Primary immune deficiencies - parts 1 Flashcards
What is the major hallmark for an immune deficiency
Recurrent infections
What is the Acronym used to identify immune Deficiency
- S - Serious infections - unresponsives to oral antibiotics
- P - Persistent infections - chronic infections, early damage
- U - Unusual infections - unsaul organism and sites
- R - Recurrent infections - Two major or one major and one recurrent minor infections in one year
What are other features that may suggest immune deficiency
- Weight loss
- Failure to thrive
- Chronic Diarrhoea
- Severe skin rashes - Eczema
- Mouth ulcers
- Unusual autoimmune disease
- Family history
How do we classify immune deficiencies in to categories
- Primary - rare, >200 diseases
- Secondary - common, subtle, often involves more than 1 part of the immune system
What conditions are associated with secondar immune deficiency
What are the compenents of the innate immune system
- Cells
- Neutrophils
- Macrophages
- Mast cells
- NK cells
- Proteins
- Complement
- Acute phase proteins
- Cytokines
What are the functions of the innate immune system
- Rapid clearance of organism
- Stimulates the aquired immune system
- Buys time while the aquired immune system is being activated
What are the components of the aquired immune system
- Cells
- B lymphocytes
- T lymphocytes
-
Proteins
1. Antibodies
What are the features of the aquired immune responce
- Aquired as an adaptive responce to an antigen
- Not gentically encoded
- Responsive is unlimited all molecules ever
- High specific
- Immunological memory
Give examples of phagocytes
- Neutrophils
- Monocytes/macrophages
What are the functions of phagocytes
- Initiation and amplification of the inflammatory responce
- Scavenging of cellular and infectious debris
- Ingest and kill microorganisms
- Produce inflammatory molecules which regulate other components of the immune system
- Resolution and repair
- Bacteria and fungi
what are the clinical feature sof phagocyte deficiencies
- Recurrent infections
- Organisms
- Common bacteria: Staph aurous
- Unusual: Burkholderia cepacia
- Mycobateria: atypica and TB
- Fungi: candida and spergillus
What can go wrong in the cycle of a neutrophil which can lead to an immune deficiency
What happens when theres is a phagocytic defect in phagocyt production, mobilisation and recruitment
Failure to produce neutrophils due to:
- Failure of stem cells to differentiate along myeloid lineage
- Primary defect: Recticular dysgenesis
- Secondary defect: after stem cell transplantation
- Neutrophil maturation specific failure
- Kostmann syndrome: severe congenital neutropaenia
- Cyclic neutropaenia: Episodic every 4-6 weeks
What is Kostmaan Syndrome
- Rare autosomal recessive disorder: Defect in specific neutrophil maturation
- Causes severe chronic neutropenia - <200 ul
What are the clinical presentation of Kostmann syndrome
Infections - within 2 weeks after birth
- Recurrent bacterial infections
- Systemic or localised infection
Non specific features: fever, irritability, oral ulcerations and failure to thrive
What is the managment of Kostmann syndrome
Supportive treatments
- Prophylactic antibodies
- Prophylactic antifungals
Definitive treatment
- Stem cell transplantation : as defect is in neutrophil precursor
- Granulocyte colony stimulating factor G-CSF - growth factor to assist maturation
What would be expected if patient had defect in endothelial adheison molecule binding of neutrophil
- Clinical features - Recurrent bacterial and fungal infections
- Blood count - Very high neutrophil counts
- Site of infection: Deep tissue infections with no pus formation
What is leukocyte adehsion Deficiency
- Failure to recognise activation markers expressed on endothelial cells
- Neutrophils are mobilised but cannot exit the bloodstream
- Rare primary immunodeficiency
- Genetic defect in leukocyte intigrins
- Clinical picture: marked leukocytosis with localised fungal and bacterial infections which are hard to detect
How do pagocytes recognise a pathogen
PRRs: PAMPS
What types of defects can arise in phagocyt recognition of pathogen
- Direct recognistion defect
- Indirect recognistion defect
What are the types of pathogen recognistion receptors on phagocytes- Direct recognistion
- Toll like receptors
- Scavenger receptors
- Lectin receptors
Therse can recognise - bacterial sugars and lipopolysaccharides
How do phagocytes carry out indirect recognition
Opsonins
- These molecules act to enhace phagocytosis by binding to pathogen
- Complement C3b, IgG, C reactive protien
Binding to receptors on phagocyte surface
- FC receptor expressed on phagocyte - allows binding of antibody that is bound to an antigen
- Complement receptor 1 - CR1 on phagocytes - bind complement fragments which are also bound to antigens
What are the defects in recognition
- Defect in opsonin receptors - defective phagocytosis - redunancy means that this doent cause significant disease
- Defect in production of complement or antibodies- inefficient opsoniation - Functional defect of phaocytosis
