Establishment of Infection

• In order to cause disease pathogen must follow a series of steps– Gain entrance to host – Adherence– Colonization – Avoid Host Defenses – Cause host damage

Portals of entry

1. Mucus membranes• Respiratory tract • Gastrointestinal tract• Genitourinary tract• Placenta

2. Skin

3. Parenteral route• Bite, puncture,

injection, wound

• Most microbes have a preferred portal of entry– Streptococci when inhaled may cause pneumonia;

when ingested they do not

• A few microbes cause illness no matter how they enter– May cause different illness based on portal– Plague has 2 forms; bubonic and pneumonic– Anthrax has 3 forms

• Adherence (adhesion)– Critical Step– Bacteria use adhesins (ligands)– Viruses has surface attachment proteins – Binding to host cells receptors is highly specific

• Colonization– Organism must multiply in order to colonize– New organisms must compete with

established organisms for nutrients and space

– May form biofilms

• Virulence factors– Structural or physiological characteristics

that aid in penetrating or avoiding host defenses

• Capsules– Avoid phagocytosis; Prevents dessication; aids

attachment

• Incomplete phagocytosis – Escape the phagosome– Prevent fusion with lysozome– Survive inside phagolysozome

• Fimbrae – Attachment

• Components of cell wall – M proteins of Streptococcus– Mycolic acid of Mycobacteria and Norcardia

– Outer membrane of Gram- bacteria

• Extra-cellular enzymes (exoenzymes)– Coagulases – Kinases– Hyaluronidase

• Dissolves hyaluronic acid

– Collagenase

– IgA proteases

– Leukocidins

• Antigenic variation– Avoid antibodies by altering surface antigens – Neisseria varies pili type

• Penetration into host cytoskeleton – Manipulate actin to penetrate cells and to move

between cells– Some pathogens induce non-phagocytic cells into

endocytosis– Disruption of cytoskeleton may cause membrane

ruffling

Damage to the Host

• In order to cause disease pathogen must cause damage– Damage facilitates dispersal of organisms

• Vibrio cholerae causes diarrhea• Bordetella pertussis causes coughing

– Damage can be direct result of pathogen such as toxin production or indirect via immune response

Bacterial Damage to Host Cells

• Use host cell’s nutrients

• Binding to and invading host cells

• Induce hypersensitivity reactions (allergies)

• Production of toxins (Toxigenicity) – May be exotoxins or endotoxins

– Exotoxins

– Produced by G+ bacteria• Produced as part of their metabolism• Secreted externally or released following

cell lysis• Proteins

– Enzymatic nature – Highly soluble– Heat Liable

– Among most lethal substances

– Toxoids

• Inactivated exotoxins• Induce antitoxins that provide immunity

– Antibodies against a specific toxin

• Passive immunity in form of antitoxin can be given as treatment

– Grouped into functional categories• Neurotoxins

• Enterotoxins

• Cytotoxins

• Staphylococcus aureus – enterotoxin – may be heat stable – exofoliatin toxin

• Scalded skin syndrome– Toxic Shock Syndrome (cytotoxin)

• Vibrio cholera– cholera enterotoxin

• Clostridium botulinum – botulinum neurotoxin

• Clostridium perfringens– Gas gangrene

• Clostridium tetani – tetanus neurotoxin

• Endotoxins – part of the outer portion of the G- cell wall– lipopolysaccharides (LPS)

• lipid portion (lipid A) – Released when cells die and cell walls lyse – Antibiotics used to treat diseases can lyse cells

• May cause an immediate worsening of symptoms

– All endotoxins produce the same symptoms• Chills, fever, weakness, aches• May activate blood clotting proteins • May cause septic shock that can be fatal

– Heat stable; not suitable for use as toxoids• Do not cause formation of antitoxins

– Antibodies may enhance action of toxins

– Salmonella typhi, Proteus spp. and Neisseria meningitidis

• Cytopathic effects• Avoiding immune responses

• Antibodies interact with extracellular viruses only• Viruses can remain intracellular by forcing

neighboring cells to fuse in the formation of syncytium

• Viruses can outpace body’s capacity to produce antibody

Mechanisms of Viral Pathogenesis

• Some virus-infected cells release interferons to warn neighbor cells– Anti-viral proteins – Helps limit viral replication– Some viruses encode specific proteins to

interrupt activity of interferons

Mechanisms of Eukaryotic Pathogenesis

• Fungi– Generally opportunistic– Most serious fungal infections caused by

dimorphic fungi– Some produce mycotoxins

• Claviceps; Ergot toxin• Aspergillus; Aflatoxin• Amanita; Neurotoxins

• Parasites– Most live within intestinal tract or enter

body via bite of an arthropod– Use host nutrients– Presence of parasite interferes with host

function– Parasite's metabolic waste can cause

symptoms

• Algae– A few species produce neurotoxins

• Alexandrium produces toxin that causes paralytic shellfish poisoning

• Produces symptoms similar to botulism

Portals of Exit• Respiratory and

gastrointestinal tracts– Most common

• Genitourinary tract

• Skin/wounds

• Biting insects

• Contaminated needles and syringes