25. Autoimmunity I Flashcards
is autoammunity more autologous with hypersensitivity or immunodeficiency?
hypersensitivity
systemic autoimmune disease is mediated by what?
circulating immune complexes
organ/tissue specific autoimmune disease is mediated by what?
T or B cells
systemic or organ specific…Type II hypersensitivity?
organ/tissue specific (insoluble self-antigen)
systemic or organ specific…Type III hypersensitivity?
systemic (soluble self-antigen)
systemic or organ specific….Type IV hypersensitivity?
organ/tissue specific (local interaction b/w APCs, T cells, innate immune cells)
Insulin Dependent diabetes mellitus - autoreactive T cells against what? Consequence?
against pancreatic B-cell antigens: insulin, glutamic acid, decarboxylase, etc
conseq: B-cell destruction
Multiple sclerosis - autoreactive T cells against what? consequence?
against: myelin basic protein
consequence: brain invasion by CD4+ T cells, paralysis
goodpasture’s disease
Type II injury in autoimmunity
IgG against collagen type IV in glomerular and alveolar basement membrane
bloody urine, decreased urine output, cough with bloody sputum, nonspecific chest pain
use immunoflourescense to stain the autoantibodies - should be smooth, linear distributoin
difference b/w SLE and goodpasture’s on immunoflourescence of glomerulus?
godpastures is type II hypersensitivity and is thus linear all along BM
SLE is type III hypersensitivity and is thus “lumpy bumpy” due to precipitation of immune complexes (but no Ab vs BM)
what are the common mechanisms of disease for auto-Ab mediated disesae?
- C’ and FcR mediated inflammation and subsequent damage
- opsonization and phagocytosis of cells and ADCC
- binding to surface molecules and stimulating or blocking receptors
other
myasthenia gravis
Type II injury in autoimmunity
autoantibodies inhibit Ach receptor function at neuromuscular junction (Abs bind to AchR, this activates C’ and MAC formation, this destroys junctonal folds/decreases surface area, cross linking of AchR by Ab causes internalizaiton of AchR and thus decreased receptor number, and remaining AchR are blocked by Ab)
*** COMPLEMENT PLAYS A MAJOR ROLE IN MEDIATING THE INJURY
- young women mostly
- *muscle weakness worsening with use
- anti-AchR antibody
- ocular MG develops in many but not all patients w/MG: *misaligned eyes, diplopia, ptosis
- 80% of pts w/MG develop thymic hyperplasia
- *15% develop a THYMOMA
Graves disease
Type II injury in autoimmunity
- Autoantibody vs. TSH receptor activates thyroid to produce thyroid hormone (thus high T3/T4 feeds back and decreases pituitary release of TSH)
- *goiter (painless, diffuse enlargement of thyroid gland)
- *ophtalmopathy: expothalmos (proptosis) (due to inflammation/infiltration of retroorbital tissue and deposition of glycosaminoglycans)
- hyperthyroidism: *rapidly lose weight w/out dieting, hyperactive, irritable, anxious, can’t sleep, tachycardia, arrhythmia, tremor, diarrhea, warm moist skin, heat intolerance
- usu women but also men
hashimoto thyroiditis
Type II injury (autoantibodies directed at thyroglobulin and thryroid peroxidase interfere w/iodine uptake and binding by thyroglobulin) mixed with type IV injury (intense mononuclear cellular infiltrate in thyroid, autoreactive CD4+ T cells release pro-inflammatory cytokines (TNF-a) to collaborate with thryoid autoantigen-responsive B cells to produce anti-thryoid autoantibodies, recruit and actiate macrophages, autoreactive CD8 cells, & NK cells which mediate tissue destruction)
inflammation cause tissue damage by triggering apoptosis in thyrocytes by inducing expression of a death receptor (Fas)
*Auto-antibody AND CD4+ T cells (help autoimmune B cells and create appropirate cytokine env’t for apoptotic death of thyrocytes)
- fatigue
- weight gain
- feeling cold
- dry skin/hair
- heavy menstrual flow
- constipation
- slowed thinking
Graves Disease vs Hashimoto Thyroiditis
Graves: high energy, weight loss, fatigue from exhaustion, more frequent bowel movements, ophthalmopathy,
Hashimono: autoabs vs thyroglobulin, weight gain, feeling cold, dry skin and hair, heavy menstrual flow, constipation, slowed thinking (high TSH, low T3/T4)
