CHAPTER 15 NONSPECIFIC HOST DEFENSE MECHANISMS Skin and Mucous Membranes as Physical Barriers

INTRODUCTION ● Skin - The intact, unbroken skin that covers our bodies represents a
> Host defense mechanisms - ways in which the body protects itself nonspecific host defense mechanism, in that it serves as a physical or
from mechanical barrier to pathogens.
pathogens - can be thought of as an army consisting of three ○helminth infections (e.g., hookworm infection, schistosomiasis) are
lines of
acquired by penetration of the skin by parasites; it is unlikely that
defense
many,
if any, bacteria are capable of penetrating intact skin.
> Nonspecific host defense mechanisms - the first two lines of defense
○ Even the tiniest of cuts can serve as portals of entry for pathogens.
are
nonspecific; - these are ways in which the body attempts to
destroy all ● Mucous Membranes - The sticky mucus that is produced by goblet
types of substances that are foreign to it, including pathogens; - cells within the mucous membranes serves to entrap invaders; thus, it is
are considered part of the first line of defense.
general and serve to protect the body against many harmful Cellular and Chemical Factors
substances. Factors that inhibits colonization by many pathogens:
× Dryness of most areas of skin; Acidity (pH _5.0); Temperature (_37°C)
○innate or inborn resistance - observed among some species of
× Oily sebum that is produced by sebaceous glands in the skin contains
animals
fatty acids, which are toxic to some pathogens.
and some persons who have a natural resistance to certain
× Perspiration by flushing organisms from pores and the surface of the
diseases.
skin; contains the enzyme, lysozyme, which degrades peptidoglycan in
> Specific host defense mechanisms - the third line of defense, the bacterial cell walls (especially Gram-positive bacteria)
× Sloughing off of dead skin cells removes potential pathogens from the
immune
response, is very specific. skin.
× Sticky Mucuos – trap pathogens and contains
○antibodies - special proteins, usually produced in the body in
> Lyzozyme - destroys bacterial cell walls by degrading
response
peptidoglycan.
to the presence of foreign substances
> Lactoferrin - is a protein that binds iron, a mineral that is
○antigens - are the foreign substances “antibody-generating” required by all pathogens.
substances because they stimulate the production of specific > Lactoperoxidase - is an enzyme that produces superoxide
antibodies radicals, highly reactive forms of oxygen, which are toxic to
bacteria.
FIRST LINE OF DEFENSE
||| Respiratory system would be particularly accessible to invaders that > Candida albicans in the vagina may lead to yeast vaginitis.
could ride in on dust or other particles inhaled with each breath||| > Clostridium difficile in the colon may lead to C. difficile–associated
diseases known as antibiotic-associated diarrhea (AAD) and
× Cilia (mucociliary covering) - present on epithelial cells of the pseudomembranous colitis (PMC).
posterior nasal membranes, nasal sinuses, bronchi, and trachea sweep
the trapped dust and microbes upward toward the throat, where they ● Bacteriocins - antibacterial substances are bacteria produce proteins
are swallowed or expelled by sneezing and coughing.
that kill other bacteria: narrower range of activity than do antibiotics,
× Swallowing of saliva because thousands of bacteria are removed from
but
the oral cavity every time we swallow. Humans swallow approximately
they are more potent than antibiotics.
1 L of saliva per day.
Ex:
× Pathogens entering the GI tract are often killed by digestive enzymes
> Colicin produced by certain strains of Escherichia coli
or the acidity of stomach (pH 1.5) or alkalinity of intestines
> Other Bacteriocins produced by some strains of Pseudomonas and
Bacillus species as well as by certain other bacteria
||| Peristalsis and urination serve to remove pathogens from the GI tract
and urinary tract, respectively. |||
SECOND LINE OF DEFENSE
Transferrin
× The low pH of vaginal fluid usually inhibits colonization of the vagina
a glycoprotein synthesized in the liver, has a high affinity for iron;
by pathogens.
normal function is to store and deliver iron to host cells; sequestering
Microbial Antagonism
iron and depriving pathogens of this essential nutrient.
When resident microbes of the indigenous microflora prevent
colonization by new arrivals to a particular anatomical site
Fever
body temperature greater than 37.8°C (100°F); slow down the rate of
The inhibitory capability of the indigenous microflora has been
growth of certain pathogens and can even kill some especially fastidious
attributed to the following factors:
pathogens.
×Competition for colonization sites
| Normal Body Temp. = 36.2°C and 37.5°C (97.2°F and 99.5°F)
×Competition for nutrients
| Average Body Temp. = 37°C (98.6°F).
×Production of substances that kill other bacteria

