Chapter 11: Primary Immunodeficiencies Flashcards
List some defects of phagocytic cells?
- CGD
- Leukocyte adhesion deficiency
- Chediak-Higashi synndrome
- Glucose-6-phosphate dehydrogenase deficiency (G6PD)
- Myeloperoxidase deficiency
- Hyperimmunoglobulin E syndrome (formerly Job syndrome)
Defect in CGD?
deficiency of NADPH oxidase (any one of 4 component proteins); failure to generate superoxide anion, other O2 radicals
Symptoms of CGD?
recurrent infections with catalase-positive bacteria and fungi
Defect in LAD?
absence of CD18 - common β chain of the leukocyte integrins
What are 3 integrins the contain CD18?
LFA-1, MAC-1 and gp150/95
What are the symptoms of LAD?
recurrent and chronic infections, failure to form pus, and delayed separation of umbilical cord stump
What are the defects found in Chediak Higashi syndrome?
nonsense mutation in the lysosomal trafficking regulator, CHS1/LYST protein, leads to aberrant fusion of vesicles
What are some of the symptoms found in Chediak Higashi?
recurrent infection with bacteria; chemotactic and degranulation defects; absent NK activity, partial albinism
What are the defects found in G6PD deficiency?
deficiency of essential enzyme in hexose monophosphate shunt
Symptoms of G6PD deficiency?
Same as CGD, with associate anemia
Defect in myeloperoxidase deficiency?
defect in MPO affect the ability to convert hydrogen peroxide to hypochlorite
Symptoms of myeloperoxidase deficiency?
mild or none
What is the defect found in Job syndrome?
Defects in JAK-STAT signaling pathway leading to impared Th17 function; decreased IFN-gamma production.
What are the symptoms of Hyperimmunoglobulin E syndrome?
Characteristic facies, severe recurrent sinopulmonary infections, pathologic bone fractures, retention of primary teeth, increased IgE, eczematous rash
List some defects of humoral immunity.
Bruton (X-linked) agammaglobulinemia, X-linked hyper-IgM syndrome, selective IgA deficiency, common variable immunodeficiency, transient hypogammaglobulinemia of infancy
What is the defect found in Bruton (X-linked) agammaglobulinemia)?
deficiency of the Bruton tyrosine kinase (btk), which promotes pre-B cell expansion; faulty B-cell development
What are some symptoms of Bruton agammaglobulinemia?
increased susceptibilty of encapsulated bacteria and bloodborne viruses, low immunoglobulins of all isotypes, absent or low levels of circulating B- cells stage while maintaining cell mediated immunity
How do you treat Bruton agammaglobulinemia?
monthly gamma-globulin replacement, antibiotics for infection
What is the defect in X-linked hyper-IgM syndrome?
deficiency of CD40L on activated T cells
What are some signs/symptoms of X linked hyper-IgM syndrome?
high serum titers of IgM without other isotypes, normal B and T-cell numbers, susceptibility to encapsulated bacteria and opportunistic pathogens
How do you treat X-linked hyper-IgM syndrome?
antibiotics and gammaglobulins
What is the cause of selective IgA deficiency?
multiple genetic causes
What are some signs and symptoms of selective IgA deficiency?
decreased IgA levels and normal IgM and IgG with elevation of IgE. Repeated sinopulmonary and gastrointestinal infections, inc. atopy
How do you treat selective IgA deficiency?
antibiotics, not immunoglobulins
What are the molecular defects found in common variable immunodeficiency?
collection of syndromes; several associated genetic defects
What are the signs and symptoms of common variable immunodeficiency?
onsets in late teens, early twenties, B cells present in peripheral blood, immunoglobulin levels decrease with time; inc. autoimmunity
What is the treatment for common variable immunodeficiency?
antibiotics
What is the defect in transient hypogammaglobulinememia of infancy?
delayed onset of normal IgG synthesis
What are the signs and symptoms of transient hypogammaglobulinemia of infancy?
detected in month 5-6 of life, resolves months 16 - 30; susceptibility to pyogenic bacteria
What is the treatment option for transient hypogammaglobulinemia of infancy?
antibiotics and in severe cases, gamma-globulin replacement
What are the 3 types of deficiencies in complement components?
classic pathway, both pathways, and deficiencies in complement regulatory proteins
What are the deficiencies in the complement classic pathway?
