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Inflammation block > Immunology of RA & SLE > Flashcards

Immunology of RA & SLE Flashcards

1
Q

What is SLE& what type of hypersensitivity reactivity reaction is it

A
  • Systemic Lupus Erythematosus
  • Skin rash caused by complexes of DNA & anti-DNA abs becoming localized in the skin to cause inflammation
  • Type III hypersensitivity reaction
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2
Q

Outline the epidemiology of Lupus

A
  • Most common in African-Americans ( 1 in 1000)
  • Gender bias 10:1 female to male
  • Age of onset: peaks in the 3rd/4th decade ( female)
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3
Q

What are the clinical features of SLE?

A
  • Any organ/tissue
  • Common patterns
  • Immune complex deposition in the synovial membranes in the joints
  • Skin( diverse patterns, photosensitivity, alopecia)
  • Joints (non-erosive arthritis and tendinitis)
  • Sicca symptoms ( salivary, lacrimal, genital tract)
  • Glomerulonephritis ( several patterns: mesangial, membranous & peripheral)
  • Neurological: CNS, eye, PNS
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4
Q

What pathologies can SLE bring to the eye?

A
  • Blindness
  • Retinal exudates
  • Conjunctivitis
  • Sjogrens syndrome
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5
Q

What pathologies can SLE bring to the skin covering?

A
  • Baldness
  • Discoid LE
  • Butterfly rash
  • Raynauds syndrome
  • Photosensitivity
  • Mucosal ulcers of the nose, mouth & vagina
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6
Q

What pathologies can SLE bring to the kidney?

A
  • proteinuria
  • kidney failure
  • odedema
  • Hypertension
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7
Q

What pathologies can SLE bring to the GI tract?

A
  • Poor appetite
  • Vomiting
  • Diarrhoea
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8
Q

What pathologies can SLE bring to the musculoskeletal system?

A
  • Arthralgias
  • Arthritis
  • Mastalgias
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9
Q

What pathologies can SLE bring to the Reproductive system?

A
  • Menorrhagia
  • Amenorrhoea
  • Prematurity
  • Still births
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10
Q

What pathologies can SLE bring to the Lining membranes?

A
  • Pericarditis
  • Pleurisy
  • Endocarditis
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11
Q

Define menorrhagia

A

abnormally heavy bleeding at menstruation

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12
Q

Explain lymphadenopathy in SLE

A
  • Can cause liver & spleen enlargement
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13
Q

What is pleurisy and what is its most common symptom

A

-Inflammation of the pleura ( the sheet-like layers that cover the lungs)
Most common symptom= sharp chest pain when breathing deeply

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14
Q

What pathologies can SLE bring to the blood?

A
  • Decreased platelets

- Abnormal autoantibodies

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15
Q

What pathologies can SLE bring to the CNS?

A
  • seizures
  • paralysis
  • neuropathies
  • psychiatric disorders
  • Headaches or migraines
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16
Q

Outline the clinical immunology of SLE

A

Abnormal apoptosis exposes nuclear antigens…

  • antinuclear autoantibodies (ANA): multiple components
  • Anti-dsDNA
  • Anti-histone
  • Antibodies to extractable nuclear antigens( ENA): anti-Ro/ Anti-La ( RNA processing) ; anti-RNP/ anti-SM( spliceosome)
  • Rheumatic factor
  • Anti-cardiolipin antibodies
17
Q

Function of a spliceosome?

A

Removes introns from a transcribed pre-mRNA, a type of primary transcript

18
Q

Cardiolipin function?

A

Found almost exclusively in the inner mitochondrial membrane where it is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism.

19
Q

Outline the mechanisms of antibody injury in SLE

A
  • Direct cytotoxicity (& clearance) e.g autoimmune haemolytic anaemia, thrombocytopenia
  • Immune complex formation& deposition eg skin rashes, glomerulonephritis
  • Trigger pro-inflammatory responses in cells carrying Fc gamma receptors
  • Promote NK cell activation and/or cytotoxicity
20
Q

How does the immune system present in SLE?

A
  • Complement consumption ( by immune complexes)
  • Excess production of alpha-IFN ( many cells): a state of ‘pseudo-viral infection’ by immune complexes
  • Activation of Toll-like receptors (TLR7/9 bind DNA & RNA)
  • Activation of neutrophils
21
Q

What type of hypersensitivity reactions is RA

A

Type II, III & IV

22
Q

How can we use the start of the disease to distinguish between RA & OA?

