IMM2022 Lecture Notes - Lecture 7: Maraviroc, Purine, Chemokine
30 May 2018
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Department
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IMMUNODEFICIENCY
Features of immunodeficiency diseases:
Congenital (primary)
Immunodeficiency
o Genetic abnormalities in one or more components of the immune
system
o Inherited gene defects
o Blocks maturation and function of immune cells (B and T cells)
o Increases susceptibility to infections that may manifest after birth
(potentially fatal) and infections that are detected in adult life
Acquired (secondary)
Immunodeficiency
o Defects in the immune system that result from infections, nutritional
abnormalities or medical treatments (eg. Chemotherapy)
o Human immunodeficiency virus (HIV)
o Parthenogenesis of AIDS
o Clinical features of HIV infection and AIDS
• Congenital immunodeficiency:
o Defect in lymphocyte maturation
o Defect in lymphocyte activation
o Defect in innate immunity (phagocyte and complement system)
o Lymphocyte abnormalities often associated with other diseases
o Treatment:
-SCID is fatal in early life unless immune system is reconstituted
-Boe arro trasplats oly ay they’ll surie -> ablation of recipient bone marrow
-For B cell defects, patients may be given pooled immunoglobulin (passive immunity)
SCID (severe
combined
immunodeficiency)
- Defect in
lymphocyte
maturation
o Disorders in the adaptive immune system
o 50% are x-linked affecting only male children
o Mutation in a signalling subunit of a receptor for cytokines
Eg. Impaired Y chain deficiency:
Pro-T cells (immature) cannot proliferate in response IL-7 (leads to cell
death) -> reduced survival and maturation of T lymphocytes
o End result: low T cell numbers, immunity and defective humoral
immunity (no T cell help)
find more resources at oneclass.com
find more resources at oneclass.com
o 50% pf autosomoal SCID are caused by mutations in adenosine
deaminase enzyme which is involved in breakdown of purines (cells
that are proliferating) -> causes accumulation of toxic purine
metabolites -> toxic in developing cells -> ADA deficiency leads to block
of T cell maturation and lesser extent B cells
o RAG deficiency: rare case of autosomal, mutations in RAG1 and RAG2
(hypomorphic mutation where children have normal or increased
number of activated T cells, suffer from opportunistic pathogens)
RAG is required for VDJ recombination -> lymphocyte maturation
X-linked
agammaglobulinemia
Bruto’s
- Defect in
lymphocyte
maturation
o Most commo clinical syndrome caused by a block in B cell maturation
o B cells fail to mature beyond pre-B cell stage
o Marked decrease of mature B cells and serum Ig
o Mutation in tyrosine kinase gene (Bruton Tyrosine Kinase –ATK)
BTK needs a signal and is activated by pre-B cell receptor -> biochemical
signal to promote maturation of B cells -> male offspring who receive X
chromosome from carrier mother
(gene located on X chromosome)
-no B cell development
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Immunodeficiency: genetic abnormalities in one or more components of the immune system. Inherited gene defects: blocks maturation and function of immune cells (b and t cells) Increases susceptibility to infections that may manifest after birth (potentially fatal) and infections that are detected in adult life. Scid is fatal in early life unless immune system is reconstituted. Bo(cid:374)e (cid:373)arro(cid:449) tra(cid:374)spla(cid:374)ts (cid:894)o(cid:374)ly (cid:449)ay they"ll sur(cid:448)i(cid:448)e(cid:895) -> ablation of recipient bone marrow. For b cell defects, patients may be given pooled immunoglobulin (passive immunity) Defect in lymphocyte maturation: disorders in the adaptive immune system, 50% are x-linked affecting only male children, mutation in a signalling subunit of a receptor for cytokines. Rag is required for vdj recombination -> lymphocyte maturation. Btk needs a signal and is activated by pre-b cell receptor -> biochemical signal to promote maturation of b cells -> male offspring who receive x chromosome from carrier mother (gene located on x chromosome)
