Ontogeny of the Immune System and T Cells Flashcards
Please define stem cell.
Stem cells are undifferentiated cells which, when they divide, ►give rise on average to another stem cell and a daughter committed to differentiation.
Please define B cell and pre-B cell.
B cells are lymphocytes that play a large role in the humoral immune response. They make antibodies and become memory B cells.A Pre-B cell is a precursor to the development of B cells. A cell with cytoplasmic IgM but no surface IgM is called a pre-B cell.
Please define T cell and pre-T cell.
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They have t cell receptors and mature in the Thymus.In the bone marrow one finds pre-T cells, which do not yet have the characteristic surface markers that distinguish T cells from other cells (differentiation antigens), but are committed to expressing them in the right environment.
Please define self tolerance.
the process by which the body does not mount an immune response to self antigens
Draw an outline diagram which shows bone marrow, thymus and lymph node. Indicate the development and movement of cells of the B and T lines, starting with the hematopoietic stem cell and ending with mature T and B cells.
T cells: They carry out their development in three different locations: the bone marrow, then the Thymus, and finally the peripheral lymphoid organs. In the bone marrow one finds pre-T cells, which do not yet have the characteristic surface markers that distinguish T cells from other cells (differentiation antigens), but are committed to expressing them in the right environment. These go to the thymus, where they rearrange their receptor genes and then are selected for their responsiveness to “self plus antigen.”
Define the Bursa of Fabricius, and discuss where its functions take place in mammals.
The abbreviation B in B cell comes from the bursa of Fabricius in birds where they mature. In mammals immature B cells are formed in the bone marrow which is used as a backronym for the cells’ name.
Describe the sequence of appearance of cytoplasmic and surface immunoglobulins in developing B cells. Using these data, derive a model that could explain self-tolerance at the B cell level (“clonal abortion”).
If an immature B cell (sIgM but no sIgD) is exposed to antigen, this signal causes the cell to try receptor editing; if that fails it activates a suicide program (apoptosis), and dies.This deletion mechanism is called clonal abortion, and it partially explains why we do not make antibody to self: in the bone marrow pre-B cells are differentiating into immature B cells; you can imagine that any cell whose receptors happen to be anti-self will almost surely encounter self in the environment of the bone marrow, and either make a new receptor, or be aborted.If it does not encounter antigen (because its receptors are not against self) then it will mature further so that it expresses both sIgM and sIgD. Then, when it meets antigen, it will be stimulated, not aborted.
Draw a graph showing the antibody response to a typical antigen in a primary and in a secondary response. Show both IgM and IgG antibody levels.
During primary (initial exposure) B cell responses to antigen, IgM is secreted first, then for most antigens, helper T cells get involved and there is a switch to IgG, or possibly to IgA or IgE. The helper T cells in the gut and lung preferentially drive the M to A switch. The ‘switch helper’ mechanism indicates that B cells in general do what T cells tell them to. As we’ll see later, an inappropriate antibody response may often be the T cell’s fault.
Draw a graph which shows relative IgG and IgM levels in a normal infant from conception to one year of age. Distinguish maternal from infant’s antibodies.
The fetus makes IgM before birth, but only acquires the capacity to make IgG about 3-6 months postnatally. However, at birth the baby has as much IgG in its blood as does an adult; this IgG is maternal, because IgG crosses the placenta, by active transport, from mother to fetus (no other class of immunoglobulin does). The half life of IgG is about 3 weeks, so in 7 half lives = 21 weeks after birth there is less than 1% of the starting amount of maternal IgG left; fortunately, the infant should be making reasonable amounts of its own IgG from about 12 weeks. IgA also starts about 2-3 months.
Given a newborn’s antibody titer, interpret its significance if the antibody is IgG, or IgM. If IgG, calculate what the titer will be at 4 months of age, and state the assumptions you made when you did the calculation.
If it is IgG, the baby has the mother’s antibodies. If it is IgM, then they have been making it in utero, which is normal. The maternal IgG half life is 3 weeks, so in four months, it will have undergone about 5 half lives, so it will be down to 3%, but the baby will have just started making its own at 12 weeks, so it will be slightly more then 3% of adult levels.
Discuss the decrease in diversity seen in the immune repertoire of older people.
People can completely reconstitute their T cell numbers and diversity up to about 40 years of age, then diversity becomes increasingly limited, and more and more cells show a ‘memory’ phenotype while fewer are naïve; old people have fewer but larger clones than do the young. A similar change takes place in B cells, too, possibly a decade or two later.►So older folks generally make good responses to antigens they saw in their youth, but fail to respond well to new antigens.
Please tell me about Th0 cells.
Helpers begin as an undecided precursor: we’ll call it Th0 (zero). When their correct antigen is brought to them by dendritic cells (DC), they begin to divide and differentiate, becoming either Th1, Th17, Th2, Tfh, or Treg cell
Please tell me about Th1 cells.
TH1: hypersensitivity T cell: The most important lymphokine secreted by Th1 is interferon gamma (IFNγ) which is pro-inflammatory, being chemotactic for blood monocytes and tissue macrophages.
Please tell me about Th17 cells.
Th17 CELLS. There is a newly described, intensely researched Th subset called Th17 because it makes the inflammatory lymphokine IL-17 among others. It resembles the Th1 in that its main job seems to be causing inflammation; not surprisingly, then, it has been implicated in several autoimmune diseases, as has the Th1. It must do something useful for a living, of course; maybe that is resistance to particularly difficult pathogens.
Please tell me about Th2 cells.
Th2 CELLS. Activated Th2 cells derived from Th0 leave the lymph node as do Th1, and circulate through blood and lymph until they encounter their antigen again in the tissues.Here the IL-4 and IL-13 they make have other actions: attracting and activating macrophages, but differently than IFNγ; such macrophages are called alternatively activated or M2, and are more involved in healing (debris removal, scar formation, walling off pathogens that angry macrophages have failed to kill).IL-4 is also chemotactic for eosinophils, cells specialized for killing parasites like protozoans and worms.
