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MHD V: Renal > 11:9: Autoimmunity > Flashcards

11:9: Autoimmunity Flashcards

1
Q

What is autoimmunity?

A
  • Immune rxn against self antigen

- Can be directed against single tissue/organ or against many

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2
Q

What is self tolerance?

A
  • Lack of responsiveness to self antigens
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3
Q

What is immunologic tolerance?

A
  • Making lymphocytes unresponsive to self antigen
  • “Self tolerance”
  • Result of central tolerance
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4
Q

What is central tolerance?

A
  • Clonal deletion of self reactive T and B cells
  • Occurs in thymus for T cells
  • Occurs in marrow for B cells
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5
Q

What is peripheral tolerance?

A
  • Removal of self reactive T cells that escape intrathymic negative selection
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6
Q

What happens to T cells that to not recognize self antigen?

A

Allowed to undergo clonal proliferation

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7
Q

What is AIRE?

A

“Autoimmune regulator”

  • Transcription factor promoting expression of self antigen by thymic epithelial cells
  • Allows for elimination of self directed T cells
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8
Q

What is APECED?

A
  • Occurs when you lack AIRE
  • Develop organ specific autoimmune disease
  • Often shows problems with eyes, teeth and fingers
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9
Q

What is receptor editing?

A
  • Rearrangements altering specificity of B cell receptor to avoid autoreactivity
  • Occurs in bone marrow
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10
Q

4 mechanisms of peripheral tolerance?

A
  1. Anergy
  2. Suppression by Tregs
  3. Clonal deletion by induced cell death
  4. Antigen sequestration
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11
Q

What is anergy?

A
  • A reaction between self reactive T cell and its antigen that leads to expression of proapoptotic proteins and silencing of those T cells
  • Most self antigens do not possess stimulatory molecules necessary to mount T cells response
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12
Q

How to Tregs impact T cells?

A
  • Release cytokines to suppress function of autoreactive T cells
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13
Q

What is Fas-FasL ligand?

A

Leads to apoptosis of self reactive T cells in periphery

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14
Q

What is antigen sequestration?

A
  • Certain areas such as brain eyes and testis have limited exposure to T cells so the celf antigens here are protected
  • Can lead to prolonged inflammation / infection because of this as well
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15
Q

What is molecular mimicry?

A
  • Virus or bacteria shares epitopes with self proteins expressed on human
  • Leads to immune response against human as well
  • Rheumatic fever is example of this
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16
Q

What is exposure of cryptic self?

A
  • Infection in area usually not exposed to immune system allows self antigen to spread to areas it is not normally present
  • Can lead to autoimmune rxn
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17
Q

What is SLE?

A

“Systemic lupus erythematosus”

- Multisystem autoimmune disease caused by variety of antibodies

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18
Q

What is necessary for SLE?

A
  1. Ptn. must have multiple susceptibility genes
  2. Triggering factor
  3. Abnormal immune response: hyperactive B/T cells with inadequate regulation
19
Q

What are some triggering factors for lupus?

A
  1. UVB light
  2. Sex hormones
  3. Dietary factors
  4. Infections agents
  5. Drugs
  6. Smoking
20
Q

Why does UVB exposure exacerbate SLE?

A
  • Sun kills skin cells releasing self antigen leading to development of autoantibodies
21
Q

Who is more at risk for LUPUS?

A

Females: due to sex hormones

African Americans

22
Q

What drugs can trigger lupus?

A 
"For example (IE), private message (PM) the PHD
Isoniazid
Ethosuximide
Phenytoin
Minocycline
Procainamide
Hydralazine
D-penicillamine
23
Q

How can you identify drug induced lupus?

A

Presence of antihistone antibodies

24
Q

What is necessary to diagnose lupus?

A

4 of 11 symptoms

25
Q

What are the symptoms of lupus

A
  1. Butterfly rash: face
  2. Discoid rash: anywhere on body
  3. Photosensitivity
  4. Oral or nasal ulcers
  5. Arthritis: non deforming
  6. Serositis: fluid around lungs or heart
  7. Kidney disease
  8. Brain disease: seizures or psych
  9. Low RBC, WBC, or Platelet count
  10. Antinuclear antibodies
  11. Specific autoantibodies
26
Q

What is SSA associated with?

A

Neonatal SLE

27
Q

Role of IC in SLE?

A
  • Low levels can be seen
  • C1/2/4 deficiencies can be associated with SLE
  • Immuno fluorescence can show deposition of IC
28
Q

What are antiphospholipid antibodies?

A
  • Found to be circulating in SLE
  • Lead to prolonged PTT and false pos VDRL
  • Lead to thrombocytopenia
  • Ptn with these is more prone to thrombotic episodes than bleeding and spontaneous abortion
29
Q

What can antiphospholipid antibodies lead to?

A

Anemia
Neutropenia
Thrombocytopenia

30
Q

What is neutropenia?

A

Low WBCs

31
Q

What is thrombocytopenia?

A

Low platelets

32
Q

What is systemic sclerosis?

A
  • Multisystem disorder
  • Characterized by inflammatory, vascular and fibrotic changes of skin and organ systems
  • Pathogenesis is not known
33
Q

Two type of scleroderma?

A
  1. Diffuse cutaneous

2. Limited cutaneous: CREST syndrome

34
Q

What does presence of anticentromere antibody indicated?

A

CREST syndrome

35
Q

What does CREST stand for?

A

Calcinosis- Ca deposits on skin
Raynaud’s - Low blood flow to hands
Esophageal dysmotility - problems w/ contraction
Sclerodactyly - thickness of skin on fingers / toes
Telangiectasias - spider veins / small dilated vessels

36
Q

What is calcinosis?

A

Ca deposits on skin

- Seen in CREST

37
Q

What is Raynaud’s syndrome?

A
  • Low blood flow to hands

- Seen in CREST

38
Q

What is Esophageal dysmotility?

A
  • Problems w/ contraction of esophagus

- Seen in CREST

39
Q

What is Sclerodactyly?

A
  • Thickness of skin on fingers / toes

- Seen in CREST

40
Q

What is Telangiectasias?

A
  • Spider veins / small dilated vessels

- Seen in CREST

41
Q

What is anticentromere antibody associated with?

A

Systemic sclerosis

42
Q

Clinical presentation of systemic sclerosis?

A
  • Raynaud’s phenomenon
  • fibrosis of the skin (scleroderma)
  • telangiectasia, calcinosis
  • esophageal hypomotility
  • arthralgias and /or arthritis
  • intestinal hypofunction
  • pulmonary fibrosis - from fibrosis
  • hypertension - from fibrosis
  • renal failure (leading cause of death) - from fibrosis
43
Q

What is skin fibrosis indicative of in sclerosis?

A
  • The more skin fibrosis the more underlying organ fibrosis
44
Q

How to test Scleroderma?

A
  1. CXR
  2. ESR
  3. Antibody testing
  4. Urinalysis for renal involvement

MHD V: Renal (28 decks)

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