1 - Overview

MICROBIAL
INTERACTIONS
WITH HUMAN HOSTS
Tuti Parwati Merati
November 10th 2015
Infection and (Infectious)
Disease
A. Definitions
B. The Normal Flora of Humans
C. Generalized Stages of Infection
D. Virulence Factors and Toxins
A. Definitions
• Disease and Infectious Disease
– Disease
• Any deviation from a condition of good
health and well-being
– Infectious Disease
 A disease condition caused by the presence
or growth of infectious microorganisms or
parasites
A. Definitions
• Pathogenicity and Virulence
– Pathogenicity
• The ability of a microbe to cause disease
• This term is often used to describe or compare
species
– Virulence
• The degree of pathogenicity in a
microorganism
• This term is often used to describe or compare
strains within a species
A. Definitions
• Acute infection vs. chronic infection
– Acute Infection
• An infection characterized by sudden onset,
rapid progression, and often with severe
symptoms
– Chronic Infection
• An infection characterized by delayed onset
and slow progression
A. Definitions
• Primary infection vs. secondary infection
– Primary Infection
• An infection that develops in an otherwise
healthy individual
– Secondary Infection
• An infection that develops in an individual
who is already infected with a different
pathogen
A. Definitions
• Localized infection vs. systemic infection
– Localized Infection
• An infection that is restricted to a specific
location or region within the body of the host
– Systemic Infection
• An infection that has spread to several
regions or areas in the body of the host
A. Definitions
• Clinical infection vs. subclinical infection
– Clinical Infection
• An infection with obvious observable or
detectable symptoms
– Subclinical Infection
• An infection with few or no obvious
symptoms
A. Definitions
• Opportunistic infection
– An infection caused by microorganisms that are
commonly found in the host’s environment
This term is often used to refer to infections
caused by organisms in the normal flora
A. Definitions
• The suffix “-emia”
– A suffix meaning “presence of an infectious agent”
• Bacteremia = Presence of infectious bacteria
• Viremia = Presence of infectious virus
• Fungemia = Presence of infectious fungus
• Septicemia = Presence of an infectious agent in
the bloodstream
A. Definitions
• The suffix “-itis”
– A suffix meaning “inflammation of”
• Examples:
– Pharyngitis = Inflammation of the pharynx
– Endocarditis = Inflammation of the heart
chambers
– Gastroenteritis = Inflammation of the
gastointestinal tract
A. Definitions
• Epidemiology
– The study of the transmission of disease
• Communicable Disease
– A disease that can be transmitted from one individual to
another
• Contagious Disease
– A communicable disease that is easily spread from one
individual to another
• Noncommunicable Disease
– A disease that is not transmitted from one individual to another
A. Definitions
• Endemic Disease
– A disease condition that is normally found in a
certain percentage of a population
• Epidemic Disease
– A disease condition present in a greater than usual
percentage of a specific population
• Pandemic Disease
– An epidemic affecting a large geographical area;
often on a global scale
A. Definitions
• Reservoir of Infection
– The source of an infectious agent
• Carrier
– An individual who carries an infectious agent
without manifesting symptoms, yet who can
transmit the agent to another individual
• Fomites
– Any inanimate object capable of being an
intermediate in the indirect transmission of an
infectious agent
A. Definitions
• Animal Vectors
– An animal (nonhuman) that can transmit an infectious
agent to humans
– Two types: mechanical and biological
• Biological animal vectors: The infectious agent must
incubate in the animal host as part of the agent’s
developmental cycle; eg, the transmission of malaria by
infected mosquitoes
• Mechanical animal vectors: The infectious agent is
physically transmitted by the animal vector, but the agent
does not incubate or grow in the animal; eg, the
transmission of bacteria sticking to the feet of flies
A. Definitions
• Direct Mechanisms of Disease Transmission

– Directly From Person to Person
– Examples:
Direct Skin Contact
Airborne (Aerosols)
A. Definitions
• Indirect Mechanisms of Disease Transmission

