Immunopathology Flashcards
What is a Type I Hypersensitivity Reaction?
Immediate with rapid reaction within minutes. Characterized by shock, edema, and respiratory compromise
What is Type II Hypersensitivity Reaction?
Antibody-mediated, caused by Abs against cell surface or ECM antigens
What is Type III Hypersensitivity Reaction?
Immune complex-mediated, damaging inflammatory reaction to antigen-Ab complexes especially in blood or glomeruli
What is Type IV Hypersensitivity Reaction?
Cell-mediated, delayed, caused by sensitized CD4 T cells, producing granulomas
What does anti-CCP test for?
Rheumatoid Arthritis
Anti-centromere?
CREST syndrome (limited systemic sclerosis)
Anti-Jo-1
Polymyositis/dermatomyositis
Anti-Scl70 = Anti-DNA topoisomerase
Systemic Sclerosis (diffuse)
Anti-RNA Polymerase
Systemic Sclerosis, with renal crisis
Anti-U1 RNP
Mixed connective tissue disease
Anti-Sm
Lupus
Anti-ddDNA
Lupus
Anti-Nuclear (ANA)
Lupus and many other rheumatic disease
Anti-SSA
Sjogren’s Syndrome, Neonatal Lupus, Subcut, Lupus
Anti-SSB
Sjogren’s Syndrome, Neonatal Lupus, Subcu Lupus
Anti-Myeloperoxidase, P-ANCA
Microscopic Polyangiitis, Eosinophilic granulomatosis with polyangiitis
C-ANCA
Granulomatosis with polyangiitis
What are general types of therapy used?
Chemotherapy, corticosteroids, transplant rejection medicines
What are immunosuppressive chemotherapeutic drugs freqeuntly used?
Methotrexate and Cyclophosphamide
What effect to corticosteroids have?
Anti-inflammatory
What are two transplant rejection drugs?
Cyclosporine and Tracrolimus
What is the method of transplant rejection drugs?
They are calcineurin inhibitors. Bind intracytoplasmic receptor proteins called immunophilins, which inhibit calcineurin. Calcineurin normally dephosphorylates regulatory proteins, allowing them to pass into the nucleus of the lymphocyte, promoting T cell activation and secretion of TNF, IFN-GAMMA, IL2 AND IL4.
What is mycophonelate mofetil (cellcept)?
Reversible inhibitor of inosine monophosphate dehydrogenase in purine biosyn that inhibits DNA replication, inhibiting lymphocyte proliferation
What is mycophenolate mofetil used to treat?
SLE
What is azathioprine?
Messes up DNA replication, used in SLE, Rheumatoid Arthritis, and other AI diseases
What is hydroxycholoroquine?
Anti-malarial antibiotic with anti-inflammatory activity used to treat SLE and Rheumatoid Arthritis
What are gross pathologies of Systemic Lupus Erythematosus?
Non-erosive synovitis, pluritis, pericarditis, peritonitis, splenomegaly
What are microscopic pathology of SLE?
Acute necrotizing vasculitis of arteries, nephritis, cerebritis
What are signs of SLE?
Butterfly skin rash on face, edema, fatigue, weight loss, joint pain, fever, pleuritic chest pain
What are symptoms of sjogren syndrome?
Dry ocular and oral mucosa, enlarged salivary and lacrimal glands, fatigue, joint pain, conjunctival and oral ulcers
What is systemic sclerosis?
An abnormal accumulation of fibrous tissue in skin and organs. Widespread skin involvement
What is the pathogenesis of systemic sclerosis?
Abnormal immune response + vascular damage = increased growth factors leading to fibrosis.
What are symptoms of systemic sclerosis?
Joint pain, stiffness, digestive problems, edema of hands and feet, puffy fingers are first sign
later: hard or shiny skin over long bones of arms and lower legs
What are microscopic manifestations of GVHD
erythematous rash and biopsy show lymphocytic infiltrate with apoptosis of epidermal cells, especially at dermal-epidermal junction. visible by a gap between the two layers. in liver, hepatocytes undergo apoptosis
What is XLA?
Congential immunodeficiency with failure of B cells to produce Abs due to faulty Bruton’s Tyrosine Kinase
What is amyloidosis?
