Immunology - Block 3 - Part 3

davidwurbel7's version from 2015-12-15 21:07

Autoimmune Diseases


Question Answer
Antibody target platelet membrane antigensAutoimmune Thrombocytopenic Purpura
Autoimmune Thrombocytopenic Purpura is this type of hypersensitivityType II
Symptoms include Bleeding tendency, Easy bruising (purpura), Extravasation of blood from capillaries into skin and mucous membranes (petechiae)Autoimmune Thrombocytopenic Purpura
Healthy history, developed perioral and sublingual blisters over a 2 week periodPemphigus Vulgaris
Pemphigus Vulgaris is this type of hypersensitivityType II
In Pemphigus Vulgaris antibodies targetsDesmoglein (cadherin)
Consequence of the loss of cadherinCompromised Tight Junctions
Patient comes in with soughing of epithelial cells (especially in the mouth) and blister formationPemphigus Vulgaris
Diagnosed by immunofluorescence anti-desmoglein IgG depositsPemphigus Vulgaris
Antibody target - Collagen type IV (basement membrane of lung and kidney)Goodpasture’s Disease
Goodpasture's Disease is this type of hypersensitivityType II
Consequence of anti-collagen antibodies - Bleeding in lung and kidney esp. glomerulonephritisGoodpasture's Disease
Dry cough, may cough up blood (bloody sputum). Difficulty breathing after activity. Generalized Swelling (edema). Burning sensation when urinating. Bloody urine. High blood pressure. Nausea and vomiting. Pale skinGoodpasture’s Disease
Antibody target - Cardiac cells (Abs produced against similar Ag of Strep pyogenes weeks after throat infection)Acute Rheumatic Fever
Consequence of antibody damage to heart and arthritisAcute Rheumatic Fever
Acute Rheumatic Fever is this type of hypersensitivityType II
Diagnosed by the presence of anti-Strep antibodiesAcute Rheumatic Fever
Symptoms includes fever. Cardiac problems (shortness of breath and chest pain). Arthritis (mainly in the knees, elbows, ankles, and wrists). Skin rash (erythema marginatum). Joint swelling; redness or warmth. Nosebleeds (epistaxis). Skin nodulesAcute Rheumatic Fever
Consequence of antibody binding to TSH receptor is hyperthyroidismGraves Disease
Graves Disease is this type of hypersensitivityType II
Symptoms include an enlarged thyroid gland and fast pulse: both signs of hyperthyroidism. In addition she has exophthalmos (protruding eyes) resulting from inflammatory cells infiltrating the orbit of the eyeGraves Disease
Diagnosed by the presence of anti-TSH receptor antibodiesGraves Disease
Antibody target - Acetylcholine Receptor (receptors are down-regulated)Myasthenia Gravis
Myasthenia Gravis is this type of hypersensitivityType II
Maternal anti-acetylcholine receptor IgG antibodies, Anti-AChR, are transferred in utero to fetus. This results in hypotonia, feeding and respiratory difficulties, weak cryTransient Neonatal Myasthenia Gravis
Consequence of anti-myelin-basic antibodies is muscle weakness (paralysis) which are symptoms of this conditionMultiple Sclerosis
MRI showed multiple lesions in the white matter of her brain around the cortex and the ventriclesMultiple Sclerosis
Th1 target is myelin-basic protein with the consequence of destruction of nerve cells Multiple Sclerosis
Multiple sclerosis is this type of hypersensitivityType IV
Auto-reactive T cells against myelin-basic protein (MBP). Th1 cells & activated macrophages secrete inflammatory cytokines leading toDemyelination
CTL target is self antigen on β-islet cells. The consequence is the destruction of insulin-producing cellsDiabetes Mellitus Type I
Diabetes mellitus type I is this type of hypersensitivityType IV
Antibodies directed against IgG Fc fragmentRheumatoid Factors (RF)
Presence of rheumatoid factor could be indicative ofRheumatoid Arthritis
Any antibody that binds to nuclear componentsAnti-nuclear Antibodies (ANA)
Presence of Anti-nuclear Antibodies could be indicative ofSystemic Lupus Erythematosus (SLE)
HLA predisposition to Rheumatoid ArthritisHLA type DR4
Genetic component of Ankylosing spondylitisHLA B27
Genetic component of Type 1 DiabetesDR 3/4
Genetic component of SLEDR 3
Genetic component of Rheumatoid arthritisDR 4
Chronic inflammatory symmetrical arthritisRheumatoid Arthritis
Rheumatoid Arthritis is the type of hypersensitivityType IV
Disease-specific antibody, present in 98% rheumatoid arthritis patientsAnti-CCP (Anti-Citrullinated Cyclic Peptide)
Auto-reactive CD4+ cells activate macrophages. Activated macrophages secrete this, leading to tissue damageTNF-α
Possibly due to defective clearance of immune complexes associated with inappropriate stimulation of immune cells. Anti-ds DNA and Anti-Sm (Smith) (ribonucleoprotein) antibodies are seen inSystemic Lupus Erythematosus (SLE)
Extreme exhaustion over a 6 month duration. Her ankles and knees begin to swell, and the edema is noted bilaterally. She also starts to complain of joint pain in her ankles, knees, elbows, wrists, and fingers. Suddenly she is having a problem with her hands and feet becoming painful and discolored when she is exposed to cold. A rash develops across the bridge of her nose when exposed to sunlightSystemic Lupus Erythematosus (SLE)
Systemic Lupus Erythematosus (SLE) is this type of hypersensitivityType III
A connective tissue disease that involves changes in the skin, blood vessels, muscles, and internal organsScleroderma
Anti-topoisomerase(Scl-70) or anti-centromere antibodies. Major clinical complications include renal crisis and failure. Pulmonary and myocardial fibrosis Diffuse Scleroderma (dSSc)
Symptoms include purplish discoloration of the fingers upon cold exposure, with redness and pain on re-warming. Fine late inspiratory crackles were heard at both lung bases. The hands and fingers were cool, diffusely swollen, and spontaneous discoloration of fingers was noted. The skin of the fingers was thickenedScleroderma
Characterized by skin induration and thickening accompanied by various degrees of tissue fibrosis. A “beak-like” appearanceSystemic Sclerosis, Scleroderma (SSc)
Anti-centromere antibodies against endotheliumScleroderma
Scleroderma is this type of hypersensitivityType III
Anti-topoisomerase(Scl-70) or anti-centromere antibodies. Renal crisis and failure. Pulmonary and myocardial fibrosisDiffuse Scleroderma (dSSc)
A milder variant of scleroderma characterized by calcinosis (hard calcified, subcutaneous nodules of the buttocks), Raynaud's phenomenon, esophageal dysmotility (difficulty swallowing), sclerodactyly (scleroderma involving the fingers), and telangiectasia (small vascular lesions of the skin)CREST Syndrome
Repeated history of dental carries, irritation in the mouth, difficulty swallowing and a dry cracked tongue and dry eyesSjögren's Syndrome
Accumulation of anti-small RNA leads to destruction of exocrine glandsSjögren's Syndrome
Sjögren's Syndrome is this type of hypersensitivityType III
Immune complexes deposition in muscle tissue. Muscle weaknessPolymyositis
Immune complexes deposition in the skin. Heliotrope eyelids-violaceous eruption (purplish rash) on the upper eyelids. Gottron’s sign-scaly, patchy redness over the knuckles.Dermatomyositis

