Chapter 2

Host-Parasite Interaction

Copyright © 2015 by Saunders, an imprint of Elsevier Inc.

A. Role of the Usual Microbial
Flora

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 2

 Origins of Microbial Flora
 Fetus
 Sterile until birth
• Exposure to environment leads to colonization
 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

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 3

 Characteristics of Indigenous
Microbial Flora
 Indigenous flora
 Microorganisms commonly found on or in healthy
persons
 Resident flora
• Microorganisms that colonize an area for months or
years
 Transient flora
• Microorganisms temporarily colonizing a host
 Carrier state
• Acute: short term
• Chronic: long term

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 4

 Factors That Determine the
Composition of the Usual Microbial
Flora
 Specific nutritional factors
 Antibacterial substances
 Bile, lysozyme, fatty acids
 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
Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 5
 Usual Microbial Flora: 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

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 6

Usual Microbial Flora: Skin
(Cont.)

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 7

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

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 8

Usual Microbial Flora: Mouth
(Cont.)

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 9

 Usual Microbial Flora:
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

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 10

Usual Microbial Flora:
Nasopharynx

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 11

Usual Microbial Flora:
Oropharynx

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 12

 Usual Microbial Flora: GI Tract
 Comprises esophagus, stomach, small intestine,
and colon
 Stomach normally sterile
 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
Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 13
Usual Microbial Flora:
GI Tract (Cont.)

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 14

 Usual Microbial Flora:
Genitourinary Tract
 Sterile sites
 Kidneys
 Bladder
 Fallopian tubes

 Nonsterile sites
 Distal centimeter of urethra
 Vagina

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 15

 Usual Microbial Flora:
Genitourinary Tract (Cont.)

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 16

 Microbial Flora and Disease
 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
Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 17
 Microbial Flora and Protection
from Disease
 Normal microbial flora
 Prime the immune system
• Anexic animals: germ free
 Sterile environments impair immune development.
 Microenvironment
 Microbial flora block colonization of pathogens.
• Antibiotics can reduce protection.

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 18

B. Pathogenesis of Infection

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 19

 Microbial Pathogenesis
 Pathogenicity
 Ability of an organism to produce disease
 Opportunistic pathogens
 Usually do not cause infection
 Special circumstances

 True pathogens
 Organisms that cause disease in healthy
immunocompetent hosts
• Examples: Y. pestis and B. anthracis
 Iatrogenic infections
 Occur from medical treatment or procedures
Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 20
Opportunistic Microorganisms

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 21

 Virulence
 Relative ability of a microorganism to cause
disease
 Degree of pathogenicity
 Numbers of organisms required to cause
disease
 Virulence factors
 Traits that determine pathogenicity and virulence
• Capsules
• Toxins
• Adhesive fimbriae

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 22

 Resisting Phagocytosis
 Phagocytes
 Major role in clearing bacterial infection
 Capsule
 Inhibit engulfment
 Prevent phagosome-lysosome fusion
 Escape to cytoplasm
 Leukocidins
 Damage or kill leukocytes
 Inhibit chemotaxis
Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 23
Interference of Phagocytosis

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 24

Interference of Phagocytosis
(Cont.)

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 25

 Ability to Resist Phagocytosis
 Prevention of phagocytosis
 Capsule
• Masks cell surface structures, inhibits complement
 Protein A
• Impairs opsonization of host antibodies
• Binds Fc portion of immunoglobulin (IgG), preventing
opsonization and phagocytosis
 Killing of phagocytes
 Panton-Valentine leukocidin
• Causes discharge into cytoplasm, killing cell

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 26

 Bacterial Structures That
Promote Adhesion
 Adhesive structures
 Fimbriae (pili)
 Surface polysaccharides

 Enable attachment to host surface structures

 Increase ability to colonize

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 27

 Cell Walls

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 28

 Intracellular Survival
 Circumvent host’s protective mechanisms
 Secretory antibody
• IgA proteases
• Antigenic variation
 Lactoferrin: binds free iron
• Meningococci can use lactoferrin for iron.
 Lysosomes
• Prevent fusion
• Escape phagosome

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 29

 Invasion
 Ability to penetrate and grow in tissues
 Localized
• Few layers or in one body area
 Disseminated
• Spread to distant areas and organs

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 30

 Exotoxins
 Toxins
 Poisonous substances secreted by organisms
 Exotoxins
 Binding subunit
• Allows toxin to enter cell
 Toxic subunit
• Disrupts or destroys cellular function

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 31

Examples of Exotoxins

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 32

Examples of Exotoxins (Cont.)

