Microbiology_Ch_23,24, 26 W2010 - Cal State LA
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Transcript Microbiology_Ch_23,24, 26 W2010 - Cal State LA
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
Microbiology: An Evolving Science
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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
Microbiology: An Evolving Science
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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
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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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