Host–Parasite Interaction

(Indigenous Microbial Flora, Bacterial

Pathogenesis and Epidemiology)

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 Learning Objectives
At the end of the USM, the students will be able to:
 define the terms related to host-microbe interaction;

 differentiate the types of infections as to etiology and

distribution;
 describe the classification of diseases according to their

occurrence;
 enumerate and discuss the host resistance factors and
the infectious agent factors;
 explain the phase of infectious diseases;

 distinguish true pathogens from opportunistic pathogens;

and
 list the virulence factors contributing to the development

of diseases.
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Introduction

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 Host–Pathogen Interaction
 Based on numerous factors including
 Host’s immune system
 Microbial factors inherent to the invading organism
 When “the stars align” disease occurs.
 When “the stars do not align” disease does not
occur.

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Origin of Microbial Biota

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 Background and Terminology

 Fetus
 Sterile until birth
• Exposure to environment leads to colonization.
 Colonization
 Refers to the growth of microbiota in or on a body site
without causing damage or notable symptoms

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 Background and Terminology (Cont.)

 Microorganism relationships
 Symbiosis: two organisms living together
• Commensalism
 Microorganism benefits while host is not harmed.
• Mutualism
 Microorganism and host benefit
• Parasitism
 Microorganism benefits while the host is harmed.

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 Characteristics of Indigenous
Microbial Biota
 Indigenous (normal) flora
 Microorganisms commonly found on or in healthy
persons
 Resident flora
• Microorganisms that colonize an area for months or years

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 Characteristics of Indigenous
Microbial Biota (Cont.)
 Indigenous (normal) flora
 Transient flora
• Microorganisms temporarily colonizing a host
 Carrier state
• Condition of hosts capable of transmitting the infection
• Acute: short term
• Chronic: long term

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 Composition of Usual
Microbial Biota
 Composition is influenced by
 Specific nutritional and environmental factors
 The affinity of microorganisms for a specific site
depends on
 The ability of the organisms to resist the antibacterial
effects of: bile, lysozyme, fatty acids

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 Composition of Usual
Microbial Biota (Cont.)
 Environmental factors
 Moist or dry
• Most microorganisms live in moist areas.
 Skin folds
 Low pH
• Female genital tract, gastrointestinal (GI) tract of breast-fed
infants
 Gaseous atmosphere
• Low oxidation/reduction potential

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Composition of Microbial Biota
at Different Body Sites

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 General Comments
 The human host is colonized by a large
number of different species of
microorganisms.
 Example: Approximately 500 different species
have been characterized in the oral cavity alone.
 Microbial infections common in
immunocompromised patients
 The clinical microbiologist must recognize
and identify the types of microorganisms
found in various body sites.

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 Normal Biota of the Skin
 Generally superficial organisms
 Skin surface and hair follicles
 Apocrine sweat glands
 Secrete substances metabolized by bacteria
• Release of odorous amines
 Normal flora
 Colonize skin surface
 Prevent pathogens from colonizing

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Microorganisms Found on the Skin

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Normal Biota of the Oral Cavity (Mouth)

 Bacterial plaque may develop on teeth.

 Low oxidation reduction potential
 Anaerobes grow
 Buccal mucosa and tooth surface
 Production of acids by microorganisms
• Tooth decay

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Microorganisms Found in the Mouth

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 Normal Biota of the
Respiratory Tract
 Upper respiratory tract
 Mouth, nasopharynx, oropharynx, larynx
 Lower respiratory tract
 Trachea, bronchi, pulmonary parenchyma
• Protected by ciliary epithelial cells and mucus
 Normally considered sterile

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Microorganisms Found in the Nose and
Nasopharynx

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Microorganisms Found in the
Oropharynx

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 Normal Biota of the GI Tract
 GI tract consists of the esophagus, stomach,
small intestine, and colon.
 GI tract is equipped with numerous defenses
and effective antimicrobial factors.
 Estimated number of possible GI microbial
residents: over 35,000

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Normal Biota of the GI Tract (Cont.)
 Stomach normally sterile due to:
 Acidic pH
• Some exceptions
 Endospores, parasitic cysts, H. pylori

 Other pathogens enter in food particles.

