Immunodeficiency

Question 1

List 4 factors that contribute to resistance to infection.

Answer 1

1 - Age.

2 - Previous exposure / vaccination.

3 - Nutrition.

4 - Disease.

Question 2

What is the Lubeck disaster of 1926?

Answer 2

• An incident where 251 infants were immunised with a virulent strain of Mycobacterium tuberculosis instead of Mycobacterium bovis BCG.
• 1/3 died.

Question 3

List 3 consequences of immunodeficiency.

Answer 3

1 - Reduced defence to infection.

2 - Reduced tumour surveillance, so greater likelihood of tumour growth.

3 - Reduced tolerance, so greater likelihood of autoimmunity.

Question 4

List 4 red flags for immunodeficiency.

Answer 4

1 - Increased frequency of infection.

2 - Unusual organism causing the infection.

3 - Increased severity of infection.

4 - Poor outcome of infection (e.g. organ damage or mortality).

Question 5

Describe the aetiology of immunodeficiency.

Answer 5

• Primary (genetic). Often in life but also in common variable immunodeficiency (CVID) in adulthood.
• Secondary (acquired). Increasing likelihood with age and comorbidities.

Question 6

List 2 factors which determine the therapy given for immunodeficiency.

Answer 6

1 - Whether the cause of the defect is quantitative or qualitative.

2 - Whether the cause of the defect is primary or secondary.

Question 7

List the characteristics of an immunodeficiency of neutrophils.

Answer 7

Type of infection:

1 - Extracellular bacteria.

2 - Fungi.

Site of infection:

1 - Skin.

2 - Mucosal surfaces.

Age of presentation:

• First month of life.
• This is true for both primary and secondary causes of immunodeficiency.

Question 8

List the characteristics of an immunodeficiency of B cells.

Answer 8

Type of infection:

• Encapsulated bacteria.

Site of infection:

• Respiratory tract.

Age of presentation:

1 - At 6 months of gestation when the concentration of maternal immunoglobulin falls.

2 - During adulthood.

*This is true for both primary and secondary causes of immunodeficiency.

Question 9

List the characteristics of an immunodeficiency of T cells.

Answer 9

Type of infection:

1 - Intracellular bacteria.

2 - Viruses.

3 - Fungi.

Site of infection:

1 - Respiratory tract.

2 - GI tract.

Age of presentation:

• First month of life.
• This is true for both primary and secondary causes of immunodeficiency.

Question 10

List 4 differences between primary and secondary immunodeficiencies.

Answer 10

1 - Primary immunodeficiencies are rarer.

2 - Defects of primary immunodeficiencies are often more discrete, i.e. a single gene, whereas defects of secondary immunodeficiencies are often broad.

3 - The infectious susceptibility is more well understood for primary immunodeficiencies.

4 - Tests to investigate immune function are more well established with primary immunodeficiencies.

Question 11

List 7 risk factors that predispose towards secondary immunodeficiencies.

Answer 11

1 - Immunosuppressive therapies.

2 - Steroids.

3 - Cancer.

4 - Autoimmunity.

5 - Advanced age.

6 - Poor nutrition.

7 - Impaired barrier defence.

Question 12

Describe 4 primary barrier defects.

Answer 12

1 - Kartagener’s syndrome. A defect in cilia leading to bronchiectasis.

2 - Cystic fibrosis. A defect in salt transfer resulting in viscous mucous secretions.

3 - Ureteric reflux. A defect in ureteric flow.

4 - Eczema. A defect in filaggrin (a protein involved in epidermal homeostasis).

Question 13

List 4 acquired barrier defects.

Answer 13

1 - Barrier defects due to surgery.

2 - Bronchiectasis (widened bronchi causing an excess build-up of mucus).

3 - GI inflammation.

4 - Poor dentition.

Question 14

List 8 neutrophil defects.

Separate the defects by primary / secondary and quantitative / qualitative.

Answer 14

Primary quantitative:

1 - Cyclical neutropenia.

Secondary quantitative:

2 - Autoimmunity.

3 - Chemotherapy.

4 - Leukaemia.

Primary qualitative:

5 - Defects of migration, e.g. leukocyte adhesion deficiency (LAD).

6 - Defects of respiratory burst, e.g. chronic granulomatous disease (CGD).

Secondary qualitative:

7 - Prednisolone.

8 - Defects of metabolism.

Question 15

Describe the pathophysiology of leukocyte adhesion deficiency (LAD).

Answer 15

• Normally, beta 2 integrins bind ICAM1 on endothelial cell surfaces to cause tight binding.
• Selectins are responsible for loose binding, and facilitate the rolling of neutrophils over endothelial surfaces.
• With leukocyte adhesion deficiency (LAD), the beta 2 integrins are dysfunctional, therefore neutrophils are able to bind loosely and roll over the endothelium but are not able to bind tightly and extravasate.

Question 16

What type of infections are common in individuals with chronic granulomatous disease (CGD)?

Answer 16

1 - Catalase positive bacterial infections.

2 - Fungal infections, especially aspergillus.

Question 17

List 2 signalling molecules involved in the functioning of toll-like receptors.

Answer 17

1 - NEMO.

2 - IRAK4.

Question 18

List 3 drug causes of secondary cytokine deficiency.

Describe the uses of these drugs.

Answer 18

1 - Anti-TNF alpha (used to suppress immune activation during fevers).

2 - Anti-IL-6 (used to reduce CRP production from the liver and in turn suppress complement and macrophage activity).

3 - Anti-IL-1 (used to suppress immune activation).

Question 19

List 3 characteristics of a fever.

Answer 19

1 - Increased blood pressure.

2 - Rigors.