C1q, C1r, C1s, C4, C2
What are the signs/diagnosis of the classic pathway complement deficiency?
marked increase in immune complex diseases, inreased infections with pyogenic bacteria
What are some deficiencies in both pathways of the complement pathway?
C3 & C5, C6, C7, C8, or C9
What are the deficiencies in complement regulatory proteins?
C1-INH (hereditary angioedema)
C3 defiency signs/diagnosis?
recurrent bacterial infections, immune complex disease
C5, C6, C7, C8, or C9 deficiency signs/diagnosis?
recurrent meningococcal and gonococcal infections
What are the signs/diagnosis of hereditary angioedema?
overuse of C1, C4, or C2, edema at mucosal surfaces
List some T-cell deficiencies and combined deficiencies
- DiGeorge Syndrome
- MHC class I deficiency
- Wiskott-Aldrich Syndrome
- Ataxia telangiectasia
- Severe combined immunodeficiency (SCID)
- Bare lymphocyte syndrome (MHC class II deficiency
Di George syndrome and MHC class I deficiency is referred to overall as what type of deficiencies?
selective T cell deficiency
Wiskott-Aldrich Syndrome and Ataxia telangiectasia are collectively referred to as what type of deficiencies?
Combined partial B- and T cell deficiency
SCID and Bare lymphocyte syndrome/ MHC class II deficiency are collectively known as what type of deficiencies?
complete functional B- and T- cell deficiency
What is the defect found in DiGeorge syndrome?
Heterozygous deletion of chromosome 22q11; failure of formation of 3rd and 4th pharyngeal pouches, thymic aplasia
What are the clinical manifestations of DiGeorge Syndrome?
characteristic facies and a clinical triad of cardiac malformation, hypocalcemia and hypoplastic thymus
What is the defect found in MHC class I deficiency?
failure of TAP 1 molecules to transport peptides to endoplasmic reticulum
What are the clinical manifestations of MHC class I deficiency?
CD8 T cells deficient, CD4+ T cells normal, recurring viral infections, DTH and Ab production normal
What is the defect in WAS?
defect in the WAS protein which plays a critical role in actin cytoskeleton rearrangement (which lead to defect in ag presentation)
What are the clinical manifestation of WAS?
defective responses to bacterial polysaccharides and depressed IgM, gradual loss of humoral and cellular responses, thrombocytopenia, and eczema
IgA an IgE may be elevated
Triad:
eczema, thrombocytopenia, immunodeficiency
What is the defect in ataxia telangiectasia?
defect in the ATM kinase involved in the detection of DNA damage and progression through the cell cycle
What are the common manifestation of ataxia telangietasia?
ataxia (gait abnormalities), telangiectasia (capillary distortions in the eye), deficiency of IgA and IgE production
What is the defect found in SCID?
3 of them
- defects in common y chain of IL-2 receptor (present in receptors for IL-4, -7, -9, -15) X- linked
- Adenosine deaminase deficiency (result in toxic metabolic products in cells)
- rag 1 or rag 2 gene nonsense mutations
SCID caused by defects in the common y chain of IL-2 produce what symptoms?
chronic diarrhea; skin, mouth, and throat lesions; opportunistic (fungal) infections; low levels of circulating lymphocytes; cells unresponsive to mitogens
SCID caused by ADA deficiency leads to what clinical manifestations?
clinical overlap with X-linked SCID plus neurologic deficiency
SCID caused by rag1 or rag2 deficiency leads to what clinical manifestations?
total absence of B+ T cells
Bare lymphocyte syndrome is caused by what deficiency?
failure of MHC class II expression, defects in transcription factors
What are the clinical manifestations of bare lymphocyte syndrome?
T cells present and responsive to nonspecific mitogens no GVHD, deficient in CD4+ T cells, hypogammaglobulinemia, Clinically observed as a severe combined immunodeficiency
