14: Immunodeficiencies Flashcards
defect in humoral (B cell) immunity
infection by extracellular bac
defect in CMI (T cell)
infection by viruses and intracellular bac, fungi
Decreased serum Ig Levels, Normal skin test reaction
B cell deficiency
Normal serum Ig levels, decreased skin test reaction
T cell deficiency
germinal centers decreased or absent
B cell deficiency
normal follicles, but decreased paracortical regions
T cell deficiency
X linked agammaglobulinemia
- Absence of mature B cells due to mutation/deletion in B cell tyrosine kinase
Common variable immunodeficiency
- mature B cells can’t differentiate into plasma cells resulting in decreased antibodies
- congenital or sporadic and linked with autoimmune diseases
Selective IgA deficiency
- most common immunodeficiency
- Asymptomatic (IgM compensates for missing IgA)
- make all the antibodies except IgA
- B cells with surface IgA don’t differentiate into plasma cells
X- linked Hyper IgM syndrome
- Overabundace of IgM antibody and lack of other antibody isotypes
- Inherited deficiency of CD40L on T cells means CD40 not engaged on B cells and isotype switching can’t occur
Hyper IgM type 2 syndrome
- Overabundance of IgM antibody and lack of other antibody isotypes
- inherited mutation in the gene activation-induced cytidine deaminase which prevents isotype switching
DiGeorge Syndrome “congenital thymic hypoplasia”
- Deficiency of T cells due to hypoplasia or agenesis of the thymus, no thymic shadow
- Defective maturation of T cells –> poor CMI against viruses and fungi
- Associated with maternal alcoholism and 22q11 deletions
SCID (general)
- Failure of B and T cells to develop from bone marrow stem cells
- Spleen, lymph nodes, tonsils, and appendix not populated by B or T cells
- bone marrow transplantation or gene therapy is curative
Autosomal recessive SCID
- deficiency of adensosine deaminase which catalyzes the deamination of adensoine and deoxyadenosine
- the accumulating adensosine and deoxyadenosine are toxic to lymphocytes
RAG1/RAG2 deficiency SCID
- Failure of VDJ rearrangement in immunoglobulin and T cell receptor genes due to mutations in the RAG genes
- without recombination –> cell death
X-linked SCID
- Mutation in gene for common gamma chain for cytokine receptors
- lymphocytes can’t develop properly without cytokine receptors
Chronic Granulomatous Disease
- recurrent bacterial infections from early childhood (especially catalase+ bacteria)
- Defect in NADPH oxidase means neutrophils can’t produce superoxide anion during respiratory burst
- Increased levels of the cytokine G-CSF accounts for elevated neutrophil levels
- negative NBT dye reduction test
Myeloperoxidase Deficiency (MPO)
- Decreased or absent myeloperoxidase ( coverts H2O2 to HOCl)
- NO increased susceptibility to infection due to compensatory mechanisms (may be decreased ability to fight fungal infections)
Chediak Higashi Syndrome
- Recurrent bacterial infections, metallic silver hair, bleeding tendencies, impaired vision, hepatospenomegaly
- Neutrophils contain large cytoplasmic granules due to fusing of lysosomes –> reduces ability to kill microbes and impairs T cell and NK cell function
Leukocyte Adhesion deficiency
- Defect in B chain of LFA1 and Mac1 adhesion molecules
- neutrophils cant adhere to endothelial cell wall for ecxtravasation
- recurrent bacterial and fungal infections of skin, lungs, blood, wound healing problems, EXTREME LEUKOCYTOSIS
Wiskott-Aldrich Syndrome
- TRIAD: immunodeficiency, eczema, thrombocytopenia
- defective cytosolic protein that helps regulate the actin cytoskeletion of bone marrow-derived cells
- normal numbers of T and B cells which cannot traffic to sites of inflammation and b and T cells cannot interact properly
- Recurrent bacterial infection, predisposition to severe autoimmune diseases
