Immunodeficiency

Question 1

Give 2 conditions that are a result of congenital antibody deficiency

Answer 1

XLA - X-linked Agammaglobulinaemia

Transient Hypogammaglobulinaemia of Infancy (young babies 6 - 7 months old)

Question 2

Who is affected by Transient hypogammaglobulinaemia of Infancy?
Describe this condition.

Answer 2

affects infants age 6 - 7 months old.
There is immature IgG production, and hence, it takes a long time for their own IgG to increase. This results in a time lag between the decline of maternal’s IgG and the baby’s own production of IgG. This condition is transient and will get better on its own.

Question 3

Who is affected by XLA? Describe this condition.

Answer 3

X-linked Agammaglobulinaemia affects mostly males.

There is very few B cells, and hence, a lack of antibodies.

Question 4

Describe the defect in Chronic Granulomatous Disease

Answer 4

Defects in killing mechanism in phagocytosis.

There is defective oxidative burst –> Unable to produce toxic oxygen reactive compounds

Question 5

What does LAD stands for?

Describe the defect in LAD

Answer 5

LAD - Leukocyte Adhesion Deficiency

Defect in adhesion molecules, affecting chemotaxis (failure of migration)

Question 6

What is patients with Chronic Granulomatous Disease very susceptible to?

Answer 6

Coagulase positive bacteria, such as Staphylococci and Fungal infections

Question 7

When is the onset of XLA?

Answer 7

6 - 12 months old

Question 8

What are the 3 classic presentations of LAD?

Answer 8

Recurrent bacterial infections, defect in neutrophil adhesion and delay in umbilical cord sloughing

Question 9

How many types of LAD are there? Which type is the most common?

Answer 9

Three types: LAD1, LAD2 and LAD3
LAD1 is the most common: Neutrophils cannot extravasate (move out of the circulation to the site of infection) bacteria proliferates and cause systemic infections

Question 10

What are the pathogens seen in phagocytic deficiencies?

Answer 10

Bacteria: Staphylococcus and Pseudomonas
Fungal: Candida and Aspergillus (mould)

Question 11

What are humoral deficiencies?

What are the pathogens seen in humoral deficiencies?

Answer 11

Humoral deficiencies refers to Antibody deficiencies.
Bacteria: encapsulated; pyogenic: Staphylococcus Aureus, Streptococcus Pneumoniae, H. Influenza
Viral: Enterovirus and Echovirus
Protozoal: Giardia lamblia: Gives Gastroenteritis infections

Question 12

What are the 4 symptoms that Chronic Granulomatous Disease presents with? Elaborate on each.

Answer 12

Suppurative Lymphadenitis: invasion of lymph nodes, resulting in rapid swelling, capsular distension, edema and eventual necrosis

liver abscess - a pocket of pus that forms in the liver due to trauma or infection

Pulmonary infiltrates - a substance denser than air, such as pus, blood, or protein that lingers in the parenchyma of lungs

Burkholderii Septicaemia

Question 13

What type of genetic condition is Chronic Granulomatous Disease and LAD?

Answer 13

Chronic Granulomatous Disease is an X-linked, autosomal recessive disorder.

LAD is an autosomal recessive disorder characterised by immunodeficiency.

Question 14

What does congenital complement deficiency leads to?
Give 2 bacteria that are the most common.

What condition results from C5 - C9 deficiency?

Answer 14

Congenital complement deficiency leads to recurrent pyogenic infections.
Streptococci and HiB are the most common.

C5 - C9 deficiency leads to recurrent meningococcal infections.

Question 15

What are the treatments for complement, antibody and neutrophil deficiencies?

Answer 15

Antibiotic prophylaxis, Antifungal prophylaxis, Replacement antibody (Ig)
Haematopoietic stem cell transplantation

Question 16

Plasmapheresis, Bortizumib and nephrotic syndrome can lead to which condition? Explain.
What is the other medication that can also lead to the same deficiency mentioned?

Answer 16

Secondary B cell deficiency.
Plasmapheresis removes Ig.
Bortizumib kills plasma cells.

Rituximab binds to CD20 found on B cells.

Question 17

What will Eculizumab lead to? State its action.

Answer 17

Eculizumab is a C5 inhibitor and can lead to secondary complement deficiency. High risk of Meningococcal disease.

Question 18

What are the pathogens seen in T cell deficiency?

Answer 18

Bacterial: Intracellular (mycobacteria) and Salmonella
Fungal: Candida, Aspergillus, Cryptococcus Neoformans
Protozoal: Toxoplasma gondii, Cryptosporidia and Pneumocystis carinii
Viral: RSV, Rotavirus, Norovirus, CMV

Question 19

What are T cells required for?

Answer 19

T cells are required against viral and fungal and protozoal infections, also required against intracellular and extracellular bacteria infections.

Question 20

What is SCID? How severe is SCID?

Answer 20

SCID - Severe Combined Immunodeficiency
Combined T and B cell deficiency

Very severe: Death by age 1 year

Question 21

What are the clinical presentations of SCID?

Answer 21

Failure to thrive. Persistent viral gut and lung infections, such as PCP.

Question 22

What is PCP? Give the clinical presentations of PCP

Answer 22

PCP - Pneumocystis Pneumonia, caused by yeast-like fungus.

Presentations: Fever, Night sweats, weight loss, shortness of breath, non-productive cough (too thick to cough up)

Question 23

What does Alemtuzumab leads to?

Answer 23

Secondary B/T cells deficiency

Question 24

Which condition has an onset on 6 to 12 months?

Answer 24

XLA

Question 25

What is NEMO Deficiency? What are the clinical presentations of NEMO Deficiency?

Answer 25

NEMO Deficiency - NF Kappa Essential Modulator Deficiency
Clinical presentations:
1. Susceptible to pyogenic infections
2. Ectodermal Dysplasia
3. Susceptible to Mycobacterial infections
4. Meningitis in first year of life is common
5. Most commonly, presents with pneumococcal infection despite vaccination

Question 26

How is NEMO Deficiency diagnosed?

Answer 26

Raised IgM or IgA but not both. (IgM not as high as classic Hyper IgM syndrome)

Question 27

What governs the peripheral and central tolerance?

Answer 27

Central Tolerance: Thymic deletion

Peripheral Tolerance: Treg

Question 28

Where is AIRE expressed? What is the function of AIRE genes and what will result if there is AIRE deficiency?

Answer 28

AIRE gene is expressed in the thymic medullary stromal cells.
AIRE genes control the expression of some proteins by turning on the peripheral genes in the thymus. Under the control of AIRE proteins, thymic medullary cells express tissue-specific proteins, leading to deletion of autoimmune reactive tissue-specific T cells.
Mutations to AIRE gene leads to APECED (autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy)

Question 29

What is HLH? Explain.

Answer 29

HLH - Haemophagocytic lymphohistiocytosis
Defects in perforin, unable to undergo apoptosis. Hyper activation of macrophages and massive cytokine release, massive hyper-inflammation, BM failure, liver failure and death.