The immune response to extracellular bacteria involves antibodies targeting bacterial capsular polysaccharides, exotoxins, and extracellular enzymes. Complement activation promotes opsonization and lysis of bacteria, and recruits phagocytic cells to the infection site. Neutrophils, monocytes, and macrophages phagocytose and kill ingested extracellular bacteria through microbicidal actions. Complement activation and phagocytosis are key innate immune responses that help rid the body of invading extracellular bacteria.

1. Immunity to Bacteria
The immune response to extracellular bacteria must counteract
all of the mechanisms of invasion elicited by these organisms.
The immune response includes-
● antibodies to capsular polysaccharides,
● to exotoxins (e.g., antistreptolysin 0 [ASO]),
● and to extracellular enzymes (antihyaluronidase)
Antibodies to tetanus toxin or diphtheria toxin can neutralize the
effects of these toxins and prevent host tissue destruction.
Complement activation promotes effective opsonization
with and without antibody. The membrane attack complex of the
terminal complement components are required to lyse and
eliminate certain gram-negative organisms (Neisseria spp.).
For other gram-negative bacteria, a synergistic
destruction by complement in conjunction with lysozyme is
necessary. Complement activation is also necessary to release
chemotactic factors to attract phagocytic cells to the site of
infection.

2. Endotoxins elicited from certain gram-negative bacteria can initiate the
activation of the complement alternative pathway in the absence of
antibody. Endotoxin can also degranulate neutrophils, enhance
cytotoxicity, and prompt a variety of other severe metabolic and
potentially lethal effects if gram-negative bacterial infections are not
efficiently treated. Immunity to intracellular pathogens is primarily
cellular immunity, i.e., delayed T-cell hypersensitivity involving
lymphocytes, cytokines, and macrophages. There are only two methods
available to detect delayed T-cell hypersensitivity: in vivo cutaneous
injection of purified antigens skin or anergy testing) or in vitro
lymphocyte transformation studies with purified antigens. Neither
method is highly reproducible and may be falsely negative due to the
immunosuppression experienced by individuals suffering from
invasion by intracellular pathogens. In many situations, antibody is
produced, but serves no demonstrable protective mechanism. If
antibody production is stimulated by the intracellular
pathogen, detection of that antibody and its class specificity can be
useful in diagnosing the invading organism(s).

3. Immunopathology of bacterial infection
Bacterial pathogens induce potent innate and adaptive immune
responses, which, in the majority of situations, are able to eradicate an
infection. This often is associated with nflammatory damage to the
infected tissues, and the balance of the virulence of the pathogen and
the timing and intensity of the host immune responses to the pathogen
determines the extent of the pathological damage to the host.
Extracellular and intracellular bacterial pathogens induce different types
of immune responses and have varying strategies for evading the host
immune responses. As a consequence, this can cause different patterns
of immunopathology. Some organisms can survive within a specialized
cellular niche despite a strong immune response and such bacteria
establish chronic infection, often in the absence of overt clinical disease.
Impairment of the host immune response may result
in unrestrained replication of bacterial pathogens and this may lead to
exaggerated damage of the infected tissue or to a different pattern of
immunopathology to that developing in an immunocompetent host.

4. Because extracellular bacteria can grow rapidly and produce
toxins, some are potent pathogens. To combat these
bacteria, higher organisms have developed a facet of the immune
system centered on antibody molecules, complement, and
phagocytes. This facet of the immune system is composed of
multiple layers of protection. In the early stage of an
infection, complement, phagocytes, and natural antibodies cross-
reacting with many antigens are important in host defense. During
the late stage of an infection, pathogen-specific antibodies appear.
These antibodies generally mediate the ultimate protection against
extracellular bacteria by triggering the protective effects of
complement and phagocytes. Although antibody molecules are
central to the process, host defense requires a broad diversity of
molecules (including CRP, TLRs, and transferrin), and antibody
molecules may cause damage instead of protection. A better
understanding of how this facet of the immune system protects
against each pathogen will aid in the development of more effective
preventive and therapeutic measures against these pathogens.

5. Pathology Of Extracellular Bacterial Infections
Bacteria rapidly colonize the skin and mucosa of the upper airways, gut, and
genital tract of mammals following birth, and the host is soon exposed to many
bacterial pathogens. Minor abrasions of the skin or mucosal surfaces permit
bacteria to enter the extracellular spaces where they are provided with rich
nutrients and rapidly replicate. The immediate or innate host immune responses
rapidly eradicate the infection in the case of most bacteria, but bacterial
pathogens have either specific virulence mechanisms or immune evasion
strategies, which allow them to persist for hours to days, and to disseminate to
other organs. The continuing innate immune responses and subsequent adaptive
immune response causes the recruitment and activation of leukocytes,
which may control the infection but at the expense of necrotic damage to the
infected host tissues. In addition, some bacteria secrete exotoxins, which lyse
host cells or bind to specific receptors resulting in characteristic damage to the
host. Examples of exotoxins, which directly damage host cells, are the
poreforming toxin of Staphylococcus aureus and streptolysin O from
Streptococcus pyogenes (Group A) or pneumolysin from
Streptococcus pneumoniae, both of which damage cell membranes leading to
lysis.

6. Innate immunity against extracellular
Neutrophil (PMN), monocyte, and tissue macrophage
phagocytosis leads to rapid microbicidal action against
ingested microbes from the extracellular environment.
The capacity of a microorganism to resist phagocytosis
and digestion in phagocytic cells is a principal feature of
its virulence. Complement activation represents a
significant mechanism for ridding the body of invading
microorganisms. A peptidoglycan layer in the cell walls
of Gram-positive bacteria as well as
lipopolysaccharide, or LPS in the cell walls of Gram-
negative bacteria are able to activate the alternative
pathway of complement without antibody. Also
associated with LPS is flagellar antigen and somatic