2-Autoimmunity Flashcards
tolerance breached
- central- autoreactive lymphs not deleted in marrow and thymus
- peripheral- normal inhib mechanisms fail (anergy, apop, suppression
famililal trends
-autoimm thyroid dis + vitiligo in same person
-lupus + sjogrens in diff members of same fam
-insulin dependent diabetes in families
-identical twin has dis then other twin high risk
predisposition factors
- abnormal lymphs and APCs
- genetic
- microbial infections
tissue injury causes
- autoreactive CTLs
- circulating autoantibodies
- immune complexes
vertical transmission of Ab
maternal autoimmune IgG affect dev fetus
-effects dissapear after birth when Ab catabolized
-organ damage irreversible like heart > bradycardia
theories behind autoimmunity
- mircobes- molecular mimicry so resemble self antigen close enough to break tolerance
-mycoplasma infections when Ab cross react with antigen on RBC and destroy - inapprop expression of MHC proteins
autoimmune hemolytic anemia
-RBC Ab vs RBC membrane proteins
-cause RBC lysis and anemia
-opsonization > removal by phagocytic cells in spleen
goodpasture’s syndrome
autoAb to alpha3 chain of type IV collagen (@ basement mem) in alveoli and glomeruli
-acts complement so kidney damage, pulmonary hemorrhage, death
-will show smooth, ribbon like appearance of BM
pernicious anemia
autoAb to intrinsic factor (transports B12) and/or gastric parietal cells
=dec absorption of vit B12 so abnormal erythropoiesis/anemia
hashimoto’s thyroiditis
hypothyroid state
-autoAb and autoreactive T cells to thyroid gland proteins
idiopathic thrombocytopenia purpura
ITP
platelets destroyed by autoAb to platelet membrane proteins
-‘purpura’ bc purple skin lesions from epidermal hemorrhage
-IVIG prevent destruction of platelets
vitiligo
depigmentation of skin by destruction of melanocytes
grave’s disease
autoAb vs TSH receptor in thyroid
-hyperthyroidism bc Ab stims receptor without ligand so lots of hormones
myasthenia gravis
autoAb to alpha chain of nicotinic acetylcholine receptor on skeletal muscle cells @ nueromusc junctions
blocks neuromuscular transmission by inhib binding of ligand to receptor so muscle weak and paralysis
type 1A diabetes
autoAb to insulin secreting beta cells, autoreactive T cells mediate destruction
dec insulin so inc blood glucose
multiple sclerosis
autoimm demyelinating dis of CNS
-TH1 and TH17 get act so drive macro act and damage to myelin containing nerve cells bc specific for myelin antigens
either be relapsing-remitting or progressive
treat with interferon-beta1b every other day or interferon-beta1a weekly or steroids
systemic lupus erythematosus
SLE
multisystem dis from broad loss of reg control that sustains self tolerance
-skin, joints, kidney most common
-autoAb vs numerous antigens for DNA, RNA, proteins, ribonucleoproteins
-more women
SLE mechanism
mediated by immune complexes (hypersens III) targets kidneys thru glomerulus and podocytes
PLUS
hypersens II with autoAb vs RBCs, WBCs, and platelets
SLE predisposition
- genetic- family members inc incidence
- drugs and some viruses- drug induced lupus coplex with nucleoproteins = autoimm
- immunologic- B cell hyperactivity, inc T helper activity, dec Treg activity
rheumatoid arthritis
progressive inflamm dis of joints so destroy joint cart and synovium, pulmonary/cardiac/ocular symptoms
-associated with HLA-DR4 haplotype
TH1, TH17, macros, B cells/plasma cells = inflamm environ with secretion of leukocyte recruiting cytokines
rheumatoid factor = IgM/IgG to Fc of IgG = immune complex
biologic agents of RA
rheumatoid arthritis
TNF-alpha important
- etanercept- TNF-a type II receptor fused to IgG1 Ab
- infliximab- chimeric mouse/human anti TNF-a monoclonal Ab
- adalimumab- recombinant human IgG1 monoclonal
sjogren’s syndrome
dry eyes and mouth from destruction of lacrimal/salivary glands
-B and T cells influx in glands
-can be alone or with RA and SLE
-women
-inc risk of dev lymphoid malignancies
scleroderma
progressive systemic sclerosis
xs collagen deposit in skin, kidneys, GI tract, heart, muscles, lungs
-antinuclear Ab in most cases but dk why
-T cells infiltrate dermis so hypersens to collagen > release IL1 and TNF-a > collagen syn = vicious cycle
polymyositis-dermatomyositis
polymyositis= muscle injury from CD4+ and CD8+ T lymphs inflitrate muscles
dermatomyositis = skin rash usually with poly
25% have autoAb to histidyl tRNA synthetase so use for dx
maybe with coxsackie B virus
corticosteroids
treatment
prednisone = anti inflamm but bone mineral loss, weight gain, diabetes, fluid retention, skin thinning
cytotoxic drugs
treatmen
azathioprine and cyclophosphamide
-interfere with DNA syn so elim dividing lymphocytes
-bone marrow suppression and damage to intestinal epi
cyclosporine and tacrolimus
nonspecific immunosupp that blocks activity of acalcineurin so block transcription of IL-2
both are nephrotoxic
plasmapheresis
treatment
removes Ag-Ab complexes but only short term alleviation
antagonists of TNF-alpha
- infliximab- humanized anti TNF-a monoclonal Ab
- etanercept- soluble TNF-a receptor fusion protein binds to TNF-a
- adalimumab- recombinant human IgG1monoclonal
- potent anti-inflamms- treat Crohns, RA, juvenile chronic arthritis, ankylosing spondylitis
