X-linked severe combined immunodeficiency (SCID)

Elements of the case

• male baby who began to get multiple infections with bacteria and fungi [and viruses] at 3 months of age (this is rather early)

• failure to thrive

• low absolute lymphocyte count; almost all lymphocytes are B cells

• no standard T cell responses

• no response to antigenic challenges, including to immunization

• normal RBC adenosine deaminase and PNP, two enzymes known to produce SCID (to be discussed on Friday)

• absent IL-2Rγ chain

• positive family history in males

Principles to understand

• thymus makes T cells, both CD4+ and CD8+

• T cells help B cells make antibody

• T cells stimulate macrophages

• T cells help helper T cells and killer T cells

• IL-2Rγ is also a part of receptors for IL-4, 7, 9, 13, 15. if you knock out only the cytokine IL-2, you don’t get any disorder nearly as serious as the X-linked SCID associated with IL-2Rγ deficiency

• IL-2Rγ gene is located on the X chromosome

T cell maturation

• BM T cell precursor goes to thymus

• after maturation, thymus pops out T cells to go to lymph nodes, spleen, mesentery, bloodstream

Histology of the thymus

• cortex contains immature cells that are learning self/non-self discrimination

• medulla contains more mature cells

• in a thymus of animals with SCID, the normal cortical/medullary structure of the thymus is changed and the thymus may be vestigial or absent

T cell markers during development

• cells that enter the thymus are CD3-4-8-

• then, they express CD3 and choose to be γ:δ or α:β

• α:β cells express CD3+4+8+; 95% of these cells are executed because they recognize self

• the remaining cells develop into CD4+ or CD8+ cells

Category: Pathology Notes