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Chapter 16
Host Defenses
Against Microbes
NONSPECIFIC
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Nonspecific Defenses
What are Nonspecific Defenses?
Defenses that protect against any pathogen, regardless of species.
two nonspecific lines of defense:
first: skin and mucous membranes
second: phagocytes, inflammation, fever, and antimicrobial substances
Specific resistance (immunity) - third line of defense…
Effective against particular pathogens (covered in Ch. 17)
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Mechanical Barriers - Skin
largest organ of human body
consists of dermis, thick inner portion made of connective tissue; and
epidermis, thinner outer portion which contains sheets of tightly packed
epithelial cells
covered with outer layer of dead epidermal cells and waterproofing
protein, keratin
provides a barrier against penetration by microorganisms
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Mechanical Barriers - Mucous Membranes
Mucous membranes line gastrointestinal, respiratory, & genitourinary
tracts.
also have epithelial layer over connective tissue
secrete mucous (prevents drying)
less protective than skin (thinner barrier)
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Lacrimal Apparatus
group of structures which manufacture and drain away tears
continual washing keeps microorganisms from settling on the surface
of the eye
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Saliva
dilutes microbes in mouth…
washes microbes from surface of teeth
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Ciliary Escalator
in respiratory tract, cilia move mucous toward the throat, physically removes
microorganisms
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Genitourinary Tract
Two methods of nonspecific protection
urine flow helps prevent colonization by microbes
vaginal secretions move microorganisms out of the body
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Chemical Factors
Sebum produced by sebaceous (oil) glands forms protective film over
surface of skin, and fatty acids in it lowers the pH of the skin
low pH discourages bacterial growth
perspiration from sweat glands not only helps maintain body
temperature, but also flush microorganisms from the skin
Sweat contains lysozyme an enzyme which can breakdown the Grampositive cell wall (less effective against Gram-negatives)
Lysozyme is also found in tears, saliva, nasal secretions and tissue
fluids & gastric juice in stomach
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Phagocytosis
"cell eating", any cells which do this are called phagocytes
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Macrophage phagocytizing bacteria
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Let’s Meet the Phagocytes!
Components of Blood
plasma is the fluid portion
formed elements: cells and cell fragments (Table 16.1)
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White Blood Cells
Phagocytic & Non-Phagocytic
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Phagocytes are White Blood Cells
Leukocytes - white blood cells
changes in WBCs detected by differential white blood cell count
three categories of WBCs include”
granulocytes (grainy cytoplasm)
agranulocytes (non-grainy cytoplasm)
 monocytes
 lymphocytes
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Actions of Phagocytic Cells
Granulocytes and monocytes migrate to the site of the infection
Monocytes enlarge and become macrophages
Some leave the blood and migrate into surrounding tissues are known
as wandering macrophages
some, called fixed macrophages, are located in specific tissues and
organs
Together, these macrophages constitute the mononuclear phagocytic
(reticuloendothelial) system
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Order of Battle for Phagocytes
Granulocytes (esp. neutrophils) dominate phagocytic role in the initial
phase of a bacterial infection – extremely active phagocytes
Later in the infectious process macrophages (agranulocytes) become
dominant as the infection progresses
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Mechanisms of Phagocytosis
Four Steps of Phagocytosis
Chemotaxis - chemical attraction of phagocytes to microorganisms
Adherence - attachment of the phagocyte’s plasma membrane to the
surface of the microorganism
Ingestion - engulfment by pseudopods, produces phagosome
Digestion - phagosome fuses with lysosome (containing digestinve
enzymes) to form a phagolysosome
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Bacterial Digestion in Phagolysome
digestive enzymes are activated at low pH of about 4 and, along with
other toxic compounds, kill and digest the bacteria
The residual body is the phagolysome containing the remaining
undigestible material after digestion, which is then ejected from the cell
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Inflammation
functions (3) of inflammation…
Destroy infections agent & remove its toxic by-products
If destruction not possible – isolate the organism & its products to
prevent spread
Repair tissue damage