A

OA starts in the weight bearing joints

RA starts in the peripheral joints ( toes/fingers) then makes its way up

23
Q

What are the differences between normal and arthritic joints?

A

Arthritic joints have:

  • Bone ends that rub together
  • Swollen inflamed synovial membrane
  • Bone erosion
  • Thinned cartilage
24
Q

What’s the female:male ratio of RA?

A

3:1

25
Q

What is RA?

A

Rheumatoid arthritis is…

  • Systemic autoimmune disease of unknown aetiology
  • Manifests mainly in joints
  • Extra-articular involvement
  • Chronic inflammatory disease
26
Q

Explain the pathogenesis of RA

A
  • Pannus (Inflammatory tissue) eats away the underlying bone
  • Extensive angiogenesis= a marker of chronic inflammation
  • Hyperplastic synovial lining :the single layer of synovial cells have proliferated; now multiple layers
27
Q

Why is RA not considered a type I hypersensitivity reaction

A

-The mast cells aren’t being activated by binding IgE & cross-linked by allergens

28
Q

Outline the evidence for cellular involvement in RA

A

Synovial membrane:

  • Synovectomy relieves symptoms for several years
  • Macrophages: Type A synoviocyte (Non-fixed cells that can phagocytose actively cell debris and wastes in the joint cavity, and possess an antigen-presenting ability.)
  • Fibroblasts: Type B synoviocyte (FLS)

MMP-1,-3 & -9
Cytokines, TNF, IL-1. IL-6
Chemokines, CCL2,CCL5, IL-8

29
Q

Explain the predisposition to RA

A

Genetic:

  • HLA-DR 1/ HLA-DR4
  • Common epitope QKRAA(Not associated with all ethnic groups)
  • Single nucleotide polymorphisms (SNPs eg PTPN22)
  • Heretability of MZ twins 15%
30
Q

What is deimination?

A
  • aka citrullination
  • The conversion of the amino acid arginine in a protein into the amino acid citrulline
  • The immune system can attack citrullinated proteins, leading to autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS)- due to anticitrullinated protein antibodies
31
Q

Explain the significance of anti-citullinated antibody cyclic citrullinayted peptide (CCP) in RA

A
  • Citrulline caused by deimination of arginine residues
  • Great specificity for RA
  • Expression of anti-CCP correlates with the carriage of certain genes on the HLA-DRB1 locus
  • Highly significant association between anti-CCP and HLA-DR4, and a weaker but still significant association with HLA-DR1
  • May predict erosive disease
32
Q

Describe the evidence for the involvement of T cells in the pathogenesis of RA

A
  1. ) Association with HLA-DR4/DR1
  2. ) RA & HIV-1 infection
  3. ) Activation of RA by IL-2 infusion
  4. ) Anti T cell therapies
  5. ) Synovial histology
  6. ) Synovial T cells: activation/cytokines
33
Q

What is the main function of IL-2

A

To promote the development of Treg cells

34
Q

Explain the evidence for the association of RA with HLA-DR

A
  • CD4 cells are MHC class II restricted
  • HLA-DR4 positivity associated with more severe disease
  • HLA-DR1 & HLA-DR4 shared epitope hypothesis QKRAA motif
35
Q

Describe rheumatoid synvoial membrane

A
  • Thickening of the synovial lining layer: Proliferation of fibroblast-like synoviocytes
  • Angiogenesis
  • Influx of mononuclear cells ( T& B cells and monocytes)
  • Production of cytokines, chemokines & matrix metalloproteinases
36
Q

What is the main autoantibody associated with RA?

A
  • Rheumatoid factor (non specific & non pathogenic)
  • Diagnosis
  • 80% RA patients are RF+
  • Present in sera many months before disease is apparent
37
Q

What can happen to the bone in RA

A
  • Bone erosions

- Osteoclast activations

38
Q

Why are T cells pro-inflammatory

A
  • Direct cell contact between activated T cells and monocytes induces IL-1Beta production
  • Direct cell contact between T cells and FLS( fibroblast like synoviocytes) induces MMP production
  • Direct cell contact between T cells and FLS induces MCP-1 production

Inflammation block (27 decks)

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