Chapter 16.

Innate Host
Defenses
Overview of Host Immunity
• Immunity: ability to defend against infection. Susceptibility: lack of immunity
• Innate Defenses
o First lines of defense against pathogens that do not depend on prior
exposure to infection.
o Cell Receptors: germline-encoded pattern recognition receptors (PRRs,
e.g., Toll-like receptors), used as sensors of foreign objects
(e.g., peptidoglycan on bacterial cell wall and viral ds-RNA)
o Mechanisms including
 Physical, chemical, and cellular barriers
 Inflammation, fever, phagocytosis
 Molecular defenses (complement systems and interferons)
• Adaptive Defenses
o Acquire defenses in response to exposure to antigens
o Activated later than innate defenses and are species-specific
o Cell receptors: antibody (B cell receptors) and T cell receptors are encoded
by genes assembled from somatic (non-germline) mutations and
recombinations
o Mechanisms
 Humoral (antibody-mediated) immunity: B cells produces
antibodies
 Cell-mediated immunity: T cells

Physical Barriers
• Skin: consists of epidermis (contains keratin, a protective protein at top layer) and
dermis
• Mucous membranes: contains epithelial layer and connective tissue layer, lining
up the entire gastrointestinal, respiratory and genitourinary tracts
• Tear, saliva, mucus, ciliary escalator, urine, vaginal secretions: washing, blocking
and trapping microbial invaders

Chemical Barriers
• Sebum (oily secretion) maintains low pH (3 - 5) of the skin
• Perspiration, tear, saliva contain lysozyme to breakdown bacterial cell walls
 • Gastric juice prevent most bacterial growth: Helicobacter pylori produce
ammonia to neutralize stomach acid to grow (and cause peptic ulcers)
• Defense by normal microflora: competitive exclusion (preventing pathogenic
microbes from colonizing skin and gastrointestinal tract)
• Transferrins bind to free iron to inhibit bacterial growth

Defensive Cells (Leukocytes)

• Granulocytes
o Basophils & Mast Cells: release histamine to initiate inflammatory
responses
o Eosinophils: involved in allergic reactions and defenses against worm
infections
o Neutrophils: a type of phagocytes that migrate quickly to infected sites;
having a short life span
o Dendritic cells: also phagocytic; plays critical role in initiation of adaptive
responses
• Agranulocytes
o Monocytes: develops into macrophages (some staying in tissues while
other wandering in blood); longer-living than neutrophils.
o Lymphocytes: B- and T-cells for adaptive defenses
o Natural killer (NK) cells: releases cytotoxic enzymes to kill virus-infected
cells

Phagocytosis
• Definition: Ingestion of a microorganism or particles by a cell. Phagocytic cells
are called phagocytes, e.g. macrophages, neutrophils, and dendritic cells

• Mechanism: (1) chemotaxis (chemical attraction of phagocytes to

microorganisms); (2) adherence (attachment of phagocytes to the surface of
invaders); (3) ingestion (surrounding of the microorganism by phagocyte's plasma
membrane); (4) digestion (phagocytes contain digestive enzymes); (5) excretion
(release of undigested material by exocytosis)

Inflammation
• Definition: a defensive responses to infection, physical or chemical injury,
indicated by redness, pain, heat and swelling.
• Mechanism: (1) histamine release by the damaged cells; (2) vasodilation
(widening and increased permeability of blood vessels, the cause of redness and
swelling); (3) phagocytosis (causing destruction of microorganisms); (4) tissue
repair (new tissues replace the damaged ones)
 • Beneficial effects of inflammation:Destruction of injurious agents; limit the
extend of damage (trapping of microorganisms through blood clotting); tissue
repair

Fever
• Definition: a systematic defensive response caused by infection from bacteria and
virus, indicated by abnormal high body temperature.
• Mechanism: Hypothalamus is body's thermostat, usually set at 37oC.
(1)Phagocytosis; (2) destruction of bacteria and release of LPS
(lipopolysacchride, an endotoxin); (3) interleukin-1 released by the macrophage
reset the hypothalamus to a high temperature, producing fever (body generates
extra heat through e.g. shivering)
• Beneficial effects of fever: inactivating temperature-sensitive bacteria and viruses;
stimulate specific defenses; increases the antiviral effect of interferons; speed up
metabolism for tissue repair

Molecular Defenses
• The complement system:
o A non-specific defense system consisting of serum proteins.
o Outcomes of complement activation
 Opsonization:enhancing phagocytosis by coating the bacterial cell
surface
 Inducing inflammation
 Causing cell lysis, or destruction of foreign cells by damaging their
cell plasma membranes

• Interferons:
o IFNs are a class of anti-vial proteins that disrupt viral multiplication
o Mechanism: viral infected cells activate the expression of IFNs, which are
released and stimulate the production of antiviral proteins of neighboring
cells. The antiviral proteins block viral replication. Not very effective,
because IFNs are short-lived and no effect for the infected cells
o Nonspecific to viral types