Immunodeficiency Flashcards
What is secondary immunodeficiency?
Immune defect is secondary to another disease process
Primary immunodeficiency?
Immune defect is intrinsic to immune system itself
Defects in B cells?
Antibody- so more bacterial infection in respiratory tract
T cell immunodeficiency?
Predominantly viral fungal and mycobacterial infections
What is immunodeficiency syndromes when it affects both antibody production and T cells?
Combined immunodeficiencies
Immunosenscence?
A combination of age related changes in the immune system that result in greater susceptibility to infection and reduced response to vaccination
What happens in immunosenescence?
Thymus involution Reduced T and B cell receptor diversity Telomere shortening in stem cells Reduced vaccine responses Reduced self tolerance Reduced neutrophil function Expansion of T cell pool responding to cytomegalovirus
Antibody deficiencies present with?
Recurrent upper and lower respiratory tract infections
What is the levels of antibody in immunodeficiency?
Low igG, but low igA/M with normal igG is rarely significant
If untreated?
Irreversible lung damage, bronchiectasis
Causes of antibody deficiency?
Physiological- transient hypogammaglobulinemia
Secondary- igG loss, due to nephrotic syndrome, extensive burns
Immunosuppressive drugs
Primary-
X-linked agammaglubulinemia
X linked hyper igM syndrome
Transient hypogaamaglobulinemia infancy?
6 months of age when mother igG is depleting and child’s has not yet begun properly
Infants with antibody deficiency usually present?
3-6 months
XLA? X linked agammaglobulinaemia?
Signalling via bruton’s tyrosine kinase required for signal transduction at pro-B stage
Maturation arrest occurs if absent- no heavy chain arrangement, no B cells leave marrow, no immunoglobulin production
X linked hyperigM syndrome?
Failure of B cell maturation
Raised igM, low igG and igA,
CD40L deficiency
3-6 months at age
How to treat antibody deficiency?
Replace immunoglobulin
Long term suppressive anti-microbial
Aggressive treatment of infections
What does cellular immunodeficiency present with?
Opportunistic infection
Viral infection
Fungal infection
Mycobacterial infection
Classic secondary cause Is HIv infection
E.g candida
CMV retinisus
Toxic plasmosis
Caposie sarcoma
Example of cellular immunodeficiency?
SCID
Absent T cells, B cells may be present but non functional
Chronic diarrhoea
Present immediately after birth
Infections
Rash- maternal lymphocyte cross placenta
What are molecular causes of SCID
RAG 1/2 deficiency
JAK 3 deficiency
Common gamma chain deficiency
Common gamma chain deficiency?
X linked SCID
Gamma chain in receptor
Cytokine receptor bound to JAK3 unit
JAK 3 deficiency?
Autosomal recessive SCID
Same to gamma chain
RAG 1 and 2 deficiency?
Autosomal recessive form of SCID
Needed for somatic recombination of VDJ
No b and T cell receptors
SCID therapy?
Stem cells harvested from HLA matched donor
Engraftment in bone marrow
Reconstitution of t and B cells
Which disease has autoimmunity and immunodeficiency?
DiGeorge syndrome
Treat by thymus transplant
Terminal complement deficiency?
C5-c9 - susceptibility to neisseria species
