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Chapter 23, 24, 26
Lecture Outline
Human Microflora,
Nonspecific and Specific
Host Defenses, and
Immunizations
Human Microbiota

Humans colonized by many microbes
 Bacteria,

archaea, fungi, protzoa, and viruses
Normal flora
 “Commensal”
(mutualistic) organisms
 Resident
 Transient

Microbe populations change constantly
 Vary


with type of tissue, condition
pH, moisture, other microbes present
Intestinal flora varies with nutrient uptake
 Can
cause disease if reach abnormal location or if
epithelial defense is impaired
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Distribution of Microbiota
Gram+
GramGram+
Gram- Gram+
Gram-
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Body Site
Lead Bacteria
Skin
Staphylococcus spec.
Nose/pharynx
Neisseria, viridans streptococci
Stomach
Sparsely populated
Small intestine
Bifidobacterium spec., Clostridium spec.
Large intestine
Bacteroides spec., E. coli
Vagina
Lactobacillus spec.
Urethra
Mycobacterium spec.
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Human Microbiota: Skin

Skin is difficult to colonize
 Dry,


salty, acidic, protective oils
Gram+ tolerate salt and dry environment well
1012 microbes in moist areas
 Scalp,

ears, armpits, genital and anal areas
Disease involvement:

Propionibacterium acnes degrades skin oil



Free fatty acid induce inflammation
Inflamed sebaceous glands
Causes acne
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Human Microflora: Nose, Mouth

Nasopharynx and Oropharynx

Many Gram+



Also Gram


Staphylococcus species
Streptococcus species
Neisseria spec.
Fusobacterium spec.
Disease involvement:

Viridans streptococci


can enter bloodstream and cause endocarditis
Streptococcus mutans



Can form biofilm around teeth
Plaque
Cause of gum disease
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Viridans Streptococci
S. mutans
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Human Microbiota: Stomach

Very high acidity


Few microbes survive
Disease involvement

Helicobacter pylori




Survive at pH 1
Burrow into protective mucous
Cause of ulcers, cancer
Loss of acidity = achlorhydria



Caused by malnourishment
Allows pathogen growth
Example: Vibrio cholerae survive

Pass through stomach
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Human Microbiota: Intestine

Vast majority of human microbiota



109-11 cells/ cm3
Feces consists primarily of bacteria
Disease development


Urinary tract infection
Microbiology: An Evolving Science
Sepsis
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Human Genitourinary Microbiota



Kidney and bladder are sterile
Urethra and vagina are populated
Vagina
 Acidic

secretions prevent pathogens
Lactobacillus acidophilus in vagina
 Composition
is influenced by hormonal
cycle
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Important Contributions of Human
Microbiota to Human Health
Production of antimicrobials hampers
colonization by pathogenic microbes
 Degradation of nutrients
 Vitamin production
 Modulation of immune system

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Probiotics





Oral uptake of microbes to the
benefit of human health
Gram-positive bacteria
Must be able to survive stomach
and small intestine
Lactobacillus
Bifidobacterium
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Risks of Microbiota

Opportunistic pathogens
 Surface
breach allows bacterial entry
 Immunocompromised hosts


E.g., Bacteroides fragilis
E.g., Clostridium difficile
Gas gangrene caused by Bacteroides
after intestinal surgery
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Host Defenses
General mechanism
 Innate Immunity
 Adaptive immunity

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General Host Defenses

Physical barriers to infection

Skin



Mucous




Keratin
Dead skin cells, washing,
remove attached cells
Trap, destroy pathogens
Mucous layers slough off,
removed
Cilia remove microbes from
lungs
Chemical barriers to infection

Acidic pH: stomach, skin,
vagina
Microbiology: An Evolving Science
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Overview of the Immune System

Innate immunity
 Widely

present in nature
 Natural immunity
 Defense system
functional at birth
 Preformed or available
within hours after
infection
 Pattern recognition
Adaptive immunity
 In
higher vertebrates
 Acquired
 Available within days
 Specificity
 Memory
 Proliferation and
clonal expansion
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Key Molecules of Our Immune System

Antimicrobial peptides and polypeptides

Natural peptide antibiotics
 Make pores in microbial membranes

Lysozyme



Complement




Peptidoglycan hydrolase
Can make membrane pores too
Innate Immunity
Makes pores in microbial membranes
Enhances phagocytosis
Alerts the host
Antibodies



Neutralize
Block
Enhance phagocytosis
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Adaptive Immunity
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Key Cells of Our Immune System
Epithelial cells
 Leukocytes

 White
blood cells
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Epithelial Cells



Innate immune system
Line all body surfaces
Equipped with receptors that recognize microbial
products (Toll-like receptors, TLRs)
 LPS
 Peptidoglycan


