Immunodeficiency diseases Flashcards
Immunodeficieny occurs when what happens?
Generally when a component from our immune system is missing
What are primary or congenital immunodeficiencies?
These are genetic defects that result in an increased susceptibility to infection
Often manifested in infancy and early childhood
What are secondary or acquired immunodeficiencies?
These develop as a consequence of malnutrition, disseminated cancer, treatment with immunosuppressive drugs or infection of cells of the immune system
T/F Toll-like receptors (TLRs) are conserved across widely diverse species? What does this mean?
True
This means that any loss of function mutation affecting a TLR has negative consequences for survival
Why are TLRs so important for immune function?
The TLRs are what recognize all of the foreign bacteria and microbes that can invade the body
What is the principal consequence of an immunodeficiency?
Increased susceptibility to infection
What helps doctors predict the type of immunodeficiency?
The types of recurring infections that the patients presents with
If you have deficient humoral immunity (B cell related), what are you more susceptible to?
Pyogenic bacteria
Where are TLRs found?
On macrophages, dendritic cells and mast cells- the sentinels of the innate immune system
If you have deficient cell-mediated immunity (T-cell related), what are you more susceptible to?
Viruses and other intracellular pathogens
How is deficient humoral immunity treated?
It’s routine- prophylactic antibiotics and/or gamma-globulin therapy
How is a deficient cell-mediated immunity treated?
Can’t really do anything- if you have this you die during childhood
What is an example of a deficiency of humoral immunity?
X-linked Agammaglobulenemia (XLA)
Tell me about XLA.
All antibody isotopes are very low- even IgM or IgD
Circulating B cells are usually absent
Fewer pre B-cells in bone marrow than normal
Lymph nodes and tonsils are small (due to lack of germinal centers)
Why are XLA individuals fine for the first 6 months or so of life?
Because they are protected by passive immunity given them by their mother
Tell me briefly about XLA.
Circulating B cells are usually absent
Pre-B cells are present in the bone marrow, but in reduced quantities
What is the defect that causes XLA?
The Bruton Tyrosine Kinase that is important for pre-B cell expansion and maturation into Ig-expressing B cells doesn’t work
What is the difference between X-linked immunodeficiency with hyper-IgM and XLA?
Well, X-linked immunodeficiency with hyper-IgM has low every other Ig but high counts IgM. Also, X-linked immunodeficiency with hyper-IgM has hyperplasia of the lymphoid tissues (enlarged)
What is the defect in X-linked immunodeficiency with hyper-IgM?
Isotype switching doesn’t occur so an abundance of IgM results.
This happens because the CD40 ligand that is expressed on helper T cells is broken
What is an example of cell-mediated immunodeficiency and what does it resemble?
DiGeorge’s syndrome and it resembles fetal alcohol syndrome
What causes DiGeorge’s syndrome?
The thymus does not develop
X-linked recessive severe combined immunodeficiency disease (XSCID) is rare and characterized by profound deficiencies in what?
T and B cell function (boy in the bubble)
What are the current treatments of immunodeficiencies and what are their aims?
Aims to minimize and control infections and replace the defective or absent component of the immune system by adoptive transfer and/or transplantation.
The treatments are:
Passive immunization with pooled gamma globulin
Bone marrow transplants
What is the result of aids?
Destruction of lymphoid tissue and depletion of CD4+ T cells
