Immunopathology Flashcards
What are cytokines
messenger molecules of the immune system
Who makes INF-Gamma
NK cells and TH1
What are the effects of mast cell activation ?
Histamine- causes increased vascular permeability, smooth muscle contraction, Mucous production, adenosine (Bronchoconstriction and inhibits platelet aggregation) Proteases which generate kinins and cleave complement
What lipid mediators are contained in mast cells ?
Prostaglandin and Leukotrienes
What does prostaglandin do ?
Generated by the cyclooxygenase pathway in the mast cell. It causes intense bronchospasm as well as increases mucous secretion
What do Leukotrienes do ?
They are the most potent vasoactive and spasmogenic agents known. Much more powerful than histamine.
What do eosinophils produce ?
Mahor basic protein and eosinophil cationic protein which are toxic to epithelial cells, LTC4 and PAF which promote inflammation
What is malaise
is a feeling of general discomfort or uneasiness, of being “out of sorts”, often the first indication of an infection or other disease. Malaise is often defined in medical literature as a “general feeling of being unwell”
What is the main immuno mechanism of lupus ?
Failure of self tolerance which results in the formation of a large array of auto-antibodies that can damage tissue directly or in the form of immune complex deposits.
What will a serum test in a patient with Lupus show ?
Anti- dsDNA Anti-Sm and Anti-Histone
What is the main pathologic problem associated with Lupus ?
The Classic presentation is a facial rash which is photo reactive and renal failure which is indicated by proteinuria hematuria ( immune complex deposition in the glomeruli ) Defective clearnace and increased burden of nuclear apoptotic bodies is the main mechanism
What is molecular mimicry
When a microbial antigen cross reacts with a normal tissue
If a patient presents with symptoms of Lupus what will be the difference between in vivo coagulation and in vitro coagulation and what is the reason for this difference ?
Antiphospholipid antibodies will interfere with the in vitro coagulation tests but in vivo
What is arthralgia ?
Joint pain
What is the most common mechanism of tissue injury in Lupus ?
Immune complex deposition. Kidney and skin biopsies will indicate heavy glandular deposits which will activate the classical complement pathway and which is a type 3 hypersensitivity.
What are the autoantibodies that are developed in SLE ?
Antinuclear antibodies against DNA, Histones, Nonhistone proteins, phospholipids
What will increase the incidence of thrombosis in SLE ?
Antiphospholipid antibodies- These will target Platelets WBC’s and RBC’s leading to cytopenias
What are the morphological patterns that will bo observed in SLE ?
Glomeruleronephritis which is due to immune deposits in the within the glomeruli which will induce inflammatory responses.
What causes Lupus Nephritis with Wire Loops ?
Deposition of antigen complexes in the sub-endothelial space of the glomerulus.
What causes the facial rash in Lupus ?
Erytheromatous or maculopapular eruption over the malar eminances
What will SLE do to the joints ?
It will cause swelling and mononuclear cell infiltration into the synovial membranes inducing pain.
What will SLE do to the heart and spleen and serosal membranes ?
It will cause enlargement of the spleen and capsular fibrosis. Inflammation of the pericardia and pleura. In the heart you will see pericarditis and myocarditis
What is pancytopenia, will you see this in SLE
A reduction in red and white bood cells. This is due to anti-phospholipid antibodies
Will you see a reduction of Complement proteins in SLE ?
Yes
What will a mutation in the common gamma chain lead to ?
Nonfunctional cytokine receptors in helper T cells. Leads to SCID
What causes wire loops in glomerulonephritis ?
Thickening of capillary walls
How do you treat SLE ?
Corticosteroids and immunosuppressants.
What is CD-40
Key mediator of T helper cell function. It binds to CD40 on B cells and macrophages, TH1 cells will be activated and produces INF-Gamma which will activate macrophages
What are TH1 cells most effective against and why ?
Intracellular pathogens because they activate macrophages but they are also involved in IgG production so play a bog role in Opsonization and initiation of the classical complement pathway
What in SLE can cause inflammation ?
Necrosis and fibrinoid deposits in the vessel walls containing, Antibody, DNA, complement fragments, Fibrinogen and leukocyte fragments. This will increase hydrostatic pressure
What is a receptor that is a target of mutation that will render a cell immune to the effects of the HIV virus ?
For the HIV virus to infect the T cells it must be taken in by a macrophage or lymphocyte. This is mediated by binding to CD-4 receptor which is a chemokine receptor on the surface of T cells and macrophages.
