Immunodeficiency diseases Flashcards
Immunodeficiency means infections that are
Opportunistic
Unusual
Unusually severe, protracted or not responding to standard therapy
Frequent
Secondary immunodeficiency
Immune defect is secondary to another disease process
Very common
Extremes of age
Malignancies (esp myeloma, lymphoma)
Metabolic e.g. diabetes
Drugs e.g. chemotherapy, steroids
Infection e.g. HIV
Primary immunodeficiency syndrome (PID)
Immune defect is intrinsic to the immune system itself
Rare
Often genetic, but not always
Over 100 characteristics PIDS
Most are fairly new diseases
- fatal in pre-antibiotic era
- characterisation required development in technology
Combined immunodeficiencies
Immunodeficiency syndromes affecting both antibody production and T cells
Immune dysregulation
Uncontrolled inflammation, autoimmune diseases
Predominantly antibody deficiency
Low IgG, other isotypes may be affected, but low IgA/ M with normal IgG is rarely significant
Manifests with recurrent pyogenic infections of the upper and lower respiratory tract
Sometimes gut infections in addition
Infections typically respond to anti-microbials, but responses may be sub-optimal and long courses required
If untreated, leads to irreversible lung damage
Some causes of antibody deficiency
Physiological
- transient hypogammaglobulinemia of infancy
Secondary
- IgG loss: renal (nephrotic syndrome), skin (extensive burns)
- impaired production: immunosuppressive drugs
Primary
- X linked agammaglobulinemia
- X linked hyper IgM syndrome
- many others
Maturation of antibody production
In healthy infants normally period of relative antibody deficiency around 6 months
Known as transient hypogammaglobulinaemia of infancy
Physiological state can be correlated with increased infections
Infants with antibody deficiency usually present after 3-6 months; up until this time they are protected by maternal IgG antibody
XLA- a prototype antibody deficiency syndrome
Signalling via Bruton’s tyrosine kinase required for signal transduction at pro-B stage
Maturation arrest occurs if absent: no heavy chain rearrangement, no B cells leave marrow, no immunoglobulin production
Disease is called X linked agammaglobulinaemia
X linked hyper IgM syndrome
Failure of B cell maturation from primary to secondary
Low IgG and IgA, raised IgM
Recurrent bacterial infections
Presents age 3-6 months
The immunological lesion actually resides on the T cell
- CD40 ligand
- interaction with CD40 on B cells required for affinity maturation
Treating antibody deficiency
Early recognition before lung damage occurs
Aggressive treatment of intercurrent infections
Replace immunoglobulin
Long term suppressive anti-microbials
Cellular immunodeficiency
When congenital, antibodies will also be affected
Manifests particularly with
- opportunistic infection
- viral infection
- fingal infection
- mycobacterial infection
Classic secondary cause is HIV infection
Severe combined immunodeficiency
Rare, life threatening primary immunodeficiency
Absent T cells
B cells may be present, but are non- functional
All basically present in a similar fashion
- usually soon after birth
- rash
- failure to thrive
- chronic diarrhoea
- infections, especially opportunistic: bacterial, mycobacterial, viral, fungal
Molecular causes of SCID
Common gamma chain deficiency
JAK3 deficiency
RAG1/2 deficiency
Common gamma chain deficiency
X linked SCID
Common gamma chain forms part of membrane receptor for several cytokines, some of which are required for T cell maturation
Absent T cells
B cells present but non-functional