Combined and T cell Immuno-Deficiencies

Question Answer
Presents with thrush and a family history of repeated viral and bacterial infections. no thymic shadow and flat, flared ribs. Blood test results show lymphocyte count was 150 cells microL-1 (normal for an infant is >3000 cells microL-1)SCID – ADA (Adenosine Deaminase Deficiency)
Mutation of the adenosine deaminase that causes build up to toxic level of adenosine causes no B, T or NK cells. Decreased Humoral and CMISCID – ADA (Adenosine Deaminase Deficiency)
Mutation in common gamma chain gene leads defective cytokine receptor signaling for IL-2. IL-4, IL-7, IL-9, IL-15, IL-21. Which leads to no NK or T cells but normal B cells. Decreased CMI, some decreased humoral SCID X-linked Common Gamma Chain
Bright red rash covering entire body and face, purulent conjunctivitis and diarrhea. Eosinophilia. Low serum Ig levels. Absence of B cells and few T cells but normal NK cells. No thymic shadow on x-raySCID – Omenn (RAG)
Mutation in RAG 1 or RAG2. No B cells. Very low T cells (autoreactive). Normal NK cells. Decreased CMI and humoral immunitySCID – Omenn (RAG)
Low-set ears. Hypertelorism (an increased distance between the eyes). Small mouth. Micrognathia. Develops opportunistic infections. Absence of thymus on x-rayDiGeorge Syndrome
Single copy deletion of TBX1 gene on chromosome 22q11. No T cells. Normal NK and B cells.DiGeorge Syndrome
Neurological symptoms including slurred speech, poor muscle coordination (ataxia), droopy eyelids, difficulty swallowing, which developed over a 1 year time period. History includes repeated respiratory infections. Physical examination revealed prominent visible blood vessels in the eyes and earsAtaxia Telangiectasia (AT)
Future prognosis premature aging, predisposition to cancers and neurodegenerationAtaxia Telangiectasia (AT)
Recessive mutation in ATM gene. Defect in DNA repair. Reduced T cell counts. Decreased CMI, neurological defectsAtaxia Telangiectasia (AT)
Mutation in DNA helicase gene. Failure to repair DNA damage. Reduced T cell number. Premature aging, CancerBloom Syndrome
Presented with bloody diarrhea. mild malar eczema and petechiae. Maternal family history. Thrombocytopenia and low platelet size and volumeWiskott-Aldrich Syndrome (WAS)
Mutation in WASP gene. Failure to signal through TCR. Impaired T cell activation and cytoskeletal defectsWiskott-Aldrich Syndrome (WAS)
Severe bronchiectasis. History of recurrent severe URI/lung viral infections. Normal CD4+ T cells. Abnormally low CD8+ T cells. Normal B cellsBare Lymphocyte Syndrome Type I / MHC Class I Deficiency
Mutation in TAP gene. No Positive selection for CD8+ Cells. Normal CD4+ T cells. Decreased CMI against viral infectionsBare Lymphocyte Syndrome Type I / MHC Class I Deficiency
Immunization without any local or systemic responses. Recurrent episodes of infections. Abnormally low CD4+ T cells. Normal CD8+ T cells. Normal B cells. HypogammaglobulinemiaBare Lymphocyte Syndrome Type II / MHC Class II Deficiency
Mutation in Transcripton factor CIITA. No Positive selection for CD4+ Cells. Normal CD8+ T cells. Decreased CMI, some decreased humoralBare Lymphocyte Syndrome Type II / MHC Class II Deficiency

