Immunodeficiency

Question 1

Immunodeficiency diseases are broadly classified into two groups:

Answer 1

• Primary, or congenital, immunodeficiencies
• Secondary, or acquired, immunodeficiencies

Question 2

Consequences of immunodeficiency

Answer 2

• increased suceptibility to infection
• susceptible to certain types of cancer
• certain immunodeficiencies are associated with an increased incidence of autoimmunity

Question 3

For primary immuneodeficiency the abnormality may be in:

Answer 3

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

Question 4

The type of opportunist infection present gives clues to the degree and cause of immunodeficiency.

Repeated infection with encapsulated bacteria is a sign of:

Answer 4

defective antibody production

Question 5

The type of opportunist infection present gives clues to the degree and cause of immunodeficiency.

Antibody deficiency (IgG and IgA) leads to:

Answer 5

recurrent respiratory infection by pneumococcus or Haemophilus spp.

Question 6

The type of opportunist infection present gives clues to the degree and cause of immunodeficiency.

Infections with staphylococci, gram-negative bacteria, and fungi are associated with:

Answer 6

reduced number or function of phagocytes

Question 7

The type of opportunist infection present gives clues to the degree and cause of immunodeficiency.

Defects in T cells or macrophages predispose to infection with:

Answer 7

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

Question 8

The type of opportunist infection present gives clues to the degree and cause of immunodeficiency.

Reactivation of latent herpesvirus infection is linked to:

Answer 8

T-cell immunodeficiency

Question 9

The type of opportunist infection present gives clues to the degree and cause of immunodeficiency.

Recurrent Candida infection is suggestive of defects in:

Answer 9

the TH17 pathway

Question 10

The type of opportunist infection present gives clues to the degree and cause of immunodeficiency.

Herpesvirus-induced tumours, notably Kaposi sarcoma (human herpesvirus 8 [HHV8]), and non-Hodgkin lymphoma (Epstein-Barr virus [EBV]) are characteristic of:

Answer 10

T-cell dysfunction

Question 11

Causes of Primary Immunodeficiency

Answer 11

• Mutations
• Polymorphisms
• Polygenic disorders ​

Question 12

Severe combined immunodeficiency (SCID)

Answer 12

• Results from a mutation
• A group of disorders that affect both T and B cells
• Infants with SCID die in the first few months of life unless treatment is given
• Many countries screen for SCID in newborns

Question 13

Common variable immunodeficiency (CVID)

Answer 13

• relatively common polygenic disorder that affect antibody production
• patients have low levels of total IgG. Levels of IgA and IgM and numbers of B and T cells are variable

Question 14

Diagnosis of severe combined immunodeficiency

Clinical presentation

Answer 14

• Children with SCID have defective T cells and B cells and therefore develop infections in the first few weeks of life.
• Unusual or recurrent infection
• Diarrhoea
• Unusual rashes

Question 15

Diagnosis of severe combined immunodeficiency

Family history

Answer 15

• Family history of neonatal death
• Family history of consanguinity

Question 16

Diagnosis of severe combined immunodeficiency

Lymphocyte count

Answer 16

• Lymphocyte numbers should be measured by flow cytometry
• Very low total lymphocyte count (less than 1 × 109/L [106/mL])

Question 17

Diagnosis of antibody deficiency

Clinical presentation

Answer 17

• Antibody deficiency presents later in life
• Babies are born with maternal immunoglobulin transferred across the placenta
• Some forms of antibody deficiency, such as CVID, do not present until adulthood
• Chronic or recurrent bacterial respiratory infection

Question 18

Antibody deficinecy investigations

Answer 18

• IgG, IgA, and IgM should be measured
• With low levels of immunoglobulins, causes of secondary immunodeficiency should be excluded
• If total Igs are normal, specific antibodies against Haemophilus spp. and pneumococcus should be measured
• If these tests are all normal, it is important to check no problems are apparent with complement or neutrophil function

Question 19

Treatment of primary immunodeficiency

Answer 19

• In mild immunodeficiency, prophylactic antibiotics may be adequate
• In more severe antibody deficiency, immunoglobulin replacement therapy

Question 20

SCID - steps that can be taken before definitive treatment is given:

Answer 20

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

Question 21

Definitive treatment for SCID

Answer 21

• SCT is most successful if it can be done within a few weeks of birth, before the infant has developed any infections
• If this is possible, SCT carries a 90% success rate and is curative
• When SCT is not an option (no suitable stem cell donor available) gene therapy may be attempted