case studies

Question 1

SCID is characterized by ____, which means ____

Answer 1

RAG deficiency- no B or T cells

Question 2

What was the first major test used to determine that baby Joe had SCID? What two cell types were lacking?

Answer 2

Complete blood count (cbc)- lymphocytes are the most affected: B and T cells lacking (way too many NK cells)
- Joe will not have normal levels on antibodies in his blood

Question 3

While NK cells are lymphocytes, they do not ______ like T and B cells.

Answer 3

undergo selection
- NK cells development and function does not depend on RAG proteins

Question 4

Hyper IgM deficiency is characterized by ___, which means ___

Answer 4

AID deficiency, only IgM & reduced diversity of B cell response

Question 5

hyper IgM syndrome- The better diagnostic test for Daisy’s deficiency was not the CBC, but an examination of the _______- Because cbc looks at the cells, not serum

Answer 5

immunoglobulin levels

Question 6

hyper IgM syndrome- Why did the physician look for evidence of the patient’s response to tetanus and H. influenzae? What would the results have been in a patient with no AID deficiency?

Answer 6

-She had been vaccinated- looking for her memory response, should also have IgG and other isotypes produced… she does not have these
-They tested her cells for CD40 expression after activation- they tested her for this because for isotype switching, you HAVE to have CD40
- she had normal CD40 on B and T cells- no obvious problem that would lead to B cell responses involving isotype switching—must be internal problem in the B cells that they cannot respond to CD40 activation
- Another signal needed after CD40 from T cells that triggers isotype switching- AID
- Point mutation in AID gene- stop codon in exon 5—truncated and defective AID protein- AID only activated when T cells help the B cells

Question 7

In this case, the mutation was in the B cell enzyme AID. Deficiencies in what other molecules are causes of hyper-IgM syndrome? And Why?

Answer 7

• CD40 or CD40L
• Defects in MHC Class II (primary molecule for T helper cells- no CD4 helper T cells to stimulate isotype switching

Question 8

X-linked Agammaglobulinemia is characterized by ___, which means ___

Answer 8

BTK deficiency, no B cells (antibodies)

Question 9

X-linked Agammaglobulinemia is x-linked, meaning…

Answer 9

shows up more in males

Question 10

x-linked Agammaglobulinemia- Based on the cell type analysis, how was this case strikingly different from SCID?
How were T and B cells detected in the flow cytometric test?

Answer 10

• Low IgG, no IgA, low IgM
• Completely normal WBC’s
• Of the lymphocytes, 85% were CD3 (T cell marker, very high)- T cell function is normal
  . No detectable B cells (CD19 marker)

Question 11

If patients with SCID fail to make B and T cells due to failure to generate a receptor, how is BTK deficiency different?

Answer 11

has normal T cells

Question 12

What is the stage of B cell development that is impacted by BTK deficiency?

Answer 12

• B cells become arrested in the pre B-cell stage (developmental path)

Question 13

Bruton’s Tyrosine Kinase (BTK) contributes to….

Answer 13

signaling for the B cell receptor (required for growth and differentiation of pre-B cells)

Question 14

in the most common form of hyper IgM syndrome, there is a defect in the gene that encodes for ____, a protein on T cells which binds to ___ on B and other immune cells

Answer 14

CD40 ligand
CD40

Question 15

Dennis Fawcett antibody level results and diagnosis

Answer 15

low IgG
IgA undetectable
high IgM
- absence of secondary follicles and germinal centers

diagnosis: hyper IgM syndrome- his activated T cells did not expressed CD40L

Question 16

males with a defect in the CD40 ligand gene have what?

Answer 16

• no isotype switching
• initial activation and expansion of T cells in response to protein antigens is greatly reduced
• activation of macrophages reduced
• neutropenia

Question 17

x-linked hyper IgM syndrome males become profoundly deficient in neutrophils, why?

Answer 17

• interaction of CD40 ligand with Cd40 on macrophages is required for secretion of GM-CSF by macrophages
• GM-CSF is crucial for mobilizing neutrophils from bone marrow