Immunology - Primary Immunodeficiencies

Question 1

What is the major hallmark of immune deficiency?

Answer 1

Recurrent infections. Slide 4

Question 2

What does SPUR stand for and what does it do?

Answer 2

Serious Infections
Persistent Infections
Unusual Infections
Recurrent Infections.
Highlights the clinical features suggestive of immunodeficiency. Alisw 5

Question 3

Which classification of immunodeficiencies are more common and why?

Answer 3

Secondary as they are often acquired instead of being born with it (primary). Slide 6

Question 4

What are some conditions associated with secondary immune deficiency?

Answer 4

HIV
Immunosuppressive therapy
Cancer of the immune system
Malnutrition. Slide 7

Question 5

What are some organisms that are clinical features of phagocyte deficiencies?

Answer 5

Burkholderia Cepacia
Mycobacteria: TB & atypical
Fungi - candida & aspergilllus. Slide 13

Question 6

What can go wrong with the movement of phagocytes/precursors in the bone marrow or tissues?

Answer 6

Maybe not be able to produce neutrophils or maturation of them. Slide 19

Question 7

What is Recticular Dysgenesis and Kostmann Syndrome?

Answer 7

RD = Failure to produce neutrophils
KS = severe congenital neutropaenia (failure of neutrophil maturation). Slide 19

Question 8

How would Kostmann Syndrome be managed?

Answer 8

Supportive treatments of antibiotics + anti-fungals and NEED definitive treatment of stem cell transplantation or G-CSF. Slide 21

Question 9

If there was something wrong with the endothelial adhesion markers at sites of infection?

Answer 9

Leukocyte Adhesion Deficiency
Activation markers expressed on the endothelial cells aren’t recognised and neutrophils don’t exit the bloodstream. Slide 24

Question 10

What would be the signs of Leukocyte Adhesion Deficiency?

Answer 10

Recurrent bacterial/fungal infections, high neutrophil counts and at the deep tissues where the site of infection is, there would be no pus. Slide 24

Question 11

If there was a fault in recognition of the organism what could happen?

Answer 11

Defects in opsonin receptors may cause defective phagocytosis.
Defect of complement/antibody production decreases efficiency of opsonisation.
The recognition is just not as efficient. Slide 30+31

Question 12

What could happen if there was a fault in phagocytosis and killing of the organism?

Answer 12

Chronic Granulomatous Disease
Deficiency of the intracellular killing mechanism of phagocytes.
Cannot generate O2 free radicals to kill the pathogen. Slide 37

Question 13

What is Chronic Granulomatous Disease?

Answer 13

Inability to clear organisms and there is excessive inflammation due to that.
Leads to granuloma formation. Slide 38

Question 14

What are the features of Chronic Granulomatous Disease?

Answer 14

Recurrent deep bacterial infections e.g. Staph., Aspergillus, mycobacterium.
Reccurent FUNGAL infections, granuloma formation, failure to thrive and lymphadenopathy. Slide 39

Question 15

How can you test for Chronic Granulomatous Disease?

Answer 15

NBT
Test patients neutrophils against E coli, add H2O2 sensitive dye and if H2O2 is produced by the neutrophils the dye changes colour. Slide 40

Question 16

How do you manage Chronic Granulomatous Disease?

Answer 16

Supportive treatment of antibiotics and anti-fungals and the definitive treatment of a stem cell transplantation. Slide 41

Question 17

What happens if there is a fault in the activation of other components in the immune system?

Answer 17

E.g. if there is a deficiency in IL-12 which stimulates the TH1 cells to produce IFNgamma then the macrophage won’t phagocytose as well causing increased susceptibility to intracellular bacteria e.g. M. TB and salmonella. Slide 45

Question 18

What are some of the tests to investigate phagocyte function?

Answer 18

Full blood count.
Presence of pus.
Chemotactic and phagocytosis assays.
NBT. Slide 46

Question 19

What is aggressive management of infection in patients with phagocyte deficiencies?

Answer 19

Infection prophylaxis
Antibiotics
Surgical draining of abscesses. Slide 48

Question 20

What is definitive therapy often include?

Answer 20

Bone marrow transplants

Specific treatment for CGD of gamma interferon therapy or gene therapy. Slide 48