CHAPTER 20: RESISTANCE AND THE IMMUNE SYSTEM: INNATE

IMMUNITY
1. Immunity: how the human body can generate resistance to a
particular disease, whether by recovering from the disease or as a
result of vaccination
a. Innate Immunity: several nonspecific defenses present in all
humans from the time of birth
b. Acquired immunity: a form of protective immunity or
resistance that is a response to a specific microbe and is directed
only against that microbe
c. Microbiological Umbrella: protects us against the torrent of
potential microbial pathogens to which we are exposed to daily
i. Host resistance to microorganisms and other agents
depends on many defenses that must function well in the
individual. The factors are innate (nonspecific) defenses
and acquired (specific) defenses.
ii. Resistance may begin to break down when one or more factors is
inoperable. When phagocytosis fails to take place, for example, some
infectious agents penetrate the umbrella of defense.
iii. Disease develops when many host defenses are compromised. Under
these conditions, the body cannot defend itself. Even when defenses are
not compromised, the aggressiveness and toxicity of the pathogen may
lead to infection.

2. Overview to Host Immune Defenses:

a. Immunology: The scientific study of how the immune system
functions in the body to prevent or destroy foreign materials,
including pathogens
b. Blood Cells form an important defense for innate & Acquired
ImmunityLeukocytes perform a variety of defense roles in the
host
i. Blood consists of: Fluid, clotting agents & Formed elements
or cells
1. Fluid
a. Serum: An aqueous solution of minerals, salts,
proteins, and other organic substances or
b. Plasma: When clotting agents are present
2. Formed Elements: Erythrocytes (RBCs) & Leukocytes
ii. Leukocytes (White Blood Cells): Have no pigments in they
cytoplasm and appear gray/unstained
iii. 4000-12000 micrLiter of blood Produced in bone marrow
1. Granulocytes: Because contain cytoplasmsic
granules
a. Neutrophils: Polymorphonuclear cells
(PMNs)Multi lobed

i. Fucntion Chiefly as Phagocytes: Cells that

carry out phagocytosis
ii. Usually in blood but can move out of
circulation to engulf pathogens
iii. Lifespan: 1-2 Days so continuously
replenished
b. Eosinophils
i. Red or Pink granule stain with Eosin
ii. Parasites, Allergies & Asthma
c. Basophils:
i. Blue Granule stain with Methylene Blue
ii. Allergic Reaction & Parasites (Along with
Mast cells)
iii. Release of chemical mediators of
inflammation
d. Eosinophils, Basophils & Mast cells in Skin,
lungs & GI
2. Agranulocytes: Lacking visible granules
a. Monocytes/Macrophages
i. Phagocytosis & Intracellular killing of
pathogens
ii. INITIATE ACQUIRED IMMUNITY but
involved in both innate & Acquired
iii. Monocytes mature into Macrophages in
tissues
iv. Monocytes (2 weeks) Macrophages
(Months)
v. More effective phagocytes than
neutrophils & Reside in spleen, lymph
nodes, thymus, Respiratory & GI tract
b. Lymphocytes: migrate from bone marrow to
lymph nodes after maturation Antibody
production & Cytotoxic properties
i. Natural Killer (NK) cells: key role in
innate immunity by destroying virus
infected cells and tumor cells
ii. B lymphocytes & T lymphocytes: key
cells of acquired immunity & Increase in
number during infections
c. Dendritic Cells: Activate lymphocytes &
Initiate Acquired immunity but involved in both
i. Found in skin (Langerhans cells), & other
tissues
c. The lymphatic system is composed of cells and Tissues Essential
to Immune FunctionThe Lymphatic system maintains and

distributes lymphocytes necessary for defense against

pathogens.
i. Lymph: Clear fluid surrounding the tissue cells and filing
the intercellular spaces
1. Supplies oxygen & Nutrients while collecting
wastes Pumped by skeletal muscle contractions
2. Lymphocytes mature, differentiate & Divide in
lymphatic tissues
a. Primary Lymphoid Tissues: Thymus & Bone
Marrow
b. Secondary Lymmphoid tissues: mature
immune cells interact with pathogens and carry
out acquired immune response
i. Spleen, lymph nodes (Contain
macrophages & Dendritic cells)
ii. Other secondary tissues:
IntestineMucosa Associated Lymphod
Tissue (MALT), RespiraptoryTonsils
d. Innate and Acquired Immunity Are Essential Components of a
fully Functional Human Immune SystemThe interactions
between innate and Acquired host defenses make infection and
disease establishment difficult
i. Innate ImmunityNonspecific resistance due to genetically
encoded molecules present in the body from birth are
capable of recognizing microbial features common to many
pathogens and foreign substances
1. Hosts early warning system against potentially
harmful pathogens, foreign cells or even our own
cells should they be damaged/cancerous
2. Responds Minutes to hours after infection
3. Elimante or try to hold an infection while sending
chemicals to signal acquired immuneity via cytokines
4. Cytokines: Small proteins released by various
defensive cells (Macrophages, lymphocytes, mast
cells & Dendritic cells) in response to an activating
substance like invading microbe
ii. Acquired immunity
1. Slow responseDays to weeks & throughout
infection
2. specific resistance only existing in vertebrates
involves production of:
a. lymphocytes
b. antibodies specific to the pathogen causing
infection
3. The Innate Immune Response

