Answers, problem set F (immune system)

48) a) Antigen-binding sites at tips of "Y"

b) Two genes are required to make a single antibody molecule.

c) heavy chain gene: V, D, J, and C

d) Antigen-binding part encoded by V, D, and J of H chain and V and J of light chain

49) Pre-B cell will rearrange the heavy chain gene.

If the heavy chain encoded by the rearranged gene is not intact, the cell will use the other copy ("allelic exclusion" - the second copy is not used if the first one is rearranged well).

The cell rearranges the light chain, and checks for a good copy in same manner as for the heavy chain gene.

IgM antibody is initially expressed in a membrane-bound form. If the B cell is not stimulated, it dies eventually. If it is stimulated (by a T_H cell in most cases), the cell proliferates, and makes secreted antibodies. Some of the progeny of the stimulated cell will also become memory cells.

50) a) Which B cells respond to an infection by a substance not previously seen?

"Naive" B cells = virgin B cells, which have already rearranged their antibody-encoding genes and can recognize antigen.

b) Which B cells respond to a second infection (one year later) by the same foreign substance? Progeny of the cells involved in the primary response: memory B cells.

c) What is the difference between the responding cells in part a) and the responding cells in part b)?

Memory B cells have switched antibody classes and undergone somatic hypermutation. Many of the memory B cells will make antibodies having a lower affinity for the antigen, but a small fraction will make antibodies having a higher affinity. Those that bind most tightly to the antigen will most likely be stimulated by T cells because they will probably display the antigen first.

51) change of one nucleotide in the Cm heavy chain gene segment - not this one as it encodes the part of the antibody that is not involved in recognizing antigen.

removal of one nucleotide in a D heavy chain gene segment - not this one as it would throws off the reading frame, resulting in a protein that is not an antibody.

change of one nucleotide in a V light chain gene segment - This might increase the affinity, because it might affect an amino acid residue involved in binding the antigen.

52) To produce antibodies against a short peptide, one generally attaches the peptide to a larger protein "carrier," and then injects the carrier + peptide into a rabbit. The rabbit then produces antibodies against both the peptide and the carrier.

a) No, a B cell will make one specific antibody which will normally recognize either the carrier or the peptide. Different B cells will produce antibodies against the carrier from those that produce antibodies against the peptide.

b) The advantage of using the carrier is that it may provide peptides that will be displayed by the MHC II molecules, thereby allowing a T cell that recognizes that MHC II/peptide complex to activate the B cell that makes antibodies against the target peptide. If the target peptide were used alone, it might not happen to be presented by one of the MHC II molecules available.

53) HIV, the virus that causes AIDS, recognizes the CD4 protein. What cells normally have this protein, and why does the virus cause immunodeficiency?

The transmembrane protein CD4 is found on helper T cells (CD8 is found on cytotoxic T cells). CD4 and CD8 (for cytotoxic T cells) assist in the recognition of MHC molecules on target cells. The HIV retrovirus enters the T helper cells by binding to CD4. It persists in a latent state until activated by some rare event, then it eventually kills the helper T cells, seriously crippling the immune defense system.

54) X-ray irradiation will kill most lymphocytes. Introduced B cells can make antibodies, but the response will be greatly weakened without assistance from the helper T cells (these two types of cells work in concert with each other). To kill foreign cells, cytotoxic T cells will be required.

a) Cytotoxic T cells are needed to kill virus-infected cells. B cells will not help except insofar as they make antibodies that recognize the extracellular (circulating) form of the virus, and even then they will also need help from helper T cells.

b) A kidney would not be rejected by B cell activity. Introduced cytotoxic T cells would reject a foreign kidney cells if the T cells shared the same MHC molecules with the recipient but not with the transplanted kidney. For example, both mice could be of the same inbred strain. Using inbred mice should also prevent attack on the host by the introduced T cells.

c) The harmless chicken protein might be recognized by antibodies made by some B cells, but without help from helper T cells those B cells will not be activated and therefore won't actually produce secreted antibodies.

For all three insults, if both B and T cells are introduced, the mouse will have the necessary cells to defend itself.

55) Name one type of cell that has the following receptors on its surface:

a) CD4 but not CD8 - Helper T cells

b) CD8 but not CD4 - Cytotoxic T cells

c) both CD4 and CD8 - Immature T cells

d) MHC class II molecule - B cells or antigen-presenting cells.

56) If a heart is transplanted from one animal to another, the recipient's immune system will reject the transplanted tissue.

a) Cytotoxic T cells recognize the foreign heart cells.

b) Cytotoxic T cells distinguish foreign cells from host cells by scanning the MHC I/peptide complexes displayed on the surface of the cells. A foreign cell with different MHC I molecules from the host will look different and therefore suspicious to the T_C cells.

c) The cytotoxic T cells kill the foreign cells.

d) The foreign cells are killed by a combination of signaling (tells the target cell to commit suicide) and physical abuse (such as proteins that make holes in the membrane).

e) During maturation in the thymus, T cells whose receptors recognize a host peptide/MHC complex too strongly are selected against and die (negative selection), eliminating those that respond to the body's own proteins. If this system breaks down, an autoimmune disease can result.