Flashcards in Nelson-Immune Diseases Deck (66)
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?
Autoimmune disease is d/t the loss of....
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?
1. Inheritance of susceptibility genes--> breakdown of self tolerance
2. Environmental triggers (infections/tissue damage)--> activation of self reactive lymphocytes
What are some of the ways that infections cause autoimmunity?
1. Up-regulate the expression of co-stimulators--> breakdown of anergy--> activation of T cells for specific (self) antigen
3. 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
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
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?
What are the key clinicial features seen in SLE?
SOAP BRAIN MD
S-serositis (inflammation of serious tissues of the body)
O- oral ulcers
B- blood disorders
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-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>
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
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