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42 Cards in this Set
- Front
- Back
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What are some warning signs of immunodeficiency disorder?
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Eight or more ear infections in one year
Two or more serious sinus infections in one year Two or more bouts of pneumonia in one year Two or more deep-seated infections, or infections in unusual areas Recurrent deep skin or organ abscesses Need for iv antibiotic therapy to clear infection Infections with unusual or opportunistic organisms Family history |
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When do primary immune deficiencies (PIDs) manifest?
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During the first years of life (> 5-6 months)
Because of maternal IgG immune deficiencies not detected in the newborn Suffer from recurrent, protracted infections - leads to diagnosis |
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How are PIDs classified?
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Bases on host-defense mechanism affected:
Antibody deficiencies (B-cells) T-cell deficiencies Combined T- and B-cell deficiencies Deficiencies of phagocytosis Complement deficiencies |
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What are B-cell deficiencies?
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Humoral immune deficiency refers to diseases resulting from impaired antibody production, because of either a molecular defect intrinsic to B cells or a failure of interactions between B and T cells
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How do B cell deficiencies present?
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Severe, upper and lower respiratory tract infections with encapsulated bacteria
Present with recurrent otitis media (children), sinusitis, and pneumonia Viral infections are uncomplicated Fungal and intracellular bacteria infections not unusual Overgrowth of commensal microflora in small intestine Chronic infections by intestine pathogens Autoimmune disorders |
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What is the testing for B cell deficiencies?
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Measurement of total serum IgG, IgA, IgM
Antibody titers to protein and polysaccharide antigens should also be measured If specific antibody levels low, booster immunization and titers measured again in 4 weeks |
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What are the classifications of B cell deficiencies?
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X-linked agammaglobulinemia
Autosomal recessive agammaglobulinemia IgA deficiency Common variable immunodeficiency X-linked hyper IgM syndrome Hypoimmunoglobulinemia M (Wiskott-Aldrich Syndrome; also partial T cell deficiency) Transient hypogammaglobulinemia of infancy Isolated IgG Subclass Deficiency |
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What is agammaglobulinemia?
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Any factor that impedes the development of the B cell lineage and/or the function of mature B cells may result in levels of serum immunoglobulins that are reduced (hypogammaglobulinemia) or nearly absent (agammaglobulinemia)
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What is X-linked agammaglobulinemia?
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Bruton Disease
Low/absent IgG, IgA, IgM T+, B-, NK+ Circulating B cells profoundly decreased Associated features - severe bacterial infections Inheritance - X-linked Genetic defects - mutations in BTK gene |
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What is autosomal recessive agammaglobulinemia?
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Low/absent IgG, IgA, IgM
T+, B-, NK+ Circulating B cells profoundly decreased Associated features - severe bacterial infections Inheritance - AR Genetic defects - mutations in mu, Ig alpha, delta 5 genes; BLNK |
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Which vaccines should be avoided in pts with XLA and autosomal recessive agammaglobulinemia?
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Live viral vaccines, particularly oral polio vaccine
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What is common variable immune deficiency (CVID)?
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Collection of hypogammaglobulinemia syndromes
Impaired B cell differentiation with defective immunoglobulin production Low total IgG, as well as low IgA and/or IgM 50% of pts have no detectable immunoglobulin Poor or absent response to immmunization T+, B+ (~70%), NK+ Recurrent bacterial infections |
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Which vaccines are contraindicated in pts with CVID?
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Live viral vaccines
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What is IgA deficiency?
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Isolated deficiency of serum IgA
Low IgA, normal IgG and IgM T+, B+, NK+ Often remain asymptomatic Recurrent respiratory and GI infections Allergic reactions in pts with Abs against IgA - may cause anaphylactic shock upon blood transfusion |
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What are hyper IgM syndromes (HIGM)?
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Deficiency of IgG, IgA, and IgE with normal or elevated serum concentrations of IgM
T+, B+, NK+ Impaired Ig class switching and somatic hypermutation Increased susceptibility to bacterial infection Low memory B cells X-linked HIGM due to mutations in CD40L gene |
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What is isolated IgG subclass deficiency?
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T+, B+, NK+
IgG, IgM, IgA, IgE are normal Decreased concentration of one or more IgG sublass Usually asymptomatic Low levels IgG2 frequent in children Many healthy people have no IgG4 Recurrent viral/bacterial infections |
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What vaccination should patient with subclass deficiency receive?
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All pts with subclass deficiency and poor responses to polysaccharide vaccines should receive conjugated pneumococcal vaccine
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Which IgG subclasses have complement-fixing properties?
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IgG1
IgG3 |
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What is transient hypogammaglobulinemia of infancy (THI)?
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T+, B+, NK+
Low IgG/IgA; IgM can be low or normal Intrinsic Ig production delayed for up to 36 months Increased susceptibility to sinopulmonary infections Ig concentrations usually normalize between 2-4 yrs |
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What is Wiskott-Aldrich Syndrome (hypoimmunoglobulinemia M)?
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Variable expression, commonly includes IgM deficiency
Low IgM; IgG normal, IgA and IgE elevated T-low, B-low, NK+ X-linked recessive syndrome Defect in Wiskott-Aldrich Syndrome Protein (WASP) - cytoskeletal protein Thrombocytopenia, eczema, infections |
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What is the role of the WASP?