 Escape stomach and enter the intestine
• Colonize the small and large intestines
 Antibiotics
 Can significantly alter the usual flora

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Microorganisms Found in the
GI Tract

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 Normal Biota of the
Genitourinary Tract
 Sterile sites
 Kidneys
 Bladder
 Fallopian tubes
 Nonsterile sites
 Distal urethra (particularly in women)
 Vagina

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Microorganisms of the
Genitourinary Tract

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 Role of Microbial Biota in the
Pathogenesis of Infectious Disease

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 Instances When Good Biota
Turn Bad
 Opportunistic infections
 Cause disease when habitat is changed
 May occur due to weakened immune system
 Trauma
 Introduce flora to sterile site
 Immunosuppression
 Immunosuppressive drugs
 Chemotherapy
 Radiation
 Immune defects

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 Instances When Good Biota
Turn Bad (Cont.)
 In patients with serious infections associated
with
 Chronic illness
• Diabetes
• Severe hepatic disease (i.e., cirrhosis)

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Role of Microbial Biota in the Host
Defense Against Infectious Disease

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 Benefits of Microbial Biota
 Normal microbial flora
 Prime the immune system
• Axenic animals: germ free
 Sterile environments impair immune development.
 Microenvironment
 Microbial flora block colonization of extraneous
pathogens.
• Antibiotics can alter the indigenous biota.

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Microbial Factors Contributing to
Pathogenesis and Virulence

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 Pathogenesis
 Pathogenicity
 Ability of an organism to produce disease
 Opportunistic pathogens
 Usually do not cause infection
 May case infection under special circumstances

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Representative Opportunistic
Microorganisms

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 Pathogenesis
 True pathogens
 Organisms that cause disease in healthy
immunocompetent hosts
• Examples: Y. pestis and B. anthracis
 Iatrogenic infections
 Occur as the result of medical treatment or
procedures

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 Routes of Transmission
 Airborne
 Food and water
 Close contact
 Cuts and bites (non-arthropod)
 Arthropods
 Bites of insects
 Zoonoses
 Contact with animals or animal products

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Routes of Entry and Exit

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Common Routes of Transmission

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 Zoonoses

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 Microbial Virulence Factors

 Relative ability of a microorganism to cause

disease
 Degree of pathogenicity
 Measured by numbers of organisms required
to cause disease
 Virulence factors
 Traits that determine pathogenicity and virulence
• Capsules
• Toxins

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 Ability to Resist Phagocytosis
 Phagocytes
 Major role in clearing bacterial infection
 Capsules
 Inhibit engulfment
 Mask cell structures that are recognized by receptors
on the phagocyte cell surface

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Ability to Resist Phagocytosis (Cont.)
 Protein A
 In bacterial cell wall of Staphylococcus aureus
 Interferes with the binding of the host’s antibodies to
the surface of the organism
 Binds Fc portion of immunoglobulin (IgG), preventing
opsonization and phagocytosis by turning the
antibody is turned around on the surface

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Ability to Resist Phagocytosis (Cont.)
 Leukocidins
 A staphylococci leukocidin called Panton-Valentine is
• lethal to leukocytes.
• contributes to organism invasiveness.
 Inhibit chemotaxis
 The movement of white blood cells (WBCs) to sites of
tissue damage
 Host is less able to direct polymorphonuclear
neutrophils (PMNs) and macrophages to the site of
infection.

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Microbial Interference with
Phagocytic Activities

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 Surface Structures That Promote
Adhesion to Host Cells and Tissues
 Adhesins are the microbial surface structures
that mediate attachment.
 Host cells must have receptors for the adhesins.
 Mutation in host or infectious agent that results
in surface structure change:
 Adhesion does not occur.
 Virulence of Infectious agent is affected.

