Immunodeficiencies & flow cytometry

Question 1

Recurrent infections by pyogenic bacteria (extracellular bacteria) are typically associated with defects in…?

Answer 1

• antibody production
• components of the complement cascade
• phagocyte function

Question 2

Recurrent infections by viruses, intracellular bacteria and fungi are typically associated with defects in…?

Answer 2

T cell function, which may impact on:
• function of CD8 cytotoxic T cells
• function of CD4 T cells, and thus
B cell and macrophage function

Question 3

What are the deficiencies that can occur in the complement system and what are their effects?

Answer 3

1. Deficiencies of the early classical pathway proteins and C3: reduce the potential to opsonise organisms for phagocytosis. leading to an increased susceptibility to pyogenic infections.
   
   2. Deficiencies of the terminal complement components: lead to susceptibility to infections with the members of the Neisseria genus because these bacteria can evade the normal phagocytic defences so formation of the MAC is critical for their control
   3. Defects in binding mannose: lead to reduced levels of MBL in serum. These deficiencies have most effect in young children, whose antibody levels are still low, and who are thus very dependent on the complement cascade being triggered by innate mechanisms (ie the alternate and lectin pathways)

Question 4

What are the deficiencies that can occur in phagocytic cells and what are their effects?

Answer 4

1. Leucocyte adhesion deficiency is characterised by an inability of the phagocytes to bind to vascular endothelium and a failure to bind bacteria coated with C3b
   
   2. Chronic granulomatous disease is a disease in which phagocytes ingest but fail to kill ingested organisms. This is because these phagocytes are defective in NADPH oxidase and thus cannot produce superoxide radicals, an important bactericidal pathway.
   3. Pattern recognition receptor defects or defects in components of their signalling pathways

Question 5

What are the deficiencies that can occur in cytokine cells and what are their effects on the innate immune system?

Answer 5

IFNγ produced by TH1 CD4 T cells, CD8 T cells and NK cells) is important in activating macrophages to kill intracellular bacteria

Question 6

What are the 3 measurements of flow cytometry?

Answer 6

1. Forward scatter: detects size
2. Side scatter: detects granularity (e.g. Neutrophils > monocytes > lymphocyte)
3. Fluorescence: fluorescence intensity represents the presence of a specific antigen on the cell surface to which the antibody is binding.