Immunology: Autoimmunity Flashcards
Type II autoimmunity
IgG
cell surface/ECM antigens
Type III autoimmunity
IgG
immune complex deposition
Type IV autoimmunity
mediated by T cells
autoimmune hemolytic anemia
type II (IgG and IgM): Rh blood group or I antigen
destruction of RBC by classical complement (MAC and C3b) and phagocytes (with Fc receptor (IgG) or C3b)
anemia
Dx: Direct Coomb’s
Tx: corticosteroids
autoimmune thrombocytopenia purpura
type II: platelet integrin, gpIIb:IIIa
inhibition of enzyme that cleaves vWF (links platelets and vessels with clots) = excessive platelet adhesions (occlude small vessels)
damage: kidney, liver, brain
abnormal bleeding, neurological symptoms, low platelets, bruises
Dx: microangioplastic hemolytic anemia
Tx: plasmaphoresis
Goodpasture’s syndrome
type II: collagen type IV of BM
classical (then alternative) complement and phagocytes cause damage
glomerulonephritis, pulmonary hemorrhage
symptoms: loss of appetite, weakness, fatigue
Dx: anti-GBM
Tx: plasma exchange and antiinflammatory drugs
pemphigus vulgaris
type II: epidermal cadhedrin: proteins desmoglein 1 and 3
blistering of skin
Dx: punch biopsy of lesion with immunofluorescent stain (IgG4 Ab = pathogenic)
Tx: corticosteroids, anti-inflammatory drugs, rituximab
acute rheumatic fever
type II: GAS (S. pyogenes) cell wall antigens; molecular mimicry (Ab cross-react with cardiac muscle)
arthritis, myocarditis, late scarring of heart valves
symptoms: chest pain, shortness of breath, fever, joint pain, endocarditis
Grave’s disease
type II: TSH receptor (agonist)
hyperthyroidism
symptoms: heat intolerance, nervous, irritable, warm moist skin, weight loss, enlarged thyroid, bulging eyes, characteristic start (eye muscle inflammation)
Pregnant women: pass IgG to fetus and fetus will have condition
Tx fetus: plasmaphoresis to remove Ab and thyroid function is restored
Myasthenia gravis
type II: Ach receptor (antagonist: endocytosed and degraded)
progressive weakness
symptoms: facial muscles (esp. eyes and eyelids) first: diplopia, ptosis; progresses to generalized muscle weakness
Tx: anti-inflammatory, pyridostigmine
Type 2 diabetes (insulin-resistant diabetes)
type II: insulin receptor (antagonist)
hyperglycemia, ketoacidosis
Hypoglycemia
type II: insulin receptor (agonist)
hypoglycemia
Scleroderma
type II: destruction of vascular endothelial cells of arterioles and sm. muscle cells; replaced with collagen and fibrous material
localized or systemic symmetrical skin thickening; hard, smooth, ivory skin
damage: kidney, vessels, liver, brain
Dx: ANA (anti-nuclear Ab), ATA (anti-topoisomerase Ab), ACA (anti-centromere Ab)
Tx: increase blood flow to extremities
rituximab
B cell marker CD20 specific mAb: Ab results in NK ADCC to B cells
Tx: pemphigus vulgaris and RA (doesn’t make sense if T cell mediated)
pyridostigmine
inhibits cholinesterase
Tx: myasthenia gravis
subacute bacterial endocarditis
type III (IgG complex): S. viridans (normal flora) antigen = inflammation of endocardium (typically previous damage to heart valves- rheumatic fever or congenital)
mediated by phagocytes that recognize opsonized bacteria (IgG and C3b) and anaphylatoxins
glomerulonephritis
mixed essential cryoglobulinemia
type III (IgG complex): rheumatoid factor IgG complexes (with or without HCV antigens)
most often: pt with B cell proliferative disorder (multiple myeloma or Waldenstrom macroglobulinemia)
systemic vasculitis
Meltzer’s triad: purpura, arthralgia, myalgia
systemic lupus erythematous
type III (IgG complex): DNA, histones, ribosomes, snRNP, scRNP
glomerulonephritis, vasculitis, arthritis, neurological
symptoms: fever, malais, joint pain, myalgias, fatigue, butterfly facial rash
Tx: anti-inflammatory
women, Asian and African descent
highly variable severity
*positive direct Coomb’s, blood in urine, reduced in complement C1 levels
cryoglobulins
immunoglobulins that become insoluble at reduced temperature
sometimes only light chains (Bence Jones proteins)
Type 1 diabetes (insulin-dependent DM)
type IV: pancreatic beta cells
Beta cell destruction
CTL effectors
European descent
untreated symptoms: many and can lead to coma and death
Tx: pig/bovine insulin (immune responses directed against foreign insulin can cause an immune complex hypersensitivity) or human recombinant insulin
Rheumatoid arthritis
type IV: unknown synovial joint antigen auto reactive T cell Anti-CCP joint inflammation and destruction Dx: production of IgG, IgM, and IgA (rheumatoid factor) specific for the Fc region of Ab molecules (rheumatoid factor not req. for Dx) most common rheumatic disease Tx: infliximab and rutiximab
Multiple sclerosis
type IV: myelin basic protein, proteolipid protein
TH1 effector cells directed at myelin sheath (macrophages)
sclerotic plaques in white matter of CNS
brain degeneration, paralysis
symptoms: motor weakness, impaired vision, lack of coordination, spasticity
Dx: oligoclonal bands of IgG in CSF
Tx: immunosuppressive drugs and IFN-b1
infliximab
anti-TNF-alpha
– TNF-alpha made by TH1 effector cells
Makes sense to treat RA
Sjogren’s syndrome
type IV: exocrine glands that produce saliva and tears
symptoms: dry eyes and mouth, sometimes skin, nose and vaginal dryness
can also effect kidney, blood vessels, liver, brain
Dx: Schirmer test to measure tear production, ANA, and rheumatoid factor
second most common rheumatic disease (rheumatoid factor not req. for Dx)
Tx: artificiae tears, goggles
Guillain Barre
type II: gangliosides
demyelination
molecular mimicry: Camplobacter jejuni
symptoms: symmetrical weakness of lower limbs, rapidly ascends to upper limbs and face, difficulty swallowing and breathing, drooling (usually regain most motor function with Tx)
Tx: plasma exchange with immunosuppressive drugs
Miller-Fisher
form of Guillain Barre
starts with facial muscles and descends
Wegener’s Granulomatosis
type II: molecular mimicry: viral or bacterial infection that cross-reacts with neutrophil determinants
ANCAs (anti-neutrophil cytoplasmic antibodies) pind to neutrophils -> activate them -> up regulate adhesin molecules-> bind vascular endothelial cells->degranulate-> vasculitis
symptoms: rhinitis and conjunctivitis; lung infiltrates, rapidly progressing kidney dysfunction leading to glomerulonephritis, granulomas found in all infected tissue
Tx: plasma exchange and anti-inflammatory drugs
