Host-Parasite Relationships

Host-Parasite Relationships: Extracellular and Intracellular Pathogens

Extracellular Pathogens

Extracellular pathogens: replicate and live in extracellular spaces; resistant to phagocytosis; phagocytosis Þ death

Pathogenicity of extracellular pathogens:

adhesion: mediated by adhesins and host cell receptors; affected by inoculum (infecting dose)

pilus or fimbrial (E.Coli); non-fimbrial (Streptacocci)

inactivate/attenuate defenses of host
toxin production: endotoxin vs. exotoxin

Host anti-parasite mechanisms:

primary barriers:

mechanical: epithelium tight junctions, flushing (urine, mucus)
chemical: low pH (stomach); enzymes (lysozymes in tears, sweat, saliva; pepsin in gut); fatty acids (skin); antibacterial peptides (definsins)
microbiological: competition from natural flora inhibits growth of invaders

innate immune response (non-adaptive, non-specific)

complement: can be inhibited by organism; deficiency in C5-C9 (MAC) Þ difficulty killing some bugs

cytokines, acute phase proteins

PMNs: acute phase cellular response

granulocytopenia (drugs, HIV, Eppstien Barre, genetic defects rare) Þ decreased effectiveness

macrophages

adaptive immune response (specific): antibody production; opsinization for phagocytosis

Normal Flora

~100 different species live in specific sites in or on the body

generally are beneficial and even help with defense against pathogens , but they can become pathogenic

aspiration pneumonia: host aspirates normal oral flora Þ infection

sites of normal colonization can be invaded by more virulent pathogens (carrier state)

Intracellular Pathogens

Intracellular pathogens: must replicate inside cells; have mechanisms to evade phagocytic death (resists intracellular killling)

faculatative (vesicular) intracellular pathogens: can survive inside host cells; usually infect macrophages

salmonella, listeria, mycobacterium tuberculosis, legionella, fungi, protozoa

generally resistant to complement and Ab, ingested by tissue macrophages, evade destruction, multiply

cell mediated immunity needed (macrophages must be activated to kill bugs in phagosomes)

IFN-g is the main activator of macrophages

obligate (cytoplasmic) intracellular pathogens: must reside in host cells to survive

viruses, clamydia, rickellsia

Mechansims of survival in phagosomes

adaptation to survive in phagolysosomes: i.e., develop enzymes that function in acid environment
escape from the phagolysosome to live in the cytoplasm
inhibition of fusion of phagosome and lysosome
inhibition of generation or function of antimicrobial effector molecule

i.e. lysosomal enzymes, reactive oxygen or nitrogen intermediates; produce ammonia to neutralize acid

Listeria monocytogenes

ubiquitous; pathogenic only in immunocompromised hosts

internalin (cell wall protein) promotes phagocytosis

fusion with lysosome (low pH) activates lysteriolysin O Þ causes lysis of phagolysosomal membrane – escapes into cytoplasm

the bug proliferates and is coated in actin which propels the bug to the cell membrane where it pushes the host’s

membrane out (forms philopods) and is taken up by other cells without contact with the extracellular environment

Mycobacterium tuberculsis

spread by aerosol route and taken up by alveolar macrophages

evade destruction via sulfatides on the bug’s surface which prevent lysosomal fusion; can escape into macrophage cytoplasm

infection spreads via lymphatics Þ thoracic duct Þ bloodstream

also produce ammonia to neutralize the lysosomal enzymes

infection contained by cellular response

T-cells activate macrophages, promote chemotaxis of immunity cells, and promote granuloma formation

INFg activates macrophages

latent foci of infection may persist and become active when triggered by an immunocompromising condition

reactivation causes a hypersensitive reaction which leads to excess cytokine production
caseation promotes extracellular reproduction and leads to chronic infection

Legionella pneumonphila

aerosolizes from water reserviors; infection more common in patients with decreased cellular immunity

enters cells via coiling phagocytosis mediated by complement receptors Þ poor oxidative burst

on the other hand, antibody reaction with legionella leads to normal phagocytosis and destruction of the bug via oxidative burst

once in the cell, bug avoids and neutralizes lysosomes; multiplies until macrophage bursts Þ taken up by other macrophages

macrophages are eventually activated by IFN-g

more phagocytosis is impeded and intracellular replication is slowed by limiting intracellular iron
however, only further growth is stopped; legionella are not actually killed by the macrophages