Page 111 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

!
LFA1 (lymphocyte function-associated antigen and to CD95 (= Fas) plays a role, as does
1) on the T cell membrane. When a T cell granzyme B (protease), which enters the cell
specific for the antigen in question docks onto through pores created by exocytosed perforins
the complex, the bond is strengthened and the (! B2).
APC dual signal stimulates the activation and Once HLA-II-restricted presentation (! B1)
clonal selection of the T cell (! B1). of antigens from intracellular vesicles (e.g.,
phagocytosed bacteria or viral envelope pro-
The APC dual signal consists of 1) recognition of
the antigen (class I or class II HLA-restricted antigen) teins = exogenous antigen presentation) has
+
by the T cell receptor and its co-receptor and 2) a co- occurred, naive CD4 T cells transform into im-
stimulatory signal, that is, the binding of the B7 mature T helper cells (T H0), which differentiate
protein (on the APC) with the CD28 protein on the T into T H1 or T H2 cells. T H1 cells induce inflam-
cell (! B1). CD8 molecules on T cytotoxic cells (T C matory responses and promote the activation
cells = T-killer cells) and CD4 molecules on T helper of macrophages with the aid of IFN-γ (! B3),
cells (T H cells) function as the co-receptors. When an- while T H2 cells are required for B-cell activation
tigen binding occurs without co-stimulation (e.g., in
the liver, where there are no APCs), the lymphocyte (! C2). T H1 and T H2 cells mutually suppress
is inactivated, i.e., it becomes anergic, and peripheral each other, so only one of the two types will
immunologic tolerance develops. predominate in any given cell-mediated im-
mune response (! B3).
The T cell can receive APC dual signals from in-
fected macrophages or B cells, provided their Specific Immunity: Humoral Immune Responses
Blood receptors have bound the antigen in question Humoral immunity arise from B cells (! C1).
(e.g., insect or snake venom or allergens). The
4 APC dual signal induces the T cell to express in- Numerous IgD and IgM monomers anchored
onto the B-cell surface bind with the respec-
terleukin-2 (IL-2) and to bind the respective IL- tive antigen (dissolved IgM occurs in pen-
2 receptor (! B1). IL-2 is the actual signal for tameric form). A resulting network of antigen-
clonal expansion of these monospecific T cells.
It functions through autocrine and paracrine bound Ig leads to internalization and pro-
mechanisms. Potent immunosuppression, e.g., cessing of the antigen-antibody complex in B
cells. However, B-cell activation requires a sec-
for organ transplantation, can be achieved ond signal, which can come directly from a
with IL-2 inhibitors like cyclosporin A.
thymus-independent (TI) antigen (e.g., bacte-
During clonal expansion, the T cells differentiate into rial polysaccharide) or indirectly from a T H2 cell
three “armed” subtypes, i.e., T cytotoxic cells (T c cells in the case of a thymus-dependent (TD) an-
or T killer cells) and T helper cells type 1 (T H1 cells) tigen. In the latter case, the B cell presents the
and type 2 (T H2 cells). These cells no longer require
costimulation and express a different type of adhe- HLA-II-restricted TD antigen to the T H2 cell
sion molecule (VLA-4 instead of L-selectins) by which (! C2). If the CD4-associated T-cell receptor
they now dock onto the endothelium of inflamed tis- (TCR) of the T H2 cell recognizes the antigen,
sues (rather than to lymphatic tissue like their naïve CD40 ligands are expressed on the T H2 surface
precursors). (CD40 ligands bind with CD40 proteins on B
T killer cells develop from naive CD8-contain- cells) and IL-4 is secreted. The CD40 ligand and
+
ing (CD8 ) T cells after HLA-I-restricted an- IL-4 (later also IL-5 and IL-6) stimulate the B
tigen presentation (! B2). Endogenous an- cell to undergo clonal selection, IgM secretion,
tigen presentation occurs when the HLA-I pro- and differentiation into plasma cells (! C3).
tein takes up the antigen (virus, cytosolic pro- Before differentiation, class switching can
tein) from the cytosol of the APC, which is usu- occur, i.e., a different type of Ig heavy chain
ally the case. With its CD8-associated T-cell re- (! p. 92) can be expressed by altered DNA
ceptor, the T killer cell is able to recognize HLA- splicing (! p. 8f.). In this manner, IgM is con-
I-restricted antigens on (virus) infected en- verted into IgA, IgG or IgE (! p. 92). All Ig types
dogenous cells and tumor cells as well as on arising from a given B-cell clone remain mono-
cells of transplanted organs. It subsequently specific for the same antigen. The plasma cells
98 drives the cells into apoptosis (programmed formed after class switching produce only a
single type of Ig.
cell death) or necrosis. Binding of the Fas lig-
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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