L16 Immunodeficiency disease Flashcards
What is an immunodeficiency?
Inability to form an immune response
Diagnosis is largely descriptive
When are infections more likely to be significant?
Infections are verified rather than simply reported
Organisms can be identified
End-organ damage has occurred
What is secondary immunodeficiency?
Immune defect is secondary to another disease process
Very common
Extremes of age
What is primary immunodeficiency syndrome?
Immune defect intrinsic to immune system itself
Rare
Often genetic but not always
What are the predominant infections in antibody-deficiency?
Bacterial infections of the respiratory tract
What are the predominant infections in cellular immunodeficiency?
Viral, fungal and mycobacterial infections
Why do CD4 T-cell defects affect B-cells?
T cell help is needed for B-cell maturation
What are combined immunodeficiencies?
Immunodeficiency syndrome affecting both antibody production and T-cells
Describe the levels of antibodies in predominantly antibody deficiency
Low IgG
Other isotopes may be affected
A low IgA / IgM with a normal IgG is rarely significant
How does predominantly antibody deficiency manifest?
Recurrent pyogenic infections of upper and lower respiratory tract
Can get gut infections
What are some physiological causes of antibody deficiency?
Transient hypogammaglobulinaemia of infancy
What are some secondary causes of antibody deficiency?
IgG loss - renal nephrotic syndrome or skin in extensive burns
Impaired production - immunosuppressive drugs
What are some primary causes of antibody deficiency?
X-linked agammaglobulinaemia
X-linked hyper-IgM syndrome
What is transient hypogammaglobulinaemia of infancy?
Healthy physiological state of relative antibody deficiency around 6 months that can be correlated with increased infections
What antibodies are infants protected with before 6 months?
Maternal IgG antibody
What is X-linked agammaglobulinaema (XLA)?
Prototype antibody deficiency syndrome
Signally via Bruton’s tyrosine kinase required for signal transduction at pro-B stage
Maturation arrest occurs if absent so there is no heavy chain rearrangement, no B-cells leave marrow and no immunoglobulin production
What is XLA also known as
Bruton’s disease
Btk deficiency
Bruton’s XLA
What is X-linked hyper IgM syndrome?
CD40L deficiency Failure of B-cell maturation Recurrent bacterial infections Presents at 3-6 months Immunological lesion resides on T-cell
Describe the immunoglobulins in X-linked hyper IgM syndrome
Low IgG
Low IgA
Raised or normal IgM
Describe treatment for antibody deficiency
Aim for early recognition before lung damage occurs
Aggressive treatment of intercurrent infections
Replace immunoglobulin using passive immunisation
Long-term suppression with antimicrobials
What is cellular immunodeficiency?
CD4 T-cell deficiency
How does cellular immunodeficiency manifest?
Opportunistic infection
Viral infection
Fungal infection
Mycobacterial infection
What is SCID?
Rare, life-threatening primary immunodeficiency
Absent T-cells
B cells may be present but are non-functional
How does SCID present?
Usually soon after birth Rash Failure to thrive Chronic diarrhoea Infections, especially opportunistic
Describe some infections in SCID
Bacterial
Mycobacterial - BCG
Viral - CMV, EBV
Fungal - PCP, oral thrush
What are the molecular causes of SCID?
Common gamma chain deficiency
JAK 3 deficiency
RAG 1 /2 deficiency
What is common gamma chain deficiency?
X-linked SCID
Common gamma chain forms part of membrane receptor for several cytokines, some are required for T-cell maturation
Absent T-cells
B cells are present but non functional
What is JAK-3 deficiency?
Autosomal recessive SCID
JAK-3 is downstream of common gamma chain
Absent T-cells
B cells present but non functional
What is RAG 1 and 2 deficiency?
Autosomal recessive form of SCID
RAG 1 and 2 required for somatic recombination evens
Deficiency means no T and B cell receptors
Describe the steps of stem cell transplant for SCID therapy
1) Stem cells harvested from HLA-matched donor
2) Given to recipient by infusion
3) Engraft in bone marrow
4) Reconstitution of T and B cells
What is DiGeorge syndrome?
Failure of migration of 3rd / 4th branchial arches
Most patients have micro deletions on chromosome 22
What is the full phenotype of DiGeorge syndrome?
Absent parathyroids - low calcium, tetany
Cleft palate
Congenital heart defects
Thymic aplasia - low T-cell numbers
What is terminal complement deficiency?
Deficiency of terminal complement components C5-C9 leads to specific susceptibility to Neisseria species.
Diagnose by functional complement assays
