Immunodeficiency Flashcards
List 4 factors that contribute to resistance to infection.
1 - Age.
2 - Previous exposure / vaccination.
3 - Nutrition.
4 - Disease.
What is the Lubeck disaster of 1926?
- An incident where 251 infants were immunised with a virulent strain of Mycobacterium tuberculosis instead of Mycobacterium bovis BCG.
- 1/3 died.
List 3 consequences of immunodeficiency.
1 - Reduced defence to infection.
2 - Reduced tumour surveillance, so greater likelihood of tumour growth.
3 - Reduced tolerance, so greater likelihood of autoimmunity.
List 4 red flags for immunodeficiency.
1 - Increased frequency of infection.
2 - Unusual organism causing the infection.
3 - Increased severity of infection.
4 - Poor outcome of infection (e.g. organ damage or mortality).
Describe the aetiology of immunodeficiency.
- Primary (genetic). Often in life but also in common variable immunodeficiency (CVID) in adulthood.
- Secondary (acquired). Increasing likelihood with age and comorbidities.
List 2 factors which determine the therapy given for immunodeficiency.
1 - Whether the cause of the defect is quantitative or qualitative.
2 - Whether the cause of the defect is primary or secondary.
List the characteristics of an immunodeficiency of neutrophils.
Type of infection:
1 - Extracellular bacteria.
2 - Fungi.
Site of infection:
1 - Skin.
2 - Mucosal surfaces.
Age of presentation:
- First month of life.
- This is true for both primary and secondary causes of immunodeficiency.
List the characteristics of an immunodeficiency of B cells.
Type of infection:
- Encapsulated bacteria.
Site of infection:
- Respiratory tract.
Age of presentation:
1 - At 6 months of gestation when the concentration of maternal immunoglobulin falls.
2 - During adulthood.
*This is true for both primary and secondary causes of immunodeficiency.
List the characteristics of an immunodeficiency of T cells.
Type of infection:
1 - Intracellular bacteria.
2 - Viruses.
3 - Fungi.
Site of infection:
1 - Respiratory tract.
2 - GI tract.
Age of presentation:
- First month of life.
- This is true for both primary and secondary causes of immunodeficiency.
List 4 differences between primary and secondary immunodeficiencies.
1 - Primary immunodeficiencies are rarer.
2 - Defects of primary immunodeficiencies are often more discrete, i.e. a single gene, whereas defects of secondary immunodeficiencies are often broad.
3 - The infectious susceptibility is more well understood for primary immunodeficiencies.
4 - Tests to investigate immune function are more well established with primary immunodeficiencies.
List 7 risk factors that predispose towards secondary immunodeficiencies.
1 - Immunosuppressive therapies.
2 - Steroids.
3 - Cancer.
4 - Autoimmunity.
5 - Advanced age.
6 - Poor nutrition.
7 - Impaired barrier defence.
Describe 4 primary barrier defects.
1 - Kartagener’s syndrome. A defect in cilia leading to bronchiectasis.
2 - Cystic fibrosis. A defect in salt transfer resulting in viscous mucous secretions.
3 - Ureteric reflux. A defect in ureteric flow.
4 - Eczema. A defect in filaggrin (a protein involved in epidermal homeostasis).
List 4 acquired barrier defects.
1 - Barrier defects due to surgery.
2 - Bronchiectasis (widened bronchi causing an excess build-up of mucus).
3 - GI inflammation.
4 - Poor dentition.
List 8 neutrophil defects.
Separate the defects by primary / secondary and quantitative / qualitative.
Primary quantitative:
1 - Cyclical neutropenia.
Secondary quantitative:
2 - Autoimmunity.
3 - Chemotherapy.
4 - Leukaemia.
Primary qualitative:
5 - Defects of migration, e.g. leukocyte adhesion deficiency (LAD).
6 - Defects of respiratory burst, e.g. chronic granulomatous disease (CGD).
Secondary qualitative:
7 - Prednisolone.
8 - Defects of metabolism.
Describe the pathophysiology of leukocyte adhesion deficiency (LAD).
- Normally, beta 2 integrins bind ICAM1 on endothelial cell surfaces to cause tight binding.
- Selectins are responsible for loose binding, and facilitate the rolling of neutrophils over endothelial surfaces.
- With leukocyte adhesion deficiency (LAD), the beta 2 integrins are dysfunctional, therefore neutrophils are able to bind loosely and roll over the endothelium but are not able to bind tightly and extravasate.
What type of infections are common in individuals with chronic granulomatous disease (CGD)?
1 - Catalase positive bacterial infections.
2 - Fungal infections, especially aspergillus.
List 2 signalling molecules involved in the functioning of toll-like receptors.
1 - NEMO.
2 - IRAK4.
List 3 drug causes of secondary cytokine deficiency.
Describe the uses of these drugs.
1 - Anti-TNF alpha (used to suppress immune activation during fevers).
2 - Anti-IL-6 (used to reduce CRP production from the liver and in turn suppress complement and macrophage activity).
3 - Anti-IL-1 (used to suppress immune activation).
List 3 characteristics of a fever.
1 - Increased blood pressure.
2 - Rigors.
3 - Anorexia.
