Autoimmune Diseases Flashcards
(17 cards)
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
Chronic discoud lupus
Coin like lesions
Remember, direct IF will show lupus band only on the tissue that is lessioned, not on regular tissue
Rheumatoid arthritis
IgG is the antigen, and IgG is the antibody (call the second one RF or rheumatoid factor)
Pannus: chronically inflamed synovial lining
Lymphocytes and round cells enter synofvium, synovial space decreases, less space btw bones
