T1 L21: Immunodeficiency diseases Flashcards
What is primary immunodeficiency syndrome (PID)?
Immune defect that is intrinsic to the immune system
Often genetic but not always
What is secondary immunodeficiency?
Immune defect secondary to another disease process
Very common
Eg. malignancies, metabolic, drugs, infection
Which cells make up the adaptive immune system?
B and T-cell
What are combines immunodeficiencies?
Those affecting antibody production and T-cells
What are the manifestations of immunodeficiency?
- Recurrent infections
- Immune dysregulation Eg. uncontrolled inflammation, autoimmune disease
What is immunosenescence?
A combination of age-related factors that cause a greater susceptibility to infection and reduced response to vaccination
What are some immunological aspects of immunosenescence?
- Thymic involution
- Telomere shortening in the stem cells reducing quality and quantity of lymphocyte output
- Reduced T and B-cell receptor diversity
- Reduced vaccine responses
- Reduced neutrophil function
- Reduced self-tolerance
What is thymic involution?
Shrinking of the thymus with age
What factors make the elderly more susceptible to infection?
- Reduced immunity, motility, nutrition, wound healing, physiological reserve
- Increased co-morbidities
What is bronchiectasis?
When the walls of the bronchi are thickened from inflammation and infection
It causes irreversible lung damage
What causes antibody deficiency?
- Transient hypogammaglobulinemia of infancy
- Loss of IgG through nephrogenic syndrome or excessive burns
- Impaired production of IgG due to immunosuppressive drugs
- X-linked agammaglobulinemia
- X-linked hyper-IgM-syndrome
What is transient hypogammaglobulinemia of infancy?
In healthy infants, there is a period at about 6 months old when there is relative antibody deficiency
This is a physiological state but can be correlated with increased infections
When do infants with immunodeficiency present?
After 3-6 months because up until then they are protected by maternal IgG
What is X-linked agammaglobulinemia?A
Also known as Bruton’s disease
Caused when there is no signalling via Bruton’s tyrosine kinase (btk) which is required for transduction at pro-B stage of B-cell maturation . It causes maturation arrest
What is maturation arrest?
When there is no heavy chain rearrangement, no B-cells leave the bone marrow, and there is no immunoglobulin production
What is X-linked hyper-IgM-syndrome?
A CD40L deficiency that causes failure of B-cell maturation from primary to secondary. It results in low IgA and IgG but raised or normal IgM
This results in recurrent bacterial infections at about 3-6months old
What is cellular immunodeficiency?
Affects CD4 T-cells
Manifests with opportunistic, viral, fungal, and mycobacterial infections
The secondary cause of this is HIV infection
What is severe combined immunodeficiency (SCID)?
Absent T-cell and B-cells may be present but they’re non functional
What are the causes OF severe combined immunodeficiency (SCID)?
- Common gamma chain deficiency
- JAK3 deficiency
- RAG1/2 deficiency
What are the characteristics of common gamma-chain deficiency as a cause of SCID?
It’s X-linked SCID. The function of the gamma chain is to be part of a membrane receptor for several cytokines, some of which are needed for T-cell maturation
There are no T-cell and the B-cell that are there are non-functional
What are the characteristics of JAK3 deficiency as a cause of SCID?
It’s an autosomal recessive SCID. JAK3 is used downstream of the common gamma chain so deficiency prevents signalling
There are no T-cell and the B-cell that are there are non-functional
What are the characteristics of RAG1/2 deficiency as a cause of SCID?
It’s an autosomal recessive SCID . RAG1/2 are needed for somatic recombination between V(D)J segments
No RAG1/2 means there are no T or B-cell receptors
How is SCID treated?
Stem cells are harvested from HLA-matched donors and given to the patient into the bone marrow
This results in reconstitution of T and B-cells
What is DiGeorge syndrome?
A failure migration of the 3rd/4th brachial arches
Most patients have micro-deletions in chromosome 22 resulting in absent parathyroids, cleft palate, congenital heart defects, thymic aplasia
Presentation: immunodeficiency, autoimmunity
What is terminal complement deficiency?
A deficiency of terminal complement components C5-C9 leading to specific susceptibility to Neisseria species
It can be diagnosed by functional complement assays
