3 BL Deficiency of adaptive immunity

Question 1

Locations of abnormalities of development in:

SCID

Answer 1

block in development of lymphoid stem cell -> results in lymphopenia of both T and B cells.

Question 2

Locations of abnormalities of development in:

X-linked (Bruton) Agammaglobinemia

Answer 2

block is between pre-B and B cells, and results in low numbers of B cells (normal T cells).

• block is a defective bruton tyrosine kinase

Question 3

Locations of abnormalities of development in:

X-Linked HyperIgM Syndrome

Answer 3

Defect in Tfh’s CD40 or in B cell CD40 →defect in IgM switching to IgG

CD40: surface marker that induces the switch

Question 4

Locations of abnormalities of development in:

Common Variable Immunodeficiency (CVID)

Answer 4

normal #s of pre-B and B cells but:

B cells cannot become plasma cells → cannot make specific antibody

Question 5

Locations of abnormalities of development in:

DiGeorge syndrome

Answer 5

large (45 gene) deletion on chromosome 22→
Abnormal development of 3rd and 4th pharyngeal pouches →
abnormal stroma →
cannot support thymic lymphoid development →
pt will have absent T cells.

Question 6

Which abnormal lymphocyte development is related to tetralogy of fallot?

Answer 6

DiGeorge

Question 7

infections you would expect in a pure B cell deficiency

Answer 7

“high grade”

(extracellular, and pyogenic) infections from bacterial pathogens such as S. aureus, H. influenzae, and S. pneumoniae.

Question 8

infections you would expect in a pure T cell deficiency

Answer 8

severe infections from intracellular pathogens such as viruses, certain bacteria, yeasts and fungi (esp. Candida albicans & Pneumocystis jirovecii).

Question 9

clinical features of DiGeorge syndrome

Answer 9

○ Hypertelorism (eyes are far apart; wide-space)
○ Down-slanting eyes
○ Fish mouth deformity
○ Micrognathia (undersized jaw)
○ Low set ears
○ Can be born with Tetralogy of Fallot, hypocalcemia, and absent T cells.

Question 10

incidence of selective IgA deficiency

- associated syndrome?

Answer 10

• Most common immunodeficiency disease with frequency of about 1 in 500.

○ 10-15x more frequent in those with celiac disease

Question 11

immunological problem of the Nude mouse

- name the human immunodeficiency condition it resembles.

Answer 11

results in absence of thymic stroma (and hair) → no T cells.

Immunologically similar to DiGeorge.

Question 12

enzyme which is absent in some cases of SCID.

Answer 12

adenosine deaminase is absent → accumulation of adenosine in cells severely impairing lymphocyte development → lymphopenia of both T and B cells.

Question 13

Possible approaches to replacing adenosine deaminase in people with SCID

Answer 13

Replace the enzyme:
transfusions of irradiated red cells can be helpful

(adenosine deaminase is abundant in blood)

Question 14

Discuss transplantation therapy in DiGeorge.

complication?

Answer 14

○ Fetal thymus or cultured thymic stromal cells have been used to try to minimize graph vs host disease;

better diagnosis of DiGeorge would aid in the selection of appropriate cases.

Question 15

Discuss transplantation therapy in SCID

complication?

Answer 15

○ BETTER to transplant purified stem cells rather than bone marrow.

• Bone marrow transplantation has had about 50% success rate, but graph vs host disease…
• Prefer sibling donors with Class II MHC match and at least one Class I MHC match.

Question 16

Intravenous Immunoglobulin (IVIG)

What is it? When would you use it?

Answer 16

Ig so clean/good that you can inject right in without reaction

Used when B cell function is deficient.

Question 17

Viruses and/or viral diseases which are immunosuppressive in humans

Answer 17

malaria
measles
mononucleosis (mono)
cytomegalovirus (CMV)
EBV