Host Pathogen Interactions / Epidemiological Concepts

infection

successful colonization with multiplication of microorganisms within a host with or without the manifestation of disease

infectious disease

illness caused by damage to host cells by an infectious agent (bacteria, virus, fungi, parasites) or its products (exotoxin) resulting in signs and symptoms

pathogen

any bacterium, virus, or fungus, protozoan or helminth (eg infectious agent) that causes disease

pathogenicity

the ability of an organism to cause disease:

• genetic makeup of the pathogen

• location in/on the host’s body

• host immune response

virulence

degree or severity of disease

• pathogens vary in degree of virulence

• pathogens use various strategies to establish virulence

• ex. rhinovirus is less virulent than ebola

virulence factors

pathogen’s ability to establish itself in a host or cause host damage

LD50 (lethal dose 50)

the number of microbes that kills 50% of an experimental group of animal hosts (lower LD=more virulent/likely to cause infection)

infectious dose (ID)

minimum number of microbes required to be taken in by the body to cause infection

ID50 (infectious dose 50)

the number of microbes that will cause infection in approximately 50% of an experimental group of hosts

primary pathogens

“true pathogens”

• cause disease in a host regardless of the host’s resident microbiota or immune system

• are never part of the normal microbiota

opportunistic pathogens

• cause disease only under opportunistic conditions (ex. situations that compromise the host’s defenses)

conditions that lead to opportunistic infections

• changes in composition of the normal microbiota (antibiotics)

• displacement of normal microbiota to another site of the body

• weakened immune system (immune suppression from chemo/organ transplants, immunodeficiency, old age

acute infection

• rapid and sudden onset of microbial reproduction

• short but possibly severe course of disease

• production of large amounts of microbes

• resolution of symptoms typically within days/weeks

chronic infection

• persistent microbial reproduction

• infection/disease that lasts a long time, possible lifespan of host

• initial symptoms are inapparent but cumulative damage over time

• not rapidly cleared by immune system

latent infection

• pathogen goes dormant for extended periods of time with no active replication

• no symptoms during latency

• pathogen can reactivate to cause acute infection

localized infection

pathogens that grow locally at the site of invasion

systemic infection

pathogens that enter the circulation and spread throughout the body

stages of pathogenesis

1. ADHESION to skin or mucosa

2. INVASION

3. INFECTION (colonization and growth)

   1. Toxins or host immune response

4. TISSUE DAMAGE/DISEASE

portals of entry

ways that pathogens enter and exit the body

fecal oral

through mucosal surfaces of gastrointestinal tract

respiratory

through mucosal surfaces of the respiratory tract

transplacental

through the placenta to infect a fetus

skin

through epithelial surfaces

urogenital

through mucosal surfaces of genital and urinary tracts

parenteral

through injection into the bloodstream (ex. insect bites or needles)

adhesion

• fimbriae (pili) adhesins

• cell wall associated adhesins

  • lipoteichoic acid

  • glucan

  • peptides in outer membrane

• glycocalyx (slime and capsular polysaccharides)

immune avoidance

• capsules

• various antigen structures

• sequestering antibodies

• secrete fake cytokines

• manipulate host cytokine production

• control virulence factor synthesis

intracellular bacteria survival within phagocytes

• differentiate into a form that tolerates lysosomal chemicals

• preventing fusion of the lysosome with the phagosome

• escaping from the phagosome before lysosome fuses

implications transportation of toxins by blood or lymph

spreads to other parts of the body

exotoxin

proteins produced by pathogenic bacteria (gram ±) and secreted

endotoxin

lipid A portions of LPS that are part of the outer membrane of the cell wall of gram negative bacteria. they are liberated when bacteria die and the cell wall breaks apart

exotoxin modes of action

1. Cytolytic toxins - disrupt cytoplasmic membrane by creating pores or degrading membrane phospholipids

2. AB toxins - B binds and transfers toxic unit A that inhibits protein synthesis or ion homeostasis

3. Superantigen toxins - overactivate the immune system by activating CD4+ T cells » excess cytokines » excess inflammatory response

source (gram + or -) for exotoxins

both

source (gram + or -) for endotoxins

gram negative

exotoxin type of molecule

proteins; often enzymes

endotoxin type of molecule

lipid A of LPS

LD50 of exotoxin

low (very toxic)

LD50 of endotoxin

high

exotoxin effect on host

localized specific damage

endotoxin effect on host

systemic effects of inflammation

exotoxin method of release

actively secreted

endotoxin method of release

released passively

exotoxin antigenicity

highly antigenic

endotoxin antigenicity

poorly antigenic

mechanisms of bacterial pathogenesis

• produce toxins that are ingested

• colonize and invade host tissues

• colonize and produce toxins (no invasion)

• colonize and invade host tissues produce toxins