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 33

Examples of Exotoxins (Cont.)

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 34

 Endotoxins
 Lipopolysaccharide (LPS)
 Cell wall component in gram-negative bacteria
 O-specific polysaccharide-core-lipid A

 Toxin activity
 Lipid A
 Effects
 Hypotension
 Fever
 Initiates coagulation

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 35

Lipopolysaccharides

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 36

Exotoxins Versus Endotoxins

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 37

 Host Resistance Factors
 Physical barriers
 Mechanical barrier
• Intact skin is effective against most pathogens.
 Cleansing mechanisms
 Desquamation of skin
 Movement of liquids
• Examples: Tears, urine, mucus secretion
 Cilia
• Clearing of debris by locomotion
 Low pH
 Stomach, vagina
Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 38
Microbes Infecting or Entering
Skin

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 39

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

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 40

Host Resistance Factors (Cont.)
 Indigenous microbial flora
 Prevent pathogen colonization
• Bacteriocidins
 Inhibit closely related bacteria

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 41

 Phagocytic Cells
 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

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 42

 Distribution of
Monocytes/Macrophages

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 43

 Diapedesis

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 44

 Steps of Phagocytosis
 Attachment
 Attachment of organism to phagocyte
• Facilitated by opsonins
 Ingestion
 Invaginates and engulfs particle
 Enclosed in phagosome
• Fuses to lysosome

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 45

 Steps of Phagocytosis (Cont.)
 Killing
 Increase in metabolic activity
 Causes production of acids and hydrogen
peroxide
 Release of enzymes
• Bacteriocidal
 Intracellular pathogens
 Circumvent this process

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 46

 Phagocytosis

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 47

 Inflammation
 Chemical mediators increase blood flow
causing
 Erythema
• Redness
 Edema
• Swelling
 Heat
 Pain
• Due to swelling
 Increases number of white blood cells
(WBCs) in tissue
Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 48
Components of Inflammation

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 49

 Immune Responses
 Innate immunity
 Natural or nonspecific immunity
• Physical barriers
• Chemical barriers
• Phagocytosis
 Adaptive or specific immunity
 Antibodies
 Lymphocytes
• B cells
• T cells
 T helper
 Cytotoxic
Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 50
Summary of Innate Immune
Defenses

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 51

Summary of Innate Immune
Defenses (Cont.)

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 52

Innate Immune Defenses of Body
Sites

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 53

 Humoral Immune Response
 B cells
 Aided by helper T cells
 Immunoglobulins (antibodies)
 IgG: monomer
• 70%-75% of serum immunoglobulin
• Opsonizing antibody, crosses placenta
 Immunoglobulin M (IgM): pentamer
• 10% to 15% of serum immunoglobulin
• Complement fixation
• First antibody produced

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 54

 Humoral Immune Response
(Cont.)
 Immunoglobulins (antibodies) (Cont.)
 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

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 55

 IgG

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 56

 IgM

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 57

IgG Versus IgM

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 58

Primary and Secondary Antibody
Responses
 Primary
 Rapid appearance of IgM
 Peak in 2 to 3 weeks followed by decline
 Gradual change over to IgG or IgA antibodies

 Secondary (anamnestic immune response)

 Rapid increase in IgG antibodies
• Higher levels of IgG with prolonged elevation
• Higher specificity
 Somatic hypermutation

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 59

Primary Versus Secondary
Response

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 60

 Cell-Mediated Immunity (CMI)
 Protection from intracellular pathogens
 T helper cells
 Lymphokines (cytokines)
• Signal activation of macrophages and other phagocytes
 Cytotoxic T cells
 Kill infected cells

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 61

Mechanisms by Which Microbes
May Overcome the Host
Defenses
 Induce immune tolerance
 Not recognized as foreign
 Immune suppression
 Actively destroy, inactivate, or limit the effect of the
immune response
 Antigenic variation
 Intracellular “hiding”

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 62

Routes of Transmission and Exit
 Airborne
 Transmission by food and water
 Close contact
 Direct contact
 Cuts and bites (nonarthropod)
 Wounds
 Arthropods
 Bites of insects
 Zoonoses
 Contact with animals
Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 63
Common Routes of Transmission

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 64

Common Routes of Transmission
(Cont.)

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 65

Routes of Entry and Exit

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 66

 Zoonoses

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 67

Zoonoses (Cont.)

Copyright © 2015 by Saunders, an imprint of Elsevier Inc. 68