8-disorders of the immune system 3 Flashcards
Other names for autoimmune diseases:
connective tissue diesase or collagen vascular disease
clonal deletion:
loss of T cell clones during maturation
-it is part of self tolerance
clonal anergy:
inactivation induced by antigens
-part of self tolerance, the last part of self tolerance is “peripheral suppression by T cells”
Mechanisms of Autoimmune disease (loss of self tolerance)
- bypass of helper T-cell tolerance (modified by drugs or costimulatory molecules/infection)
- molecular mimicry (microbes share epitopes with self antigens)
- polyclonal lymphocyte activation (endotoxin, EBV)
- Imbalance of suppressor/helper function
- emergence of sequestered antigens (eye, brain, not normally in contact with circulating immune system)
What is the greatest example of molecular mimicry?
Streptococci and rheumatic heart disease
Examples of systemic, multi-organ autoimmune diseases (many antibodies)
- Systemic Lupus Erythematosus
- Rheumatoid Arthritis
- Spondyloarthropathies
- Sjogren’s Syndrome
- Scleroderma
Examples of Organ-specific disorders (antibodies against organ)
- Thyroiditis; adrenal failure
- autoimmune hepatitis
- Type I diabetes Mellitus
- Pernicious Anemia
- multiple sclerosis
symptoms of Systemic Lupus Erythematosus
- butterfuly rahs
- discoid lupus (disc shaped rash)
- photosensitivity
- oral ulcers
- arthritis
- serositis
- neurologic disease
- hematologic disease
- immunologic disease: LE cell, anti-DNA, anti-Sm, false positive for STS
- anti-nuclear antibody
What is the incidence of SLE?
1:2500
what is the proportion of Female:male incidence?
10:1
When does SLE start?
2nd/3rd decade of life (teens and 20’s)
What ethnicity does SLE affect most?
Blacks
What areas of the body of SLE affect most?
skin, kidney, serosal membranes, joints, heart
ANA=?
Anti-Nuclear Antibodies
What disease is ANA associated with?
SLE
What method is used to test ANA?
indirect immunofluorescent method
-Hep2 cells+patient serum+fluor anti-human Ig
What are the different antibodies associated with ANA?
-Abs to: DNA, histone, non-histone proteins bound to RNA, nucleolar antigens
ANA Patterns:
- Homogeneous: DNA, histone
- Speckled: Sm, RNP, SS-A, SS-B
- Nucleolar
- patterns are NOT DIAGNOSTIC
- antibodies against RBCs, WBCs, platelets, phospholipids
- even centromere ANA
what monitoring test is used for SLE
erythrocyte sedimentation rate
Genetic factors of SLE
- 30% concordance in monosygotic twins
- increased risk in family members
- HLA-DQ locus and SLE association
- inherited deficiency of complement and SLE
Non-Genetic factors of SLE
- drugs: procainamide, hydralazine
- sex hormones (estrogens>androgens)
- UV light
***fundamental cause of disease in SLE
- Anti-DNA Ab forms complexes with DNA normally released into blood from cells turning over
- These circulating immune complexes (CIC) deposit in small blood vessels
- complement binds to CIC deposits causing tissue damage and attracting WBCs to cause more damage
The fundamental disease in SLE happens in small blood vessels all over the body in many different organs, but especially in:
the glomeruli of the kidney
What serosa does SLE affect?
pericardium and pleura
What affect does SLE have of the heart?
valvular endocarditis
SLE in kidneys is called?
glomerulonephritis
SLE in the central nervous system:
microinfarcts
What drugs are used to treat SLE?
steroids; immunosuppressive drus
-for the kidneys, it may progress to end stage renal disease=transplantation
Rheumatoid Arthritis
- proliferative synovitis
- destruction of articular cartilage: disabling
- extra-articular lesions of skin, heart, blood vessels, lungs, muscles (similar to SLE, SS)
Prevalence of RA
1%,
When does RA usually start?
4th/5th decade of life
RA for female:male
3-5:1
Predisposition for RA:
genetic predisposition with microbial initiation
blood tests for RA
- rheumatoid factor: anti-IgG Fc
- Anti-CCP
Spondyloarthropathies
- ligamentous attachments to bone affected
- sacroiliac joints; uveitis (inflam of eye)
- absence of RF
- HLA-B27 association
how is spondyloarthropathies distinguished from rheumatoid arthritis?
spondyloarthropathies=absence of RF
Which HLA is associated with spondyloarthropathies?
HLA-B27
infectious triggers of spondyloarthropathies:
-Yersinia, shigella, salmonella, helicobacter, campylobacter
ankylosing spondylitis; reactive arthritis (arthritis, conjunctivitis, urethritis/cervicitis)
spondyloarthropathies
Sjogren’s Syndrome
-immune-mediated destruction of lacrimal and salivary glands, (with swelling)
=keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth)
-pseudolymphoma in 10%
-B cell lymphoma in 1%
HLA-DR3
associated with the primary disease state of SjS
-“sicca syndrome”
Secondary disease state of SjS
HLA-DR4, RA, SLE
who does SjS affect the most?
Women over 40
Systemic Sclerosis (scleroderma)
- inflammation/fibrosis of interstitium of organs (thickening)
- skin: fingers, upper extremities, shoulders, neck, face
- GI: esophagus, difficulty swallowing
- Musculoskeletal: joints and muscles
- lungs: diffuse interstitial fibrosis
- kidneys, heart
- raynaud’s phenomenon: reversible vasospasm
Raynaud’s phenomenon:
reversible vasospasm, systemic sclerosis
inflammatory myopathies: (affect muscles)
- dermatomyosistis
- polymyositis
Mixed connective tissue disease
- features not characteristic of other disease
- anti-RNP
- little renal disease
Amyloidosis
- amyloid replaces normal functioning tissue
- intercellular pink translucent material on H&E
- chemical nautre: beta-pleated fibrillar protein
- organ deposition: kidney, spleen, liver, heart, endocrine
- prognosis poor
diagnosis of amyloidosis:
- congo red stain
- rectal/gingival biopsy
- serum/urine protein electrophoresis
