Nelson-Immune Diseases Flashcards
What is an autoimmune disease?
An immune mediated inflammatory disease>
immune reactions to self antigens>
tissue and cell injury
What are the mediators of autoimmune disease?
Autoantibodies
Immune complexes
T lymphocytes
Autoimmune disease is d/t the loss of….
self tolerance
What is self tolerance?
Unresponsiveness when a lymphocyte is exposed to an antigen
What is the difference between central tolerance and peripheral tolerance?
Central (BM, thymus)
Peripheral tolerance (in the periphery, associated w/ anergy)
What is central tolerance?
killing immature self reactive T and B lymphocyte clones that recognize self antigens in BM/thymus
What is peripheral tolerance?
Irreversible inactivation of lymphocytes
suppression by T reg cells
deletion by activation induced cell death
What are the two factors that combined together lead to autoimmune disease?
- Inheritance of susceptibility genes–> breakdown of self tolerance
- Environmental triggers (infections/tissue damage)–> activation of self reactive lymphocytes
What are some of the ways that infections cause autoimmunity?
- Up-regulate the expression of co-stimulators–> breakdown of anergy–> activation of T cells for specific (self) antigen
- Molecular mimicry
- Infection–> tissue injury > release of self antigens > alteration of self antigens so they’re able to activate T lymphocytes
What is molecular mimicry?
Offending org can express antigens w/ same AA seq as self antigens–> IR so self antigens
What are examples of molecular mimicry?
Rheumatic heart disease: Ab against streptococccal proteins react w/ myocardial proteins–> myocarditis
EBV/HIV: polyclonal B cell activation > production of autoantibodies
What is clinical course of untreated autoimmune disease?
Directed at specific org/tissue–> specific disease
Directed at widespread antigen–> systemic/generalized disease
What are the general features of autoimmune disease?
once initiated is progressive
sporadic relapses/remissions
inexorable tissue damage if untreated
What is SLE?
Multisystem autoimmune disorder>
formation of autoantibodies (antinuclear) >
widespread multiorgan tissue injury)
What are some key features of SLE?
Acute or insidious
chronic-relapsing and remitting
Febrile illness
Injury to skin, joints, kdiney, serosal membranes
What causes SLE?
You can’t maintain self tolerance
Susceptibility genes + env triggers > loss of self tolerance and persistence of nuclear Ag> formation of Ag-Ab complexes> deposited in tissues> injury (type II hypersensitivity)
What is the potential complication of the presence of anti-phospholipid Ab in SLE?
False pos syphillis test
prolong partial thromboplastin time
Complications of hypercoaguable state (secondary anti-phospholipid Ab syndrome)
What is secondary anti-phospholipid Ab syndrome?
Venous/arterial thrombosis
spontaneous miscarriages
cerebral ischemia
What are the key clinicial features seen in SLE?
SOAP BRAIN MD S-serositis (inflammation of serious tissues of the body) O- oral ulcers A- arthritis P- photosensitivity B- blood disorders R-renal disease A- anti-nuclear ab pos I- immunologic abnormalities N- neurologic disease M- malar rash D- discoid rash
How does SLE cause renal disease?
Immune complex deposition in the glomeruli–> glomerular injury
How does SLE effect the skin?
immune complex deposition at the dermoepidermal junction
How is joint characterized in SLE (different from RA)?
non erosive
non-deforming small joint involvement
What sersitises are seen w/ SLE?
Pericarditis, endocarditits, pleuritits
What is a characteristic pathological findings of lupus nephritis?
wire loop lesions representing extensive subendothelial deposits of immune complexes
What is RA?
Chronic systemic inflammatory disorder
Primarily attacks joints>
inflammatory synovitis>
destruction of cartilage and ankylosis
What is the end result of RA?
stiffening/immobility of joints
What are genetic factors that contribute to RA susceptibility?
Specific HLA genes
HLA-DRB1
PTPN22
What are environmental arthritogens that contribute to RA susceptibility?
Ag from infectious organisms
Citrullinated proteins formed in the body
What is the pathogenesis of RA?
Exposure to arthritogenic antigen>
genetically predisposed individual>
breakdown of self tolerance>
chronic inflammatory reaction
How can initial acute arthritis lead to a continuing autoimmune reaction?
Activation of CD4 helper T cells>
release of inflammatory mediators + cytokines>
destruction of joint
Describe the immunopathogenesis of RA.
CD4 T cells>
form a pannus (mass of inflamed synovium)>
grows over joint cartilage>
inflammatory destruction of joint
What are the two main autoab involved in RA?
