HOST DEFENSES

 Host defenses are composed of two

complementary, frequently interacting
systems:
 (1) innate (nonspecific)defenses, which protect
against microorganisms in general
 (2) adaptive (specific) immunity, which
protects against a particular microorganism.
 Innate defenses
 The first line of defense against pathogens is
the innate, or non-specific, immune response.
Innate defenses can be classified into three
major categories:
 (1) physical barriers, such as intact skin and
mucous membranes
 (2) phagocytic cells, such as neutrophils,
macrophages, and natural killer cells
 (3) proteins, such as complement, lysozyme,
and interferon.
INNATE (NONSPECIFIC) IMMUNITY
 Skin & Mucous Membranes
 Inflammatory Response & Phagocytosis
 Fever
 Skin & Mucous Membranes

 Intact skin is the first line of defense against many organ-

isms. In addition to the physical barrier presented by
skin, the fatty acids secreted by sebaceous glands in the
skin have antibacterial and antifungal activity.
 A second important defense is the mucous membrane of
the respiratory tract, which is lined with cilia and
covered with mucus. The coordinated beating of the cilia
drives the mucus up to the nose and mouth, where the
trapped bacteria can be expelled. This mucociliary
apparatus, the ciliary elevator can be damaged by
alcohol, cigarette smoke, and viruses; the damage
predisposes the host to bacterial infections.
 Other protective mechanisms of the respiratory
tract involve alveolar macrophages, lysozyme in
tears and mucus, hairs in the nose, and the cough
reflex, which prevents aspiration into the lungs.
 The nonspecific protection in the gastrointestinal
tract includes hydrolytic enzymes in saliva, acid in
the stomach, and various degradative enzymes and
macrophages in the small intestine. The vagina of
adult women is protected by the low pH generated
by lactobacilli that are part of the normal flora.
 Additional protection in the gastrointestinal
tract and in the lower respiratory tract is
provided by defensins. These are highly
positively charged (cationic) peptides that
create pores in the membranes of bacteria,
which kills them.
 Inflammatory Response
 The presence of foreign bodies, such as bacteria within the
body, provokes a protective inflammatory response
 this response is characterized by the clinical findings of
redness, swelling, warmth, and pain at the site of infection.
These signs are due to increased blood flow, increased
capillary permeability, and the escape of fluid and cells into
the tissue spaces.
 The increased permeability is due to several chemical
mediators, of which histamine, prostaglandins, and
leukotrienes are the most important.
 Complement components, C3a and C5a, also contribute to
increased vascular permeability. Bradykinin is an important
mediator of pain.
 Neutrophils and macrophages, both of which are
phagocytes, are an important part of the inflammatory
response. Neutrophils predominate in acute pyogenic
infections, whereas macrophages are more prevalent in
chronic or granulomatous infections.
 Macrophages perform two functions: they are phagocytic
and they produce two important “proinflammatory”
cytokines: tumor necrosis factor (TNF) and interleukin-1
 Certain proteins, the best known of these are C-reactive
protein and mannose-binding protein, which bind to the
surface of bacteria and enhance the activation of the
alternative pathway of complement
 Neutrophils and macrophages are attracted to
the site of infection by small polypeptides
called chemokines (chemo-tactic cytokines).
Chemokines are produced by tissue cells in the
infected area, by local endothelial cells, and by
resident neutrophils and macrophages.
 phagocytosis
 Phagocytosisis the process of engulfment and
destruction of solid particles such as bacteria,
dead tissue and foreign particles by the cells.
 The cells performing phagocytosis are called
phagocytes.
 The cell types are
Neutrophils
Monocytesand
Macrophages
 Steps
 1.Margination
 2.Diapedesis
 3.Chemotaxis
 4.Opsonization→ attachment stage
 5.Engulfment stage
 6.Secretion (degranulation) stage
 7.Degradation stage
Margination (migration +
adhesion)
Diapedesis the passage of blood
cells through the intact walls of the
capillaries,
Chemotaxi
s
Chemotaxi
s
 Potent chemotactic substances or
chemokines are
• Leukotriene
• C5a, C3a
• Cytokines
 Opsonization → Attachment
stage
• Opsonization refers to the process of coating of
bacteria by the opsonins.
• The principal opsonins are IgG opsonin and
C3b opsonin.
• The opsonin coated bacteria gets attached to
the surface of phagocyte through the opsonin
receptors
 Engulfment

• Formation of cytoplasmic pseudopods by the

phagocytes around the bacteria.
• The bacteria is endocytosed and is contained
in a vesicle thus forming a phagosome
• The phagosome fuses with nearby lysosome
to form phagolysosome.
Engulfment stage

Pseudopodia
 Degranulation stage
• Release of lysosomal enzymes into the vesicles
 Degradation stage
• Oxygen dependent bactericidal mechanism
mediated by oxidizing agents
(hypochlorite ion).

• Oxygen independent bactericidal mechanism

mediated by lysosomal enzymes.
 Fever
 Infection causes a rise in the body temperature
that is attributed to endogenous pyrogen (IL-1)
released from macrophages. Fever may be a
protective response because a variety of
bacteria and viruses grow more slowly at
elevated temperatures.