Immunodeficiency

Question 1

What are the 4 categories of infection that suggest immunodeficiency?

Answer 1

Serious - unresponsive to oral antibiotics
Persistent - structural damage, chronic infection
Unusual - unusual organisms or sites
Recurrent - 2 minor or 1 major and recurrent minor infections in 1 year

Question 2

What are some features hat may suggest the presence of an immune deficiency?

Answer 2

Weight loss
Eczema
Chronic diarrhoea
Mouth ulceration
Unusual autoimmune disease
Lymphoproactive disorders - uncontrolled lymphocyte production disorders
Cancer

Question 3

What are the 2 classes of immunodeficiency disorders?

Answer 3

Secondary
Primary

Question 4

What are the characteristics of a secondary immunodeficiency disorder?

Answer 4

Acquired via environmental factors
Common
Subtle
Often involves more than one immune component
Acquired

Question 5

What are some conditions associated (Can cause) with secondary immunodeficiency disorders?

Answer 5

Cancers of the immune system
e.g. Lymphoma, leukaemia, myeloma
Metastatic cancers
Malnutrition
Renal insufficiency
Diabetes mellitus
Mineral deficiency
HIV
Measles

Question 6

What are the characteristics of a primary immunodeficiency disorder?

Answer 6

Inherited genetically

Question 7

What are some upper respiratory complications caused by primary immunodeficiency disorders?

Answer 7

Sinusitis - inflammation of the sinus lining
Otitis media - inflammation of the middle ear
Laryngeal angiodema - Fluid build up in the deep layers of the larynx

Question 8

What are some lower respiratory complications caused by primary immunodeficiency disorders?

Answer 8

Malignancies
Interstitial lung diseases
Pneumonia
Bronchitis
Bronchiectasis - widening of the airways leading to increased mucus production

Question 9

What is agammaglobulinaemia/hypogammaglobulinaemia?

Answer 9

A deficiency of antibodies in the blood stream

Question 10

What are the 3 stages of the neutrophil life cycle?

Answer 10

Development
Transendothelial migration
Phagocytosis and killing

Question 11

What defect can occur during neutrophil development?

Answer 11

Severe congenital neutropenia (Kostmann syndrome)

Question 12

What are the clinical manifestations of Kostmann syndrome?

Answer 12

Severe chronic neutropenia (Absolute neutrophil count <200/µL\
Accumulation of precursor cells in bone marrow
Recurrent bacterial/fungal infection

Question 13

What is the treatment for Kostmann syndrome?

Answer 13

Recombinant G-CSF (Granulocyte Colony Stimulating Factor)
This is a cytokine that drives the maturation of precursor cells in the bone marrow

Question 14

What are the risks of G-CSF treatment for Kostmann syndrome?

Answer 14

Increased risk of AML (Acute Myeloid Leukaemia) and myelodysplasia (Cancer in which cells do not mature in the bone marrow)

Question 15

What is an example of an immunodeficiency disorder that affects transendothelial migration of neutrophils?

Answer 15

leukocyte adhesion deficiency - defect in the CD18 gene that expresses integrins on the neutrophil surface

Question 16

What are the clinical manifestations of leukocyte adhesion deficiency?

Answer 16

leukocytosis
Localised bacterial infection e.g. omphalitis (Infection of the umbilicus)

Question 17

What is an example of a deficiency that affects neutrophil phagocytosis and killing?

Answer 17

Chronic granulomatous disease (CGD) - Deficiency of the intracellular killing mechanisms, so there is no respiratory burst (ROS- killing). This is caused by a gene that codes for a component of NADPH oxidase

Question 18

What are some clinical manifestations of chronic granulomatous disease?

Answer 18

Recurrent, deep bacterial infections - staphylococcus, aspergillus, pseudomonas cepacia
Recurrent fungal infections
Failure to thrive
Lymphadenopathy - Swollen lymph nodes
Hepatoplenomegaly - Swelling of the liver and spleen
Granuloma formation

Question 19

What are the treatment options for phagocyte deficiencies?

Answer 19

Immunoglobulin replacement therapy (IVIg)
Aggressive infection management with antibiotics and antifungals
Haematopoietic stem cell transplantation
Gene therapy

Question 20

What is the cause of immunodeficiency in sufferers of DiGeorge syndrome?

Answer 20

They do not have a thymus so can’t produce matured T cells, preventing cell mediated immunity

Question 21

What is SCID?

Answer 21

Severe Combined Immunodeficiency, in which none of multiple lymphocytes are produced

Question 22

What is the cause of X-linked SCID?

Answer 22

Mutation of a component of the IL-2 receptor, which is a growth factor that stimulated T cell proliferation and activation
This leads to the inability to respond to cytokines and failure of T and natural killer cell development, as well as the failure to produce mature B cells

Question 23

What are some common clinical manifestations of SCID?

Answer 23

Unwell by 3 months old
Persistent diarrhoea
Failure to thrive
Many, varied infections
Unusual skin diseases e.g. Graft versus Host disease, in which the infants empty bone marrow is colonised by maternal lymphocytes