a. Depends on General well-being of individual & Proper body

functioning
b. Physical, Chemical, and Microbiological Barriers Limit Entry of
PathogensThe Skin, Mucous Membranes, Chemical inhibitors,
and microbes represent barriers to infection
i. Physical, Chemical, and Microbiological Barriers Are
Exposed First Lines of Defense
ii. Physical Barriers:
1. The skin is a mechanical barrierTough,
impenetrable, & poor source of nutrition
a. Breaches of the skin (cuts or abrasions) may
allow microbes to enter the blood
b. If a pathogen is detected by Langerhans cells,
they phagocytize it and induce an acquired
immune response
2. Mucous membrane cells (Mucosa) are the moist
epithelial lining of digestive, urogenital and
respiratory tract, they produce mucus to trap
microbes
iii. Chemical Barriers: inhibit microbial growth or viral
replication
1. Lactobacillus in the human vagina decrease the pH,
which resists infection, if low, can get opportunistic
infection
2. The low pH (2.0) in the stomach destroys most
pathogens
a. Polio, Hep A, Typhoid & Tubercle bacilli & H.
Pylori survive
b. Bile from gallbladder serves as inhibitory
substance as well as other duodenal enzymes
3. Defensins are antimicrobial peptides found in
various bodily secretions produced by phagocytic
cells and epithelial cells of Respiratory, GI, and GU
tracts (Ex. Sebum Secretes 12 defensins)
a. Some produces continuously while others are
induced by microbial products
b. Damage membranes killing the pathogens
through cell lysisGram positive & Negative
4. Lysozyme, found in tears, sweat, and saliva, lyses
gram-positive bacterial cells by disrupting cell wall
5. Interferons are cytokines that trigger:
a. macrophage activation
b. production of substances to interfere with RNA
viral reproduction
iv. Cellular Barrier: Phagocytosis and trigger inflammatory
response to destroy pathogens

1. The normal microbiota of the body outcompete

pathogens for nutrients and attachment sites
c. Phagocytosis Is a Nonspecific Defense Mechanism to Clear
Microbes from Infected TissuesCellular defenses can
phagocytize pathogens
i. Phagocytosis: the capture and digestion of foreign
particles including pathogens by phagocytes
ii. Foreign Pathogen breaches external defensesintruder
recognized, ingested and killed by neutrophils and
macrophagesphagocytes release cytokines to trigger
inflammatory response & Activate acquired response
iii. Chemokines are cytokines that attract macrophages and
neutrophils to infected tissues
iv. Macrophages extend thin cytoplasmic protrusions
(Filopodia) that wave, if the filopodia catches pathogen,
it quickly contracts
1. Phagocytized microbes are held in a phagosome:
Internalized vacuole
2. The phagosome is acidified, killing or inactivating the
pathogen
3. Phagosomes also fuse with lysosomes
(phagolysosome)
4. Enzymes and other products kill and digest the
pathogen
v. Phagocytosis also triggers Respiratory Burst which
produces toxic metabolites (H202, NO, O2-, & Bleach)
vi. Neutrophils are first cells at infection site but are short
lived so macrophages kill most pathogens Some
Neutrophils after contacting pathogen transform into
Extracellular fibers called Neutrophil Extracellular Traps
(NETs)
1. Neutrophils become deformed and rupture, the NET
components (Nuclear DNA & Granule antimicrobial
proteins mix) which interact with pathogens
degrade and kill pathogens without phagocytizing
vii. Phagocytosis also releases lysosome enzymes and other
products that damage surrounding tissue Pus: composed
of dead and dying neutrophils=Sign of infection
viii. Opsonins attach to microbes to increase the ability of
phagocytes to adhere (opsonization)
d. Inflammation Plays and Important Role in Fighting InfectionThe
inflammatory response brings effector molecules and cells to the
infection sites
i. Inflammation: Nonspecific defensive response by the body
to traumamechanical, chemical or infectious (pathogen)
1. Limits the spread of infection

