1.introductory lecture

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MICROBIAL PATHOGENESIS INTRODUCTORY LECTURE BY WALTER WASWA WALTER WASWA

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Page 1: 1.introductory lecture

MICROBIAL PATHOGENESIS

INTRODUCTORY LECTURE

BY WALTER WASWA

WALTER WASWA

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• 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

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DEFINATIONS

• Pathogen is a microorganism that is able to cause disease in a plant, animal or insect.

• Pathogenicity is the ability to produce disease in a host organism.

• Microbes express their pathogenicity by means of their virulence, a term which refers to the degree of pathogenicityof the microbe.

• Determinants of virulence of a pathogen are any of its genetic or biochemical or structural features that enable it to produce disease in a host.

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• 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

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• 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

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• 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

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• 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

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• 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

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• 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

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– Animal Vectors

– An animal (nonhuman) that can transmit an infectious agent to humans

– Two types: mechanical and biological

– Mechanical animal vectors: The infectious agent is physically transmitted by the animal vector, but the agent does not incubate or grow in the animal; e.g, the transmission of bacteria sticking to the feet of flies

• Biological animal vectors: The infectious agent must incubate in the animal host as part of the agent’s developmental cycle; e.g, the transmission of malaria by infected mosquitoes

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• 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

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• The relationship between a host and a pathogen is dynamic, since each modifies the activities and functions of the other.

• The outcome of such a relationship depends on: the virulence of the pathogen and

• the relative degree of resistance or susceptibility of the host, mainly due to the effectiveness of the host defense mechanisms

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Infectious Agents in Humans

• Prion - scrapie

• Viruses – HIV, influenza

• Bacteria – Mycobacterium tuberculosis

• Fungi – Candida albicans

• Protozoa – Plasmodium falciparum

• Helminths – Schistosoma mansoni

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normal abnormal

Prion

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Virus

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Bacteria

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Fungi

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Protozoa

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Helminths

Ascaris lumbricoides : human intestinal roundworm

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Barriers

Physical barrier: Skin, Mucosal gel overlaying epithelium (respiratory, gastrointestinal, urogenitary)

Microbiological barrier: Normal microbioflora

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Initiation of Disease

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Transmission

• Aerosols to respiratory mucosa

• Fomite to nasopharyngial or conjungtive mucosa

• Fecal – Oral Route

• Mucosal surface to mucosal surface

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Transmission

Multiplication

Dissemination

Invasion

Breach of epithelium

Colonization of mucosa

Infectious Disease Cycle

or

Attachment to target cells

to subepithelial or intracellular space

Evasion ofhost defense

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Evasion/Manipulation of Host Defense

• Modulation of innate/inflammatory response

• Resistance to phagocytic killing in subepithelial space

• Serum resistance

• Antigenic variation

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Resistance to phagocytic killing in subepithelial space

• Survive within phagocyte

• Inhibit phagocyte mobilization :(chemotaxis, complement activation)

Inhibit chemoattractants: Streptococcus pyogenes degrades C5a

Inhibit chemotaxis: Pertussis toxin causes intracellular rise in cAMP in neutrophils to impair chemotaxis

• Avoid ingestion

kill phagocytes: Streptolysin O lyses PMNs; Staphylococcus aureus alpha, beta and gamma toxins and leucocidin lyses PMNs

capsular protection from opsonization: M proteins, Streptococcus pyogenes

Bacterial capsules that resemble self: Neisseria meningitidis (sialic acid); Streptococcus pyogenes (hyaluronic acid)

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Survival within phagocyte

Escape endosome or phagolysosome:

- Shigella, Listeria monocytogenes

Inhibit phagosome-lysosome fusion

- Legionella pneumophila, Mycobacterium tuberculosis, Salmonella

Survive within phagolysosome (resist enzymatic degration or

neutralize toxic products)

- Inactivate reactive oxygen species: Salmonella, via superoxide dismutase, catalase, recA

- Resist antimicrobial peptides: Host cationic peptides complexed with SapA peptide

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Cell and Tissue Damage

• Induction of apoptosis and necrosis

• Virus-induced cytopathic effect

• Induction of damaging host immune response

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Cell lysis

accumulation of reactive

oxygen intermediatesmacrophages

virusesaccumulation of nitrogen

intermediates

accumulation of intracellular

calcium

Rotavirus,

cytomegalovirus, HIV

Syncytia

formation

Paramyxoviruses

(respiratory syncytial

virus, parainfluenza

viruses, measels virus,

herpesvirus, some

retroviruses)

viral-encoded

fusion proteins

Virus-Induced Cytopathic Effect: Part 1

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production of

eosinophilic or

basophilic

inclusion

bodies

viruses

host cell

transformation

DNA viruses

Burkitt's

lymphoma

(EBV)

inactivation of p53 and Rb,

chromosomal destabilization,

enhancement of foreign DNA

integration and mutagenecity

cervical

carcinoma

(human

papilloma

viruses)

retroviruses

adult T-cell

leukemia

(human T-cell

lymphotropic

virus type 1)

Virus-Induced Cytopathic Effect: Part 2

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Induction of Damaging Host Immune Response

autoimmune

response

cross-reactivity between self

and mycobacterial heat shock

proteins

cross-reactivity between

components of endocardium

and joint synovial membrane

molecules and antigens in the

streptococcus cell wall

Acute rheumatic

fever after group A

streptococcal

pharyngitis

hypersensitivity

reactions

granuloma

formation

Mycobacterium

tuberculosis

septic

shock/sepsisbacteria

LPS, peptidoglycan,

lipoteichoic acid,

toxins acting as

superantigenstoxic shock

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The end

QUESTIONS?

WALTER WASWA