What are the two primary cell lines from hematopoietic stem cells and the final products of each?
The daughter cells of hematopoietic stem cells (HSC) become Common Lymphoid Progenitors (CLP) or Common Myeloid Progenitors (CMP). CLPs give rise to T-cells and B-cells. CMPs give rise to erythrocytes, megakaryocytic (platelets), eosinophils, mast cells/basophils, neutrophils, and monocytes.
What are the first antibody chains to be found in developing B-cells and what does this indicate?
The first detectible Ig chains are the mu chains in the cytoplasm. This indicates that the B cells rearrange their heavy chains before their light chains. This is likely because they only have two copies of the heavy chain genes, and if one is damaged in recombination (VDJ leads to frame shifting in 2/3 of attempts) they then try the other before starting with the light chains.
What is the overall process of antibody chain production and B-cell maturation?
Mu heavy chains appear in the cytoplasm first, then light chains are made, cytoplasmic IgM appears (monomers), cell displays monomeric IgM on its surface and is termed an immature B-cell (if this antibody recognizes anything, the cell dies). 24 hours later, alternative splicing of the VDJ-md primary transcript allows the creation of IgD and IgD is displayed on the cell surface. It is now a mature B cell (displaying both IgD and IgM on its surface), which may produce pentameric IgM when it encounters antigen.
What is clonal deletion?
Clonal deletion is the process an immature B-cell undergoes when it encounters an antigen it recognizes. Because the entirety of the B-cell's immature phase is spent in the bone marrow (before it forms IgD), anything it encounters there is nearly certain to be "self". Thus, clonal deletion is the first line of protection against autoimmune disease.
What triggers a B-cell that is creating IgM to undergo class switching?
T-follicular helper cells trigger the class switch from IgM to IgG (or IgA or IgE). The Tfh cells in the gut and lung preferentially drive the class switch to IgA and IgE. B cells are responsive to what the Tfh cells instruct.
Why are immune booster shots needed?
The IgG response that is generated after the initial immunization is greater than the IgM response, but not particularly large or long lasting. A second, booster immunization creates a much larger and longer lasting IgG response.
Where does most of a newborn's Ig come from and when can it produce the various Ig forms it needs?
Most of a newborn's Ig is IgG which has been transported across the placenta from its mother. Most of this transfer occurs in the last 3-4 weeks of pregnancy, complicating the effects of premature birth. The fetus may begin producing IgM many months before birth, but not IgG until 3-4 months after birth. IgG has a half life of 3 weeks, so the time period from 3-9 months is a window of low levels of Ig.
Where do T cells develop?
T cells have different stages of development that occur in the bone marrow, then the Thymus ('T' cells), and finally in the peripheral lymphoid tissues.
What are the differences in antigen detecting processes between T cells and B cells?
The rearrangement of V(D)J regions in T cells occurs in the Thymus, and also involves completely different genes from the B-cell. The receptors are tested for their sensitivity to "self plus antigen" b/c they recognize antigen in MHC complexes on the surface of cells (antigen presenting cells), whereas B cells can recognize it in solution.
What is immunological aging?
Individuals can completely reconstitute their T cell numbers and diversity up to 40 y/o, but after that the cell diversity becomes limited. More cells are memory cells and fewer are naive, thus older people have larger clones than younger people and have more trouble responding to novel pathogens.
What are the consequences of immunological aging?
Think of it as experience versus ability to learn. Older people have larger clones which allow them to mount quicker defenses to antigens they have encountered in the past (they were more resistant to the 1918 influenza). However, they are less capable of producing new clones to novel antigens. Thus, vaccinating the elderly with flu shots has questionable results.