Week 5 - Immunodeficiency

Question 1

What are primary immunodeficiencies?

Answer 1

• Rare congenital diseases characterised by history of repeated infections with same or similar pathogens
• Usually manifest early in life
• Usually caused by mutations in recessive genes

Question 2

What are secondary immunodeficiencies?

Answer 2

• Acquired later in life
• Environmental factors -> HIV, Measles // Malnutrition // Cancer // Medical treatments

Question 3

What is Chronic Granulomatous Disease characterised by?

Answer 3

• undue susceptibility to persistent bacterial and fungal infection in the first 2 years of life
• Phagocytes are unable to eliminate pathogens

Question 4

What are treatments for Chronic Granulomatous Disease?

Answer 4

• Prophylactic antibiotics
• Anti-inflammatories
• Haemopoietic Stem cell transplant

Question 5

When do Granulomas form?

Answer 5

form when an intracellular pathogen cannot be eliminated

Question 6

What are Granulomas made of?

Answer 6

infiltrate of infected macrophages, multinucleated giant cells, Th1 cells

Question 7

What is the mechanism/cause behind Chronic Granulomatous Disease?

Answer 7

The process of Phagocyte Oxidase is disrupted because of a defect in NADPH oxidase -> NADPH oxidase doesn’t produce superoxide ions

Question 8

What is the fault in NADPH Oxidase that lead to disfunction?

Answer 8

= a multi-subunit complex
- mutations of any components lead to CGD
- GP91 is the most commonly mutated gene and it exists on the X chromosome

Question 9

What are characteristics of Leukocyte Adhesion Deficiency?

Answer 9

• Recurrent severe bacterial infections that are eventually fatal if untreated
• white blood cells = abnormally high in blood
• delays in wound healing

Question 10

What typically happens in Leucocyte recruitment to the site of inflammation?

Answer 10

• B2 integrins are adhesion molecules that adhere to ligands on blood endothelial cells -> there is a defect of this in LAD

Question 10

What happens to B2 integrin in LAD?

Answer 10

= defective

Question 11

What is Severe Combined Immunodeficiency (SCID)?

Answer 11

= series of genetic defects that cause defective development of T cells

• B cell & NK cell development affected
• Almost complete ablation of T cell dependent immunity

Question 12

What are clinical outcomes of SCID?

Answer 12

• in first few months, patients can be protected by maternal Abs
  After that however, they develop:
• Thrush
• Coughs & Pneumonia from viral infections
• Diarrhoea

Question 13

What are treatments for patients with SCID?

Answer 13

• Prophylactic antibiotics
• IV immunoglobulins
• Hygiene measures
• Avoidance of live attenuated vaccines

Question 14

What is X-linked SCID - Common gamma chain deficiency?

Answer 14

• gamma chain deficiency leads to cytokines not working because they cant be signalled which is normally done by gamma chains

Question 15

What are RAGs (Recombination activating genes)?

Answer 15

They are essential for recombining antigen receptor gene segments

In the absence of RAG, developing lymphocytes cannot express antigen receptors and cannot get positively sleected

Question 16

What are Purine Salvage Pathway enzyme?

Answer 16

= enzymes involved in nucleic acid catabolism
- deficiency leads to accumulation of metabolites that are toxic to lymphocytes

Question 17

What are treatments for SCID?

Answer 17

• Bone marrow transplant
• Enzyme replacement therapy for ADA deficients
• Gene therapy using autologous BM cells

Question 18

What are the characteristics of X-linked agammaglobulinaemia with hyper-IgM?

Answer 18

• IgM = very high // IgG, IgA, IgE = low or absent
• suffer from pyogenic bacterial infections
• susceptible to opportunistic intracellular pathogens

Question 19

Germinal centres in X-linked agammaglobulinaemia with hyper-IgM

Answer 19

Germinal centres are T cell dependent