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Chapter 15
Nonspecific Lines of Defense
Vocabulary
Interferons Interleukin pyrogens defensins Interferon
Complement Properdin Pathway
Lysozyme phagocytosis
Eosinophils Langerhans
cells microglia
Küpffer cells Basophils Eosinophils Neutrophils
Innate Resistance
" Resistance to most
plant and animal pathogens
" Resistance due to
physiological processes of humans that are incompatible with those of the
pathogen
" Correct
chemical receptors not present on human cells
" Temperature
and pH may be incompatible with those necessary for the pathogens survival
" When humans don’t
have innate resistance to a pathogen, that organism may cause disease
First Line of Defense
" Structures,
chemicals, processes that work to prevent pathogens entering the body
" Nonspecific defenses
" Includes the skin
and mucous membranes of the respiratory, digestive, urinary, and reproductive
systems
Skin – Physical Components of
Defense
" Two major layers
" Epidermis
" Outer layer
composed of multiple layers of tightly packed cells
" Few
pathogens can penetrate these layers
" Shedding of
dead skin cells removes attached microorganisms
" Epidermal
dendritic cells
" Also termed
Langerhans cells
" Phagocytize
pathogens
Skin – Physical Components of
Defense
" Dermis
" Contains
protein fibers called collagen
" Give skin
strength and pliability to resist abrasions that could introduce microorganisms
Skin – Chemical Components of
Defense
" Perspiration
secreted by sweat glands
" Salt-
inhibits growth of pathogen by drawing water from their cells
" Lysozyme-
destroys cell wall of bacteria
" Sebum secreted by
sebaceous (oil) glands
" Helps keep
skin pliable and less likely to break or tear
" Lowers the
pH of the skin to a level inhibitory to many bacteria
Mucous Membranes
" Line all body
cavities open to the outside environment
" Two distinct
layers
" Epithelium
" Deeper
connective layer that supports the epithelium
Epithelium
" Thin, outer
covering of the mucous membranes
" Unlike surface
epidermal cells, epithelial cells are living
" Tightly packed to
prevent entry of pathogens
" Continual shedding
of cells carries attached microorganisms away
Microbial Antagonism
" Normal microbiota
help protect the body by competing with potential pathogens
" Various activities
of the normal microbiota make it hard for pathogens to compete
" Secrete antimicrobial
substances that limit pathogen growth
" Consumption
of nutrients makes them unavailable to pathogens
" Create an
environment unfavorable to other microorganisms by changing pH
Microbial Antagonism
" Helps
stimulate the body’s second line of defense
" Promote
overall health by providing vitamins to host
Other First-Line Defenses
" Many body organs
secrete chemicals with antimicrobial properties
" Lacrimal glands
that bathe the eye
Second Line of Defenses
" Operates when
pathogens succeed in penetrating the skin or mucous membranes
" Nonspecific
defense
" Composed of cells,
antimicrobial chemicals, and processes but no physical barriers
" Many of
these components are contained or originate in the blood
Blood
" Composed of cells
and portions of cells within a fluid called plasma
" Plasma is
mostly water containing electrolytes, dissolved gases, nutrients, and proteins
" When the
clotting factors, a group of plasma proteins, are removed from plasma, the
remaining fluid is called serum
" Other plasma
proteins include complement proteins and antibodies
" The cells
and cell fragments in plasma are called formed elements
Formed Elements
" Three types of
formed elements
" Erythrocytes-
carry oxygen and carbon dioxide in the blood
" Platelets-
involved in blood clotting
" Leukocytes-
involved in defending the body against invaders
" 2 groups
" Granulocytes
" Agranulocytes
Granulocytes
" Contain large
granules that stain different colors based on the dye used
" 3 types
" Basophils-
stain blue with the basic dye methylene blue
" Eosinophils-
stain red/orange with the acidic dye eosin
" Neutrophils-
stain lilac with a mixture of acidic and basic dyes
" Neutrophils and
eosinophils can phagocytize pathogens
" Neutrophils and
eosinophils are capable of diapedesis
Agranulocytes
" Cytoplasm appears
uniform under a light microscope
" 2 types
" lymphocytes-
most involved in specific immunity
" monocytes-
leave the blood and mature into macrophages
Macrophages
" Phagocytic cells
of the second line of defense
" Wandering macrophages
leave the blood via diapedesis and phagocytize throughout the body
" Fixed macrophages
do not move throughout the body and often phagocytize within a specific organ
" Include
Langerhans cells (epidermis), alveolar macrophages (lungs), microglia (central
nervous system), Küpffer cells (liver)
" All macrophages,
plus monocytes attached to endothelial cells, constitute the mononuclear
phagocytic system
Lab Analysis of Leukocytes
" The differential
white blood cell count test can signal signs of disease
" Increased
eosinophils can indicate allergies or parasitic worm infection
" Bacterial
diseases often show increase in leukocytes and in neutrophils
" Viral
infections show increase in lymphocytes
Components of the Second Line of
Defense
" Phagocytosis
" Extracellular killing
by leukocytes
" Nonspecific
chemical defenses
" Inflammation
" Fever
Phagocytosis
" Cells capable of
phagocytosis (certain leukocytes or their derivatives) are called phagocytes