What will a deficiency in CD40 cause
Hyper IgM syndrome
What is the defect that leads to hyper IgM syndrome
CD-40 deficiency.
What allows T cells to class switch and produce antibodies of another type ?
The interaction of cytokines as well as contact mediated signals from CD4 T cells via the CD-40 cell surface ligand
Other than Ab deficiencies, what other problems will patients with CD-40 deficiencies have ?
They will have difficulty mounting a cell mediated immune response. CD-40 is critical in activation of macrophages.
What do Hyper IgM patients present with ?
Recurrent Pyrogenic infections because they fail to produce IgG and thus cannot opsonize bacteria. They are normally male and will present with tons of infections. Remember they cannot opsonize anything.
What will happen in adenosine deaminase deficiency ?
SCID- ADA is involved with purine biosynthesis and if defective it will halt DNA synthesis and kill the Leukocyte
What are the two most common causes of SCID ?
Gamma chain deficiency and Adenosine Deaminase
How does the common gamma chain deficiency result in the death of a leukocyte ?
The common gamma chain is critical to the cytokine receptor and if defective there will be no way that IL-7 can bind to and stimulate maturation of T and B cells
What will Burtons Thymadine Kinase Deficiency cause ?
Complete lack of antibodies in the blood
What antibodies will be elevated in the blood if the patient is presenting with lupus ?
Anti-Centromere and Anti- Double Stranded DNA
What is Sjogren’s Syndrome ?
It is an autoimmune disease caused by CD4+ T cell reactions against unknown antigens in the exocrine glands and the ductal epithelium.
What will the serum autoantibodies be in Sjogren’s syndrome ?
Anti-RNP, SS-A, and SS-B
A defect in NADPH will result in what ?
Chronic Granulamatous disease
What is amyloidosis ?
A heterogeous group of chronic diseases characterized by progressice organ dysfunction due to the relentless deposition of abnormal insoluble protons in the blood vessels and interstitium
What population does amyloidosis most commonly affect ?
late middle aged and the elderly
What is the pathogenesis of amyloidosis ?
Abnormal folded proteins. All folded into Beta Sheets
What are the specific proteins found in amyloid A ?
Immunoglobulin light chains, Amyloid A, Transtheyretin
What does primary amyloidosis affect ?
Heart, Gut, Nerves, and Skin. Composed of Amyloid Light Chains (AL)
How will you be able to detect Primary Amyloidosis ?
The patient will have free light chains in their urine. Increased Plasma Cells in their bone marrow
What does Secondary Amyloidosis Primarily Affect ?
This disease is secondary to chronic inflammatory conditions. It involves the Kidneys, Liver, Slpeen, Lymphnodes, adrenals and thyroid.
What protein is deposited in 2nd Amyloidosis ?
Amyloid A which is thought to arise from Aerum Amyloid A which is an acute Phase protein
What conditions is Secondary Amyloidosis associated with ?
Rheumatoid Arthritis, Osteomylitis, Tuberculosis,
What organs does induced amyloidosis involve ?
The Nerves, Bones, Joints, Gut, and Tongue. It is strongly associated with Hemodialysis.
What protein is deposited in Induced Amyloidosis ?
Beta-2 Microglobulin which will eb found in the blood and urine
Who is most probable to have Hereditary Amyloidosis
Arabs, Sephardic Jews, Armenians.
What is hereditary Amyloidosis ?
Mediterranian Fever, Peritonitis, Pleuritis, and Synovitis which will lead to AA deposits in the liver, spleen, kidneys, and adrenals
What is Amyloid Poly Neuropathy
Autodomal Dominant. Peripheral and autonomic neuropathy due to deposition of Amyloid Transthyretin.
What is Cardiac Amyloidosis ?
IT involves ATTR deposition in the centricles or AANF, amyloid Atrial Natriuretic factor, deposition in the atria.
What is cenile amyloidosis ?
Cerebral Amyoidosis involves the deposition of amyloid beta (AB) and amyloid precursor protein (APP) in alzhymers disease and down syndrome
Deposition of Calcitonin … ?
Thyroid Amyloidosis
Obstruction of the islets of langerhans
Pancreatic Amyloidosis which is a feature of Type 2 diabetes
What is the minor protein deposited in all the types of amyloidosis ?
Amyloid P (AP)
What will a microscopic examination of Amyloidosis look like ?