3 - Anorexia.

Question 20

List 3 forms of leukocytosis.

State the type of infection associated with each form.

Answer 20

1 - Neutrophilia - associated with bacterial infection.

2 - Lymphocytosis - associated with viral infection.

3 - Eosinophilia - associated with parasitic infection or allergy.

Question 21

What are type 1 cytokine defects?

Answer 21

Defects of defence against intracellular bacteria.

Question 22

List 3 signalling molecules involved in type 1 cytokine defects.

Answer 22

1 - IL-12.

2 - IFN-gamma.

3 - TNF-alpha.

Question 23

What type of infection is associated with type 1 cytokine defects?

Answer 23

Atypical mycobacterial infections:

1 - Mycobacterium avium.

2 - BCGosis.

Question 24

List 2 treatments for atypical mycobacterium infections due to type 1 cytokine defects.

Answer 24

1 - Antibiotics and IFN-gamma injection.

2 - Bone marrow transplantation.

Question 25

What type of infections are typical with classical complement deficiencies?

Answer 25

Encapsulated bacterial infections.

Question 26

What type of infections are typical with alternative complement deficiencies?

Answer 26

Neisseria infections (a genus of bacteria).

Question 27

What is immune complex disease? Give an example of a cause of immune complex disease.

Answer 27

- A group of inflammatory conditions characterised by antigen–antibody deposition and attendant activation of complement. - Can be caused by classical complement deficiencies.

Question 28

What type of infections are typical with defects of the membrane attack complex (MAC)?

Answer 28

Neisserial and other pyogenic (pus-forming) infections.

Question 29

What inheritance pattern does C1 esterase inhibitor deficiency show?

Answer 29

Autosomal dominant.

Question 30

Describe the pathophysiology of C1 esterase inhibitor deficiency.

Answer 30

Lack of C1 esterase inhibitor causes sudden uncontrolled activation of complement and bradykinin pathways.

Question 31

List 3 symptoms of C1 esterase inhibitor deficiency.

Answer 31

1 - Non-itchy oedema. 2 - Acute abdomen (abdominal pain). 3 - Asphyxiation.

Question 32

Which types of antibody do B cells express once in the circulation before class switching / exposure to antigen?

Answer 32

IgM and IgD.

Question 33

What is common variable immune deficiency (CVID)?

Answer 33

An umbrella term for antibody deficiencies where there is a problem of terminal differentiation and high affinity antibody production.

Question 34

Give an example of a cause of Hyper-IgM syndrome.

Answer 34

A defect in the CD40 ligand on T cells (or CD40 on B cells).

Question 35

What would be visually abnormal in a biopsy of a lymph node from a patient with hyper-IgM syndrome?

Answer 35

There would be no germinal centres.

Question 36

What might hypotrophic tonsils indicate?

Answer 36

A decrease in lymphoid cell production, e.g. due to a T or B cell defect such as with hyper-IgM syndrome.

Question 37

List 6 secondary causes of antibody deficiency.

Answer 37

1 - Marrow suppression, e.g. with a myeloma / leukaemia. 2 - Immunosuppression due to steroids. 3 - Immunosuppression due to cytotoxic drugs, e.g. chemotherapy. 4 - Increased loss due to nephrosis. 5 - Increased loss due to enteropathy. 6 - Increased loss due to rituximab use (a drug which targets CD20 for autoimmune diseases and cancers).

Question 38

What is the function of CD20?

Answer 38

It plays a role in B cell development and differentiation into plasma cells.

Question 39

List 2 clinical manifestations of antibody deficiency.

Answer 39

1 - Infection by encapsulated pyogenic bacteria. 2 - Respiratory tract infections.

Question 40

List 2 encapsulated pyogenic bacteria.

Answer 40

1 - Streptococcus pneumoniae. 2 - Haemophilus influenzae B.

Question 41

List 5 respiratory tract infections / complications of respiratory tract infections.

Answer 41

1 - Otitis media. 2 - Sinusitis. 3 - Bronchitis. 4 - Pneumonia. 5 - Bronchiectasis.

Question 42

List 2 treatments of antibody deficiency.

Answer 42

1 - Immunoglobulin G replacement therapy. 2 - Prophylactic antibiotics.

Question 43

Given the importance of IgA for mucosal immunity, why are most people with IgA deficiency asymptomatic?

Answer 43

Because there is a compensatory increase in other types of antibody production.

Question 44

With which other antibody deficiency is IgA deficiency associated? List 2 complications this might cause.

Answer 44

- IgG2. Complications might include: 1 - Increased susceptibility to infection. 2 - Autoimmunity.

Question 45

List 2 primary causes of T cell deficiency.

Answer 45

1 - Severe combined immunodeficiency (failure to produce lymphocytes). 2 - DiGeorge syndrome (failure of the thymus to develop).

Question 46

List 3 secondary causes of T cell deficiency.

Answer 46

1 - Immunosuppression for preventing graft rejection or treating autoimmune disease. 2 - HIV. 3 - Lymphoid malignancies.

Question 47

List 4 symptoms of T cell deficiency.

Answer 47

1 - Severe bacterial, viral and fungal infections. 2 - Failure to thrive. 3 - Diarrhoea, especially with Cryptosporidium infection (a genus of parasites). 4 - Pneumonia, especially with Pneumocystis carinii (a protozoan).

Question 48

List 5 treatments and management techniques for T cell deficiency.

Answer 48

1 - Haematopoietic stem cell transplant (HSCT). 2 - Immunoglobulin replacement therapy. 3 - Prophylactic antibodies such as septrin. 4 - Irradiation of blood products. 5 - Avoidance of live vaccines such as BCG and MMR.