05 - Diseases of the Immune system Flashcards
Results from activation of TH2 CD4+ helper T cells by environmental antigens, leading to the production of IgE antibodies, which become attached to mast cells; examples: Anaphylaxis, Allergies, Bronchial asthma
Type I Hypersensitivity (Immediate)
Caused by antibodies that bind to fixed tissue and cell antigens and promote phagocytosis and destruction of the coated cells or trigger pathologic inflammation in tissues; examples: Goodpasture syndrome, Autoimmune hemolytic anemia, Immune thrombocytopenia, Pemphigus vulgaris, ANCA vasculitides, Acute rheumatic fever, Graves disease, Myasthenia gravis, Insulin-resistant diabetes, Pernicious anemia, hyperacute and acute humoral rejection
Type II Hypersensitivity (Antibody-mediated)
Caused by antibodies binding to antigens to form complexes that circulate and may deposit in vascular beds and stimulate inflammation secondary to complement activation; examples: SLE, serum sickness, Arthus reaction, PSAGN, PAN, Reactive arthritis
Type III Hypersensitivity (Immune-complex mediated)
Cell-mediated immune responses in which T lymphocytes cause tissue injury, either by producing cytokines that induce inflammation and activate macrophages, or by directly killing cells; examples: Allergic contact dermatitis, Multiple sclerosis, Tuberculosis, PPD, RA, IBD, Acute cellular and chronic rejection, Type 1 DM and Hashimoto thyroiditis (the last two have Type 2 components as well)
Type IV Hypersensitivity (T-cell-mediated/delayed)
32/F presents to the clinic with symptoms of fatigue, joint pains, and malar rash. CBC revealed anemia and low platelet count. What is the diagnosis?
SLE
Hallmark of SLE.
Production of autoantibodies
Mechanisms of organ damage in SLE.
Type III (most); Type II (opsonization, hematologic manifestations)
Most common autoantibody in SLE.
ANA (98%)
Most specific autoantibodies for SLE.
anti-Sm (Smith), anti-dsDNA (anti-dsDNA correlates with disease activity)
Autoantibodies associated with congenital heart block in neonatal lupus.
Anti-Ro (SS-A), Anti-La (SS-B)
Histopathologic findings in SLE with skin involvement.
LM: Liquefactive degeneration of basal layer, edema at DEJ, mononuclear infiltrates around blood vessels and skin appendages
IF: Deposition of Ig and complement at DEJ
Type of LE that associated with Hydralazine, INH, Procainamide, D-Penicillamine intake; rarely involves kidneys and brain; rarely associated with anti-dsDNA; associated with anti-histone antibodies.
Drug-induced lupus
Immune complexes in mesangium only; no alterations detectable by light microscopy.
Lupus nephritis Type I (Minimal mesangial)
Immune complexes in mesangium with mild to moderate increase in mesangial matrix and cellularity.
Lupus nephritis Type II (Mesangial proliferative)
Lesions visualized in fewer than half of the glomeruli, segmentally or globally distributed within each glomerulus; with cell proliferation, swelling, and infiltration of neutrophils and fibrinoid deposits.
Lupus nephritis Type III (Focal)
Most serious form and most commonly encountered; involvement of half or more glomeruli; with diffuse hypercellularity and wire-looping due to extnsive subendothelial deposits.
Lupus nephritis Type IV (Diffuse)
Widespread thickening of capillary wall due to subepithelial immune complexes.
Lupus nephritis Type V (Membranous)
Complete sclerosis of greater than 90% of glomeruli; presents with end-stage renal disease.
Lupus nephritis Type VI (Advanced sclerosing)
A clinicopathologic entity with a triad of dry eyes, dry mouth and other manifestations, such as arthritis.
Sjogren syndrome
Most common and most important autoantibody detected in Sjogren syndrome.
Anti-Ro (SS-A) and anti-La (SS-B) (90%)
Triad of 1. chronic inflammation (autoimmunity); 2. widespread damage to small blood vessels; 3. progressive interstitial and perivascular fibrosis in the skin and multiple organs.
Systemic sclerosis
Most common autoantibody associated with diffuse cutaneous systemic sclerosis.
Anti-DNA topoisomerase I (anti-Scl 70)
Common autoantibody associated with limited scleroderma (limited cutaneous systemic sclerosis).
Anti-centromere antibodies
Most common antibody associated with scleroderma renal crisis.
