Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 110

Adaptive immune system associated with antigen-specific B- and T-cell receptors
on B and T lymphocytes relies on immunological memory, i.e., immune repertoire
of BCRs and TCRs that depends on cell history vis-a-vis antigens.
When B- and T-cell receptors recognize and bind a given antigen, clones of
B and T lymphocytes that produce these receptors expand and become effector cells
( expansion phase )[ 210 ]. Pathogen-specific immunocytes become activated and pro-
liferate over 1 wk to generate thousands of daughter effector cells. B lymphocytes
secrete antibodies. T lymphocytes kill antigen-containing cells.
Once the immune response is finished, only a small fraction of B and T lympho-
cytes survives ( contraction phase ). Remaining long-lived memory cells maintain
long-term immunity after infection or vaccination. During the third memory main-
tenance phase , stable populations of long-lived memory cells reside in lymphoid
and non-lymphoid tissues, where they search for eventual previously encountered
pathogens. The fourth and last phase ( recall response ) occurs when memory cells
re-encounter their cognate antigen.
Secondary lymphoid organs are loci where most immune responses are initiated.
However, many types of memory cells lodge preferentially in the bone marrow,
such as CD4 + and CD8 + T lymphocytes and long-lived plasmocytes. In particular,

CD4 memory T cells, which give rise to different functional subsets (effector

memory [T EM ], central memory [T CM ], and follicular helper [T FH ]) T cells with
given functional capacities and sites of action, assist in the generation of high-
affinity memory B cells and long-lived plasmocytes and in the maintenance and
secondary expansion of memory CD8

+

memory T cells pro-
mote the production of high-affinity antibodies and the generation of bone marrow,
long-lived plasmocytes in the late phase of immune responses. Bone marrow-
resident CD4

+ T cells [ 212 ]. CD4 +

T lymphocytes (memory helper T lymphocytes) have a particular
plasmalemmal molecule expression pattern characterized by bone marrow-homing
receptors

+

α 2 -integrin and C-type lectin CLec2c [ 212 ]. 97 Early activation marker

CD69 in CD4 memory T cells enables their accumulation in the bone marrow in

dedicated memory niches, where they link to laminin

+

+ stromal and epithelial cells

and can receive necessary survival signals [ 213 ].
Like cytotoxic T lymphocytes of the adaptive immunity, natural killer cells
of the innate immunity (Sect. 3.11.5 ) possess an immunological memory against
cytomegalovirus owing to killer cell lectin-like receptors KLRa8 98 and KLRb1c
[ 211 ]. 99 Natural killer cells that proliferate 1,000-fold in spleen and liver after
the initial infection remain in the immune system for months and confer viral
resistance. After the contraction phase, a subset of virus-experienced natural killer
cells survives and maintains the capacity of becoming effector cells.

97 A.k.a. type-2 membrane, homodimeric activation marker CD69. Trafficking molecule CD69 con-
nects to S1P 1 receptor and inhibits S1P-S1P 1 -mediated cell egress from the bone marrow [ 212 ].
CD69

+ T cells are able to enter the bone marrow. CD69 + ,CD4 + memory helper T cells of the

bone marrow contact stromal cells, but not CD69 − ,CD4 + cells.

98 A.k.a. lymphocyte surface glycoprotein Ly49h.
99 A.k.a. natural killer cell-surface protein NK1.1.