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 Surface Structures That Promote
Adhesion to Host Cells and Tissues (Cont.)
 Adhesive structures
 Fimbriae (pili)—main adhesin in bacteria
 Surface polysaccharides
 Enable bacteria attachment to host surface
structures
 Increase ability to colonize
 Provide resistance to phagocytosis

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Surface Bacterial Structures Involved in
Pathogenesis of Disease

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 Ability to Survive Intracellularly and
Proliferate
 Mechanisms to prevent organisms from being
killed intracellularly:
 Secretory antibody
• IgA proteases
• Antigenic variation
 Lactoferrin: binds free iron
• Meningococci can use lactoferrin for iron.
 Lysosomes
• Prevent fusion
• Escape phagosome

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 Ability to Survive Intracellularly and
Proliferate (Cont.)
 Invasion
 The ability of pathogens to penetrate and grow in
tissues
• Localized
 Few layers or in one body area
• Disseminated
 Spread to distant areas and organs

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 Ability to Produce Extracellular Toxins
and Enzymes—Exotoxins
 Toxins
 Poisonous substances secreted by organisms
 Exotoxins
 Secreted by the organism into extracellular
environment or are released on lysis of organism
 Binding subunit
• Allows toxin to enter cell
 Toxic subunit
• Disrupts or destroys cellular function

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Examples of Exotoxins of Pathogenic
Bacteria

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 Ability to Produce Intracellular Toxins and
Enzymes—Endotoxins
 Endotoxins
 Composed of the lipopolysaccharide (LPS) portion of
the outer membrane of gram-negative bacteria (cell
wall has two layers)
 Three regions
• O-specific oligosaccharide
• Core polysaccharide
• Inner lipid A (also called endotoxin)

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 Ability to Produce Intracellular Toxins and
Enzymes—Endotoxins (Cont.)
 Endotoxins
 Lipid A (endotoxin) stimulates the release of
proinflammatory cytokines that aid in mounting an
innate immune response.
 These chemical mediates (cytokines) produce effects
of endotoxin resulting in dramatic changes in:
• Blood pressure, clotting, body temperature, circulating blood
cells, metabolism, humoral and cellular immunity, and
resistance to infection

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 Ability to Produce Intracellular Toxins and
Enzymes—Endotoxins (Cont.)
 Endotoxin exposure causes:
 Simulation of the fever centers in the hypothalamus
 Hypotension
 Septic or endotoxic shock
 Coagulation initiation
 Severe neutropenia
 Immune system disturbance

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Bacterial Exotoxins Versus Endotoxins

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Host Resistance Factors

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 Host Resistance Factors
Physical Barriers/Cleansing Mechanisms
 Physical barriers
 Mechanical barrier
• Intact skin is effective against most pathogens.
 Cleansing mechanisms
 Desquamation of skin surface
 Movement of liquids
• Examples: tears, urine, mucus secretion

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 Host Resistance Factors
Cleansing Mechanisms/Low pH
 Cleansing mechanisms
 Cilia
• Clearing of debris by locomotion
 Low pH
 Stomach, vagina

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Microbes That Infect or Enter the Body
via the Skin

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 Host Resistance Factors
Antimicrobial Substances
 Antimicrobial substances
 Fatty acids on skin
 Hydrochloric acid (HCl) in the stomach
 Lysozymes
 Immune proteins
• IgA
• Low-molecular-weight cationic proteins
 β-lysins
• Complement
 These synergize to increase effectiveness of killing.
• Interferon inhibits proliferation of viruses

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 Host Resistance Factors
Microbial Flora/Vitamins and Nutrients

 Indigenous microbial flora

 Prevent pathogen colonization
• Bacteriocidins
 Substances that Inhibit growth of closely related bacteria

 Vitamins and other essential nutrients

 Synthesized by certain bacteria in intestine
 Appear to contribute to over host health

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 Host Resistance Factors
Phagocytosis/Chemotaxis
 Phagocytosis
 Engulfing cells
• Neutrophils (PMNs)
• Macrophages
 Chemotaxis
 Chemically caused movement to a location
 Necessary to mobilize phagocytes to infection
 Diapedesis
• Movement from blood vessels to tissues

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 Tissue Distribution of
Monocytes/Macrophages

