Lecture 26 Flashcards
What are the two sates of immunodeficiency?
Congenital where the immunodeficiency is due to a genetic defect, these are quite rare conditions
Acquired of secondary when another disease or treatment causes immunodeficiency
What are the 7 common causes of acquired immunodeficiency?
HIV via destruction of CD4 lymphocytes Drug therapy systemic disease malnutrition or alcoholism stress or depression advanced age over exercise
What is severe combined immunodeficiency?
Genetic disorder which affects both the B and T lymphocytes of the immune system, babies typically only survive for a year with these conditions
What are the examples of sever combined immunodeficiency studied in class?
Adenosine deaminase deficiency
Purine nucleoside phosphorylase deficiency
X linked SCID
RAG-1, RAG-2 gene mutations
What is adenosine deaminase deficiency?
A primary immune deficiency which leads to a build of toxic products from cell metabolism as purines are unable to be broken down leading to adenosine and adenine accumulation in plamsa, and ADP, GTP, ATP accumulation in lymphocytes
Deoxy-ATP can become toxic inhibiting synthesis of DNA precursors preventing lymphocyte proliferation and therefore reducing the number of circulating lymphocytes
What is the potential treatment for adenosine deaminase deficiency?
Gene therapy has been trialled via infusion of T lymphocytes that have been manipulated to induce ADA expression
What is purine nucleoside phosphorylase deficiency?
Defects in the gene prevents metabolization of purines inosine and guanosine, their accumulation can be toxic resulting in a loss of T cells and a suppression of B cell responses as they lack T cell help
What are the treatments for ADA and PNP deficiencies?
Bone marrow transplantation, stem cell treatment, enzyme replacement therapy and gene therapy
What is X linked SCID?
Most common SCID, mutation of gamma chain for IL-2 and receptors for IL-4,7,9,15 leading to widespread immune system affects as it does not develop or function correctly there are low T and NK cells as well as non-functional B cells
What is X linked SCID also known as?
Bubble Boy disease
What is the only chance of a permanent cure for X linked SCID?
A compatible bone marrow transplant
What occurs in RAG-1 and RAG-2 mutations?
Inability to form the typical hetero-dimer resulting in an inability to undergo the initiation step in B and T cell antigen receptor gene segment assembly causing the cell to be unable to undergo recombination of antigen receptor genes causing Band T cells to have reduced or no function resulting in the patient suffering from opportunistic pathogens
What is X-linked agammaglobulinemia or Bruton agammaglobulinaemia?
First described Immunodeficiency,
Presents in childhood with recurrent pyogenic infections
Caused by a mutation of the tyrosine kinase enzyme which has a key role in cell development, this results in loss of B cells and therefore a loss of antibodies
How is X-linked agammaglobulinemia/ Bruton agammaglobulinaemia treated?
Infusion of human antibodies every 3-4 weeks for life
What is leukocyte adhesion deficiency 1?
Defect in the beta2 sub unit of integrin cell adhesion molecules (alphaLbeta2, alphaMbeta2, alphaXbeta2) which results in leukocytes and neutrophils cannot adhere to endothelial cells and therefore cannot reach the inflammed/infected sites
What is leukocyte adhesion deficiency 2?
Defect in the glycosyltransferases required to decorate selectin ligands with sugar moieties resutling in leukocytes not being able to migrate from the blood
How are LAD-1 and LAD-2 treated?
Bone marrow transplantation
What is Hyper IgM syndrome?
Very high expression o IgM antibodies, but low IgG and IgA levels causing susceptibility to upper respiratory tract bacterial infections and intracellular parasites
This is caused by B cells neing unable to make the switch from production of IgM to other antibody types typically due to a mutation in CD40 or CD40L
