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tolerance and autoimmune diseases Flashcards

1
Q

T cell tolerance: Positive selection

A

double positive

Interact with MHC + self = survive

(MHC restriction)

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2
Q

T cell tolerance: Negative selection

A

Single positive

high affinity with TCR - MHC + self = death

intermediate affinity with MHC + self =survive

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3
Q

AIRE gene

A

autoimmune regulator gene in the thymus

role in negative selection

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4
Q

Defect in AIRE

A

results in incomplete deletion of auto reactive T cells

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5
Q

APECED Syndrome

A 
Autoimmune 
PolyEndocrinopathy 
Candidiasis 
Ectodermal 
Dystrophy 
syndrome

(polyglandular autoimmune syndrome)

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6
Q

Central Tolerance

A

Deletion of immature self reacting lymphocytes, receptor editing B cells Negative selection T cells

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7
Q

Peripheral Tolerance Due to:

A
  • Sequestration,
  • Treg
  • Anergy: Lack of costimulatory signal,
  • Too high conc. Of self antigens
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8
Q

peripheral tolerance T regulatory cells

A

CD4+
CD25+
*** Foxp3+

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9
Q

FoxP3+

A

master regulator gene

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10
Q

Mutation in FOXP3 gene

A

IPEX syndrome

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11
Q

IPEX syndrome

A

• Immune dysregulation
Polyendocrinopathy
Enteropathy
• X linked causes early death

– Watery diarrhea
– Eczematous dermatitis
– Polyendocrinopathy
– Coob’s test +

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12
Q

What causes Breakdown of Immune Tolerance?

A

Infection: molecular mimicry (cross reactivity)

Mutation in FOXP3, and AIRE genes

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13
Q

Organ-specific

A

Response is against antigens in localized particular organ

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14
Q

Systemic

A

gens

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15
Q

Mechanism of tissue injury

A

Hypersensitivity type II, III, IV

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16
Q

Autoimmune Hemolytic Anemia

A

Rh blood group antigens ->
destruction of RBCs

  • ** –Coombs test: +
  • ** –Spherocytes in blood smear
17
Q

Autoimmune Thrombocytopenia Purpura

A

platelet intrgrin -> abnormal bleeding

18
Q

*** Goodpasture’s Syndrome

A

basement membrane collagen type 4 ->
glomerulonephritis, pulmonary hemorrhage

Diagnosis: anti human IgG labelled with fluorescence: Smooth or linear pattern using Direct fluorescent staining

19
Q

Pemphigus Vulgaris

A

epidermal cadherin, desmoglein 1 and 3, desmosomal adhesion molecules ->
Oral and dermal blisters as a result of intra-epidermal splitting (acantholysis), and erosion

High frequency in Ashkenazi Jews

20
Q

Acute Rheumatic Fever

A

streptococcal call wall antigens, antibodies cross-react with cardiac muscle ->
arthritis, myocarditis, late scarring of heart valves

21
Q
  • Grave’s Disease
A

TSH receptor -> ->
over production of thyroid hormone (T4 thyroxine and T3 triiodothyronine)
hyperthyroidism

*** HLA DR 3 association

22
Q
  • Myasthenia Gravis
A

Ach receptor ->
progressive weakness

*** DR3

23
Q

SLE (systemic lupus erythematosus)

A

dsDNA ->
butterfly rash on the face, glomerulonephritis, vasculitis, arthritis

type III hypersensitivity

** Risk gene HLA-DR2 or DR3

24
Q

Type 1 diabetes (insulin-dependent DM)

A

glutamic decarboxylase, cross-reactive with Coxsackie virus proteins

destruction of insulin due to specific autoantibody and T CD8 cell

** HLA DR3/DR4 association

25
Q

Rheumatoid Arthritis

A

unknown synovial joint antigen ->
joint inflammation and destruction

Fc region of human IgG and/or = Rheumatoid factor

Type IV /Type III hypersensitivity - influx of immune cells and release of inflammatory mediators

  • Auto reactive Th1 and Th17 ->
    Auto reactive Th1 and Th17
  • Risk HLA-DR4 , Smoking & HLADR4 – antibodies against citrullinated proteins

Treatment:
TNF alpha (Infliximab)
CD20 (rituximab)

26
Q

Multiple Sclerosis (MS)

A

myelin basic protein, proteolipid protein ->
brain degeneration, paralysis

Cell mediated
Type IV HSR
auto reactive Th1 cells and activated macrophages.

Disruption of neural transmissions

*** HLA DR6
(Epstein Barr virus)

27
Q

Hemolytic Anemia: Pernicious Anemia

A

Auto-antibodies to intrinsic factor, a protein secreted by gastric parietal cells that facilitates vitamin B12 uptake

Megaloblastic anemia with hyper-segmented neutrophils

28
Q
  • Hashioto’s diseases
A

Hypothyroidism: Type II and IV

Autoantibodies and cytotoxic cell (CD8) specific against thyroid gland cells. Thyroid gland cell death ( apoptosis and necrosis) progressive tissue damage

enlargement of the thyroid gland - goiter

29
Q

Cyclosporine and Tacrolimus

A

block IL-2 synthesis

30
Q

Rapamycin

A

interfere with IL-2 response (signaling)

31
Q

Monoclonal antibodies

A

against TCR, CD3, CD4/CD8, CD40, B7, IL-2R (CD25)

32
Q

Soluble CTLA-4

A

compete with CD28 on T cells for B7 on APC

33
Q

Block B cell

A

anti-CD20 (rituximab)

34
Q

Azathioprine

A

inhibits synthesis of nucleic acid

35
Q

Cyclophosphamide

A

prevent correct DNA duplication

Micro 1 (15 decks)

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