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Actin cytoskeleton remodeling
Absence impacts formation of immunologic synapse that depends upon generation of lipid rafts WASP deficiency - T cell function defective; selective depletion of circulating mature B cells |
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What is the presentation of WAS?
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Infants present with: prolonged bleeding from circumcision site, bloody diarrhea, excessive bruising
Recurrent infection by encapsulated bacteria Pts with WAS at risk for: autoimmune disease, cancer |
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What is severe combined immunodeficiency (SCID)?
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Profound deficiencies of T-cell and B-cell function (and sometimes NK cell)
Demonstrate severe lymphopenia Severe opportunistic infections, or chronic diarrhea and failure to thrive in infancy |
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Which vaccines can be fatal in SCID?
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Live vaccines
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What is adenosine deaminase deficiency (ADA)?
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T-, B-, NK-
Low IgM, IgG, and IgA Mutations in ADA gene; autosomal recessive |
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What is the role of adenosine deaminase?
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Essential for the metabolic function of various cells, especially T cells
ADA leads to an accumulation of toxic metabolic by-products - adenosine and deoxy-ATP --> lymphocytes die |
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What is common gamma chain deficiency?
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Most common form of SCID
T-, B+, NK- Low IgG, IgA and IgE No functional B cells since T cells unable to help X-linked recessive |
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What is deficiency of Jak3?
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SCID caused by mutation in gene on Chr 19 that encodes a lymphocyte Janus kinase 3 (Jak3)
T-, B+, NK- Low IgG, IgA, and IgE Defect in IL-2 receptor signaling Autosomal recessive |
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What is DiGeorge Syndrome (DGS)?
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Defective development of the pharyngeal pouch system
Thymic hypoplasia - range of T cell deficits Most pts have mild defects in T cell numbers - not clinically immunodeficient Approx. 1% have complete absence of thymic tissue and profound immunodeficiency (complete DGS) |
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What is the cause for most cases of DGS?
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Deletion of 22q11 chromosome
DGS results from abnormalities during embryogenesis Comprises hypocalcemia arising from parathyroid hypoplasia, thymic hypoplasia, and malformation of outflow vessels of the heart Hypocalcemia is key biochemical feature -- may present in neonates as tetany or seizures |
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How is DGS diagnosed?
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Facial abnormalities
Major outflow tract defect of the heart Hx of recurrent infections Cardiac defects are focus of clinical management Lack of T cells, susceptible to opportunistic infections |
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What is ataxia telangiectasia?
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Deficiency in IgA and IgE production
Gene involved encodes protein that detects double-strand breaks in DNA Pts prone for recurrent infections, autoimmune diseases, malignancies |
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What is bare lymphocyte syndrome?
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Deficiency in CD4+ T cells
Rare recessive genetic condition Mutations in genes which encode for transcription factors that normally regulate expression of MHC II genes No MHC Class II expression of professional APCs Variable HYPOGAMMAGLOBULINEMIA (IgA and IgG2) |
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What is CD8+ T cell deficiency?
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MHC Class I Deficiency
Mutations in TAP1 molecules to transfer peptides to ER Only CD8+ cells are deficient -- recurrent viral infections Normal Ab production Normal DTH (delayed type hypersensitivity) |
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What is chronic granulomatous disease (CGD)?
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Most frequent phagocytic primary immunodeficieny
More common in males Biochemical cause - enzymatic deficiency of NADPH oxidase in phagocytes Failure to generate superoxide anion and other O2 radicals Defective elimination of extracellular pathogens; formation of granulomas Susceptible to recurrent infection with catalase-positive organisms |
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How is CGD diagnosed and managed?
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Diagnosis made by neutrophil function testing and mutation analysis
Management: early diagnosis of infections, antimicrobial and immunomodulatory prophylaxis, and aggressive management of infectious complications |
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What is Chediak-Higashi Syndrome (CHS)?
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Autosomal recessive disorder
Molecular defect in granule structure (abnormal giant granules in neutrophils) Granules contain no cathepsin G and elastase Defects in chemotaxis and degranulation Prone to recurrent pyogenic infections with bacteria |
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What is the diagnostic criterion for CHS?
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Partial albinism
No NK activity Demonstration of giant azurophilic cytoplasmic inclusions in blood cells |
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What are the two phases of CHS?
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First: susceptibility to infections
Second: accelerated lymphoproliferative syndrome with hepatosplenomegaly and lymphadenopathy |
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What is G6PD deficiency?
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X-linked recessive disease
Most are asymptomatic Manifestation same as CGD Lack of substrate for NADPH Associated with anemia |
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What is leukocyte adhesion deficiency?
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Mutation and lack of expression of LFA-1
Defective migration of leukocytes (neutrophils) Delayed detachment of umbilical cord *Can receive routine vaccinations, including live virus vaccines |
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What are complement deficiencies?
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Disruption of one of the proteins involved in activation pathways of the complement cascade
More common - defects in classical pathway Pts have high number of autoimmunity disorders -- lupus-like syndromes Pts with alternative pathway defects present with Neisseria infection |
