Invasion of host tissue

■ Toxin-induced damage to host cells

Host-defense mechanisms act at each of these steps, and many bacteria have evolved ways to circumvent some of these host defenses (Table 17-3).

Some bacteria have surface structures or molecules that enhance their ability to attach to host cells. A number of gram-negative bacteria, for instance, have pili (long hairlike projections), which enable them to attach to the membrane of the intestinal or genitourinary tract (Figure 17-9). Other bacteria, such as Bordetella pertussis, secrete adhesion molecules that attach to both the bacterium and the ciliated epithelial cells of the upper respiratory tract.

Secretory IgA antibodies specific for such bacterial structures can block bacterial attachment to mucosal epithelial cells and are the main host defense against bacterial attachment. However, some bacteria (e.g., Neisseria gonorrhoeae, Haemophilus influenzae, and Neisseria meningitidis) evade the IgA response by secreting proteases that cleave secretory IgA at the hinge region; the resulting Fab and Fc fragments have a shortened half-life in mucous secretions and are not able to agglutinate microorganisms.

Some bacteria evade the IgA response of the host by changing these surface antigens. In N. gonorrhoeae, for example, pilin, the protein component of the pili, has a highly variable structure. Variation in the pilin amino acid sequence is generated by gene rearrangements of its coding sequence. The pilin locus consists of one or two expressed genes and 10-20 silent genes. Each gene is arranged into six regions called minicassettes. Pilin variation is generated by a process of gene conversion, in which one or more minicassettes from the silent genes replace a minicassette of the expression gene. This process generates enormous antigenic variation, which may contribute to the pathogenicity of N. gonorrhoeae by increasing the likelihood that expressed pili will bind firmly to epithelial cells. In addition, the continual changes in the pilin sequence allow the organism to evade neutralization by IgA.

Some bacteria possess surface structures that serve to inhibit phagocytosis. A classic example is Streptococcus pneu-moniae, whose polysaccharide capsule prevents phagocytosis very effectively. There are 84 serotypes of S. pneumoniae that differ from one another by distinct capsular polysaccharides.

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VISUALIZING CONCEPTS

VISUALIZING CONCEPTS

Toxin Neutralization

(J) Toxin neutralization

Complement activation

(J) Toxin neutralization

(2) Complement-mediated lysis

(3 Opsonization and phagocytosis

(J) Anaphylatoxins mediate mast cell degranulation

Complement activation

C3b C3b

C3b C3b

Macrophage

Macrophage

(2) Chemotaxis

Mast cell

(J) Anaphylatoxins mediate mast cell degranulation

(2) Chemotaxis

Mast cell

Antibodies Neutralizing Muscle

FIGURE 17-8

Antibody-mediated mechanisms for combating infection by extracellular bacteria. (1) Antibody neutralizes bacterial toxins. (2) Complement activation on bacterial surfaces leads to complement-mediated lysis of bacteria. (3) Antibody and the complement split product C3b bind to bacteria, serving as opsonins to increase phagocytosis. (4) C3a, C4a, and C5a, generated by antibody-initiated complement activation, induce local mast cell degranulation, releasing substances that mediate vasodilation and extravasation of lymphocytes and neutrophils. (5) Other complement split products are chemotactic for neutrophils and macrophages.

Host immune responses to bacterial infection and bacterial evasion mechanisms infection process

Host defense

Bacterial evasion mechanisms

Attachment to host cells

Blockage of attachment by secretory IgA antibodies

Secretion of proteases that cleave secretory IgA dimers (Neisseria meningitidis, N. gonorrhoeae, Haemophilus influenzae)

Antigenic variation in attachment structures (pili of N. gonorrhoeae)

Proliferation

Phagocytosis (Ab- and C3b-mediated opsonization)

Complement-mediated lysis and localized inflammatory response

Invasion of host tissues Ab-mediated agglutination

Production of surface structures (polysaccharide capsule, M protein, fibrin coat) that inhibit phagocytic cells Mechanisms for surviving within phagocytic cells Induction of apoptosis in macrophages (Shigella flexneri) Generalized resistance of gram-positive bacteria to complement-mediated lysis

Insertion of membrane-attack complex prevented by long side chain in cell-wall LPS (some gram-negative bacteria) Secretion of elastase that inactivates C3a and C5a (Pseudomonas)

Toxin-induced damage Neturalization of toxin by antibody to host cells

Secretion of hyaluronidase, which enhances bacterial invasiveness

During infection, the host produces antibody against the infecting serotype. This antibody protects against reinfection with the same serotype but will not protect against infection by a different serotype. In this way, S. pneumoniae can cause disease many times in the same individual. On other bacteria, such as Streptococcus pyogenes, a surface protein projection called the M protein inhibits phagocytosis. Some pathogenic staphylococci are able to assemble a protective coat from host proteins. These bacteria secrete a coagulase enzyme that precipitates a fibrin coat around them, shielding them from phagocytic cells.

Urethral Epithelial Cells

FIGURE 17-9

Electron micrograph of Neisseria gonorrhoeae attaching to urethral epithelial cells. Pili (P) extend from the gonococcal surface and mediate the attachment. [From M. E. Ward and P. J. Watt, 1972, J. Inf. Dis. 126:601]

FIGURE 17-9

Electron micrograph of Neisseria gonorrhoeae attaching to urethral epithelial cells. Pili (P) extend from the gonococcal surface and mediate the attachment. [From M. E. Ward and P. J. Watt, 1972, J. Inf. Dis. 126:601]

Mechanisms for interfering with the complement system help other bacteria survive. In some gram-negative bacteria, for example, long side chains on the lipid A moiety of the cell-wall core polysaccharide help to resist complement-mediated lysis. Pseudomonas secretes an enzyme, elastase, that inactivates both the C3a and C5a anaphylatoxins, thereby diminishing the localized inflammatory reaction.

A number of bacteria escape host defense mechanisms by their ability to survive within phagocytic cells. Some, such as Listeria monocytogenes, do this by escaping from the phago-lysosome to the cytoplasm, which is a more favorable environment for their growth. Other bacteria, such as Mycobacterium avium, block lysosomal fusion with the phagolysosome; and some mycobacteria are resistant to the oxidative attack that takes place within the phagolysosome.

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  • bisirat semhar
    What is antibodymediated agglutination of microbes?
    6 years ago

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