Autoimmunity Flashcards
What two mechanisms must be breached to develop autoimmunity?
Central and peripheral tolerance
What are the major factors that influence the development of autoimmune diseases?
Autoreactive CTLs
Microbial infections
Lymphocyte abnormalities
Genes
Can autoimmune diseases be tranferred to fetueses from their mothers (not genetically)?
Yes, but will be ~3 weeks long (IgG half life time)
What is epitope spreading? What begins this process?
Trauma induced spreading of self antigens not normally present in the blood (like d/t blood brain barrier)
How could viruses potentially play a role in the development of autoimmunity?
Similar antigens to self (“molecular mimicry”)
Allow for inflammation cytokines to be present when attempting to tolerize T cells
What can mycoplasma infections induce?
Transient autoimmunity d/t cross-reaction of antibodies to RBCs
What do the antibodies of rheumatic fever cross react with?
Heart tissue
How can inappropriate expression of MHC class I molecules lead to autoimmunity? What are the two example diseases for this?
Activate T cells inappropriately
Grave’s disease and DM I
What is vitiligo?
Autoimmune disease against melanocytes
How can expression of TCRs specific for MHC proteins on thymocytes bypass negative selection?
Expression of certain MHC proteins with self peptides during T cell selection in the thymus might allow enough binding to enable positive selection of autoreactive T cells, but might not bind with high enough affinity to elicit negative selection.
What are the three major ways that tissue injury can be brought about in an autoimmune disease?
- Autoreactie CTLs
- Circulating autoantibodies
- Immune complexes
What antibody type can cross the placenta?
IgG
What is the pathogenesis of autoimmune hemolytic anemia? (2)
RBC antibodies produced against RBC membrane proteins causes RBC lysis
Opsonization of RBCs prompt removal by spleen
What is Goodpasture syndrome?
Autoantibodies prodced against Type IV collagen, leading to lung and kidney damage, and death
What is the histological features of Goodpasture syndrome?
Smooth, ribbon like appearance to glomerulus
What is the pathogenesis of pernicious anemia?
Autoantibodies to intrinsic factor or gastric/parietal cells
What is the pathogenesis of hashimoto’s thyroiditis?
Hypothyroid state induced by autoantibodies and autoreactive T cells to thyroid glands proteins
What is idiopathic thrmobocytopenia (ITP)?
Platelets destroyed by autoantibodies to platelet membrane proteins, causing skin leasions/epidermal hemorrhage
What is the treatment for ITP?
IVIG
What is Grave’s disease?
Autoantibodies to TSH receptor, causing hyperthyroidism d/t over stimulation
What is myasthenia gravis?
Autoantibodies attack alpha chain of nicotinic acetylcholine receptors, blocking muscle signals
What is the pathogenesis of DM I?
Autoantibodies to Beta cells in pancreas, cause CTLs to kill (type IV)
What type of hypersensititivty is myasthenia gravis?
Type II
What is the pathogenesis of MS?
Th1 and Th17 cells specific of myelin antigens become activated, and attack myelin nerve cells
What are the treatments available for MS?
Interferon beta-1b
Interferons Beta 1a
What is lupus?
A broad loss of regulatory control that sustains self tolerance.
What is the pathogenesis of lupus?
Formation of immune complexes, leading to kidney problems
Which type of hyper sensitivity could lupus be considered?
Type III
How can drugs cause lupus? Is this reversible?
In slow drug metabolizers, the drugs could complex with nucleoproteins and generate autoimmunity.
The disease reverses upon removal of the drug.
Why is the kidney susceptible to type III hypersensitivities?
Express CR1 protein that bind C3b and C4b
What are the immunologic factors to lupus?
B cell hyper activity
Increased Th activity
Decreased Treg activity
What haplotypes are assocaited with RA?
HLA-DR4
What is the pathogenesis of RA? (Inflammation and tissue damage)
Inflammation of joints by Th1, Th17 macrophages, Bcells, and plasma cells.
Tissue damage by rheumatoid factor (IgM/IgG to Fc portion of IgG) causing immune complexes
What is the major chemical involved in RA?
TNF-alpha
What are the three treatments for RA? How does these work?
Etanercept-TNF-alpha type II receptor fused to IgG1
Infliximab-same as above
Adalimumab-
What is Sjögren’s syndrome? What is its pathogenesis?
an autoimmune disease manifested by dry eyes and dry mouth due to the destruction of lacrimal and salivary glands.
Influx of B and T cells, but o/w not known
What is scleroderma?
Excessive deposition of collagen, and antibodies produced against collagen.
What are the major inflammatory chemicals release in scleroderma? What is the consequence of this?
IL-1 and TNF-alpha, leads to collagen production = vicious cycle
What is polymyositis dermamyositis? Pathogenesis?
Skin rash and muscle injury possibly brought about by CD4+ and CD8+ T lymphocytes that have infiltrated the muscles
What virus could play a role in polymyositis-dermatomyositis?
Coxsackie B virus
What are the current therapies for autoimmune diseases?
Nonspecific immunosuppression with corticosterids/cyclosporine
What is the mechanism of action of corticosteroids against autoimmune diseases?
Anti-inflammatory effects
What is the mechanism of action of azathiporine and cyclophosphamide against autoimmune diseases?
interferes with DNA synthesis to eliminate dividing lymphocytes
What are the side effects of prednisone?
Bone mineral loss, weight gain, DM, fluid retention, skin thinning
What are the side effects of azathiprine and cyclphosphamide?
Bone marrow suppression and damage to intestinal epithelium
What is the mechanism of action of cyclosporine and tacrolimus?
Blocks calcineurine, IL-2 transcription
How can plasmaphersis help fight against autoimmune diseases?
Removes Ag-Ab complexes
25% of people with polymyositis-dermatomyositis have autoantibodies to what?
histidyl tRNA synthetase
What causes scleroderma?
T lymphocytes infiltrate the dermins prior to fibrosis, causing a hypersensitivity to collagen deposits. TNF-alpha and IL-1 are expressed to further the problem
What is Infliximab?
Humanized anti-TNF-alpha monoclonal antibody
What is Etanercept?
TNF-alpha receptor fusion protein