● Pyrogens or pyrogenic substances - substances that stimulate the

● Superinfection - overgrowth by bacteria or fungi that are resistant to
production of fever
the antibiotic(s) being administered or “population explosion” of
>Pyrogens from outside the body include pathogen and various
organisms; The antibiotics reduce or eliminate certain members of the
pyrogenic substances that they produce or release (e.g., endotoxin)
indigenous microflora (e.g., the vaginal and gastrointestinal flora)
Ex:
>Pyrogen that is produced within the body include Interleukin 1 (IL-1)
(i.e., it is an endogenous pyrogen).
Fever augments the host’s defenses in the following ways:
× By stimulating white blood cells (leukocytes) to deploy and destroy
invaders
× By reducing available free plasma iron, which limits the growth of
pathogens that require iron for replication and synthesis of toxins
× By inducing the production of IL-1, which causes the proliferation,
maturation, and activation of lymphocytes in the immunologic response
Interferons
are small, antiviral proteins produced by virus infected cells; they
“interfere” with viral replication;
- not virus specific, meaning that they are effective against a variety of
viruses, not just the particular type of virus that stimulated their
production;
- species-specific, meaning that they are effective only in the species of
animal that produced them.
three known types of interferon:
> alpha α-Interferon is produced by B lymphocytes (B cells),
monocytes, and
macrophages;
>beta β-interferon, by fibroblasts and othervirus-infected cells;
>gamma γ-interferon, by activated T lymphocytes (T cells) and natural
killer cells (NK cells).
The Complement System
is not a single entity, but rather a group of approximately 30 different
proteins (including nine proteins designated as C1 through C9) that are
found in normal blood plasma.
it is complementary to the action of the immune system.
it assists in the destruction of many different pathogens.
● Complement components - the proteins of the complement system,
● Complement cascade - stepwise manner where the complement
components interact with each other
The major consequences of complement activation are listed here:
× Initiation and amplification of inflammation
× Attraction of phagocytes to sites where they are needed (chemotaxis;
to be discussed later)
× Activation of leukocytes
× Lysis of bacteria and other foreign cells
× Increased phagocytosis by phagocytic cells (opsonization)
● Opsonization - is a process by which phagocytosis is facilitated by the
deposition of opsonins, such as antibodies or certain complement
fragments, onto the surface of particles or cells.
> One of the products formed during the complement cascade, called
C3b, is an opsonin. It is deposited on the surface of microorganisms.
Neutrophils and macrophages possess surface molecules (receptors)
that can recognize and bind to C3b.
> Complement fragments C3a, C4a, and C5a cause mast cells to
degranulate and release histamine, leading to increased vascular
permeability and smooth muscle contraction.
Acute-Phase Proteins
Plasma levels of molecules; increase rapidly in response to infection,
inflammation, and tissue injury.; enhancing resistance to infection and
promoting the repair of damaged tissue.

