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.
List 3 forms of leukocytosis.
State the type of infection associated with each form.
1 - Neutrophilia - associated with bacterial infection.
2 - Lymphocytosis - associated with viral infection.
3 - Eosinophilia - associated with parasitic infection or allergy.
What are type 1 cytokine defects?
Defects of defence against intracellular bacteria.
List 3 signalling molecules involved in type 1 cytokine defects.
1 - IL-12.
2 - IFN-gamma.
3 - TNF-alpha.
What type of infection is associated with type 1 cytokine defects?
Atypical mycobacterial infections:
1 - Mycobacterium avium.
2 - BCGosis.
List 2 treatments for atypical mycobacterium infections due to type 1 cytokine defects.
1 - Antibiotics and IFN-gamma injection.
2 - Bone marrow transplantation.
What type of infections are typical with classical complement deficiencies?
Encapsulated bacterial infections.
What type of infections are typical with alternative complement deficiencies?
Neisseria infections (a genus of bacteria).
What is immune complex disease?
Give an example of a cause of immune complex disease.
- A group of inflammatory conditions characterised by antigen–antibody deposition and attendant activation of complement.
- Can be caused by classical complement deficiencies.
What type of infections are typical with defects of the membrane attack complex (MAC)?
Neisserial and other pyogenic (pus-forming) infections.
What inheritance pattern does C1 esterase inhibitor deficiency show?
Autosomal dominant.
Describe the pathophysiology of C1 esterase inhibitor deficiency.
Lack of C1 esterase inhibitor causes sudden uncontrolled activation of complement and bradykinin pathways.
List 3 symptoms of C1 esterase inhibitor deficiency.
1 - Non-itchy oedema.
2 - Acute abdomen (abdominal pain).
3 - Asphyxiation.
Which types of antibody do B cells express once in the circulation before class switching / exposure to antigen?
IgM and IgD.
What is common variable immune deficiency (CVID)?
An umbrella term for antibody deficiencies where there is a problem of terminal differentiation and high affinity antibody production.
Give an example of a cause of Hyper-IgM syndrome.
A defect in the CD40 ligand on T cells (or CD40 on B cells).
What would be visually abnormal in a biopsy of a lymph node from a patient with hyper-IgM syndrome?
There would be no germinal centres.
What might hypotrophic tonsils indicate?
A decrease in lymphoid cell production, e.g. due to a T or B cell defect such as with hyper-IgM syndrome.
List 6 secondary causes of antibody deficiency.
1 - Marrow suppression, e.g. with a myeloma / leukaemia.
2 - Immunosuppression due to steroids.
3 - Immunosuppression due to cytotoxic drugs, e.g. chemotherapy.
4 - Increased loss due to nephrosis.
5 - Increased loss due to enteropathy.
6 - Increased loss due to rituximab use (a drug which targets CD20 for autoimmune diseases and cancers).
What is the function of CD20?
It plays a role in B cell development and differentiation into plasma cells.
List 2 clinical manifestations of antibody deficiency.
1 - Infection by encapsulated pyogenic bacteria.
2 - Respiratory tract infections.
List 2 encapsulated pyogenic bacteria.
1 - Streptococcus pneumoniae.
2 - Haemophilus influenzae B.
List 5 respiratory tract infections / complications of respiratory tract infections.
1 - Otitis media.
2 - Sinusitis.
3 - Bronchitis.
4 - Pneumonia.
5 - Bronchiectasis.
List 2 treatments of antibody deficiency.
1 - Immunoglobulin G replacement therapy.
2 - Prophylactic antibiotics.
Given the importance of IgA for mucosal immunity, why are most people with IgA deficiency asymptomatic?
Because there is a compensatory increase in other types of antibody production.
With which other antibody deficiency is IgA deficiency associated?
List 2 complications this might cause.
- IgG2.
Complications might include:
1 - Increased susceptibility to infection.
2 - Autoimmunity.
List 2 primary causes of T cell deficiency.
1 - Severe combined immunodeficiency (failure to produce lymphocytes).
2 - DiGeorge syndrome (failure of the thymus to develop).
List 3 secondary causes of T cell deficiency.
1 - Immunosuppression for preventing graft rejection or treating autoimmune disease.
2 - HIV.
3 - Lymphoid malignancies.
List 4 symptoms of T cell deficiency.
1 - Severe bacterial, viral and fungal infections.
2 - Failure to thrive.
3 - Diarrhoea, especially with Cryptosporidium infection (a genus of parasites).
4 - Pneumonia, especially with Pneumocystis carinii (a protozoan).
List 5 treatments and management techniques for T cell deficiency.
1 - Haematopoietic stem cell transplant (HSCT).
2 - Immunoglobulin replacement therapy.
3 - Prophylactic antibodies such as septrin.
4 - Irradiation of blood products.
5 - Avoidance of live vaccines such as BCG and MMR.
