Autoimmune Diseases Flashcards
Pernicious anemia:
Antigen
Pathogenesis
Clinical symptoms
Tx
Antigen: intrinsic factor, which normally binds to vit B12 for B12 absorption
Pathogenesis: works like Type II hypers: autoantibody against IF—>lack of vit B12 absorption
Clinical symptoms, all due to B12 deficiency
—megaloblastic anemia: fewer RBCs produced, lower O2 delivery, cardiac output increases
—>hypersegmented PMNs
—>effects hematopoetic cells, GI epithelium
- triad: weakness, sore tongue, paresthesia
Tx: B12 injections
Autoimmune hemolytic anemia:
Antigen
Pathogenesis
Clinical symptoms
Tx
Antigen: neoantigens (drugs) on surface of RBCs (absorbed, these are like haptens)
Pathogenesis: auto- IgG or IgM leads to RBC lysis, phagocytosis
Clinical symptoms:
- jaundice, splenomegaly, fatigue, weakness, pale skin, inc HR, dyspnea
—>warm agglutinins (IgG): reactive with RBCs at 37°
—> cold agglutinins (IgM): bind below 30°C in extremeties (one cause of Raynaud’s)
Tx: RBC transfusion, steroids/immunosuppressants
Autoimmune Thrombocytopenia
Antigen
Pathogenesis
Clinical symptoms
Tx
Antigen: membrane glycoprotein IIb/IIIa complex on platelet membranes
Pathogenesis: anti-platelet IgG or IgM lead to platelet destruction
Clinical symptoms: low platelet count, megakaryocytes in bone marrow, petechiae, purpura, mucosal bleeding, risk of organ bleeds
Tx: splenectomy
Myasthenia Gravis
Antigen: acetylcholine receptors, postsynaptic muscle membrane
Pathogenesis: autoAB against receptors, decreases number of functional receptors
Clinical symptoms: neuromuscular disorders
— skeletal muscle VERY easily fatigued: difficulty swallowing. respiratory distress or even paralysis
—ophthalmic: weak extra-ocular muscles (ptosis, diplopia)
Tx- anti-cholinesterase, immunotherapy
Graves’ Disease
Antigen
Pathogenesis
Affects women 7x more than men
Antigen: TSH receptor.
Pathogenesis: IgG auto-antibody ACTIVATES TSH receptor. Call it a TGI (thyroid growth immunoglobulin), or TSI (thyroid stimulating immunoglobulin).
—>leads to hyperthyroidism (can’t turn off T3 and T4 production)
Graves’ Disease
Gross and histopathology
Clinical symptoms
Tx
Gross: bilateral, symmetric enlargement of thyroid (visible via palpation, on dissection, and through radio iodine)
Follicular epithelium hypertrophy/hyperplasia, colloid in lumen is “scalloped shaped” bc there’s so many FE cells
Histology: thyroid cell proliferation—>lots of thyroid cells, smaller acini
Symptoms: low TSH, fine hair, exophthalmos (eyes bugging out), goiter, muscle wasting, sweating, tachycardia, dyspnea (short breath), tremors, nystagmus
Treatment: address symptoms, radioiodine ablation, remove thyroid and take thyroid hormone replacement after
Hashimotos thyroiditis
Facts
Antigen
Pathogenesis
Histology
Most common hypothyroidism when iodine is sufficient. 45-65 yo, women 10x more likely than men
Antigen: thyroglobulin (thyroid peroxidase)
Pathogenesis: both humoral and cellular
- auto antibody: ADCC (antibody dependent cell cytotoxicity), sometimes immune complex
- DTH: t-cell infiltration, thyrocytes targeted by Cytotoxic T-cells and/or activated macrophages
Histo:
Thyroid enlarges due to infiltration of lymphocytes and plasma cells, follicles atrophy, epithelia abundant and eosinophilic. Lots of round cells, inflammation, loss of glands/ascini
Hashimotos Thyroiditis
Symptoms
Treatment
Symptoms:
ELEVATED TSH, Goiter, hypothyroidism: fatigue, cold, weight gain, slow reflexes, depression,
