Immunodeficiency Flashcards
Give 2 conditions that are a result of congenital antibody deficiency
XLA - X-linked Agammaglobulinaemia
Transient Hypogammaglobulinaemia of Infancy (young babies 6 - 7 months old)
Who is affected by Transient hypogammaglobulinaemia of Infancy?
Describe this condition.
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.
Who is affected by XLA? Describe this condition.
X-linked Agammaglobulinaemia affects mostly males.
There is very few B cells, and hence, a lack of antibodies.
Describe the defect in Chronic Granulomatous Disease
Defects in killing mechanism in phagocytosis.
There is defective oxidative burst –> Unable to produce toxic oxygen reactive compounds
What does LAD stands for?
Describe the defect in LAD
LAD - Leukocyte Adhesion Deficiency
Defect in adhesion molecules, affecting chemotaxis (failure of migration)
What is patients with Chronic Granulomatous Disease very susceptible to?
Coagulase positive bacteria, such as Staphylococci and Fungal infections
When is the onset of XLA?
6 - 12 months old
What are the 3 classic presentations of LAD?
Recurrent bacterial infections, defect in neutrophil adhesion and delay in umbilical cord sloughing
How many types of LAD are there? Which type is the most common?
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
What are the pathogens seen in phagocytic deficiencies?
Bacteria: Staphylococcus and Pseudomonas
Fungal: Candida and Aspergillus (mould)
What are humoral deficiencies?
What are the pathogens seen in humoral deficiencies?
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
What are the 4 symptoms that Chronic Granulomatous Disease presents with? Elaborate on each.
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
What type of genetic condition is Chronic Granulomatous Disease and LAD?
Chronic Granulomatous Disease is an X-linked, autosomal recessive disorder.
LAD is an autosomal recessive disorder characterised by immunodeficiency.
What does congenital complement deficiency leads to?
Give 2 bacteria that are the most common.
What condition results from C5 - C9 deficiency?
Congenital complement deficiency leads to recurrent pyogenic infections.
Streptococci and HiB are the most common.
C5 - C9 deficiency leads to recurrent meningococcal infections.
What are the treatments for complement, antibody and neutrophil deficiencies?
Antibiotic prophylaxis, Antifungal prophylaxis, Replacement antibody (Ig)
Haematopoietic stem cell transplantation
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?
Secondary B cell deficiency.
Plasmapheresis removes Ig.
Bortizumib kills plasma cells.
Rituximab binds to CD20 found on B cells.
What will Eculizumab lead to? State its action.
Eculizumab is a C5 inhibitor and can lead to secondary complement deficiency. High risk of Meningococcal disease.
What are the pathogens seen in T cell deficiency?
Bacterial: Intracellular (mycobacteria) and Salmonella
Fungal: Candida, Aspergillus, Cryptococcus Neoformans
Protozoal: Toxoplasma gondii, Cryptosporidia and Pneumocystis carinii
Viral: RSV, Rotavirus, Norovirus, CMV
What are T cells required for?
T cells are required against viral and fungal and protozoal infections, also required against intracellular and extracellular bacteria infections.
What is SCID? How severe is SCID?
SCID - Severe Combined Immunodeficiency
Combined T and B cell deficiency
Very severe: Death by age 1 year
What are the clinical presentations of SCID?
Failure to thrive. Persistent viral gut and lung infections, such as PCP.
What is PCP? Give the clinical presentations of PCP
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)
What does Alemtuzumab leads to?
Secondary B/T cells deficiency
Which condition has an onset on 6 to 12 months?
XLA
What is NEMO Deficiency? What are the clinical presentations of NEMO Deficiency?
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
How is NEMO Deficiency diagnosed?
Raised IgM or IgA but not both. (IgM not as high as classic Hyper IgM syndrome)
What governs the peripheral and central tolerance?
Central Tolerance: Thymic deletion
Peripheral Tolerance: Treg
Where is AIRE expressed? What is the function of AIRE genes and what will result if there is AIRE deficiency?
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)
What is HLH? Explain.
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.
