Page 55 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

antigen by the T-cell receptor with its corecep- After HLA II–associated presentation of the
tor (CD8 in cytotoxic T cells and CD4 in helper antigen (from intracellular vesicles, e.g.,
T cells [see below]), and 2) the costimulation phagocytized bacteria or proteins of the viral
signal, i.e., the binding of the B7 protein (on membrane), the CD4-T cells change into im-
the APC) to the CD28 protein of the T cell. (If mature effector T cells (T H0 ). Through differen-
antigen binding occurs without costimulation tiation these turn into helper T cells, either in-
[e.g., in the liver, where there are usually no flammatory T cells (T H1 ), which activate macro-
APCs], the lymphocytes are actually inactivat- phages by means of IFN-γ (→ B6), or Type 2
ed, i.e., they become anergic [peripheral im- helper T cells (T H2 ), which are essential for B
mune tolerance]). The T cell can also obtain cell activation (→ B4). These two cell types in-
the APC double signal from infected macro- hibit each other (suppression), so that only one III
phages or from B cells that have taken up the type predominates once the course is set
antigen with their receptors (e.g., insect or (→ B6). II +
snake poisons, allergens). The APC double sig- The specific humoral immune defense origi-
nal starts the expression of interleukin 2 (IL-2) nates in B lymphocytes (→ B3). IgD and mono- Defense
in the T cell as well as the incorporation of the mers of IgM are anchored on their surface (dis-
appropriate IL receptor into the cell membrane. solved IgM is present in the form of penta-
IL-2 (or IL-4, IL-7, IL-15) is the actual (autocrine mere); several of which bind to the appropri- Immune
and paracrine active) signal for clonal expan- ate antigen. The resulting antigen cross-linkage
sion of these monospecific T cells. In this pro- causes internalization and processing of the an-
cess the T cells differentiate into three armed tigen–antibody complex. However, a second
types (killer T cells, T H1 -cells and T H2 -cells) signal is essential for the subsequent activa-
that no longer require costimulation and ex- tion of the B cells. In the case of the so-called
press new adhesion molecules (VLA-4 instead thymus-independent (TI) antigens this can
of L-selectin), so that they are now “anchored” come from the antigens themselves (e.g., bac-
on the endothelium of inflammatory tissue terial polysaccharides); in the case of thymus-
portions (and not in lymphatic tissue as are dependent (TD) antigens it comes from T H2
their naive mother cells). The importance of cells to which the B cells present the HLA II–as-
the IL signal can also be judged from the fact sociated TD antigen (→ B4). Should the T-cell
that highly effective immune suppression can receptor of the T H2 cell “recognize” the antigen,
be achieved with IL inhibitors such as cyclo- it expresses the CD40 ligand (which binds to
sporin A or rapamycin (e.g., in organ transplan- the CD40 protein of the B cell) on the surface
tations). and also secretes IL-4. CD40 ligand and IL-4
Cytotoxic T cells (killer T cells) originate (later also IL-5 and IL-6) trigger clonal selection
from naive CD8 T cells after HLA I–associated of the B cells, secretion of monospecific IgM,
antigen presentation, HLA I having mostly and differentiation to plasma cells. Depending
taken its antigen from the cytosol (viruses, cy- on recoding for the Fc region (class jump,
tosolic proteins, endogenous antigen presenta- switch), these now produce IgA, IgG, or IgE in
tion). Through their CD8-associated T-cell re- such a way that all Ig originating from one
ceptors, the cytotoxic T cells then recognize B cell clone is specific for the same antigen.
the corresponding HLA 1–bound antigen on
the surface of (virus) infected body cells, tu-
mor cells, and cells of transplanted organs,
and kill them (→ B2). Perforins form pores
through which granzyme B (protease) reaches
the inner cell and cause both apoptosis and cy-
tolysis. Apoptosis is also caused by binding of
the CD95 ligand of the T cell to CD95 (= Fas) of
the target cell (→ B2 and p.12).
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Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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