Session 9 ILOs - The Immunocompromised Host

Question 1

Describe the main reasons for a patient to be immunocompromised

Answer 1

Immunodeficiency is caused by defects in 1 or more of the components of the immune system

2 main forms:

1. Primary immunodeficiency
   - Due to intrinsic gene defect (missing protein or cell, or non-functional components)
2. Secondary immunodeficiency
   - Due to an underlying disease or treatment
   - Decreased production/function or loss/catabolism of immune components

Question 2

Describe the immune defects associated with the immunodeficiency diseases

Answer 2

Primary immunodeficiency disease:

B cell abnormality (innate)
- Bruton’s disease

T cell abnormality (innate)

• DiGeorge Syndrome
• CD3 deficiency
• TAP1/2 deficiency
• Class 2 deficiency

B and T cell abnormality (innate)

• SCID (Severe Combined immunodeficiency)
• Ataxia talengtasia

Antibody abnormalities (innate)

• Common Variable immunodeficiency
• Selective IgA deficiency
• IgG subclass deficiency
• Hyper IgM syndrome

Macrophage abnormality (adaptive)
- Chronic Granulomatous disease

Neutrophil abnormality (adaptive)

• Cyclic neutropenia
• LAD protein deficiencies

Lysosome/proteosome abnormality (adaptive)
- Chediak-Higashi syndrome

Question 3

Describe the warning signs that suggest a primary immunodeficiency disease

Answer 3

When to suspect immunodeficiency - SPUR
Severe
Persistent 
Unusual
Recurrent

Also 10 warning signs in children and adults

Children:

• A family history of a PID
• Failure of an infant to gain weight or grow normally
• Persistent thrush in mouth or on skin

Adults

• A family history of a PID
• Persistent thrush in mouth or elsewhere
• Chronic diarrhoea with weight loss

Question 4

Use of the clinical presentation to understand the immune defects and guide the management of primary immunodeficiency diseases

Answer 4

Presentation / onset:
Onset < 6 months:
- T cell
- Phagocyte

Onset 6 months to 5 years:

• B cell / antibody
• Phagocyte

Onset < 5 years:

• B cell / antibody / complement
• Secondary immunodeficiency (most commonly malnutrition)

Clinical picture:
Complement deficiency:
- Pyogenic infections
- Meningitis/Sepsis/Arthritis
- Angioedema 

Phagocytic deficiency:

• Skin/mucous infection
• Deep seated infections
• Invasive fungal infections e.g. Aspergillous

Antibody deficiency:

• Sino-resp infectoins
• Arthropathies
• GI infections
• Malignancies
• Autoimmunity

T cell defect:

• Death if not treated
• Failure to thrive
• Deep skin and tissue abscesses
• Opportunistic infections

Question 5

Describe the common causes of secondary immunodeficiencies

Answer 5

1. Decreased production of immune components
   - Malnutrition (top!)
   - Infection e.g. HIV
   - Liver diseases
   - Haematological malignancies
   - Theraputic treatment e.g. corticosteroids
   - Splenectomy
2. Increased loss of immune components
   - Protein-losing conditions e.g. nephropathy, enteropathy
   - Burns