Immunodefiencies Flashcards
What is immunodeficiency?
Caused by defects in one or more components of the immune system
May lead to serious and often fatal syndromes or diseases
Collectively called immunodeficiency diseases
Classified as primary and secondary immunodeficiencies
Data difficult to estimate as no current screening program at birth exists
What characterises primary (congenital) immunodeficiencies?
A condition resulting from a genetic or developmental defect.
The defect is present from birth and is mostly inherited
May not be clinically observed until later in life.
Abbreviated as PID
What characterises secondary immunodeficiencies?
Originate as a result of malnutrition, cancer, drug treatment or infection
By far the most well-known and commonly occurring is AIDS
What are the clinical features of primary immunodeficiency?
Recurrent infections (normal: >6-8 URI/year for the 1st 10 years; 6 otitis media(infection of the year) and 2 gastroenteritis/year for the 1st 2-3 years)
Severe infections, unusual pathogens (Aspergillus, Pneumocystis), unusual sites (liver abscess, osteomyelitis)
What can be the cause of primary immunodeficiencies?
These deficiencies may effect either the innate or adaptive immune function
Defects in innate immunity are generally caused by a defect in phagocytic or complement function
Lymphoid cell disorders may affect T cells or B cells or both (combined immunodeficiency.
What is the B cell disorder, X-linked agammaglobulinaemia (Bruton’s disease)?
Also known as Bruton’s disease
Defect in BTK gene (X chromosome)
- this btk gene Encodes Bruton’s tyrosine kinase
so there is a Block in B-cell development (stop at pre-B cells)
patients present with Recurrent severe bacterial infections
2nd half of first year (lung, ears, GI)
Autoimmune diseases (35% of patients)
above summarised in a sentence:
X-linked agammaglobulinaemia (Bruton’s disease) is a defect in Bruton’s tyrosine kinase (Btk) protein which is needed for pre-B cell receptor signalling. The result block in B-cell development at pre-B stage
How is X-linked agammaglobulinaemia (Bruton’s disease) diagnosed and treated?
Diagnosis: (using flow cytometry and immunoelectrophoresis)
B cells absent / low; plasma cells absent
All immunoglobulins absent / very low
T cells and T cell-mediated responses normal
Treatment:
IVIg: 200-600mg/kg/month at 2-3 wk intervals
or subcutaneous Ig weekly
prompt antibiotic therapy (URI /LRI)
Do not give live-attenuated vaccines
What is Severe combined immunodeficiency?
SCIDs- affect both T cells and B cells
Lymphocyte subsets: T, B, NK (% and numbers) result low total lymphocyte count meaning SCID sign
Pattern: very low/absent T; normal/absent B, sometimes also absent NK (γ-chain defect affecting IL-15 receptor)
Immunoglobulins are low
T cell function reduced proliferation and cytokine production
What does treatment include for SCID?
What are the statistics for the outcomes of this?
Isolation to prevent further infections
Do not give live vaccines
Blood products from CMV-negative donors
IV Ig replacement (because they don’t have enough antibodies)
Infection prophylaxis
Bone marrow/haematopoietic stem cell transplant
Gene therapy (for ADA and γ-chain genes)
Outcome:
Dependent on promptness of diagnosis
Survival >80% (early diagnosis, good donor match, no infections pre-transplant)
Survival <40% (late diagnosis, chronic infections, poorly matched donors)
Regular monitoring post Bone Marrow Transplant => engraftment
What is DiGeorge Syndrome? What is the best treatment for it?
Thymic hypoplasia due to 22q11 deletion
Results in failure of development of 3rd+4th pharyngeal pouches
Complex array of developmental defects
Dysmorphic face: cleft palate, low-set ears, fish-shaped mouth
Hypocalcaemia, cardiac abnormalities
Variable immunodeficiency ( Complete DiGeorge- absent thymus Incomplete DiGeorge - reduced thymus. These result in absent or partial T cell development
Best treatment: thymus transplantation (GOSH)
What is Wiskott-Aldrich syndrome?
X-linked
Defect in WASP (protein involved in actin polymerization. T cells remodel cytoskeleton for correct signalling)
characterised by thrombocytopenia, eczema, infections
Progressive immunodeficiency (T cell loss)
Progressive ↓ T cells; ↓ T cell proliferation
Antibody production is low because of the problems associated with T cells (↓ IgM, IgG; high IgE, IgA)
How can Chronic granulomatous disease (phagocyte defect) be diagnosed?
Nitro blue tetrazolium reduction test (looking at NADP levels)
or more accurately:
doing a Dihydrorhodamine assay
What is Chediak-Higashi syndrome?
Phagocyte defect
Characteristics:
Rare genetic disease
Defect in LYST gene (regulates lysosome traffic) (so lysosomes cannot fuse with phagosome to produce phagolysosomes)
Neutrophils have defective phagocytosis
Repetitive, severe infections
Diagnosis:
Decreased number neutrophils
Neutrophils have giant granules
Summarise treatment for Primary immunodeficiencies
Aims.
- Minimise/control infection
Prompt treatment of infection
Prevention of infection: isolation, antibiotic prophylaxis, vaccination (not live vaccines)
Nutrition
Replace defective/absent component of the immune system
(Bone marrow, stem cell or thymus transplant)
Gene therapy
What are the main treatment options for Secondary immunodeficiencies? (mostly AIDS)
HAART-Highly Active Antiretroviral Therapy (stops progression of HIV into AIDS)
Also PrEP (stops transmission)-
Pre-exposure prophylaxis is the use of medications used to prevent the spread of disease in people who have not yet been exposed to a disease-causing agent, usually a virus. The term typically refers to the specific use of antiviral drugs as a strategy for HIV/AIDS prevention
