I - Primary Immune Deficiencies

Question 1

Recurrent infections are the major hallmark of immune deficiency. These are characterised by SPUR - what does SPUR stand for?

Answer 1

S - serious infections
P - persistent infections
U - unusual infections (organism or site)
R - recurrent infections

Question 2

Give examples of the following types of immunodeficiency:
Physiological
Infection
Treatment interventions
Malignancy

Answer 2

Physiological - prematurity/elderly
Infection - HIV (knocks out CD4 cells); measles; cancer (affects bone marrow)
Treatment investigations - corticosteroids (inhibit T and B cell processes)
Malignacy - cytotoxic anticancer drugs e.g. chemo(bone marrow damaged)

Question 3

What are the cells of the innate immune system?

Clue - they begin with MMNN

Answer 3

Macrophages
Mast cells
Neutrophils
Natural killer cells

Question 4

What are the three types of protein involved in the innate immune system?

Answer 4

Complement
Acute phase
Cytokines

Question 5

Phagocytes
Example of cells
Functions
Important against what?

Answer 5

Neutrophils; monocytes/macrophages
Initiate and amplify the inflammatory response
Scavenge cellular and infectious debris
Ingest and kill microorganisms
Important in defence against bacteria and fungi

Question 6

Clinical features of phagocyte deficiency
What site if affected?
What is the most common organism?

Answer 6

Affects usual and unusual sites

Staph Aureus is most common

Question 7

Defects of phagocyte production - failure to produce neutrophils.
What are the two main problems here?

Answer 7

1. Failure of stem cells to differentiate along myeloid lineage (e.g. to granulocyte, monocyte etc)
2. Specific failure of neutrophil maturation. Can result in Kostmann syndrome or cyclic neutropaenia (every 4-6 weeks)

Question 8

Kostmann Syndrome
What type of genetic disorder?
Characterised by what?
Clinical presentation?
Management?

Answer 8

Rare autosomal recessive disorder

Characterised by severe chronic neutropaenia - absolute neutrophil count

Question 9

What syndrome would you expect to occur if a patient's phagocytes were unable to recognise endothelial adhesion molecules?
Clinical features?
Blood count?
Site of infection?
Primary or secondary immunodeficiency/

Answer 9

Leukocyte adhesion deficiency- failure to recognise activation markers expressed by endothelial cells. Neutrophils are mobilised but cannot exit blood stream.
Clinical features - recurrent bacterial or fungal infection.
Blood count - very high neutrophil count
Site of infection - deep tissues; NB - no pus formation
Primary immunodeficiency

Question 10

Failure of oxidative killing mechanisms - what disease would you expect? 
What does this incur? 
Features and common organisms?
Tests (hint - NBT)?
Treatment?

Answer 10

Chronic Granulomatous Disease
Deficiency of the intracellular killing mechanism of phagocytes.
Results in persistent accumulation of neutrophils, activated macrophages, and lymphocytes & also excessive inflammation.
Features - recurrent deep infections, especially Staph, Aspergillus.
Also causes formation of granulomas from the base of the wound.
Nitroblue tetraolium (NBT) test - feed patient neutrophils a source of E.coli.
Treatment is either prophylactic antibiotics & antifungals, or stem cell transplant.

Question 11

Defence Against Intracellular Organisms

1. Why is this necessary?
2. Which signal things are involved?

Answer 11

1. Some pathogens hide from the immune system within other cells, e.g. Salmonella, Chlamydia, so need specific strategies to clear this.
2. Stimulates IL12-gIFN network which activates NADPH oxidase.
   Any defect of the IL12 or gIFN things will cause susceptibility to mycobacterial infections.