– Examples:
Food & Waterborne Transmission
Fomites
Animal Vectors
B.The Normal Flora of Humans
• Types of Symbiosis
1. Mutualism
A symbiotic relationship in which both
species benefit
2. Commensalism
A symbiotic relationship in which one species
benefits, and the other species is neither
helped nor harmed
B. The Normal Flora of Humans
• Types of Symbiosis (cont.)
3. Parasitism
• A symbiotic relationship in which one
species benefits, and the other species is
harmed
• Generally, the species that benefits (the
parasite) is much smaller than the species
that is harmed (the host)
• Normal flora is present in
– skin
– upper respiratory tract
– oral cavity
– intestine, especially large intestine
– vaginal tract
• Very little normal flora in eyes & stomach
• Notably absent in most all internal organs
– Absent in:
• lower respiratory tract
• muscle tissue
• blood & tissue fluid
• cerebrospinal fluid
• peritoneum
• pericardium
• meninges
• Benefits of the normal flora

– Nutrient production/processing
eg Vitamin K production by E. coli
– Competition with pathogenic microbes
– Normal development of the immune system
• Normal flora and opportunistic infections
C.Generalized Stages of Infection
1. Entry of Pathogen
– Portal of Entry
2. Colonization
– Usually at the site of entry
3. Incubation Period
– Asymptomatic period
– Between the initial contact with the microbe
and the appearance of the first symptoms
4. Prodromal Symptoms
– Initial Symptoms
5. Invasive period
– Increasing Severity of Symptoms
– Fever
– Inflammation and Swelling
– Tissue Damage
– Infection May Spread to Other Sites
– Acme (Fastigium)
6. Decline of Infection
7. Convalescence
D.Virulence Factors and Toxins
• State of the Host Immune System
• Number of Pathogenic Cells

encountered by the Host
– Infectious Dose
• Enzymatic Virulence Factors
– Examples:
• Coagluase (Staphylococcus aureus)
• Streptokinase (Streptococcus pyogenes)
• Hyaluronidase (Many pathogens)
• Collagenase (Many pathogens)
• Leucocidin (Many pathogens)
• Hemolysin (Many pathogens)
• Adhesion Factors
– Examples:
• Protein A (Staphylococcus aureus)
• Protein M (Streptococcus pyogenes)
• Exotoxins
– A type of bacterial toxin with the following
properties:
• May be produced by either gram-positive or gram-
negative bacteria
• Is secreted by the bacteria
• The action of the exotoxin does not necessarily
require the presence of the bacteria in the host
• Most exotoxins are peptide or protein
• Most exotoxins are heat sensitive (exception:
enterotoxin of Staphylococcus aureus)
• Exotoxins (cont.)
– Classes of exotoxins: Neurotoxic, cytotoxic, or
enterotoxic exotoxins
• Neurotoxins: Interfere with proper synaptic
transmissions in neurons
• Cytotoxins: Inhibit specific cellular activities, such
as protein synthesis
• Enterotoxins: Interfere with water reabsorption in
the large intestine; irritate the lining of the
gastrointestinal tract
• Endotoxins
– A type of bacterial toxin having the following
properties:
• Produced only by gram-negative bacteria
• Endotoxins are a component of the gram-negative
cell wall
• The action of endotoxin requires the presence of the
bacteria in the host. The endotoxin may be released
from the cell wall as the cells die and disintegrate
• Endotoxins (cont.)
• Endotoxin is composed of Lipid A: Part of the
lipopolysaccharide layer
• Mode of action: Irritation/inflammation of
epithelium, GI irritation, capillary/blood vessel
inflammation, hemorrhaging
Localization of the agent in the Host
Depending on the properties and size of the pathogens, either have
the capacity to seek intracellular sites or remain extracellular.
eg.
• Intracelluler : malaria parasites : Plasmodium vivax binds to the