Rhematoid factor (not specific for RA--seen in 1-5% of healthy people) Ab to citruline-modified peptides
What is Sjogren syndrome?
Chronic disease characterized by dry eyes and dry mouth
d/t
immune mediated destruction of lacrimal and salivary glands d/t abberrant T and B cell activation
What population is sjogren syndrome usually found in?
Middle aged women
What are the pathological findings of srogrens?
Lymphocytic inflammation
Fibrosis of lacrimal and salivary glands
parotid enlargement
What are clinical findings associated w/ sjogren syndrome?
Pt’s have abs to SS-A and SS-B
How do you diagnose sjogrens?
clinical findings +
clinical test (tear production/clearance, conjunctival damage)
Measurement of Abs
lip biopsy
What type of neoplasm can be seen in sjogren syndrome?
Lymphoma
What is systemic sclerosis?
Chronic inflammation w/ widespread damage to blood vessel>
progressive interstitial and perivascular fibrosis of skin and multiple organs
Scleroderma (SS) primarily occurs in what pop?
Adults
3:1 F:M
What is most commonly affected in SS?
skine
Pts w/ SS may have Ab to ….
Scl-70 (DNA topo I)
Raynaud’s phenomenon is often seen w/ what disease?
Systemic sclerosis
Exaggerated vasospastic response to cold or emotional stress
How does systemic slcerosis affect the skin?
sclerotic atrophy and sclerosis (hardening of tissue)
starts in distal fingers and extens proximally
can involve face
How does systemic sclerosis affect the GI tract?
involved in 90% of pts
esophageal fibrosis–> dysmotility w/ dysphagia and reflux
small bowel involvement–> loss of villi and dysmotility w/ malabsorption, cramps and diarrhea
How does systemic sclerosis affect the lungs?
Interstitial fibrosis (resp failure commone cause of death)
How does systemic sclerosis affect the musculoskeletal system?
non-destructie arthritis
how does systemic sclerosis affect the kidneys?
vascular thickening–> hypertension
What are the differences between diffuse and limited sclerosis?
Diffuse:
widespread skin involvement
rapid progression
early visceral involvement
Limited: skin involvement confined to fingers, forearms, face indolent form late visceral involvemnt CREST syndrome
What is CREST syndrome?
Calcinosis Raynoud's phenomenon Esophageal dysmotility Sclerodactly Telanglectasia
What is dermatomyositits?
Inflammatory disorder of the skin and skeletal muscle.
How does the pathogensis of dermatomyosistis and polymyositis differ?
Dermatomyositis-
immunologic injury to small blood vessels and capillaries in skeletal muscle
secondary to autoantibodies and activation of T lymphocytes
Polymyositis
T-cell/autoantibody mediated in injury of myocyte (Jo1 antibodies)
How do the muscle biopsies differ in dermatomyositis and polymyositis?
Dermatomyocities:
lymphocytic inflammation around small blood vessels and in CT
perifasicular mycotye atrophy
necrotic muscle fibers which regenerate
Polymyositis
lymphocytic inflammation surround and invdaing muscle fibers with NO perifasicular atrophy
Necrotic and regenerating muscle fibers
NO vascular injury
How do dermatomyocitis and polymyocitis differn in clinical presentation?
Polymyoctits is mainly seen in ADULTS.
Muscle and sytemic infolvement similar to dermatomyosistis except for lack of skin involvement.
What are the common clinical findings of dermatomyocitis?
- Classic rash is violaceous
- Muscle weakness
- interstitial lung disease, vasulitits, myocarditits
- juvenial form- abdominal pain and GI tract involvement
How do you treat polymyoctitis and dermatomyocitis?
Immunosuppressives
What are the main types of mixed connective tissue disease?
SLE RA Systemic sclerosis Polymyositis Dermatomyositits Secondary sjogren syndrome
What is secondary sjogren syndrome?
Occurs when another CT disease is present
What is mixed CT disease?
Overlap features and presence of distinctive anti-U1-RNP Ab
Autoantibodies present:
RA
cirillunated proteins
Autoantibodies present:
Sjogren
SSA-RO
SSB/LA
Autoantibodies present:
CREST
Centromere abs
Autoantibodies present:
SLE + CNS involvement
Ribosome P
w/out- SM abs
Autoantibodies present:
MCTD
RNP Abs
Autoantibodies present:
Scleroderma
Scl-70
Autoantibodies present:
POlyomyositits
Jo-1
