Flashcards in Immunology - Primary Immunodeficiencies 2 Deck (19):
What is the life cycle of a T lymphocyte?
Differentiate from haematopoetic stem cells in the bone marrow and then move to the thymus as pre-T cells. Only 10% full mature and survive and then they enter circulation and reside in lymph nodes and secondary lymph tissues. Slide 7
What is the normal B lymphocyte development?
Pro B cells
Pre B cells
IgM B cells that can go through immunoglobin class switch. Slide 12
What would happen if there were defects of haemopoetic stem cells?
Recticular Dysgenesis meaning there will be failure of lymphocyte production too. Slide 16
What is SCID and what does it mean?
Severe Combined Immunodeficiency Disease.
There are defects of lymphoid precursors so lymphocytes are not produced. Slide 17
What is the clinical phenotype of SCID and why would they be unwell at roughly 3 months of age?
Failure to thrive
Infections of all types
Unusual skin disease
FH of early infant death.
They would be unwell at 3 months due to no weaning supply of IgG from mother and decreased IgA in breast milk. Slide 18
What is Transient Hypogammaglobulinamia of infancy?
When the IgG and IgA from mother to child is reduced and the baby starts producing its own but is still at low levels. Slide 19
What are some causes of SCID?
Deficiency of cytokine receptors
Deficiency of signalling molecules
Defective receptor rearrangements. Slide 20
What is the clinical phenotype of X-linked SCID?
Very low or absent T cells due to IL-2 being a T cell growth factor.
Normal/increased B cells
Poorly developed thymus. Slide 21
What is the treatment for SCID?
No live attenuated vaccines
Definitive treatment of stem cell transplant
What are the possible outcomes for someone who has no thymus or an small thymus?
Can get DiGeorge Syndrome which causes physical disfigurations or low set ears, small mouth/jaw.
Can cause hypocalcaemia, congenital heart disease and T cell lymphopenia. Slide 25
What causes DiGeorge syndrome and what are the clinical signs from lab investigations?
Developmental defect of 3rd/4th pharyngeal pouch.
Absent or decreased number of T cells
Normal/increased B cells but do not work as well due to lack of activation from T cells
Normal NK cell numbers.
What happens if there is something wrong with T lymphocyte activation and effector function?
Can cause problems with:
Cytokine production, cytotoxicity
and T to B cell communication. Slide 30
If there is a deficiency through T cells in their cytokine production, what problems can it cause?
IL-12 deficiency meaning macrophages won't get stimulated by INFgamma and the patient will get many infections e.g. TB. Slide 32
What would happen if there was a failure in normal apoptosis?
Autoimmune Lymphoproliferative Syndromes.
The patient would get recurrent and opportunistic infections and have malignancies at young age. Slide 34
What is the line of management of T cell deficiency investigations?
1st line: total white cell count
2nd line: functional tests of T cell activation and proliferation.
HIV test is essential. Slide 35
What happens if there is a fault in the B cell maturation?
Bruton's X-linked hypogammaglobulinaemia.
Where Pro B cells cannot progress on to Pre B cells. Slide 39
What other B cell maturation defects can their be?
Failure of costimulation from the T folicular helper cells.
Failure of IgA production (severe IgA deficiency).
Failure of production of IgG antibodies. Slide 43
What are clinical features of B cell deficiencies?
Antibody mediated autoimmune disease. Slide 44