ii. Macrophages secrete cytokines that trigger vasodilation &

Increase capillary permeabilityedema at the infection site
iii. Chemokines attract more phagocytes (Neutrophils and
monocytes) towards infection and they migrate between
capillary cells (diapedesis)
iv. Chemokines attract mast cells which secrete histamine and
bolster inflammatory response
v. Cardinal Signs of Inflammation:
1. Redness (Blood accumulation)
2. Heat (Warmth of blood)
3. Swelling (Fluid accumulation)
4. Pain (Local tissue damage)
vi. Eventually fibrin clot forms
vii. If pus is walled offAbscess or boil forms
viii. Inflammation is/should be short response, if chronic, may
lead to diseases like RA, CHD, Atherosclerosis, Alzheimers
or Cancers
1. Cytokine storm may lead to septic shock: collapse
of circulatory and respiratory systems due to
endotoxins from Gram Negatives
e. Moderate Fever Benefits Host DefensesFever, usually one sign
of possible infection, can help immune defenses
i. Fever: Abnormally high body temperature that remain
elevated above the normal 37 C & Helps body gain
advantage over pathogen
ii. Low to moderate fever supports the immune system by:
1. inhibiting rapid microbial growth
2. encouraging rapid tissue repair
3. heightening phagocytosis
iii. Pyrogens are endogenous cytokines that affect the
hypothalamus, causing elevated body temperature & are
produced by:
1. some leukocytes
2. activated macrophages
3. fragments from pathogens
iv. If a temperature rises above 105F in an adult, host
metabolic inhibition can occur
1. This can cause convulsions and death
f. Natural Killer Cells Recognize and Kill Abnormal CellsNatural
Killer ells are nonspecific lymphocytes
i. Natural Killer (NK) cells are another type of defensive
leukocyte besides phagocytes
ii. NK cells are formed in the bone marrow, and migrate to:
1. Tonsils
2. lymph nodes
3. spleen

iii. When activated, NK cells produce cytokines that trigger

response by macrophages and other cells
iv. hen they move into blood and lymph where they kill:
1. cancer cells
2. virus-infected cells
v. NK cells are NOT phagocyticWhen an NK cell recognizes a
cell as nonself via MHC I Proteins, it releases cytotoxic
perforinswhich drill holes in the target cells, and
granzymesWhich are cytotoxic enzymes inducing the
target to undergo apoptosis
g. Complement Marks Pathogens for DestructionComplement
proteins assist innate immunity in identifying and eliminating
pathogens
i. Complement (Complement system) is a series of (30)
proteins that circulate in the bloodstream and activate in
the presence of microbes
ii. Assist in the inflammatory response and phagocytosis as
well as destruct the invading bacterial cells or viruses
through cell or virion lysis
iii. Classical, Alternative and Lectin pathway all culminate in
the activation of an enzyme called C3 ConvertaseSplits
C3 into C3a and C3b C3b activated C5 C5 hydrolyzed
into C5a and C5b
1. C3a & C5a trigger inflammatory response via
vasodilation & Increased capillary permeability
2. C3b acts as opsonin and enhances phagocytosis
3. C5b triggers Membrane Attack Complexes (MACs)
which range from C5b-9, form large holes in the
membranes of many microbes (Gram negative
bacteria and enveloped viruses mainly)Lysis occurs
and kills pathogens
h. Innate Immunity Depends on Receptor-Recognition of Common
Pathogen-Associated MoleculesPattern Recognition receptors
trigger the innate immune response
i. Pathogen-associated molecular patterns (PAMPs):
unique, highly conserved microbial molecular sequences
not found in host cellshelp the innate immune system
recognize pathogens
1. Recognized by protein receptors called Toll-like
Receptors (TLRs)
ii. Toll-like receptors (TLRs) are signaling receptors on
plasma membrane and phagosome membranes of:
Macrophages, dendritic cells & endothelial cells
iii. TLRs mediate a specific response to distinct PAMPs

iv. They stimulate the secretion of cytokines and are sensed

by immune cells and other nonimmune cells in the innate
immune response
1. Some cytokines stimulate liver to produce and acute
phase proteins: defensive blood proteins, which
activate the lectin pathway or complement system
and elevate inflammation
v. TLRs activation in macrophages and dendritic cells induce
them to differentiate into cells active in acquired immune
response
i. Interferon Puts Cells in an Antiviral StateInterferons are natural
proteins capable of triggering proteins to block viral replication
i. Virus infected cells produce cytokines called Interferons,
that alert surrounding cells to the viral threat
ii. IFN alpha and IFN-beta trigger a nonspecific reaction via
TLR-3 to protect against the stimulating virus as well as
others
1. They dont directly interact with virus, but via the
cells they alert
iii. IFNs are produced when virion releases its genome into the
cell, High concentration of DS-RNA induce cells to
synthesize and secrete IFNs Bind to receptor sites on
adjacent cell surface and signal pathway synthesis of
Antiviral Proteins (AVPs)
1. Those cells with AVPs are now in Antiviral state and
are capable of inhibiting viral replication
2. Pharm companies mass produce synthetic IFN-alpha
for disease treatments along with other drugs (Hep
B, Hep C & Genital warts)