Ch 4: Autoimmune Rubin's Flashcards
These cards are directly from the Rubin’s textbook.
What is central tolerance?
Self reactive T and B lymphocytes deleted during their maturation in thymus/bone marrow
What is negative selection?
In thymus: self reactive T-cell recognize self-peptides (with compatible self MHC) and are induced to undergo apoptosis
Occurs after + selection (self-MHC restriction)
In bone marrow: called clonal deletion for B-cells
What is peripheral tolerance?
Regulating T-cells that escape negative selection
held in check in periphery via anergy, suppression, and/or activation induced cell death
What is molecular mimicry? Give an example.
Helper T-cell tolerance is overcome via
Antibodies against foreign antigens that cross reacts with self-antigens.
NO AUTOANTIBODY MADE
Ex: rheumatic fever, anti-S.pyogenes antibody cross-reacts with antigens from cardiac muscle
What is a Type I hypersensitivity Response?
Immediate type hypersensitivity rxn
1) IgE binds its Fc domain to mast/basophil cells
2) Subsequent antigen binding = cxrlink IgE and degranulation of histamine etc.
urticaria, asthma, anaphylaxis
What is a Type II hypersensitivity Response?
1) IgM or IgG formed against antigen on fixed cell surface or EC antigen
2) Antigen-Ab coupling on fixed cell surface activates complement via the Ig Fc domain= cell lysis (cytotoxicity) or ECM damage (MAC, opsonization)
What is a Type III hypersensitivity Response?
1) IgM or IgG response
2) Antigen-Ab coupling in circulation = Immune complex formed in circulation
3) IC deposited in tissue
4) Complement activation at site of IC deposition = wbc recruitment = tissue injury
What is a Type IV hypersensitivity Response?
Cell-mediated/delayed type rxn
DOSEN’T INVOLVE Abs
Antigen activation of T-cell and macrophage recruitment = release products = tissue injury
What are the 5 THEORIES of the molecular pathogenesis of autoimmunity?
1) Inaccessible Self-Antigens
2) Abnormal T-cell fxn
3) Molecular mimicry
4) Polyclonal B-cell activation
5) Tissue Injury/Hypersensitivity Rxns
What is the idea behind inaccessible self-antigens causing autoimmune disease?
Intracellular antigens are not normally exposed
Tissue injury will expose them
Immune response develops
*pathogenic infrequently, remember no evidence that antisperm antibodies cause generalized injury, except for localized orchitis
What is the idea behind abnormal T-cell fxn causing autoimmune disease?
Defects in suppressor T-cells described in many autoimmune diseases
Helper T cells may become autoreactive in autoimmune disease (normal job: antigen-specific B-cell activation, T-cell tolerance induced by low doses of antigen then get cray cray autoreactive)
***Drug induced lupus = ex of DNA hypomethylation leads to upreg leukocyte antigen and B-cell activation independent of antigen
T cell autoreactivity and loss of antigen specificity
What is the idea behind polyclonal B cell activation causing autoimmune disease?
B-cells directly activated by bacterial cell walls/viruses (with complex and numerous antigenic sites)
Ex = post bacterial, viral, parasitic infections shown dev of Rheumatoid Factor (RA) and anti-DNA antibodies (SLE)
What is the prototypical systemic immune complex disease?
SLE
What does SLE characteristically affect?
skin, joints, serous membranes, kidneys
What are the two autoantibodies that are pathognomonic but not directly cytotoxic in SLE?
Types of anti-nuclear antibodies to:
1) Sm antigen
2) dsDNA
Who do we typically see with SLE?
common and severe in AAs/hispanics
over 80% of cases are in women of childbearing age (whatever the hell that means….stupid Rubin)
What are some potential etiological factors in SLE?
virus (EBV)
hormones (estrogen)
genetic predispositions (HLA B8)
Drugs (procainamide, hydralazine, isoniazid)
What is the pathogenesis of SLE?
1) potential etiological factors
2) loss of tolerance, acquired sensitivity to auto-antigens
3) Autoreactive CD4 T-cells
4) polyclonal B cell hyper-reactivity
5) Autoantibody production (anti-dsDNA ab)
6) Immune complex formation in circulation & tissues
7) Tissue injury: glomerulonephritis, vasculitis, serositis, arthritis
How is joint disease (polyarthralgia) in SLE different from that in rheumatoid arthritis?
Joint destruction is unusual in SLE
What is the prototypical skin involvement in SLE?
erythematous rash in sun-exposed sites
malar “butterfly” rash
perivascular lymphoid infiltrate & liquefactive degeneration of basal cells
Ig and complement deposition
What is the prototypical renal disease seen in SLE?
glomerulonephritis (3/4 of SLE pts)
Immune complexes between DNA and IgG abs to dsDNA deposit in glomeruli
What can be a consequence of serous membrane involvement in SLE? Resp system in SLE?
pleuritis and pleural effusion
less frequently: pericarditis, peritonitis
pneumonitis
progressive interstitial fibrosis
pulmonary hypertension
What is the cardiac involvement in SLE?
commonly pericarditis (but all layers can be affected)
What is Libman-Sacks endocarditis?
Associated with SLE
small nonbacterial vegetations on valve leaflets
diff from larger/bulkier bacterial endocarditis vegetations
What is CNS involvement with SLE?
vasculitis»_space; hemorrhage and infarction of brain
What are antiphospholipid antibodies associated with in SLE?
1/3 pts
thromboembolic complications, Budd-Chiari, DVT, stroke, PE, spont abortions
How is joint disease (polyarthralgia) in SLE different from that in rheumatoid arthritis?
Joint destruction is unusual in SLE
What is primary Sjogren Syndrome?
intense lymphocytic infiltrates in salivary and lacrimal glands (CD4 T-cells)
leads to acini destruction»_space; keratoconjunctivitis and xerostomia
w/o other CT disease
What is secondary SS?
SS associated with other CT disease
What are some clinical features of SS?
dry mouth, dry eyes, dysphagia w/GI tract involvement, lymphoid infiltration»_space; atrophic gastritis
Name the disease!
vasculopathy, excessive collagen deposition in skin and lungs (diffuse interstitial fibrosis)/GI tract/heart/kidneys (focal hemorrhage/cortical infarct), lesions in arteries/arterioles/capillaries, thickening and fibrosis of vessels
Scleroderma
What is the difference between generalized form of scleroderma and the limited variant?
limited form: a milder disease, usually present with skin involvement, CREST syndrome within this category
What are some clinical features of scleroderma?
“stone facies”: tightening of facial skin/restricted motion of mouth Raynaud phenomenon painful tendonitis joint pain hypomotility and dysphagia of esophagus intestinal motility problems b/c fibrosis pulmonary fibrosis scleroderma renal crisis
What is mixed connective tissue disease?
SLE symptoms (rash, Raynaud, arthritis, arthralgias) Scleroderma signs (swollen hands, esophageal hypomotility, pulmonary interstitial disease) RA
What is autoimmune disease?
Immune response against self-antigen
No longer able to differentiate b/t self- and non-self antigens
Loss of immune tolerance