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 Steps of Phagocytosis
Attachment/Ingesting
 Step 1: Attachment
 Attachment of organism to phagocyte
• Facilitated by opsonins
 Step 2: Ingestion
 Invaginates and engulfs particle
 Enclosed in phagosome
• Fuses to lysosome

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 Steps of Phagocytosis Killing
 Step 3: Killing
 Increase in metabolic activity
 Causes production of lactic acid and hydrogen
peroxide
 Release of enzymes
• Bacteriocidal
 Intracellular pathogens
• Circumvent this process

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Phagocytosis: Chemotaxis Migration of
Phagocytes

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Engulfed Bacterial Cells Inside
Phagosomes

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 Inflammation
 Chemical mediators increase blood flow causing
 Erythema
• Redness
 Edema
• Swelling
 Heat
 Pain
• Due to swelling
 Increases number of WBCs in tissue

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Components in Acute and Chronic
Inflammatory Responses

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 Immune Responses
 Resultant action of immune system in response
to exposure to a foreign antigen
 Example: Antibody production to an antigen
 Immunity
 Complex mechanism that allows the body to protect
itself from foreign invaders
 The mechanism is the immune system.

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Summary of Defenses Used By
Human/Animal Hosts

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 Innate, or Natural, Immunity
 Innate immunity components
 Natural or nonspecific immunity
• Physical and chemical barriers
• Blood proteins that act as infection mediators
• Cellular mechanism capable of phagocytosis
• Complement

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Innate Immune Defenses Located at
Different Body Sites

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 Adaptive, or Specific, Immunity
 Antibodies
 Lymphocytes
 B cells
 T cells
• T helper
• Cytotoxic
 Immunogens
 Antibodies produced in response to foreign invaders

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 Nature of the Immune Response to
Infectious Agents
 Humoral immune response
 Nature of the immune response to infectious
agents
 B cells
• Aided by helper T cells
• Undergoes multiple divisions and forms Plasma Cells
 Plasma cells
• Secrete proteins called immunoglobulins or antibodies

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 Classification and Characteristics of
Antibodies
 Immunoglobulin G (IgG): monomer
 70% to 75% of serum immunoglobulin
 Opsonizing antibody, crosses placenta
 Immunoglobulin M (IgM): pentamer
 10% to 15% of serum immunoglobulin
 Complement fixation
 First antibody produced

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Immunoglobulin G (IgG)

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Immunoglobulin M (IgM)

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IgG Versus IgM

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Classification and Characteristics of
Antibodies
 Immunoglobulin A (IgA): dimer
• 15% to 20% of serum immunoglobulin
• Secreted at mucous membranes
 Immunoglobulin E (IgE): receptor bound
• Very low serum concentration
• Role in clearance of parasites and allergies
 Immunoglobulin D (IgD): surface bound
• Very low serum concentration
• Role in signaling of B-cell receptors, otherwise unknown

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 Primary and Secondary Antibody
Responses
 Primary
 Rapid appearance of IgM
 Peak in 1 to 2 weeks followed by gradual decline
(over the few next months)
 Gradual change over to IgG or IgA antibodies
continuing to increase for about 1 month
 IgG levels remain elevated for months then slowly
decline (often remains low but detectable for years).

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 Primary and Secondary Antibody
Responses (Cont.)
 Secondary (anamnestic immune response)
 Rapid increase in IgG antibodies
• Higher levels of IgG with prolonged elevation
• More gradual decline
• Higher specificity
 Somatic hypermutation
 IgM plays minor role.

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Primary Versus Secondary Response

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 Cell-Mediated Immune Response
 Protection from intracellular pathogens
 T cells do not secrete antibody molecules.
 T helper cells
 Lymphokines (cytokines)
• Signal activation of macrophages and other phagocytes
 Cytotoxic T cells
 Kill infected cells

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Mechanisms by Which Microbes
May Overcome Host Defenses

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 Microbe Mechanisms
 Induce immune tolerance
 Not recognized as foreign
 Immune suppression
 Actively destroy, inactivate, or limit the effect of the
immune response
 Antigenic variation
 Intracellular “hiding”

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