Chapter 23, 24, 26 Lecture Outline Human Microflora, Nonspecific and Specific Host Defenses, and Immunizations

Chapter 23, 24, 26Lecture Outline

Human Microflora, Nonspecific and Specific Host Defenses, and Immunizations

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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

Microbiology: An Evolving Science © 2009 W. W. Norton & Company, Inc. 3

Distribution of Microbiota

Gram+

Gram-Gram+

Gram-

Gram- Gram+


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.


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


Human Microflora: Nose, Mouth Nasopharynx and Oropharynx

Many Gram+ Staphylococcus species Streptococcus species

Also Gram- 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


S. mutans

Viridans Streptococci


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


Human Microbiota: Intestine Vast majority of human microbiota

109-11 cells/ cm3

Feces consists primarily of bacteria

Disease development Urinary tract infection Sepsis


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


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


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


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


Host Defenses

General mechanism Innate Immunity Adaptive immunity


General Host Defenses Physical barriers to infection

Skin Keratin Dead skin cells, washing, remove

attached cells Mucous

Trap, destroy pathogens Mucous layers slough off, removed Cilia remove microbes from lungs

Chemical barriers to infection Acidic pH: stomach, skin, vagina

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Overview of the Immune System Innate immunity

Widely present in natureNatural immunityDefense system

functional at birthPreformed or available

within hours after infection

Pattern recognition

Adaptive immunity In higher vertebratesAcquiredAvailable within daysSpecificityMemory

Proliferation and clonal expansion


Key Molecules of Our Immune System Antimicrobial peptides and polypeptides

Natural peptide antibiotics Make pores in microbial membranes

Lysozyme Peptidoglycan hydrolase Can make membrane pores too

Complement Makes pores in microbial membranes Enhances phagocytosis Alerts the host

Antibodies Neutralize Block Enhance phagocytosis

Innate Immunity

Adaptive Immunity


Key Cells of Our Immune System

Epithelial cells Leukocytes

White blood cells


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

Epithelial Cell Defense

TLR

Microbial Products(LPS, PG, etc)

Antimicrobial Peptides

Cytokines

TLR: Toll-like receptor (pattern recognition)LPS: lipopolysaccharidePG: peptidoglycan

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Leukocytes Neutrophils and monocytes

Engulf and destroy bacteria and fungi Monocytes are immature cells that eventually

differentiate into macrophages and dendritic cells

Basophils and eosinophils Release toxins to poison parasites

Natural killer cells Eliminate virus infected cells

Lymphocytes 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

granules with toxin

InnateImmunity

AdaptiveImmunity


Main Steps of Phagocytosis Adhesion Engulfment (ingestion) Phagosome formation Phagolysosome

formation Killing Digestion



Acute Inflammatory Response

Initial lesionMicrobial specific structures activate epithelial cells and attract nearby phagocytes

Cytokines from epithelial cells and local phagoctes make capillaries permeable and attract neutrophils

Phagocytes engulf microbes.

Microbes are killed, wound heals, and return to normal.


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


Innate Defense by Interferon Type 1 interferons produced by infected

host cellsCells with viral or bacterial pathogensSecrete small interferon proteinsNearby cells respond to interferons

Causes recipient cells to resist virusSynthesizes ds RNA endonucleaseMakes proteins to prevent protein translation

from viral RNA


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

Immunological Memory Mediated by Lymphocytes


+

Specific antigen recognition

Clonal proliferationm

Memory

mm

mm

mm

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Basic Structure of Antibodies (Immunoglobulins) Made by B lymphocytes

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


Antibody Isotypes have Different Functions

IgM—First antibody in immune response Forms pentamer, agglutinates

IgG—Primary circulating antibody in blood 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


Antibody Response Primary antigen exposure

Disease or vaccinationAntibodies 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 antigenPathogen or booster dose

Antibodies appear in blood within hours Mostly IgG antibodies Some new IgM are also formed


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


Active and Passive Immunizations

Active Antigen (active, inactivated

or attenuated) is introduced into host

Natural infection Vaccination

Host mounts immune response

Antibodies T cell mediated immunity

Long-term protection Host must be

immunocompetent

Passive 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


Vaccines Most vaccines administered in childhood

Most administered as multiple booster dosesExcept influenza—new vaccine every year

Herd immunityProtects from person-to-person transmission If 70% of community is immune

Vaccinated or recovered from disease

Remaining individuals protected

Documents

Chapter 23, 24, 26 Lecture Outline Human Microflora, Nonspecific and Specific Host Defenses, and Immunizations