Primary Immunodeficiency

Question 1

What can lead to immunodeficiency diseases?

Answer 1

Defects in one or more components of the immune system can lead to serious and often fatal disorders, which are collectively called immunodeficiency diseases.

Question 2

What are the major consequences of immunodeficiency?

Answer 2

increased susceptibility to infection.
also susceptible to certain types of cancer.
Certain immunodeficiencies are associated with an increased incidence of autoimmunity.

Question 3

What causes primary immunodeficiencies?

Answer 3

mainly caused by genetic aberrations

A smaller number of primary immunodeficiencies are caused by autoimmunity

Question 4

Where may the abnormality be in Primary Immunodeficiency?

Answer 4

Components of the innate immune system
• Stages of lymphocyte development
• Responses of mature lymphocytes to antigenic stimulation

Question 5

What is repeated infection with encapsulated bacteria a sign of?

Answer 5

a sign of defective antibody production.

Question 6

What does an antibody deficiency lead to recurrent infections with?

Answer 6

leads to recurrent respiratory infection by pneumococcus or Haemophilus spp.

Question 7

What infections may a reduced number of phagocytes lead to?

Answer 7

• Infections with staphylococci, gram-negative bacteria, and fungi

Question 8

What do defects in T cells or macrophages predispose to infection with?

Answer 8

intracellular organisms such as protozoa, viruses, and intracellular bacteria, including mycobacteria.

Question 9

What is reactivation of latent herpesvirus infection linked to?

Answer 9

T-cell

immunodeficiency.

Question 10

What is non-Hodgkin lymphoma (Epstein-Barr virus [EBV] characteristic of?

Answer 10

T-cell dysfunction.

Question 11

What is a gene mutation?

Answer 11

A gene mutation is a permanent alteration in the DNA sequence that makes up a gene, such that the sequence differs from what is found in most people.

Question 12

What do polymorphisms involve?

Answer 12

Polymorphism involves one of two or more variants of a particular DNA sequence. The most common type of polymorphism involves variation at a single base pair. Polymorphisms can also be much larger in size and involve long stretches of DNA.

Question 13

What are polygenic disorders?

Answer 13

These are disorders caused by the combined action of more than one gene.
• Polygenic disorders of the immune system are relatively common and affect mainly antibodies.

Question 14

What is the treatment for SCID?

Answer 14

Stem cell transplant can cure SCID but it has to be done quickly. If it is performed very soon after birth, 90% infants survive; if it is delayed for a few months, only 50% infants survive the transplant procedure.

Question 15

What are genetic polymorphisms?

Answer 15

Genetic polymorphisms are alleles (different forms) of the same gene occurring at a single locus in at least 1% of the population.

Question 16

What is mannan-binding lectin?

Answer 16

Mannan-binding lectin (MBL) is a collagen-like protein that binds sugars in bacterial cell walls and activates the classic complement pathway.

Question 17

What are the common polgenic disorders?

Answer 17

CVID
IgA deficiency
Specific antibody deficiency

Question 18

What is the most common primary immunodeficiency requiring treatment

Answer 18

CVID

Question 19

Describe antibody and lymphocyte levels in CVID.

Answer 19

Patients have low levels of total IgG. Levels of IgA and IgM and numbers of B and T cells are variable.

Question 20

Describe how CVID may present.

Answer 20

CVID causes recurrent respiratory tract infections.
Infections that involve the gut, skin, and nervous system also occur. Autoimmunity is common in CVID.
Many patients have a history of other affected family members or of consanguinity, which suggests autosomal-recessive inheritance.

Question 21

What organisms are common in infections in those with polygenic immunodeficiencies?

Answer 21

pneumococcus or Haemophilus

Question 22

What infection is often found in autoimmune polyendocrinopathy candidiasis ectodermal dysplasia (APECED)?

Answer 22

severe recurrent Candida infection.

Question 23

Mutations in what gene cause APECED?

Answer 23

AIRE gene

Question 24

What signs in the first week of life suggest SCID?

Answer 24

Unusual or recurrent infection
• Diarrhoea
• Unusual rashes

Question 25

What is used to measure lymphocyte count in SCID?

Answer 25

flow cytometry

Question 26

When do most forms of antibody deficiency present?

Answer 26

Adulthood

Question 27

What pattern of infection is commonly seen in CVID?

Answer 27

Recurrent resp infections

Question 28

Describe the use of gene therapy in the treatment of SCID

Answer 28

Gene therapy uses recombinant technology to correct the genetic defect in the patient’s own stem cells, which can then reconstitute the immune system.
used in patients with SCID for whom no suitable stem cell donor was available.

Question 29

What steps are taken to avoiding infection in SCID?

Answer 29

• Avoiding live vaccines (eg, measles, mumps, rubella, polio)
• Prophylaxis against opportunist infections such as Pneumocystis jiroveci.

Question 30

When is SCT most successful in SCID?

Answer 30

within a few weeks of birth, before the infant has developed any infections.

Question 31

What is the common defect in chromic granulomatous disease?

Answer 31

Phagocyte