47. Plasma cells are specialized for secreting antibodies. They circulate in the blood stream.

Activated B
cells go to the germinal center so they can encounter follicular dendritic cells. The B-cells that have high
affinity will be able to pluck off the antigen from the FDC and therefore survive the selection and proceed
onto differentiation into a plasma or memory B cell.

48. BM makes new B cells as long as you live. However, T cells once made, could last the duration of
your lifetime. During surgery, the thymus can be removed from the adult and the patient will still have
enough T cells to protect the pt.

49. The order is pre-B, IgM, IgD. Before antigen encounter, you have the pre-B cells rearranging their
light chains. After this is done, it is carried to the cell surface and forms IgM. Now the immature B-cell
goes through negative selection. This is if they recognize self antigen, they will die of apoptosis (clonal
deletion). If they encounter soluble antigen, then they will become anergenic. If they don't encounter any
antigen in the bone marrow, they will mature and go express IgD on their surface..then migrate out to the
periphery. Remember the antigens they are encountering are located in the bone marrow, and hence are
self. So if they recognize self, they die.

**' 50. The beta locus rearranges first, and then there is a pre-T alpha that appears. This is the signal that
says it has made a good beta rearrangement and so can proceed.

51. Flow cytometry is used for sorting cells. If you use an antibody tag, you can call it FACS.
Fluorescence Activated Cell Sorter.

52. DN are found at the cortex. SP are found in the medulla. DN closest to being the stem cell. Order of
development is DN, DP, SP. Major population 60-70% CD4, 30%CD8+.

53. No TCR = Death. This is positive selection. Doesn't recognize self-peptide and MHC = Death. Binds
too well to self peptide-self MHC = Death. Binds with intermediate affinity = Life.

54. More MHC peptides = greater capacity to present peptides, therefore we have the polymorphism. Your
T cells must recognize the MHC. Peptides are products of gene translation. In order to get more variety
of peptides; you need more alleles than just one allele per person.

55. Central tolerance refers to the primary lymphoid organ. T cells the central tolerance occurs in the
thymus B-cell in the Bone Marrow (BM). This is where selection occurs. Don't forget peripheral
tolerance.

56. You get autoimmunity.

57. Lymph fluid is plasma that leaks from the tissues and into the lymphatic vessels. Antigens enter the
LN via the afferent lymphatics. Path of naive lymphocytes enter via afferent bloodstream and exit via
efferent lymphatic vessel. Once in, B cells migrate to the primary lymphoid follicle in the cortex. T-cells
hang out in the paracortical areas. Lymphocytes that recognize the antigen, they stop recirculating and
become active. They migrate to the area between the B-cell region and T cell region to look for their
respective B/T cell that recognized the same antigen (thus forming the primary focus). After recognition,
B-cell is now activated and undergoes somatic hypermutation, and travels to the germinal center to
proliferate and undergo affinity maturation. Afterwards, the B cell must encounter T-cell to get co-
stimulatory signal to differentiate into a memory of plasma cell. W/o signal the B-cell dies. Activated
lymphocytes leave the LN via efferent lymphatic vessel.
Lymphocytes roll along the blood vessel, using L-selectin (Lymphocyte) and Gly-Cam I, then they stop
w/ LFA-1 (on lymphocyte) and I-Cam I. Chemokine on epithelia wall binds to lymphocyte receptor for
chemokine and increases the bonding strength of LFA-1 and I-CamI. After this step, diapedesis occurs
and the lymphocyte squeezes through.

58. APC's in secondary lymphoid organs present antigen. In LN, the follicular dendrict cells present
antigen to activated B cells and is involved in the process of affinity maturation. In LN, the dendritic cells
present antigen to T-cells for activation.

59. Signal #1 for T cells comes from CD3 (on T cell) and second signal is CD28 on T cell interaction w/
B7 on APC. For B cell, first signal is the binding of Ag, and second is CD 40 on B cell and CD 40L on T
cell. In TI-1, first signal is binding of Ag, second is the binding of the innate immune receptor on the B
cell off bacterial cell wall product. In TI-2, the repetitive epitopes on the bacterial wall sends a strong
signal from cross-linking many IgMs that triggers antibody production.

60. Co-stimulation is necessary to elicit T cell activation. Without it, the T cell will be anergized. Co-
stimulatory signal appears only during an infection. Selection isn't perfect cuz it doesn't have all the self
proteins represented in the thymus.

61. Anergy

62. CD 28 is the co-stimulatory ligand on the T cell. Interacts w/ B7 of APC. B7 appears when there is an
infection.

63. CTLA-4 is on T cells binds better than CD28. CTLA-4 sends signal to T cell to stop proliferating.

64. w/o CTLA-4 get non-stop proliferation that leads to leukemia which leads to death of the organism

65. Cyclosporin A inhibits calcineurin (a phosphatase), prevents organ rejection

**'66. If you are talking about autocrine mech. Then Th1 is IFN-gamma, and Th2 is IL-4, 5

67. Macrophages fuse lysosomes w/ their intracellular vesicles. Macrophages and B cells are activated.
B cells are activated to isotype switching to IgG2a.

68. Factors: genetic and type of infection

69. If you have lepromatous leprosy, you are activating Th2. Th2 secret IL-4, 5, which in tern stimulate B-
cells to isotype switch into producing IgG and IgE antibodies. The problem is that the bug is residing the
macrophages' vesicles that are not accessible to the Ab. This is not effective in clearing the infection.
Th1, which secretes IFN-& stimulates the destruction of Mphage's vesicles, will help clear the bug.

70. Killer T-cell. Cytotoxic. Kills cells via Fas (on T cell) and Fas Ligand (on APC) via apoptosis and as
a back up, it releases sacs of enzymes via exocytosis…These sacs of enzymes contain perforins which
make holes in the infected APC and then the granzymes enter to digest and kill the cell from the inside
sacs of enzymes via exocytosis…These sacs of enzymes contain perforins which make holes in the
infected APC and then the granzymes enter to digest and kill the cell from the inside out.