Progressive organ dysfunction that can be systemic or localized.
What are symptoms of amyloidosis?
Nonspecific complaint such as weakness, fatigue, weight loss. Later, renal disease (gaining water weight), hepatomegaly, splenomegaly, or cardiac abnormalities
A man gets a platelet transfusion and gets growing areas of itchy skin edema. What’s the mechanism?
Mast cells, IgE, and leukotriene
What do mast cells release?
Histamine
What is the major prostaglandin that mast cells release
PGD2
What are mast cell products?
Histamine chemokines, kallkrein generating factors, granule-associated proteases, peroxidase, proteoglycans
What is urticaria?
Hives, type I immediate hypersensitivity reaction caused by antigen reaction with preformed IgE on surface of mast cells.
What plus what plus…. = type I immediate hypersensitivity?
Mast cells + IgE + histamine + leukotrienes + PGD2
A 5 yo gets a sore throat, week later onset of malaise, nausea and slight fever. Her urine is smoky brown and decreased. What is mechanism of her disease?
Antigen-Xs immune complexes. Ab-antigen complexes accumulate in the kidneys. Poststreptococcal acute glomerulonephritis
What is Goodpasture’s Syndrome?
Affects lungs and kidneys, Abs to alveolar and glomerular basement membranes. Hemoptysis and hematuria. Usually in 20-40 yo. Kidneys - rapidly progressive glomerulonephritis with glomerular crescent formation. Lungs - heavy, areas of red-brown consolidation from bleeding and hemosidering deposition. LINEAR deposits of IgG
What kind of IgG deposits are present in SLE?
Granular subendothelial deposits of IgG thickening capillaries circumferentially.
What is poststreptococcal acute glomerulonephritis?
Most common in 6-10 yo. Fever, malaise, nausea, smoky urine. Hematuria, edema, proteinuria, hypertension. Increased IgG, decreased C3 complement. Granular deposits of IgG and C3. Swelling periorbital region due to edema
What are symptoms of AIDS?
Acute phase - sore throat, myalgia, fever, rash and sometimes aseptic meningitis
Crisis phase - fever of more than one month, fatigue, weight loss, and diarrhea
What are symptoms of amyloidosis?
nonspecific complaints such as weakness, fatigue, weight loss, Later, renal disease (severe edema), hepato,splenomegalies, cardiac abnormalities
What are symptoms of heart failure?
Dyspnea, orthopnea, paroxysmal noctural dyspnea (waking up short of breath),
Hepatic Failure symptoms
jaundice, bleeding (decreased clotting factors), edema, hepatic encephalopathy (confusion progressing to coma)
What are symptoms of SLE?
Weight loss, fatigue, joint pain, fever, butterfly rash, pleuritic chest pain
What is the time course of HIV viral load?
Acute phase - increases to peak of 10 million/ml plasma at about 6 weeks
Clinical latency - decreases to about 10,000/ml plamsa
Final crisis stage - 11 years and back up to 10 million
What is the course of CD4 load in HIV?
Acute phase - initial normal of 1000 to around 500 at six weeks
Clinical latency - gradual decline to around 50/cu mm at about 9 years
Final crisis stage - down to around 5/cu mm
At what CD4 load count to symptoms begin? At what count to opportunistic infxns begin?
200/cu mm
100/cu mm
What is primary amyloidosis?
Deposition of Amyloid-Light chains. Associated with multiple myeloma
What is secondary amyloidosis?
Amyloid-Associated. Associated with chronic inflammation
What is localized amyloidosis?
Deposition in a single organ. associated with alzheimers. Most common form of dementia. Alpha-Beta chains
What is the common patient for systemic sclerosis (scleroderma)?
Women of childbearing age
What is the classic patient for SLE?
Women of childbearing age
What is induced amyloidosis?
It’s frequently dialysis patients because they cannot get rid of the HLA,so you accumulate MHC Class I.
What is scleroderma?
Scleroderma excess fibrous deposition and tissue. Typically associated with CREST. Due to xs inflammation an tissue destruction. IgG-mediated with rheumatoid factor. Assocaited with Scl-70. Results in contracture. Mask face, claw hand! No treatment. Vasculature and smooth muscle replaced by collagen.
