Immunodeficiency diseases Flashcards
What is the definition of immunodeficiency disease
Infections which are opportunistic, unusual, unusually severe, protracted/unresponsive to standard therapy and occur frequently
Infections are verified and organisms can be identified and end organ damage has occurred
State the differences between primary and secondary immunodeficiency disease
PRIMARY
- defect is intrinsic to immune system itself
- RARE, often genetic
- > 100 characterised
- fairly ‘new’ as characterisation required technological development. Fatal before antibiotics
SECONDARY (to another disease process)
- very common, at extremes of age
- causes: malignancies (myeloma, lymphoma), metabolic (diabetes), drugs (chemotherapy, steroids), infections (HIV)
How are immunodeficiency disease classified?
+ Presentation
INNATE - variety of manifestations
ADAPTIVE
- B cells: ‘Antibody deficiency’ predominantly bacterial infections of respiratory tract
- T cells: ‘Cellular immunodeficiency’ predominantly viral, fungal and mycobacterial infections
What is meant by combined immunodeficiency?
CD4 T cells affect B cells as T cells help B cell maturation. This has a marked effect in infants where B cells are widely immature
- This is known as combined ID
How do immunodeficiency syndromes typically manifest?
- immune dysregulation
- uncontrolled inflammation
- autoimmune disease
Consider (Predominantly) AB deficiency
Which antibody is deficient?
How does it manifests?
Treatment?
What happens if left untreated?
- Low IgG predominantly
- Manifests with recurrent pyogenic (pus forming) infections of URT/LRT, sometimes guy infections in addition
- infections respond to anti-microbials but response may be suboptimal and long courses required
- if untreated –> irreversible lung damage (bronchiectasis)
Consider (Predominantly) AB deficiency
State the primary and secondary causes
SECONDARY
- Physiological - transient hypogamma globulinaemia of infancy
- IgG loss- renal nephrotic syndrome, skin (extensive burns)
- Impaired IgG production- immunosuppressive drugs
PRIMARY
- X linked hyper IgM syndrome
- X linked agamma globulinaemia
What is transient hypogammaglobulinaemia of infancy?
Presentation?
When is this most pronounced?
Prolonged period of hypogammaglobulinaemia
- After physiological hypogammaglobulinaemia (first 5-6 months of life) caused by passive transfernce of maternal IgG in utero. This IgG declines from birth until approx 6 months.
- Recurrent infections
- Premature babies have less time in utero to receive IgG from mother
What is the relevance of Bruxtons’ tyrosine kinase in X linked agammaglobulinaemia
- Signalling via Bruxtons’ tyrosine kinase (BTK) required for signal transduction at pro-B stage
- An absence/defect of this is the cause of XLA
- Maturation arrest occurs if absent –> no heavy chain rearrangement, no B cells leave marrow, no Ig productin
- Dont present with infections at birth as covered by maternal IgG
What happens in X linked hyper-IgM syndrome (CD40L deficiency)
How does it present (serum and clinical study)?
- failure of B cell maturation from primary to secondary
- low IgG and IgA, raised (or normal) IgM
- presentation: recurrent bacterial infections between 3-6mo
- an immunological lesion resides on Tcell. Interaction between CD40L and CD40(on B cell) required for affinity maturation
(Naive B cell + surface IgM encounter antigen in lymphoid tissue --> somatic hypermutation and class switch recombination. Leads to high affinity IgG antibodies) - NO class switch in syndrome
Describe the management of antibody deficiency
- early recognition, prior to lung damage
- aggressive treatment of intercurrent infections
- replace IgG
- long term suppressive anti microbials
Consider Cellular immunodeficiency
If congenital how does it presentation differ?
How does it manifest?
- Congenital cause affects antibodies as well
- Opportunistic infections: viral, fungal, mycobacterial
- HIV infection
- toxiplasma (brain), kaposis sarcoma, candidiasis, CMV
What is SCID?
When does it manifest?
What causes the rash?
What other symptoms? Be specific about the type of infections (mycobacterium, viral, fungal)
- RARE
- Life threatening immunodeficiency with absent T cells and present B cells (that are non-functional)
- Soon after birth
- Maternal lymphocyte engraftment in fetal bone marrow causes host v graft syndrome
- Failure to thrive, chronic diarrhoea
- BCG
- CMV, EBV
- PCP, oral thrush
Consider the molecular causes of cellular immunodeficiency
Describe Common gamma chain deficiency
- X linked SCID
- Common gamma chain forms part of membrane receptor for several cytokines, some of which required for T cell maturation
–> absent T cells, B cells present but non-functional
Consider the molecular causes of cellular immunodeficiency
Describe JAK3 deficiency
- Autosomal recessive SCID
- JAK3 is downstream of common gamma chain; deficiency prevents signalling
–> absent T cells, B cells present but non-functional
