Immuno: Primary Immune Deficiencies 2 Flashcards
Name a defect in stem cells that causes SCID and name the gene that is mutated.
Reticular dysgenesis - adenylate kinase 2 (AK2)
NOTE: this is a mitochondrial energy metabolism enzyme
What is the most common type of SCID?
X-linked SCID
Which mutation is responsible for X-linked SCID?
- Mutation in common gamma chain on Xq13.1
- IL-2 Receptor deficient
- This is a component of many cytokine receptors leading to an inability to respond to cytokines,
- Causing arrest in T and NK cell development and the production of immature B cells
Describe the typical cell counts you would expect to see in X-linked SCID.
- Very low T cells
- Very low NK cells
- Low monocytes
- Normal or increased B cells (but non-functional due to lack of T cells)
- Low immunoglobulin (B cells need signalling from T cells to produce immunoglobulins)
Describe the pathophysiology of ADA deficiency.
Form of SCID
- ADA - adenosine deaminase
- This is an enzyme required by lymphocytes for cell metabolism
- ADA deficiency leads to failure of maturation along any lineage
Describe the typical cell counts you would expect to see in ADA deficiency.
- Very low T cells
- Very low B cells
- Very low NK cells
Describe the clinical phenotype of SCID.
- Unwell by 3 months age (once protection by maternal IgG dissapates)
- Infections of all types
- Failure to thrive
- Persistant diarrhoea
- Unusual skin disease (colonisation of infant’s empty bone marrow by maternal lymphocytes can cause a graft-versus-host disease-like condition)
- Family history of early death
What are the two mechanisms by which CD8+ T cells kill cells?
Perforin and granzyme
Fas ligand
Which cellular insults are CD8+ T cells particularly important in protecting against?
- Viral infections
- Tumour
Outline the immunoregulatory functions of CD4+ T cells.
- Provide help to mount a full B cell response
- Provide help for some CD8+ T cell responses
In which group of syndromes does the thymus gland fail to develop properly.
- 22q11.2 deletion syndromes (e.g. Di George syndrome)
- This is characterised by failure of development of the pharyngeal pouch
What are the main clinical features of 22q11.2 deletion syndromes?
- Facial abnormalities (high forehead, low set ears, cleft palate, small mouth and jaw)
- Underdeveloped parathyroid gland (resulting in hypocalcaemia)
- Oesophageal atresia
- Underdeveloped thymus
- Complex congenital heart disease
What are the immunological consequences of an underdeveloped thymus gland?
- Normal B cell count
- Low T cell count
- Homeostatic proliferation with age (T cell numbers increase with age as thymus continues to develop)
- Immune function is mildy impaired and tends to improve with age
What condition is caused by a deficiency of MHC Class II? Briefly outline its pathophysiology.
- Bare lymphocyte syndrome (BLS) type 2
- Deficiency of MHC Class II means that CD4+ T cells cannot be selected in the thymus leading to CD4+ T cell deficiency
Which defect leads to Bare lymphocyte syndrome?
Defects in the regulatory proteins involved in expression of class II genes:
- Regulatory factor X
- Class II transactivator
Describe the typical cell counts that you would expect to see in Bare Lymphocyte syndrome type 2.
- Normal CD8+
- Very low CD4+
- Normal B cell count
- Low IgG
NOTE: BLS Type 1 is a similar condition caused by failure of expression of HLA Class I