Lec16 Immunodeficiency Flashcards
8 Main Types of Primary immune Defects
- combined defects
- antibody defects
- phagocyte defects
- complement defects
- well-defined systemic defects
- immune dysregulation
- defects of innate immunity
- auto inflammatory defects
What is a combined defect?
- Defect in both T and B cells
- usually with lymphoid stem cells
What is pneumocystis carinii pneumonia a sign of?
- Common disease in infants with immunodeficiency / serious T cell defects
What is typical clinical phenotype of severe combined immunodeficiency?
- onset in first year of life
- serious infections: pneumonia, sepsis, meningitis, viral + fungal infections
- failure to thrive [poor growth]
- diarrhea, skin rashes [thrush]
- many different causes
- have very few lymphocytes
What is X linked SCID?
- mutation in x-linked gene for common gamma chain that is used in cytokine receptors
- in IL-2, IL-4, IL-7, IL-9, IL-15, IL-21
- if altered or lacking don’t get any of these cytokines
- treatment: get bone marrow transplant
- have no T cells or NK cells, and have B cells that are just not functional
What is effect of adenosine deaminase deficiency?
- get no T, B, or BK
What is IL-7Ra chainIL7RA mutation?
- get N T and have B and NK deficiency
What is recombinase activating gene [RAG] 1/2?
- get no lymphocytes [T or B], do get NK cells
What are TRECS?
- T cell receptor excision circles that are created in new T cells as they rearrange their T cell receptor [TCR]
- still persists in cell and get diluted
- can test newborn blood for TRECs to see if have T cells [look for SCID]
What is bare lymphocyte syndrome?
- deficiency in MHC II
- still have T cells [unlike in traditional SCID] but have very few CD4 and few gammaglobulins
- autosomal recessive
What are common antibody defects?
- XLA
- Hyper IgM
What is XLA?
X-linked agammaglobulinemia
- molecular defect Btk [b cell cytoplasmic tyrosine kinase]
- BCR activation signal can’t happen
clinical
- affects males
- severe infections in first year of life
- low serum IgG, IgA, IgM, no antibody production
- tiny tonsils [tonsils normally B cells]
- normal lymphocyte numbers but few B cells
- pre-B cells in bone marrow but few mature [plasma cells]
- get chronic sino-pulmonary infections, respiratory failure
treat: life long gamma globulin therapy
What disease: 3 year old boy, failure to thrive, pneumonia, low IgA/IgG, normal IgM, normal B/T/etc cells
- low IgG so think XLA but you see normal B cell quantities
- possible: CD40L deficiency so B cells never get info to switch
- basically hyper IgM but without the high IgM
What does AID deficiency cause?
- AID = activation induced cytidine deaminase
- deficiency means can’t get class switching of antibodies so have just IgM not IgG/IgA/IgE
What are common neutrophil defects
- neutropenia = too few neutrophils
- defect in function
- – adhesion
- – locomotion
- – killing
- – abnormal structure