> C-reactive protein (which is used as a laboratory marker for, or
indication of, inflammation), serum amyloid A protein, protease
inhibitors, and coagulation proteins.
Cytokines
are chemical mediators that are released from many different types of
cells
in the human body.
Enable cells to communicate with each other and act as chemical
messengers both within the immune system and between the immune
system and other systems of the body.
Inflammation or inflammatory response
a complex series of events where the body normally responds to any
local injury, irritation, microbial invasion, or bacterial toxin
The three major events in acute inflammation are:
× An increase in the diameter of capillaries (vasodilation), which
increases blood flow to the site
× Increased permeability of the capillaries, allowing the escape of
plasma and plasma proteins
× Escape of leukocytes from the capillaries and their accumulation at
the site of injury
The primary purposes of the inflammatory response are to:
× Localize an infection
× Prevent the spread of microbial invaders
× Neutralize any toxins being produced at the site (destroy and detoxify
pathogens)
× Aid in the repair and healing of damaged tissue
Vasodilation - an increase in the diameter of capillaries,—leads to
redness, heat, and edema.; mediated by vasoactive agents (e.g.,
histamine and prostaglandins) released from damaged cells.
The four cardinal or main signs and symptoms of inflammation are
> Redness and heat vasodilation allows more blood to flow to the site
> Swelling (edema; edematous) Plasma escapes from the capillaries into
the surrounding area
> Heat results from increased metabolic activities in the tissue cells at
the site.
> Pain result from actual damage of the nerve fibers because of the
injury, irritation by microbial toxins or other cellular secretions (such
as prostaglandins), or increased pressure on nerve endings because of
the edema.
● Inflammatory Exudate - the accumulation of fluid, cells, and cellular
debris at the inflammation site
> purulent exudates or pus - exudate is thick and greenish yellow,
containing
many live and dead leukocytes
● Pyogenic Microbes (pus-producing microbes), such as staphylococci
and streptococci, the exudate is often bluish green in infections caused
by Pseudomonas aeruginosa; caused by the bluish green pigment
(called pyocyanin)
● Lymphatic System - the primary functions include draining and
circulating intercellular fluids from tissues, transporting digested fats
from the digestive system to the blood, removing foreign matter and
microbes from the lymph, and producing antibodies and other factors
to aid in the destruction and detoxification of any invading microbes.
 Phagocytosis and much more efficient at phagocytosis than eosinophils
the process by which phagocytes (phagocytic white blood cells)
surround and engulf (ingest) foreign material >Macrophages produces monocytes inflammatory response to
infections;
found in tissues of the reticuloendothelial system (RES).
● Professional Phagocytes two most important groups of phagocytes in Wandering macrophages leave thebloodstream and migrate to
the human body infected
> macrophages “cleanup crew” to rid the body of unwanted and often areas
harmful substances, such as dead cells, unused cellular secretions, Fixed macrophages (also known as histocytes or histiocytes)
debris, and microorganisms. remain
> neutrophils most abundant and much more efficient at phagocytosis within tissues and organs and serve to trap foreign debris.
than eosinophils
>Lymphocytes
Cellular Elements of Blood B cells recognize the surface antigens of bacteria and viruses
1. Erythrocytes (red blood cells) T cells recognize viral antigens outside the infected cells
2. Thrombocytes (platelets) × Helper T cells (TH cells) help activate B cells to secrete
3. Leukocytes (white blood cells) antibodies
Three major categories of leukocytes and macrophages to destroy ingested microbes, and also help
>Granulocytes named for the prominent cytoplasmic granules activate
that they cytotoxic T cells
possess. × Cytotoxic T cells (TC cells) kill infected target cells.
Basophils involved in allergic and inflammatory reactions, Natural killer cells (NK cells) host-rejection of both tumours and
contain virally
histamine and other chemical mediators. infected cells.
Eosinophils involved in parasitic infection, an allergic reaction
or cancer Four Steps in Phagocytosis
× eosinophilia abnormally high number of eosinophils in 1.Chemotaxis- the directed migration when phagocytes move to the site
the where they are needed.
peripheral bloodstream ex. allergies and ● chemotactic agents is the result of chemical attractants (also called
helminthinfections chemotactic factors, chemotactic substances, and chemoattractants)
Neutrophils (polymorphonuclear cells, polys, and PMNs) most produced during the complement cascade and inflammation
abundant
 > chemokines - chemotactic agents that are produced by various cells
of the human body
||| The phagocytes move along a concentration gradient (low to high
chemotactic agents concentration); highest concentration is the site
where the chemotactic agents are being produced or released— often
the site of inflammation. |||
2.Attachment- attachment of the phagocyte to the object (e.g., a yeast or
bacterial cell) to be ingested; Phagocytes can only ingest objects to
which they can attach.
3.Ingestion - the phagocyte then surrounds the object with
pseudopodia, which fuse together, and the object is ingested (is
phagocytized or phagocytosed)
Phagocytosis is one type of endocytosis, the process of ingesting
material from outside a cell. Phagosome membrane-bound vesicle
4.Digestion - the phagosome next fuses with a nearby lysosome to form
a digestive vacuole (phagolysosome), within which killing and
digestion occur.
Mechanisms by which Pathogens Escape Destruction by Phagocytes
Capsules serve an antiphagocytic function, protecting encapsulated
bacteria from being phagocytized
● leukocidin an exoenzyme produced by bacteria which kills
phagocytes
For example, waxes in the cell wall of Mycobacterium tuberculosis
protect the organism from digestion.
Ehrlichia and Anaplasma spp., closely related to rickettsias, are
obligate, intracellular, Gram-negative bacteria that live within
leukocytes (i.e., they are intraleukocytic pathogens). These organisms
cause two endemic, tickborne diseases in the United States.
> Ehrlichia spp. cause human monocytic ehrlichiosis (HME), a
condition in
which the bacteria infect monocytic phagocytes.
> Anaplasma spp. cause human anaplasmosis (or human granulocytic
ehrlichiosis (HE) , as it is sometimes called), a condition in which the
bacteria
infect granulocytes.
Disorders and Conditions that Adversely Affect Phagocytic and
Inflammatory Processes
Leukopenia
Condition where the patient have an abnormally low number of
circulating leukocytes; may result from bone marrow injury as a result
of ionizing radiation or drugs, nutritional deficiencies, or congenital
stem cell defects.
● Neutropenia -is an abnormally low number of circulating
neutrophils; neutropenia = neutrophilic leukopenia.)
Disorders and Conditions Affecting Leukocyte Motility and
Chemotaxis
The inability of leukocytes to migrate in response to chemotactic agents
may be related to a defect in the production of actin, a structural
protein associated with motility.

● Chediak-Higashi syndrome (CHS) decreased neutrophil chemotaxis

also occurs in the inherited childhood disease

Disorders and Conditions Affecting Intracellular Killing by Phagocytes

The phagocytes of some individuals are capable of ingesting bacteria,

but are incapable of killing certain species. usually the result of
deficiencies in myeloperoxidase or an inability to generate superoxide
anion, hydrogen peroxide, or hypochlorite

● Chronic granulomatous disease (CGD) is an often fatal genetic

disorder that is characterized by repeated bacterial infections.