Immunodef. disorders Flashcards
Leukocyte Adhesion Deficiency (LAD) pattern of inheritance
Autosomal, recessive
Pathogenesis = defective activation of all beta–integrins; not just the CD18 family
LADIII (rare)
severely mentally retarded; short in stature; delays in motor development
LADII (rare)
Three potential etiologies for SCID: 1) deficiency–> needed for purine metabolism
1) Adenosine deaminase
Low immunoglobulin due to impaired B-cell differentiation;
Common Variable Immunodeficiency Disorder (CVID)
Treatment = antibiotics and fucose supplementation
LADII (rare)
Recurrent oral candidiasis, failure to thrive, and protracted diarrhea and/or acute interstitial pneumonitis caused by Pneumocystis jiroveci
Severe Combined Immunodeficiency Disorder (SCID)
Defective in both cell-mediate and humoral immunity; B-cell and T-cell deficiency
Severe Combined Immunodeficiency Disorder (SCID)
DiGeorge Syndrome: Aortic defects and congenital heart defects due to 1)
abnormal development of pharyngeal system;
Pathogenesis = absence or defect in beta 2-integrin (CD18) family
LADI
why are CGD patients at high risk of Catalase positive bacteria?
Catalase positive organisms neutralize their own H2O2 (peroxide), leaving pahagocytes with less ROS
Lack of a NADPH oxidase
Chronic Granulomatous Disease (CGD)
Clinical manifestations = recurrent bacterial infections, particularly of the skin and mucosa; leukocytosis; periodontitis; no pus formation; impaired wound healing
LADI
Chronic Granulomatous Disease (CGD) inheritance pattern
70% X-linked recessive
Clinical manifestations = less severe and fewer infections than LADI; severely mentally retarded; short in stature; delays in motor development
LADII (rare)
Decreased function of regulatory T (Treg) cells
Wiskott-Aldrich Syndrome diagnosis:
Inc. risk autoimmune disorders
Common Variable Immunodeficiency Disorder (CVID):
Dihydrorhodamine 123 (DHR) test Nitroblue tetrazolium (NBT) test
Chronic Granulomatous Disease (CGD) diagnosis: Both will be negative
Inc. risk lymphoma
Common Variable Immunodeficiency Disorder (CVID):
Three potential etiologies for SCID: 1) deficiency–> leads to defective lymphocyte receptor rearrangements
1) MHC Class II
Pathogenesis • Lack of a NADPH oxidase subunits • Lack of adapter/ activating proteins; This is needed for respiratory burst for killing mechanism of neutrophils
Chronic Granulomatous Disease (CGD)
SCID s/s: susceptible to 1)
1) fungal, viral, and bacterial infections;
Clinical manifestations = infections similar to LADI with bleeding complications
LADIII (rare)
Impaired chemotaxis of phagocytic cells
Wiskott-Aldrich Syndrome diagnosis:
Wiskott-Aldrich Syndrome pneumonic: WATER
water: Wiskott Aldrich Thrombocytopenic purpura Eczema; Recurrent infection
Pathogenesis = absence of fucosylated carbohydrate ligands for selectins
LADII (rare)
Bombay blood group
LADII (rare)
DiGeorge Syndrome: Heterozygous chromosomal deletion at 1) resulting in abnormal development of the embryonic pharyngeal system; as a result, patient lack thymus (therefore 2)) and parathyroids (3))
1) 22q11.2 2) T-cell deficient 3) hypocalcemia
Aspergillus fumigatus inc, risk
Chronic Granulomatous Disease (CGD)
Leukocytes, particularly neutrophils, cannot migrate from blood vessel into tissues
Leukocyte Adhesion Deficiency (LAD)
Treatment • ImmunoGlobulin replacement therapy
Common Variable Immunodeficiency Disorder (CVID):
Treatment of CGD
Prophylaxis with trimethoprim/sulfamethoxazole
Common Variable Immunodeficiency Disorder (CVID): Markedly reduced serum 1) with low levels of 2)
1) IgG 2) IgA and/or IgM
Wiskott-Aldrich Syndrome diagnosis: High immunoglobulins–> 1) Decreased to normal Ig–> 2)
1) high IgA and IgE 2) low to normal IgG and IgM
Three potential etiologies for SCID: 1)signaling deficiency
1) Cytokine
DiGeorge Syndrome: predominant cell that is deficient
T-cell
Ataxia Telangiectasia: 1) disorder associated with 2) mechanisms Chromosome 11q22.3
1) Autosomal recessive 2) defective DNA repair
Reduced IgA; Cerebellar Ataxia
Ataxia Telangiectasia:
Treatment = bone marrow or hematopoetic stem cell transplantation
LADIII (rare)
Clinical manifestations • Deep tissue bacterial and fungal abscesses
Chronic Granulomatous Disease (CGD)
Wiskott-Aldrich Syndrome; 1) disorder caused by mutations in the gene that encodes the 2); this affects 3) leading to deficits in immunologic synapse;
1) X-linked 2) Wiskott-Aldrich syndrome protein (WASp) 3) cytoskeletal proteins
high risk of Aspergillus fumigatus
Chronic Granulomatous Disease (CGD)
LADI diagnosis
absence of CD18 and the associated alpha subunits on the leukocyte surface by flow cytometry
Burkholderia cepacia inc. risk;
Chronic Granulomatous Disease (CGD)
ATM gene on Chromosome 11 is responsible for repairing DNA double strand breaks; a mutation here leads to 1)
Ataxia Telangiectasia:
Diagnosis = physical features, mental and growth retardation, recurrent but usually mild infections, marked leukocytosis, and the Bombay blood group
LADII (rare)
Diagnosis = bleeding complications from birth
LADIII (rare)
Impaired phagocytic killing mechanisms of neutrophils and macrophages
Chronic Granulomatous Disease (CGD)
Diagnosis = bleeding complications from birth, severe bacterial infections, leukocytosis, demonstration of impaired integrin activation
LADIII (rare)
In CGD, Nitroblue tetrazolium (NBT) test will be 1) indicating that 2)
1) NEGATIVE 2) ROS are not being made by neutrophils
Inc risk of Catalase-positive bacteria (S. aureus and Serratia marcescens)
Chronic Granulomatous Disease (CGD)
SCID pts; acute interstitial pneumonitis caused by 1)
1) Pneumocystis jiroveci
DiGeorge Syndrome diagnosis: Reduced numbers of 1) with characteristic triad of features • Demonstrated deletion in chromosome 2)
1) CD3+ T cells 2) 22q11.2
Leukocyte migration: Endothelial cells activated by release of 1); neutrophils are recruited and they begin rolling which is mediated by 2) then neutrophils are activated, which occurs due to 3); then the neutrophil “sticks” to the endothelial cell by 4)
1) histamine and IL-1Beta; 2) selectins (LADII if deficient) 3) integrins; (LADIII, if deficient) 4) ICAM (LAD I, if CD18 family of integrins deficient)