B cell, Innate, and Complement Immuno-Deficiencies

Question Answer
Mutation in BTK. T-cell count is normal. No Mature B cells. Decreased humoral immunity. Defective B Maturation is the reason for no mature B cells.X-linked Agammaglobulinemia BTK
Mutation in various genes involved in B cell activation. Defective B cell activation (inability to class-switch and differentiate into a plasma cell). Normal B cells. Normal to low IgM. Very low IgG, IgA. Decreased humoral immunityCommon Variable Immuno-Deficiency (CVID)
History of recurrent bacterial infections with multiple hospitalizations for pneumonia. Presents with with important pulmonary sequelae, including bronchiectasis. Lab work up shows hypogammaglobulinemia with hyper-IgMX-linked Hyper IgM Syndrome (CD40L)
X-linked recessive Mutation in CD40L. Defective B activation (no activation of AID). No class-switching or somatic hypermutation. Normal B cells. High levels of IgM. None to very low IgG, IgA, IgE. Decreased humoral immunityX-linked Hyper IgM Syndrome (CD40L)
Recessive mutation in AID. Defective B activation (no activation of AID). No class-switching or somatic hypermutation. Normal B cells. High levels of IgM. None to very low IgG, IgA, IgE. Decreased humoral immunityAID Deficiency
Most common immune deficiency. Many patients have no symptomsSelective IgA Deficiency
Mutation in CD18 (LFA-1). Neutrophils and T cells cannot bind to ICAM integrin. Neutrophils and T cells cannot migrate to tissue. Leukocytosis. Susceptibility to bacterial infectionsLeukocyte Adhesion Deficiency
Mutation in NADPH Oxidase. Defective phagosomal killing of bacteria due lack of ROS. Innate cells accumulate forming granulomas and chronic abscessesChronic Granulomatous Disease (CGD)
Diagnosed by NitroBlue Tetrazolium Test (NBT). Tetrazolium is yellow and turns blue in presence of NADPH oxidase. Tetrazolium remains yellowChronic Granulomatous Disease (CGD)
Generalized lymphadenopathy, hepatosplenomegaly, skin hypopigmentation, and silvery hair (Oculo-Cutaneous Albinism). Bone marrow aspirate revealed prominent granules within the lymphocytes and myeloid cellsChediak-Higashi
Mutation in LYST (lysosomal trafficking regulator gene). Defective intracellular trafficking including lysosome phagosome fusion. Failure to kill bacteria. Increased bacterial infectionsChediak-Higashi
Highly susceptible to Neisseria bacterial infectionsComplement Deficiencies
Recurrent manifestations of face and upper extremities swelling. Family historyC1INH Hereditary Angioneurotic Edema
Mutation in C1INH. Spontaneous activation of complement that leads to swelling and edemaC1INH Hereditary Angioneurotic Edema
Mutation in Complement inhibitors. Spontaneous activation of complement. Hemolysis. Dark color urine in the morning. Urine collected over the course of the day will be very dark urine in the morning and urine gets lighter as the day goes onParoxysmal Nocturnal Hemoglobinuria