" Phagocytosis is
not completely understood
" Can be divided
into 5 stages
Host Cell Protection
" The host’s cells
are protected from destruction by the phagocytes
" Some
phagocytes have receptors for bacterial surface components, such as flagellar
proteins or cell wall components, that are lacking on the body’s cells
" Opsonins
such as complement and antibody provide a signal to the phagocyte
Extracellular Killing by Leukocytes
" 2 Cell types that
kill extracellularly
" Eosinophils
" Mainly
attack parasitic helminths (worms) by attaching to their surface
" Secrete
toxins that weaken or kill the helminth
" Eosinophilia,
or elevated eosinophil levels, is often indicative of a helminth infection
Extracellular Killing by Leukocytes
" Natural
killer lymphocytes (NK cells)
" Secrete
toxins onto the surface of virally infected cells and tumors
" Differentiate
normal body cells because they have membrane proteins similar to the NK cells
Nonspecific Chemical Defenses
" Augment
phagocytosis
" Some attack
pathogens directly
" Some enhance
other features of nonspecific resistance
" Includes various
chemicals
" Lysozyme
" Complement
" Interferon
" Defensins
Complement System
" Set of serum
proteins designated numerically according to the order of their discovery
" Complement
activation results in lysis of the foreign cell
" Complement can be
activated in several ways
" Classical
Pathway
" Alternate
Pathway
The Classical Pathway
" Complement named
for the events of this originally discovered pathway
" Various complement
proteins act nonspecifically to “complement” the action of antibodies
The Alternate (Properdin) Pathway
" Activation occurs
independent of antibodies
" Less efficient
than the classical pathway
" Useful in early
stages of infection before antibodies have been made
" Initiated by
interaction between properdin factors B, D, and P and the endotoxins and LPS
from bacteria and fungi
" Stabilizes
molecules of C3b that are normally in the blood in small quantities
The Alternate (Properdin) Pathway
" Stabilized C3b
combines with the properdin factors to form an enzyme that cleaves C3 to
produce more C3b
" C3b combines with
properdin B to form a different enzyme which cleaves C5 molecules
" The complement
cascade then continues as in the classical pathway
Inactivation of Complement
" Body’s own cells
withstand complement cascade
" Membrane-bound
proteins on many cells bind with and break down activated complement proteins
" High
turnover rate for cell membranes means any bound membrane attack complexes are
shed or endocytosed before any damage occurs
Interferons
" Protein molecules
released by infected host cells to nonspecifically inhibit the spread of viral infections
" Particularly
effective against viruses with RNA genomes
" Cause many
symptoms typically associated with viral infections-chills,fever, muscle aches
" 3 Classes
" Alpha
" Beta
" Gamma
Interferons
" Alpha and beta
interferons are present early in the infection
" Gamma interferon
appears later in the course of infection; produced by activated T-lymphocytes
" Stimulates
macrophages to migrate and phagocytize
The Characteristics of Human Interferons
Interferon Therapy
" It was thought
that this might be a good antiviral treatment
" Many viral
infections don’t respond to interferon therapy at all
" Only a slight
effect is seen with those viral infections that do respond
Defensins
" Small peptides
that function nonspecifically to protect against a broad range of pathogens
" Act against
pathogens in various ways
" Punch holes
in cytoplasmic membranes
" Interfere
with internal signaling and other metabolic processes
" Interfere
with the protein that preserves the shape of bacterial proteins under heat
stress
" In humans,
inflammation increases the production of defensins
Inflammation
" Nonspecific
response to tissue damage resulting from various causes
" Characterized by
redness, heat, swelling, and pain
" Two types
" Acute
" Chronic
Acute Versus Chronic Inflammation
" Acute inflammation
" Develops quickly
and is short lived
" Is usually
beneficial
" Important in
the second line of defense
" Dilation and
increased permeability of the blood vessels
" Migration of
phagocytes
" Tissue
repair
" Chronic
inflammation
" Develops
slowly and lasts a long time
" Can cause
damage to tissues
Chemical Mediators of Inflammation
Fever
" A body temperature
over 37°C
" Results when
chemicals called pyrogens trigger the hypothalamus to increase the body’s core
temperature
" Various types of
pyrogens
" Bacterial
toxins
" Cytoplasmic contents
of bacteria released by lysis
" Antibody-antigen
complexes
" Interleukin-I
(IL-1)
Fever Production
" IL-1 production
causes the hypothalamus to secrete prostaglandin which resets the hypothalamic
“thermostat”
" Communication with
the brain initiates muscle contractions, increased metabolic activity, and
constriction of blood vessels which raises the body’s temperature
" Chills associated
with fever are due to the reduced blood flow of constricted vessels
" Decrease in IL-1
production results in the body’s temperature returning to normal
Benefits of Fever
" Enhances the
effects of interferons
" Inhibits growth of
some microorganisms
" May enhance the
performance of phagocytes, cells of specific immunity, and the process of
tissue repair
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