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Inflammation
…a defensive response triggered by damage to body tissues
symptoms include
redness
pain
heat
swelling
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Process of Inflammation
Damage occurs
Vasodilation (blood vessels expand)
Blood vessel permeability increases (become leaky so phagocytic
cells can leave bloodstream & enter tissues)
Phagocytes migrate to damaged area & begin cleaning up bacteria &
cellular debris
Damage tissue repaired
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Vasodilation
Vasodilation is the increase in diameter of blood vessels
increases blood flow to damaged areas
responsible for redness and heat associated with inflammation
increase permeability of blood vessels permits fluid and other elements
of blood to enter the injured area
responsible for edema (swelling) of inflammation
these effects caused by chemicals released by damaged cells
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Vasodilation Causing Substances
Substances which lead to vasodilation/permeability
histamine - released by injured cells, also a part of the complement
system
kinins - present in blood plasma, when active also play a role in
chemotaxis of phagocytic granulocytes
prostaglandins - released by damaged cells, intensifies effects of
histamines and kinins, helps phagocytes move through capillary walls
leukotrienes - produced by mast cells - increase permeablility of blood
vessels and help attach phagocytes to pathogens
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Phagocyte Migration
within 1 hour of initiation of inflammation, phagocytes arrive on the
scene
phagocytes stick to inner surface of lining of blood vessels (called
margination)
collected phagocytes squeeze between endothelial cells to reach the
damaged area (migration)
monocytes follow the granulocytes into the affected area
once in the tissue, the monocytes transform into macrophages &
actively phagocytize
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Tissue Repair
the final stage of inflammation
dead or damaged cells are replaced by new cells in stroma (connective
tissue) and parenchyma (functioning portion of tissue)
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Fever
abnormally high body temperature
most frequently caused by bacterial infection (or toxins) or viruses
Interleukin-1 (IL-1) – produced by phagocytes resets hypothalamic
thermostat to a higher temperature (may also be induced by endotoxins)
blood vessel constriction, increased rate of metabolism, and shivering
all contribute to temperature rise - maintained until IL-1 is eliminated
Higher body temperature makes some antiviral proteins (interferons)
more effective & may inhibit growth of some microbes
crisis: period of sweating, indicates that temperature is falling
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Antimicrobial Substances
Complement System
Interferons
both to be discussed in some detail in following slides…
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Complement System
Complement is a defensive system of blood serum proteins that
participate in lysis of foreign cells, inflammation, and phagocytosis
activated in two ways:
immune reaction of antibodies to antigens (classical pathway)
direct interaction of certain proteins with polysaccharides (alternative
pathway)
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components: at least 20 interacting proteins
major components labeled by numbering system from C1 to C9
alternative pathway consists of proteins called factor B, D, and P, along
with C3, C5-C9
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Common Link in Pathways
The factor in common between the Classical & Alternate pathway
Production of the activating factor
C3b
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Inflammation & Complement
Inflammation can be induced by the complement system…
When C5a & C3a bind to mast cells, histamine is released
C5a acts as a chemical signal to call in phagocytes (chemotaxis)
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Consequences Of Complement Activation
Cytolysis - complement system components damage the plasma
membranes of the foreign cells, causing them to leak
Inflammation - cleavage products from C3 and C5 can contribute to
the development of acute inflammation, C5a also a powerful
chemotactic factor
Opsonization - immune adherence -- binding of C3b to the microbe
can interact with receptors on phagocytes
Inactivation of complement -regulatory proteins quickly inactivate
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Interferons
Interferons (IFNs) - class of similar antiviral proteins produced by
certain animal cells in response to viral infection
How do they function? Interferons interfere with viral multiplication
Where do they come from? Excreted by host cell
What do they do? Stimulate production of antiviral proteins (AVPs) by
neighboring cells
AVPs are enzymes that disrupt various stages of viral multiplication
IFNs are effective for short times, and do not affect viral multiplication
in cells already infected
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