Immunology - Primary Immunodeficiency

Question 1

What are the types of primary immunodeficiency?

Answer 1

Antibody disorders
T cell disorders
Phagocyte disorders
Complement deficiencies
Autoimmune and immune dysregulation syndromes
Auto-inflammatory syndromes

Question 2

What is a primary immunodeficiency?

Answer 2

Chronic disorders in which part of the body’s immune system is missing or functions improperly
Caused by single genetic defects

Question 3

What are secondary immunodeficiencies?

Answer 3

Acquired diseases affecting the immune system and/or treatments negatively influencing the immune system
Caused by environmental/iatrogenic insults
Components of the immune system itself are all present and functional

Question 4

Environmental secondary immunodeficiencies

Answer 4

Malnutrition
Trauma
Burns

Question 5

Disease secondary immunodeficiencies

Answer 5

Infection
Diabetes
Renal failure
Asplenia
Malignancies

Question 6

Iatrogenic secondary immunodeficiencies

Answer 6

Surgery
Splenectomy
Drug

Question 7

Drugs secondary immunodeficiencies

Answer 7

Immunosuppressives
Antirheumatics
Antiepileptics

Question 8

How are the causes of antibody deficiencies in primary immunodeficiency characterised?

Answer 8

By a deficiency of one of more (sub)classes of antibodies due to defective B-cell function
Absence of mature B cells

Question 9

How are cellular immunodeficiencies characterised in primary immunodeficiency?

Answer 9

Impaired T-cell function or the absence of normal T-cells

Question 10

Causes of innate immune disorders

Answer 10

Defects in phagocyte function
Complement deficiencies
Absence or polymorphisms in Pathogen Recognition Receptors

Question 11

Recognition of primary immunodeficiencies

Answer 11

Severe
Persistant
Unusual (uncommon organism)
Recurrent
Familial

Question 12

Presentation of primary immunodeficiency

Answer 12

Infection
Auto-inflammation
Invasive fungal infections

Question 13

What are some neutrophil defects?

Answer 13

Congenital neutropenia
Leucocyte adhesion defect
Deficiencies of PRR
Chronic granulomatous disease

Question 14

What is congenital neutropenia?

Answer 14

Absence of neutropenia

Question 15

PRR

Answer 15

Pattern recognition receptor

Question 16

22q11 deletion syndrome symptoms

Answer 16

Cardiac abnormality
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcemia/hypoparathyroidism

Question 17

What are the possible abnormalities that result in primary immunodeficiency?

Answer 17

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

Question 18

What is repeated infection with encapsulated bacteria a sign of?

Answer 18

Defective antibody production

Question 19

What does antibody deficiency (IgG and IgA) lead to?

Answer 19

Recurrent respiratory infection by pneumococcus or Haemophilus spp.

Question 20

What are infections with staphylococci, gram-negative bacteria, and fungi are associated with?

Answer 20

Reduced number or function of phagocytes

Question 21

Which infections are people with defects in T cells or macrophages predisposed to?

Answer 21

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

Question 22

What is reactivation of latent herpes virus related to?

Answer 22

T cell immunodeficiency

Question 23

What are the overall causes of primary immunodeficiency?

Answer 23

Mutationns
Polymorphisms
Polygenic disorders

Question 24

SCID

Answer 24

Severe combined immunodeficiency

Question 25

How is SCID treated?

Answer 25

Stem cell transplantation in the newborn - must be done very soon after birth

Question 26

MBL

Answer 26

Mannan-binding lectin

Question 27

What is mannan-binding lectin?

Answer 27

A collagen like protein that binds sugars in bacterial cell walls and activates the classic complement pathway Polymorphisms in MBL and complement affect the risk for infections

Question 28

What are genetic polymorphisms?

Answer 28

Alleles of the same gene occurring at a single locus in at least 1% of the population

Question 29

Common polygenic disorders

Answer 29

CVID IgA deficiency Specific antibody deficiency

Question 30

What do patients with VID have low levels of?

Answer 30

Total IgG | Levels of IgA and IgM and numbers of B and T cells are variable.

Question 31

CVID

Answer 31

Common variable immunodeficiency

Question 32

What type of recurrent infection does CVID cause?

Answer 32

Respiratory tract

Question 33

Clinical presentation of severe combined immunodeficiency

Answer 33

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 34

Family history of severe combined immunodeficiency

Answer 34

Neonatal death | Consanguinity

Question 35

Lymphocyte count of severe combined immunodeficiency

Answer 35

Very low

Question 36

Clinical presentation of antibody deficiency

Answer 36

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 37

Aim of treatment of primary immunodeficiency

Answer 37

To prevent infection

Question 38

Treatment in mild immunodeficiency

Answer 38

Prophylactic antibiotics

Question 39

Treatment of more severe antibody deficiency

Answer 39

Ig replacement therapy

Question 40

Treatment of primary immunodeficiency

Answer 40

``` Stem cell treatment (definitive treatment) Avoid live vaccines Prophylaxis against opportunistic infection Gene therapy (if SCT is not an option) ```

Question 41

What is gene therapy?

Answer 41

Use of recombinant technology to correct the genetic defect in the patient’s own stem cells, which can then reconstitute the immune system

Question 42

SPUR

Answer 42

Serious, persistant, unusual or recurrent infections - indicates immunodeficiency

Question 43

What is the most common presentation of antibody deficiency?

Answer 43

Recurrent RTI

Question 44

What is the most common presentation of patients with defects in cellular immunity?

Answer 44

Invasive and disseminated viral, fungal and opportunistic bacterial infections involving any organ