Page 54 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

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certain circumstances, even other endogenous (IFN), namely by IFN-α and IFN-β, which are re-
cells are unfavorably affected. leased by leukocytes and fibroblasts, as well as
Phagocytosis and lysosomal digestion are by IFN-γ, which is released from activated T
increased (and made possible in those bacteria cells and from the NK cells themselves. IFNs,
with polysaccharide capsules) when the anti- which are released especially from infected
gen surface is “larded” with IgM, IgG, or com- cells, also induce increased virus resistance in
plement component C3b (opsonification; cells which have not yet been infected. Defen-
→ A1, 2). Phagocytes have receptors for the an- sins are peptides (with ca. 30 amino acids) that
tigen-independent Fc part of the immunoglob- are released by phagocytes and act (among
ulins and for C3b, through which they can at- other methods, by forming ion channels in the
tach themselves to the opsonized antigen target cell membrane) in a nonspecific cyto-
(especially important for TI antigens; see be- toxic manner, even on pathogens that are re-
low). In this way the phagocytosis, which is ac- sistant to NK cells.
tually nonspecific, participates in specific im- Macrophages are formed from monocytes
mune defense. Furthermore, the mannose- that have immigrated or stay at one site (but
binding protein (MBP), which binds to mannan move freely there), such as the liver sinuses
groups (polymers of mannose) on the surface (Kupffer cells), pulmonary alveoli, splenic si-
of bacteria and some viruses, seems to have nuses, peritoneal lining, lymph nodes, skin
an opsonizing effect as a “nonspecific anti- (Langerhans cells), joints (synovial A cells),
body”. brain (microglia), and epithelium (e.g., renal
Blood with Ig (so-called classical path), but also glomeruli). Together they are referred to as
In addition, pathogens that are opsonized
the mononuclear phagocytotic system (MPS) or
3 those that are not opsonized (so-called alter- reticuloendothelial system (RES). Macrophages
native path) and possibly also MBP, set in mo- can recognize relatively nonspecific carbohy-
tion the complement cascade (→ A1). At the drate components on the surface of bacteria
end of this the membrane attack complex is and thereupon phagocytize and digest them.
formed from the complement components Macrophages have to be activated in order to
C5–C9. This complex perforates the outer be able to deal with those pathogens that sur-
wall of (Gram-negative) bacteria, which vive in the phagosomes (see below and B6).
causes their death. At the same time, lysozyme The specific cellular immmune defense by
(also present in plasma, lymph, and secretions) armed T effector cells that are activated rela-
breaks down the wall of bacteria enzymatical- tively slowly (taking days [delayed immune re-
ly (cytolysis; → A3). sponse]) presupposes that the prepared anti-
The so-called natural killer cells (NK cells, gen (peptide fragments) is presented to the
NKC) specialize in nonspecific defense, partic- passing naive T cells by “professional” anti-
ularly against viruses, mycobacteria, and tumor gen-presenting cells (APC) (presentation;
cells. They identify their “victims”, the patho- → B1). As a result the antigen is built into
gen, the virus infected cell or the tumor cell, MHC class I and MHC class II proteins, in hu-
by their foreign surface (lack of own HLA mans also called HLA class I or II, respectively
type; cf. below) or couple to their Fc receptors (HLA= human leukocyte antigen). (The appro-
on IgG-opsonized antigens on the surface of priate gene locus is the major histocompatibil-
the victim (antigen-dependent cell-mediated ity complex [MHC]). It is especially dendritic
cytotoxicity [ADCC]; → A3). In each case the cells, to be found mainly in lymphatic tissue,
killer cells perforate the victim’s membrane which act as APCs. For presentation (→ B1),
with exocytic perforins and thus cause the ICAM is bound on the APC surface to lympho-
death of the cell being attacked (cytolysis; cyte function-associated antigen 1 (LFA1) on
→ A3). This takes away not only the invading the T-cell membrane. When a T cell that is spe-
viruses’ ability to multiply (the cell’s enzyme cific for the antigen docks, the binding is
apparatus), but makes them (and also other in- strengthened and the T cell is activated by a
tracellular pathogens that are still alive) more double signal that triggers clone selection
44 vulnerable to attack from other defense sys- (→ B1). The double signal consists of: 1) recog-
tems. The NK cells are activated by interferons nition of the (HLA I–bound or HLA II–bound)
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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