Autoimmunity Flashcards
How can autoimmunity arise?
escaped normal clonal deletion and are suppressed in periphery
breakdown of regulation of self=reactive lymphocytes
_____ and _____ tolerance mechanisms must be breached
central
peripheral
What central mechanism gets breached during autoimmunity
autoreactive lymphocytes not deleted in bone marrow and thymus
What peripheral mechanism gets breached during autoimmunity
normal inhibitory mechanisms fail
Predisposing factors to autoimmunity
abnormalities of lymphocytes and APCs
genetic predisposition
microbial infection
How can tissue injury be brought about in autoimmunity
autoreactive CTLs
circulating autoantibodies
immune complexes
Molecular mimicry
resemble self antigens closesly enough to break tolerance
Mycoplasma infections
antibodies can cross-react with an antigen on RBCs to cause destruction
rheumatic fever
caused by cross-reaction of streptococcal antibodies with heart valve tissue
What happens when a cell that doesn’t normally expresses MHC starts to
activates T lymphocytes
may allow positive selection of autoreactive T cells
Autoimmune hemolytic anemia
RBC antibodies produced against RBC membrane proteins
causes RBC lysis and anemia
opsoninzation (removal by phagocytic cells in spleen)
Goodpasture’s syndrom
autoantibodies to the alpha3 chain of type IV collagen of the lung and kidney
causes complement activation
causes kidney damage, pulmonary hemorrhage, death
has a smooth ribbon like appearance
Pernicious anemia
autoantibodies to intrinsic factor and/or gastric parietal cells
decreased absorption of vitamine B12 causes abnormal erythropoiesis/anemia
Hasimoto’s thyroiditis
hypothyroid state
autoantibodies and autoreactive T cells to thyroid gland proteins
Idiopathic thrombocytopenia purpura (ITP)
platelets destroyed by autoantibodies to platelet membrane proteins
IV immunoglobin can prevent destruction of platelets
Purpura
purple skin lesions due to epidermal hemorrhage
Vitiligo
depigmentation of skin by destruction of melanocytes
Grave’s disease
caused by autoantibodies against TSH receptor
example of type II hypersensitivity
causes hyperthyroidism
Myasthenia graves
autoantibodies to alpha chain of nicotinic acetylcholine receptor on skeletal muscle cells at neuromuscular junctions
blockage of neuromuscular transmission causes muscle weakness and paralysis
example of type II hypersenstivity
Type 1A diabetes
autoantibodies to beta cells.
damage to beta cells results in decrease of insulin and increase in blood glucose
Multiple sclerosis
autoimmune demyelinating disease of CNS
TH1 and TH17 cells specific for myelin antigens become activated, which drives macrophage activation and subsequent damage to myelin-containing nerve cells
treat with interferon-beta1b, interferon-beta1a, and IV steroids
Systemic Lupus Erythematosus
multisystem
broad loss of regulatory control that sustains self-tolerance
autoantibodies against numerous antigens including DNA, RNA, proteins, and ribonucleoproteins
more common in women
What is the priniciple danger of systemic lupus erythematosus
kidney failure due to the passage of immune complexes through the glomerulus and deposition on the renal podocytes
Drug-induced lupus
slow drug metabolizes, drugs complex with nucleoproteins to generate autoimmunity
reverses upon removal of drug
Immunologic factors in lupus
B cell hyperactivity, increased Th activity and/or decreased treg activity
Rheumatoid arthritis
inflammatory disease of joints, destruction of joint cartilage and inflammation of synovium
TH1, TH17, macrophages, B cells, and plasma cells create an inflammatory environment consisting of secretion of leukocyte-recruiting cytokines
Rheumatoid factor
IgM/IgG to Rc portion of IgG
not in all patients
Sjogren’s syndrome
dry eyes and mouth due to destruction of lacrimal and salivary glands
B and T cell influx into glands, but not known whether CMI or humoral immunity responsible for damage
occurs alone of in conjuction with RA or SLE
increased risk for developing lymoid malignancies
mostly women
Scleroderma
Excessive deposition of collagen
T cells have hypersenstivity to collagen
results in release of IL-1 and TNF-alpha which results in production of collagen and you get a vicious cycle
Polymyositis
muscle injury possibly brought about by CD4+ and CD8+T lymphocytes infiltration of muscles
Dermatomyositis
skin rash that often accompanies polymyositis
Corticosteroid
anti-inflammatory
Azathioprine and cyclophosphamide
cytotoxic drugs that interfere with DNA synthesis and eliminate dividing lymphocytes
Cyclosporine and tacrolimus
block activity of calcineurin, blocks transcription of IL-2
nephrotoxic
Plasmapheresis
removes Ag-Ab complexes
results in short-term alleviation of symptoms
Infliximab
humanized anti TNF-alpha monoclonal antibody
Etanerccept
soluble TNF-alpha receptor fusion protein that binds TNG-alpha
Adalimumab
recombinant human IgG1 monoclonal