgias
33
Q

SLE signs:

A
  • 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
Q

SLE dx:

A

ANA, present in 100%

also present in 15% of normal people

35
Q

SLE tx:

A

corticosternoids

immunosuppressive meds

36
Q

SLE prognosis:

A

90% 5 yr survival

80% 10 yr ‘’’’

37
Q

Define Sjogren Syndrome

A

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
Q

Sjogren Syndrome Epidemiology:

A

90% 35-45 y/o women

secondary form more common than primary form

39
Q

Sjogren Syndrome: pathogenesis

A

T cell mediated immunological attack of self-Ag in ductal epithelial cells.

  • or viral infection that has tropism in cells of these glands
40
Q

Sjogren Syndrome Gross Patho:

A

dry ocular and dry mouth

- enlarged salivary and lacrimal glands

41
Q

Sjogren Syndrome Micro Path:

A

1) infiltration of CD4 T cells
2) destruction of gland architecture
+/- plasma cells,
+/- germinal centers

Renal: interstitial nephritis rather than glomerulonephritis

42
Q

Sjogren Syndrome Symptoms:

A

dry eyes, dry mouth

43
Q

Sjogren Syndrome Signs:

A

dry mucous membrane of eyes and mouth

  • conjunctival ulcers
  • oral ulcers
  • enlarged salivary and lacrimal glands
44
Q

Sjogren Syndrome Dx:

A

Anti-SSA, SSB.

45
Q

Sjogren Syndrome Tx:

A

topical therapy

  • systemic cholinergic agents
  • hydroxychloroquine
46
Q

Sjogren Syndrome prognosis:

A

notorious for developing lymphoma

47
Q

Systemic Sclerosis definition:

A

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
Q

Systemic Sclerosis epidemiology:

A

10-20 M / year
F:M - 3:1
50-60 y/o
most severe: black women

49
Q

Systemic Sclerosis Pathogenesis

A

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
Q

Systemic Sclerosis gross path:

A

skin

  • areas initially edematous, ultimately fibrotic
  • begin in face and fingers
  • decrease motility leads to masklike face and clawlike hands

GI involvement 90%

51
Q

Systemic Sclerosis micro path:

A

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
Q

Systemic Sclerosis symptoms:

A

Raynaud’s phenomenon

  • numbness/tingling/ cyanosis of peripheral skin
  • jt pain
53
Q

Systemic Sclerosis sign:

A

edema of hands and feet, most prominent in the morning

later: thickened, hard / shiny skin – long bones/ lower legs

54
Q

Systemic Sclerosis Dx:

A

generalized cutaneous sclerosis, HTN, renal failure, pulmonary HTN and fibrosis.

55
Q

Systemic Sclerosis Tx:

A

Exercise, splinting, avoid cold

Pharm: antifibrotic
Hemotopoietic stem cell transplantion

56
Q

Systemic Sclerosis Prognosis:

A

Age, gender adjusted mortality rate increase 5-8 times.

57
Q

Hyperacute Transplant Rejection:

A

Hypersensitivity Type 2
- vascular injury after attachment (kidney, heart)

  • ABO blood type
  • cytotoxic Ab against donor organs

-

58
Q

Acute Rejection

A

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
Q

GVH:

A

Donor lymphocytes produce IL-2, which activates NK cells (effectors of GVH injury)

-

Common Mechanisms of Disease-2 (24 decks)

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