Primary Immunodeficiency 2 Flashcards
Outline the life cycle of a T lymphocyte.
- Produced from stem cells in the bone marrow.
- Naive T cells exported to thymus, selection takes place
- Mature T cells travel to lymphoid tissue and follicles, where they reside.
Two main classifications of T cells?
- CD4+
2. CD8+= Cytotoxic T cell
Function of CD4+ cells?
- Immunoregulatory functions
- Stimulate CD8 & B cells
- Produce cytokines - Recognise peptides on MHC class II molecules
Function of CD8+ cells?
- Recognise peptides on MHC class I molecules
- Directly kill pathogens via perforin release
- Important in viral and tumour defence
What are the functions of B lymphocytes? (2)
Antibody production & presentation
What are the two types that B cells differentiate into?
- Memory B cells
2. Plasma cells that produce antibodies
Functions of antibodies? (4)
- Identify pathogens
- Stimulate other components of immune system (complement, NK, phagocytes)
- Neutralise toxins
- vital for Bacterial infection defence
What is reticular dysgenesis?
Defect of haemopoetic stem cells which causes lack of production of
- Neutrophils
- Macrophages
- Lymphocytes
- Platelets
Fatal if not corrected with bone marrow transplant
What happens in severe combined immunodeficiency (SCID)?
Failure to produce lymphocytes
Some common clinical presentations of SCID?
- Recurrent infections
- Persistent diarrhoea
- Failure to thrive
- Unusual skin disease (graft vs host disease)
Dont get acutely unwell until 3 months of age because of maternal IgG in colostrum
What is the commonest form of SCID? (genetic)
X linked
What is the result of X linked SCID?
IL2 mutation
- Failure to produce T cells
- Immature B cells produced
Treatment for SCID?
- Prophylactic- Antibiotics, antifungals, IV immmunoglobin.
2. Definitive- stem cell transplant
SCID is suitable for gene therapy. T/F?
True
What happens in Digeorge syndrome?
Failure in thymic development- Developmental defect of 3/4th pharyngeal pouch
What are the clinical features of Digeorge’s? (5)
- Congenital heart defects
- Cleft palate
- T lymphopenia
- Hypothyroidsim & hypocalcaemia
5 Psychiatric disorders, developmental delay
Digeorge’s is caused due to a deletion at chromosome 22q11. T/F?
True
Digeore syndrome makes someone susceptible to what?
Recurrent infections- bacterial, fungal and viral
What do investigations reveal in Digeorge? (immune cell count)
- Absent or low T cell count
- Normal/High B cell- Low IgG, E, A
- Normal NK
Management Digeorge’s?
- Correct metabolic/cardiac issue
- Prohylactics
- Aggressive antibiotics
- Ig replacement therapy
What are the disorders of T Cell effector functions?
- Cytokine production
- T-B cell communication
- Cytotoxicity
What are the two main T cell effector disorders?
- IL12 Deficiency
2. IFNy deficiency
Clinical presentations of T cell effector disorders? (3)
- Recurrent infections- TB, atypical mycobacteria, BCG, aspergillus
- Malignancies at young age
- Autoimmune diseases
What are the investigations for T cell deficiencies?
- 1st line
- WBC
- Serum immunoglobins, protein electrophoresis
- Quantify sub lymphocyte numbers - 2nd line
- Test T cell activation & proliferation
- Additional lymphocyte lineage test
- HIV test