Duffy blood group antigens, reticulocyte binding proteins.;
viruses
• Extracelluler , reside at epithelial surface: bacteria such as N.
gonorrhoeae, H. pylori, Vibrio cholerae, and E. coli, and
helminths such as adult Ascaris lumbricoides, hookworms, and
Trichuris trichiura
• Mechanisms of host immune responses to the microorganisms
vary depending on their sites of localization.
The immune system
• is a network of cells, tissues, and organs that
work together to defend the body against
attacks by “foreign” invaders.
• These invaders are primarily microbes(germs)
—tiny, infection-causing organisms such as
bacteria, viruses, parasites, and fungi.
• The immune system is amazingly complex. It
can recognize and remember millions of
different enemies, and it can produce
secretions and cells to match up with and wipe
out each one of them.
The immune system
• is composed of multiple elements, including
innate immunity and adaptive immunity.
• Anything that can trigger this immune
response is called an antigen.
• An antigen can be a microbe such as a
virus, or even a part of a microbe.
Host cell- Agent interaction
• Thus, host cell receptor and microbial ligand
interactions have an impact on the geographic
range of infections based on host genetic
differences in requisite receptor expression and
on the specific cells that a microbe may enter.
• Example: Plasmodium vivax binds to the Duffy
blood group antigens, reticulocyte binding
proteins.;
Another example
• Microbe-receptor interactions has been
recognized with HIV-1.
• Although CD4 is the primary cellular
receptor for HIV entry, binding to CD4
alone is not sufficient for entry of HIV-1
into cells. HIV need cellular coreceptors
(CCR3,CCR5, CXCR4)
Host cell molecules that function as viral
receptors
• CD4 molecule, CCR5, CXCR4, for HIV
• A complement regulatory protein, for measles;
• The integrin, intracellular adhesion molecule-1
(ICAM-1), for rhinovirus;
• Erythrocyte P antigen for parvovirus B19;
• C3d complement receptor (CR2) for Epstein–
Barr virus
Intracelluler
• Microbes that exist principally within the
cytoplasm are sequestered from many immune
response mechanisms active on extracellular
pathogens, including antibody and phagocytic
cells.
• Viral intracellular proteins will be processed
and
• displayed with class I major histocompatibility
complex (MHC) proteins, which enable CD8
cytotoxic T cells to recognize and kill the
virally infected cell
Intracelluler
• Other microbes are internalized within
phagocytic cells, especially macrophages.
• Once internalized in host cells, organisms
such as Salmonella, Mycobacterium,
Chlamydia, and Legionella use an
extraordinary assortment of mechanisms to
prevent their phagocytic vacuole from
fusing with the host cells’ acidifying
lysosomes
Why microorganism survived intracel
• For example, Leishmania and Coxiella (unlike
other pathogens) benefit from the acidic
environment of the macrophage phagolysosome.
• Leishmania use the proton gradient across the
lysosome to drive the energy-dependent uptake of
two important substrates: glucose and proline
Toxoplasma Gondii
• Conversely, other intracellular pathogens such as
Toxoplasma gondii survive within the macrophage by
using an alternative pathway of entry that avoids
fusion of the parasitophorous vacuole with lysosome
• In contrast, dead or antibody-coated T. gondii enter
via the Fc receptor and are routed to a different
intracellular compartment, which fuses with the
lysosome, and are then killed in the phagolysosome
Intracelluler Microbe
• Other organisms, such as Shigella, Listeria, and
Rickettsia :
• breach their vacuolar membrane to multiply freely
in the cytoplasm and may also usurp host cellular
actin to propel their further spread to neighboring
cells, continuing to exploit their intracellular
sanctuary.
• Immune responses against microbes within
macrophages rely heavily on class II MHC-
mediated presentation of host antigenic peptides to
T helper 1 (Th1) types of CD4+T cells, which then
augment the microbicidal activities of the
macrophages.
Extracelluler
• Host defense against extracellular
pathogens uses antibodies, complement,
phagocytic cells, and, for helminths, IgE,
eosinophils, and mast cells
• Mucosal immune responses, including IgA
and leukocytes, participate in host immune
reactions to these pathogens.
TERIMA KASIH
MATUR SUKSMA
THANK YOU

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MICROBIAL

• Direct Mechanisms of Disease Transmission

• Indirect Mechanisms of Disease Transmission

• Benefits of the normal flora

• State of the Host Immune System

• Number of Pathogenic Cells

• Intracelluler : malaria parasites : Plasmodium vivax binds to the

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