Produce antimicrobial peptides
Produce cytokines that alert the host
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Epithelial Cell Defense
Microbial Products
(LPS, PG, etc)
TLR
Antimicrobial
Peptides
TLR: Toll-like receptor
(pattern recognition)
LPS: lipopolysaccharide
PG: peptidoglycan
Cytokines
Leukocytes

Neutrophils and monocytes

Engulf and destroy bacteria and fungi

Innate
Immunity

Basophils and eosinophils


granules
with toxin
Eliminate virus infected cells
Lymphocytes

Adaptive
Immunity
Release toxins to poison parasites
Natural killer cells


Monocytes are immature cells that
eventually differentiate into
macrophages and dendritic cells

T cells: modulate specific immune
response (T helper cells) and kill
infected host cells (cytotoxic T cells)
B cells: produce antibodies to bind
foreign antigens
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Main Steps of
Phagocytosis






Adhesion
Engulfment (ingestion)
Phagosome formation
Phagolysosome
formation
Killing
Digestion
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Microbiology: An Evolving Science
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Acute Inflammatory Response
Initial lesion
Microbial specific
structures activate
epithelial cells and
attract nearby
phagocytes
Cytokines from
Phagocytes
epithelial cells and
engulf microbes.
local phagoctes
make capillaries
permeable and
attract neutrophils
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Microbes are killed,
wound heals, and
return to normal.
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Fever

Pyrogens induce temperature rise
 Exogenous
pyrogens
LPS
 Cause release of endogenous pyrogens

 Endogenous
pyrogens
Cytokines
 Signal brain to raise temperature


High temperature stresses invading microbes
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Innate Defense by Interferon

Type 1 interferons produced by infected
host cells
 Cells
with viral or bacterial pathogens
 Secrete small interferon proteins
 Nearby cells respond to interferons

Causes recipient cells to resist virus
 Synthesizes
ds RNA endonuclease
 Makes proteins to prevent protein translation
from viral RNA
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Adaptive Immunity

Humoral immunity
 Mediated
by antibodies
 Involves B cells that respond to specific antigens and
produce specific antibodies

Cellular immunity
 Involves
T cells
 Special subtypes


T helper cells control antibody production, activate innate
immune cells
Cytotoxic T cells (killer cells) directly kill infected host cells
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Immunological Memory
Mediated by Lymphocytes
Specific antigen recognition
+
Memory
m m
Clonal proliferation
m
m
m
m
m
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Basic Structure of Antibodies
Made by B lymphocytes
(Immunoglobulins)
2 light chains





2 heavy chains
Connected by disulfide
bridges
Antigen binding region

Amino acids in this region
are highly variable
 Each B cell makes a
unique antibody

Effector region


Interact with host cells
Amino acids in this region
are highly constant
 5 different classes (M, G,
A,E,D)
 B cell can switch Ig
classes
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Antibody Isotypes have Different Functions

IgM—First antibody in immune response


IgG—Primary circulating antibody in blood




Forms pentamer, agglutinates
Coats antigen, eases engulfment by phagocytes (opsonization)
IgA—Secreted across mucosa
IgE—bound by mast cells
and basophils and plays role in allergic responses
IgD—on surface of B cells and maturation marker
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Antibody Response

Primary antigen exposure
 Disease
or vaccination
 Antibodies appear in serum after several days

B cells that bind antigen make antibodies



IgM, then switch to IgG—Isotype switching
B cells change to memory cells
Secondary exposure to antigen
 Pathogen

or booster dose
Antibodies appear in blood within hours
Mostly IgG antibodies
Microbiology: An Evolving Science
 Some new IgM are also formed
© 2009 W. W. Norton & Company, Inc.

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Natural and Artificial Immunity

Natural



Course of natural
infection
Antigen is in its natural
form


Toxin (active)
Microbe (replicative)
Artificial


Vaccination and immunizations
Antigen is modified

Inactivated


Ex: Toxoid
Attenuated



Live vaccine but unable to
cause the disease
Never give to pregnant and
immunocompromised
individuals
Ex: BCG vaccine
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Active and Passive Immunizations

Active

Antigen (active, inactivated
or attenuated) is introduced
into host





Passive

Natural infection
Vaccination
Host mounts immune
response



Antibodies
T cell mediated immunity
Long-term protection
Host must be
immunocompetent
Functional specific immune
mediators are introduced
into the host

Antibodies





Ex: maternal antibody
transfer in utero
Host does not mount an
immune response
No long-term protection
For immediate protection
Host can be
immunocompromised
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Vaccines

Most vaccines administered in childhood
 Most
administered as multiple booster doses
 Except influenza—new vaccine every year

Herd immunity
 Protects
from person-to-person transmission
 If 70% of community is immune

Vaccinated or recovered from disease
 Remaining
individuals protected
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