Deficiency of Adaptive Immunity

Question 1

What are the two categories of immunodeficiency?

Answer 1

1. Primary

2. Secondary

Question 2

What is primary immunodeficiency?

Answer 2

An immunodeficiency caused by mutations in genes required for normal development of parts of the immune system.

Question 3

What is the normal inheritance pattern for primary immunodeficiency?

Answer 3

There is no one normal inheritance pattern. Different diseases can have differing inheritance patterns with different penetrance.

Question 4

Is a congenital dysfunction of the thymus or bone marrow considered primary or secondary immunodeficiency?

Answer 4

Primary

Question 5

Immunodeficiency following treatment of immunosuppressive drugs will be considered primary or secondary immunodeficiency?

Answer 5

Secondary

Question 6

A block in the development of lymphoid stem cells would cause which cell numbers to be low?

Answer 6

T cells AND B cells

Question 7

What condition results in a block in the development of the lymphoid stem cell?

Answer 7

Severe Combined Immunodeficiency Disease, or SCID

Question 8

What are some characteristics of SCID?

Answer 8

Lymphopenia- both T and B cells

Absent thymic shadow on X-ray

Tonsils are small

Mitogen responses and serum immunoglobulins are low

Question 9

What is the inheritance patterns of most SCID cases?

Answer 9

X-linked recessive

the rest are autosomal recessive

Question 10

What is the defect in SCID-X1?

Answer 10

Gene for the gamma chain that forms part of the receptors for IL-2 and other cytokines necessary for lymphoid development

Question 11

What enzyme do most patients with SCID lack?

Answer 11

Adenosine deaminase (ADA).

Question 12

What happens when a patient has a deficiency in adenosine deaminase?

Answer 12

Adenosine accumulates in all cells but impairs lymphocyte development selectively

Question 13

What is the most common mutation that causes SCID in Navajo and Apache children?

Answer 13

Defect in V(D)J recombination

Question 14

What block would result in normal T cells but low to absent B cells?

Answer 14

Block 2

Question 15

A boy presents with recurrent bacterial infections manifesting as pneumonia, chronic diarrhea and enterovirus. What should you have on your differential diagnosis?

Answer 15

X-linked (Bruton) Agammaglobulinemia

Question 16

What patient population is the reason why we can no longer use oral polio vaccine in America?

Answer 16

X-linked (Bruton) Agammaglobulinemia

Question 17

High IgM with low IgG and IgA is seen in patients with what type of block?

Answer 17

Block 3

Question 18

What defect is seen in Block 3?

Answer 18

Either mutation in CD40 ligand on T cells or

CD40 on B cells

Question 19

What is the name of a block 3 syndrome?

Answer 19

X-linked hyperIgM syndrome

Question 20

What is the name of the condition that results in a normal number of pre-B and B cells, but the B cells are difficult to trigger to make specific antibody?

Answer 20

Common Variable Immunodeficiency (CVID)

Question 21

What is the main phenotype of common variable immunodeficiency?

Answer 21

Recurrent bacterial infection

Question 22

What is the treatment of someone with common variable immunodeficiency?

Answer 22

IVIG

SCIG

Question 23

CVID have an increase risk of what?

Answer 23

Lymphoma
Enteropathy
Autoimmunity

Question 24

What are the two components of the thymus?

Answer 24

Lymphoid part- derived from bone marrow

Stromal part- derived from endoderm and ectoderm of the 3rd and 4th pharyngeal pouch

Question 25

DiGeorge syndrome is caused by what mutation?

Answer 25

-Large (45 gene) deletion on chromosome 22

Question 26

What is the phenotypical presentation of DiGeorge syndrome?

Answer 26

- Unexplained convulsions controllable by calcium because parathyroids also derive from the pharyngeal pouches - Great vessels of the heart develop abnormally - Cell mediated immunity is depressed, so viral and fungal infections are common

Question 27

T cell deficiencies are associated with what type of infection?

Answer 27

Intracellular pathogens - viruses - certain bacteria - yeast and fungi (esp. Candida albicans and Pneumocystis jirovecii)

Question 28

B cell deficiencies are associated with what type of infections?

Answer 28

"high-grade" (extracellular, pyogenic = pus-producing) bacterial pathogens such as Staphylococcus aureus, Haemophilus influenzae and Streptococcus pneumoniae

Question 29

Issac is a 9 month old patient brought into the ER by his mother who tells you that her son has been having recurrent and persistent Gram-positive bacterial infections. You check Issac's IgG levels and see that they are low. What should be on you differential diagnosis for a patient of this age? And, how long would you expect this to last?

Answer 29

Transient hypogammaglobulinemia of infancy Up to 18 months 15% of all chronic diarrhea in infants is due to this condition

Question 30

What are the symptoms of someone with selective IgA deficiency?

Answer 30

- Usually asymptomatic - Diarrhea and sinopulmonary infections - Increased frequency and severity of allergies

Question 31

What is the inheritance pattern of ataxia telangiectasia?

Answer 31

Autosomal recessive

Question 32

What are the phenotypical characteristics of someone with ataxia telangiectasia?

Answer 32

- Sinus infections - Pneumonia - Ataxia - Telangiectasia

Question 33

What cellular deficiency is seen in someone with ataxia telangiectasia?

Answer 33

T and B cell deficiency. IgA is especially depressed

Question 34

Describe some characteristics of Wiscott-Aldrich syndrome.

Answer 34

- Platelet and B cell deficiency - Eczema - Many bacterial infections - X-linked

Question 35

Name some immunosuppressive viruses.

Answer 35

Measles Mononucleosis Cytomegalovirus (CMV)

Question 36

What is the treatment for immunodeficient patients?

Answer 36

1. BUBBLES!!!!! 2. Prophylactic antibiotics 3. Human immunoglobulin (where B cells are deficient) 4. Transplantation of fetal thymus or cultured thymic stromal cells in DiGeorge syndrome

Question 37

What is the recommended treatment of kids with SCID?

Answer 37

Transplant purified stems cells from sibling

Question 38

What is the treatment of someone with ADA-deficiency?

Answer 38

Transfusions of irradiated red cells can be helpful