Anti-RNA pol III (up to 50%)
Most common extracutaneous manifestation of systemic sclerosis.
Raynaud phenomenon
Most common cause of death in patients with systemic sclerosis.
Interstitial lung disease and pulmonary arterial hypertension
Mixture of the features of SLE, systemic sclerosis, and polymyositis; associated autoantibody: anti-RNP particle-containing U1 RNP.
Mixed connective tissue disease (MCTD)
48/M patient underwent kidney transplant suddenly developed bloody urine few hours after the procedure. Nephrectomy was done and revealed a cyanotic, mottled, and flaccid kidney and necrotic kidney cortex. There is neutrophilic accumulation in the arterioles, glomeruli, and peritubular capillaries. Glomeruli undergo thrombotic occlusion of capillaries and fibrinoid necrosis in arterial walls.
Hyperacute rejection
45/F presented with signs of kidney failure 2 months after her renal transplant. Immunohistochemical staining reveals both CD4+ and CD8+ lymphocytes. Morphologic findings showed an extensive interstitial mononuclear infiltrate with edema and mild interstitial hemorrhage.
Acute cellular (T-cell mediated) rejection
30/M developed oliguria and subsequent renal failure 3 weeks after an uneventful kidney transplant. Renal findings showed necrotizing vasculitis with endothelial cell necrosis, neutrophilic infiltration, deposition of complement, antibody and fibrin, and thrombosis.
Acute antibody-mediated rejection
24/F diagnosed with renal failure underwent renal transplant. Four years later, increasing levels of creatinine was noted, and biopsy showed an interstitial fibrosis and tubular atrophy, glomerulopathy with duplication of basement membrane, and multilayering of peritubular capillary basement membranes. Interstitial mononuclear cell infiltrates, NK cells and plasma cells were also noted.
Chronic rejection
Complication of hematopoietic stem cell transplantation, wherein immunologically competent cells attack the tissues of the immunocompromised host.
Graft vs. host disease
A constellation of genetically distinct syndromes with common feature of defects in both humoral and cell-mediated immune responses, making affected infants susceptible to severe recurrent infections by bacteria, viruses, fungi, protozoans, and opportunistic infections.
Severe combined immunodeficiency (SCID)
Two common patterns of inheritance of SCID, and the associated defects.
X-linked: common gamma chain (receptors of ILs, especially IL-7) AR: Adenosine deaminase deficiency
Primary immune deficiency characterized by absent or markedly decreased numbers of B-cells in the circulation, with depressed serum levels of all classes of immunoglobulin.
X-linked agammaglobulinemia (Bruton disease)
Cardinal features of Thymic hypoplasia (DiGeorge syndrome).
Cardiac defect (TOF), Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia, 22q11.2 chromosomal deletion (CATCH 22)
Disorder of lymphocyte activation, characterized by absence of CD40L (CD145) that results in lack of class-switching with consequent increase in IgM and decrease in IgA, IgG and IgE.
Hyper IgM syndrome
An X-linked recessive disease characterized by thrombocytopenia, eczema, and marked vulnerability to recurrent infection ending in early death.
Wiskott-Aldrich syndrome
Hereditary angioedema is secondary to:
C1 inhibitor deficiency
Deficiency of the following complement protein increases susceptibility to infections involving pyogenic bacteria.
C3
Deficiency of the following complement proteins increases susceptibility to immune complex-mediated disease.
C1q, C2 and C4
Deficiency of the following complement proteins increases susceptibility to Neisseria infections.
C5-C9
Most common secondary immunodeficiency; caused by HIV infection, characterized by profound immunosuppression that leads to opportunistic infections, secondary neoplasms, and neurologic manifestations; the virus targets CD4+ T cells
Acquired immune deficiency syndrome (AIDS)
The hallmark of AIDS:
Variable loss of T-cell mediated immunity
Cells initially infected by HIV in sexual transmission.
Dendritic cells
Glycoprotein present in HIV for attachment.
gp120
Glycoprotein present in HIV for fusion.
gp41
Most common fungal infection in patients with AIDS.
Candidiasis
Most common type of lymphoma associated with HIV infection.
B-cell lymphomas
A disorder of protein misfolding, causing extracellular deposition of pink or red colored deposits stained with Congo red, with apple-green birefringence in polarized light.
Amyloidosis
Most common organ affected in amyloidosis and also with the most serious involvement.
Kidney