myxedema (GAG accumulation): puffy face and hands, thick skin, hoarse voice, cardiac enlargement, macroglossia
Treatment: thyroid hormone replacement therapy
Rheumatic Fever
Antigen
Pathogenesis
Antigen: glycoproteins on Beta-hemolytic strep. pharyngitis, which have antigenic mimicry of heart tissue, heart valves, sometimes joints (arthritis)
Pathogenesis:
- 2-3 weeks after beta-hemolytic strep pharyngitis infection, anti-strep M protein antibodies and t-cells crossreact with cardiac sarcolemma, valve glycoproteins
—>5-15 year olds (primarily carditis)
—> recurrent in 25-35 year olds (mostly as arthritis) bc they get infection from their kids
Rare in pts over 35 years old
Rheumatic fever
Symptoms
Tx
Acute rheumatic fever:
- chest pain, palpitations
- carditis: myocardial granuloma like lesion is pathognomonic (Aschoff bodies, contains Antischkow cells: macrophages w ovular nuclei)
- fibrinous pericarditis: fibrosis and adhesions develop, “characteristic rub” that yoh can hear
Chronic Rheumatic fever (acute can progress to chronic)
- more t-cell driven than Ig driven
- valvitis: mitral valve vegetations, incompetence (murmer)
- myocarditis: chamber dilates, CHF
TX: antibiotics, anti-inflammatory drugs
Goodpasture syndrome
Antigen: basement membrane, type iv collagen
- males at higher risk
- HLA linked susceptibility
Pathogenesis:
- break tolerance bc of a viral infection, or a chemical exposure (solvents, weed killer, metallic dust etc)
- autoIgG targets BM in kidney and lung
Symptoms
- rapid progressive glomerulonephritis (hematuria, proteinuria), back pain, possible renal failure
- lung hemorrhage, can be massive and fatal
HISTO:
Glomeruli: Thick capillaries, very cellular, RBCs in tubules.
Direct IF of glomeruli: NOT lumpy bumpy. Instead, has a very regular pattern (follows BM). Can stain with anti-IgG or anti-complement and get same result
Indirect IF would work here, would get same result
Insulin dependent Diabetes Mellitus
Antigen: pancreatic Beta-cells, insulin
Pathogenesis: T cell infiltrate is destructive (insulitis), auto Ab present but not destructive
- STRONG MHC class II Association
- infectious mimicry? Mumps, rubella, coxsackie B
Symptoms
- insulin deficiency
—>glucose and FFA accumulation, polyuria, polydipsia (thirst), polyphagia (hunger), vision issues
Clinical complications: renal failure, atherosclerosis, impaired wound healing, retunopathy, neuropathy
Oral complications: higher perio disease, parotid enlargement, oral candidiasis
Sjögren Syndrome
Antigen
Pathogenesis
Etiology/antigen
- virus (? Like EBV, Hep C) changes…
- epithelial cytoskeleton protein alpha fodrin
- 9:1 female
- primary is just sicca, secondary is sicca + other diseases like RA, SLE
Pathogenesis:
- T-cells infiltrate lacrimal, salivary glands
- auto Ab present, no damage
Sjögren Syndrome
Clinical symptoms
Tx
Sicca syndrome has two major parts:
- xerostomia: dry mouth, hard to swallow or taste, enlarged parotid, dry mucosa and fissured tongue
- xeropthalmia: “kerratoconjunctivitis sicca” (dry eyes), blurred vision, burning and itching
Diagnose w lip biopsy (minor salivary glands)
SLE quick stuff
Inadequate clearance of apoptotic body
Photosensitive, red macular rash
Works like type III hype: vasculitis leading to fibrinoid necrosis
Positivr lupus band diagnostic but not pathognomonic
Proteinuria, renal knsufficiency
LE cell:neutrophil or macrophage that ingested nucleic material of another cell, very purple
