Ontogeny of the Immune System Flashcards
stem cell
undifferentiated cells which when they divide give rise to another stem cell and daughter cell committed to differentiate
B cell
lymphocytes that play a large role in the humoral immune response. They make antibodies and become memory B cells
T cell
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
pre-B cell
a B cell with cytoplasmic IgM but no surface IgM
pre-T cell
in bone marrow, don’t have characteristic surface markers that distinguish them as T cells but are committed to expressing them in the right environment. They will go to the thymus
self-tolerance
the process by which the body does not mount an immune response to self antigens
titer
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.
- *Draw this
a. In the bone marrow, you find pre-T cells (no distinguishing surface markers, but committed to expressing them in the right environment). You will also find “pro-B cell”, pre-B cells, immature B cells and mature B cells .
b. These cells go to the thymus, where they rearrange their receptor genes and are selected for their responsiveness to “self + antigen”. Cells in thymus display CD1 surface marker (not found on mature T cells in pheriphery). Most also display CD4 and CD8. Once cells have been selected in the thymus, those chosen are exported (1%) into the lymph nodes and the others die.
Define the Bursa of Fabricius, and discuss where its functions take place in mammals
a. Bursa of Fabricius: where precursors from the bone marrow go to finish their development in birds, burse is located in at the hind end of the gut.
b. The mammalian equivalent is the bone marrow where B cells develop
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”).
a. “Pro B cell” progenitors: identifiable when they begin to make detectable cytoplasmic mu chains
b. Pre B cell: a cell with cytoplasmic IgM but no surface IgM
c. Immature B cell: a cell with surface IgM only and can interact with outside world. If immature B cell is exposed to antigen, the signal causes the cell to try receptor editing, if that fails it activates a suicide program and dies. This deletion is called “clonal abortion” and explains why we do not make antibody to self. In the bone marrow pre-B cells are differentitating into immature B cells and any cell whose receptors happen to be anti-self will almost surely encounter “self” in the bone marrow and will either make a new receptor or will be aborted. If it does not encounter antigen (not anti-self) then it will mature further so it expresses sIgM and sIgD. Then when it meets antigen, it will be stimulated.
d. Mature B cell: a cell with both IgM and IgD (of the same specificity) are on cell surface
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
- *Draw this
a. During primary B cell responses to antigen, IgM is secreted first, then usually, helper T cells help B cells switch to IgG (or IgA or IgE).
b. In response to secondary (booster) immunizations, IgM response is the same as in primary, but the IgG response (helped by T cells) is sooner, faster and higher and more prolonged because of immunological memory. Anamnestic Response. If a patient has NO functional T cells, there would be no IgG curve on the graph, only 2 similar IgM curves.
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
IgM is made by the fetus before birth (IgM cannot cross placenta) and the Mother’s IgG is actively transported across the placenta so at birth the baby has 100% of adult levels (much of the increase is seen in the last 2 weeks of pregnancy—therefore preemies have problems with IgG levels). After birth, the Mother’s IgG levels drop (half life=3 weeks). 3-6 months after birth, the baby begins to make its own IgG. The most vulnerable time for babies is at about 6 months, when the Mother’s IgG is low and the baby’s IgG is low. This is the reason breast feeding is so important, the milk contains antibodies to prevent infection/disease during this vulnerable period. IgA starts at 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 that you made when you did the calculations
a. If the antibody is IgM, we know that it was produced by the baby (the baby was exposed to something) because mom’s IgM cannot cross the placenta
b. If the antibody is IgG, it is from the mother (IgG can cross the placenta). The IgG has a half-life of 3 weeks, so in 4 months (16 weeks) the antibody will be 50% ( 3wks), 25% (6 wks), 12.5% (9 wks), 6.25% (12 wks), 3.125% (15 wks) of the original amount
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 old, then diversity becomes increasingly limited, and more and more cells show a “memory” phenotype (they have been exposed to a lot more), while fewer are naïve. Old people have fewer (new clone production slows), but larger, clones. Young people have smaller, but more, clones. Old people make good responses to antigens they saw in their youth, but fail to respond to new antigens (ie: SARS—fatal in many elderly patients).
Discuss the relative values of immunizing the young and the old in an epidemic of a novel respiratory virus.
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 the past, but fail to respond well to completely new antigens. Ex. SARS epidemic—featuring a brand new pathogen—was disproportionately fatal in the elderly, as is West Nile Fever, brand new in America since 1999. It may also suggest that flu shots in the elderly (unless they are cross-reactive with an earlier strain of virus) are not as useful as we would like to think. However, for the H1N1 virus formerly known as Swine, older folks had cross-reactive immunologic memory of a related virus, and generally did better than the young.
