L25 - Immunodeficiencies Flashcards
What is an 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
What are 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 are 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 10 warning signs that could indicate PID?
Failure of a baby or child to gain weight or grow normally (failure to thrive)– there are many reasons for failing to thrive and PIDs are arare but important cause
The need for intravenous (IV) antibiotics to treat infections– the useof IV antibiotics indicates a serious infection and infants, childrenand adults should be considered for PID
A history of a PID in the family – family members should at least have a primary screen (full blood count and serum immunoglobulins)
Four or more new ear infections withinone year
Two or more new sinus infections withinone year
Two or more months on at leasttwo antibiotics at a stretch with little effect
Two or more pneumonias withinthree years
Having frequent deep skin or organ abscesses
Persistent thrush or fungal infection (more thansix months) on the skin or elsewhere
Two or more deep-seated infections, including septicaemia (blood poisoning), withinthree years.
What may PIDs affect?
These deficiencies may affect either the innate or adaptive immune function
What may cause PIDs?
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)
Describe X-linked Agammaglobulinaemia as a B-cell PID disorder?
Also known as Bruton’s disease
Defect in BTK gene (X chromosome)
Encodes Bruton’s tyrosine kinase
Block in B-cell development (stop at pre-B cells)
Recurrent severe bacterial infections
2nd half of first year (lung, ears, GI)
Autoimmune diseases (35% of patients)
Describe the diagnosis and treatment of X-linked Agammaglobulinaemia?
Diagnosis:
- 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
Describe Severe Combined Immunodeficiency (SCID)?
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
Describe some causes for Severe Combined Immunodeficiency (SCID)?
Common cytokine receptor γ-chain defect (signal transducing component of receptors for IL-2, IL-4, IL-7, IL-9, IL-11, IL-15, IL-21)
IL-7 needed for survival T cell precursors resulting in defective T cell development and concomitant lack in B cell help (low antibodies)
RAG-1/RAG-2 defect => no T and B cells
ADA (adenosine deaminase deficiency); => accumulation of deoxyadenosine & deoxy-ATP which is toxic for rapidly dividing thymocytes
Describe the treatment for Severe Combined Immunodeficiency (SCID)?
Isolation to prevent further infections
Do not give live vaccines
Blood products from CMV-negative donors
IV Ig replacement
Infection prophylaxis
Bone marrow/haematopoietic stem cell transplant
Gene therapy (for ADA and γ-chain genes)
Describe DiGeorge Syndrome?
Thymic hypoplasia due to 22q11 deletion
Results in failure development 3+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
Describe the treatment for DiGeorge Syndrome?
Treatment: thymus transplantation (GOSH
Describe Wiskott-Aldrich Syndrome
X-linked
Defect in WASP (protein involved in actin polymerization. T cells remodel cytoskeleton for correct signalling)
Thrombocytopenia, eczema, infections
Progressive immunodeficiency (T cell loss)
Progressive ↓ T cells; ↓ T cell proliferation
Antibody production (↓ IgM, IgG; high IgE, IgA
Describe Chronic granulomatous disease
Defective oxidative killing of phagocytosed microbes; mutation in phagocyte oxidase (NADPH) components
Formation of granulomas
