Immunodeficiency Flashcards
Asplenia
Affected gene: not known
Immune defect: absence of spleen
Susceptibility: encapsulated extracellular bacteria
C3 deficiency
Affected gene: C3
Immune defect: Lack of C3
Susceptibility: Recurrent infection with G- bacteria
Factor I deficiency
Affected gene: CFI (complement factor I)
Immune defect: Absence of factor I and depletion of C3
Susceptibility: Encapsulated bacteria
- upper respiratory, ears, skin, urinary tract
- pneumonia, meningitis, sepsis
- glomerulonephritis (isolated C3 deposits), rheumatoid arthritis, lupus
Deficiencies of C5, C6, C7, C8, or C9
Affected gene: C5, C6, C7, C8, C9
Immune defect: Lack of complement-mediated lysis
Susceptibility: Infections due to Neisseria species
Paroxysmal nocturnal hemoglobinuria
X-linked
Affected gene: Somatic and germline mutations in genes involved in phosphatidylinositol biosynthesis (gene: PIGA)
Immune defect: Lack of complement-regulatory proteins DAF, HRF, CD59
Susceptibility: Lysis of erythrocytes by complement
Treatment: Bone marrow transplant; Eculizumab (humanized anti-C5 Ab - prevent C5 activation)
NEMO deficiency (X-linked hypohidrotic ectodermal dysplasia and immunodeficiency)
Affected gene: IKBKG (NEMO, inhibitor of kB kinase gamma)
Immune defect: Impaired activation of NFkB
Susceptibility: Chronic bacterial and viral infections; developmental defects
Chronic granulomatous disease
defects in phagocytic cells –> persistent bacterial infections
Affected gene: NOX1 (NADPH oxidase)
Immune defect: Lack of oxidative bursts. Impaired neutrophil function
Test oxidase activity with nitroblue tetrazolium (NBT) test
Susceptibility: Chronic bacterial and fungal infections
Tx: Abx, IFN gamma therapy, gene therapy
MBL deficiency
Affected gene: MBL (mannose-binding lectin)
Immune defect: Lack of MBL
Susceptibility: Meningitis due to Neisseria meningitidis
NK-cell deficiency
Affected gene: GATA2
Immune defect: Absence of NK cells
Susceptibility: Herpesvirus infections
Hyper-IgM deficiency
X-linked; B cell immunodeficiency
Affected gene: Activation-induced cytidine deaminase (AICDA), or CD40 ligand (CD40LG), or CD40, or IKBKG
Immune defect: No isotype switching or somatic hypermutation in B cells
Susceptibility: Extracellular and Intracellular bacterial and fungal infections
Tx: Gamma globulin transfusions, Abx
IgG2 deficiency
Affected gene: Not known
Immune defect: Lack of IgG2
Susceptibility: Encapsulated bacteria
SCID
Affected gene: Various
- ADA deficiency –> No T/B
- PNP deficiency –> No T/B
- X-linked (gamma chain def.) –> No T (bubble boy)
- Autosomal (DNA repair defect) –> No T/B
Immune defect: Absence of B-cell and T-cell function
Susceptibility: All types of infection
Omenn syndrome
Affected gene: RAG1 or RAG2 or Artemis
Immune defect: Impaired V(D)J recombination
Susceptibility: All types of infection
MHC class I deficiency (bare lymphocyte syndrome type I - BLS)
Affected gene: TAP1 or TAP2 or Tapasin
Immune defect: Low MHC class I expression –> no CD8 T cells
Susceptibility: (Chronic) Respiratory virus infections
Pre-B-cell receptor deficiency
Affected gene: IGLL1 (lambda5)
Immune defect: Lack of B cells and antibodies
Susceptibility: Persistent bacterial infections
X-linked agammaglobulinemia
B cell immunodeficiency
Affected gene: BTK (Bruton’s tyrosine kinase)
Immune defect: B cells blocked at pro-B-cell stage (bone marrow)
Susceptibility: Recurrent bacterial infections, viruses
Complete DiGeorge syndrome (SCID)
Affected gene: Microdeletions in chromosomal region 22q11.2 (thymic aplasia results)
Immune defect: Absence of the thymus and T cells –> variable # of T/B cells
Susceptibility: All types of infection
Treatment: Thymus transplantation
APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy)
Affected gene: AIRE (autoimmune regulator)
Immune defect: Reduced T-cell tolerance to self antigens
Susceptibility: Autoimmune diseases
IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome)
Affected gene: FOXP3
Immune defect: Lack of regulatory T cells and peripheral tolerance
Susceptibility: Autoimmune diseases
ZAP-70 deficiency
Affected gene: ZAP70
Immune defect: T cells that cannot signal through their antigen receptors
Susceptibility: All types of infection
C4A or C4B
Affected gene: C4A, C4B
Immune defect: Impaired clearance of immune complexes
Susceptibility: Autoimmune diseases and infections
Selective IgA deficiency
B cell immunodeficiency; MOST COMMON
Affected gene: Not known; MHC-linked
Immune defect: Lack of IgA
Susceptibility: No major susceptibility (respiratory infections)
MHC class II deficiency (SCID) (BLS type 2)
Specific abnormality: Lack of expression of MHC class II Immune defect: No CD4 T cells Susceptibility: General
Describe X-linked SCID gamma chain deficiency
Cytokine receptor common gamma chain (or CD132) is cytokine receptor common to:
- IL-2
- IL-4
- IL-7
- IL-9
- IL-15
- IL-21 receptor