Amorphous Hylane Eosinophilic material in the blood vessels and the glomeruli . Congo red stain will make it appear apple green
What are the symptons of amyloidosis ?
Nonspecific Weakness and weight loss. Dyspnea, light headedness, synscope of the heart and edema of the kidneys. Heart failure, Renal Failure, and dementia
How do you treat amyloidosis ?
Transplantation
Deposition of AL
Primary Amyloidosis, the free light chains can be found in the urine. Most patients will also have a moderateincrease in plasma cells in their bond marrow
Deposition of AA
Secondary Amyloidosis. Amyloid A is a byproduct of Serum Amyloid A (Acute Phase Reactant) and travels complexed to HDL
AB2M (Beta 2 Microglobulin )
Induced Amyloidosis. Beta 2 microglobulin is the light chain of the HLA class 1 histocompatability surface receptor found on all nucleated cells. When the patient has induced Amyloidosis this will be found in the blood and the urine
Patient is on long term hemodialysis, what is the most probable amyloidosis ?
Induced Amyloidosis
AA in the liver spleen kidneys and adrenals of an arab or armenian ?
Mediterranean fecer variant of hereditary amyloidosis
Deposition of Amyloid Transthyretin (ATTR)
Amyloid Poly Neuropathy
Amyloid Atrial Natriuretic factor (AANF)
Cardiac Amyloidosis
Amyloid Beta (AB) and Amyloid Precursor Protein (APP)
Cenile Amyloidosis
COngo Red stain
Amyloidosis
What will amyloid look like under an electorn microscope ?
Nonbranching Fibrils of indefinite length
Your patient has accumulation of fibrous tissue in the skin and other organs
Systemic Scoliosis which is an abnromal immune response that causes vascular damage = Increased growth factors leading to fibrosis
What will the Ab serum tests show in Systemic Sclerosis ?
Anti-DNA Topoisomerase 1 and Anti-Centromere Antibody
What is Systemic Scoliosis ?
The abnormal accumulation of fibrous tissue in the skin and other organs.
Who is most likely to have systemic scoliosis ?
African American Females between the ares of 50 and 60
What disease is characterized by the progressive age related depletion of T Thymocytes in the peripheral blood and lymphnodes ?
Wiskott- Aldrich Syndrome
What is Wilskott Aldrich Syndrome ?
IT is an X-Linked recessive disese characterized by thrombocytopenia, eczema and marked vulnerability to recurrent infections.
What causes Systemic Scoliosis ?
Endothelial activation leads to the increased expression of adhesion molecules –> migration of activated T cells into the perivascular tissue which activate macrophages and induce collagen deposition and platelet aggregation
What serum antibodies are characterized by Systemic Scoliosis
Anti-Scl70 and Anti-Centromere
What will SS present as in the lungs ?
Pulmonary Hypertension and interstitial fibrosis
What will SS present as in the joints ?
Synovial Hyperplasia and inflammation. Symtoms similiar to RA but without the destruction of the joint.
What will SS present as in the heart ?
Patchy Myocardial fibrosis along with thickening if the inter cardiac Arterioles. Microvascular injury and resultant ischemia. Due to changes in the lung right ventricular hypertrophy and failure are common
What will SS cause in the kidney ?
Thickening of the vessel walls and interlobular arteries. IF SS is combined with hypertension the vascular alterations will be more pronounced and will be associated with fibrinoid necrosis thrombosis and infarction. This will lead to renal failure
You have a patient who presents with symptoms of SS and lupus but has U1RNP in the blood what will this be ?
Mixed Connective Tissue disease.
Serum Anti-SSA and Anti-SSB
Sogren Syndrome
Serum Anti-DsDNA and Anti-SM
Lupus
How is Wegners Different From Sclerosis
Wegners is due to the activation of neutrophils which will adhere to the endothelium and degranulate causing vasculitis.
Sclerosis is due to endothelial adhesion of T cells which migrate to the perivascular space, interact with self antigen, recruit macrophages, and lay down collagen
How are the kidney findings of Lupus different from that of Sclerosis ?
Lupus will have the deposition of ANTI-DNA, complement fragments, and immune complexes deposited in the subendothelial space which will activate inflammation,
Sclerosis will cause thickening of the vascular walls due to fibrosis. THIS IS NOT WIRE LOOPS
Wire loops
Lupus
Congo red
Amyloidosis
