What are the factors that influence the outcome of infection?
Agent infectivity
environmental pressure
host susceptibility
What are the two main parts of the immune system?
innate immune system
- first line of defense
adaptive immune system
- B-cells and T-cells
What happens when the binding of antibodies to antigens inactivates antigens?
- neutralization
- agglutination of microbes
- precipitation of dissolved antigens
- enhances phagocytosis
- activation of complement system
- leads to cell lysis
What are proteases?
enzymes that break down proteins
- C-proteases: destroy complement proteins
- Ig proteases: destroy antibodies
What are invasins?
rearrange host cell components to facilitate the movement of a microbe into a cell
- hyaluronidase: breaks down cell to cell adhesions
- collagenase: breaks down the protein collagen
- coagulase: converts fibrinogen to fibrin clot to isolate (can hid from immune system)
- kinases: break down fibrin
Evasion of entry: streptococcus spp.
M-protein is strongly anti-phagocytic and destroys complement proteins
Evasion of entry: neisseria spp.
capsule impairs phagocytosis by limiting the attachment of white blood cells
- glycocalyx
evasion of entry: yersinia spp.
injects virulence factors via type III to prevent ingestion
evasion of digestion: salmonella spp.
injects virulence factors via type III to prevent lysosome fusion with the phagosome
evasion of digestion: mycobacteria spp.
waxes resist destruction by digestive enzymes
evasion of digestion: shigella spp.
injects virulence factors via type III to escape the phagolysosome and spread to neighboring cells
- moves at last second
What are the three ways pathogens can damage host cells?
- use host nutrients depriving them of important factors
ex. siderophores: stealing iron
ex. tapeworms - cause structural or functional disruption at the site of infection
ex. COVID-19 or S. pyogenes (necrotizing fascitis) causes DIRECT damage to tissue and cells
ex. Rheumatic fever (S. pyogenes) or tuberculosis (M. tuberculosis) cause indirect damage to tissue, damage due to immune response - produce toxins
- toxins are poisonous compounds that are produced within living cells, toxigenicity is the ability of a microbe to produce a toxin- endotoxin: lipid A, a toxin found within the cell, can lead to septic shock (gram-negative)
- exotoxin: bacteria secretes exotoxin like cytotoxins, carried as genes on a plasmid and inhibit certain metabolic functions (gram-positive)
ex. clostridium botulinum
What is LD50?
median lethal dose for 50% of a sample population tested
- used to measure the potency of toxins
What are membrane disrupting toxins?
a type of exotoxin
- cause lysis of cells by disrupting the membrane, common types are hemolysins (RBCs)
ex. streptococcus
- a hemolytic: green, partial hemolysis
- b hemolytic: clear, complete hemolysis
- y-hemolytic: no hemolysis
- causes lysis of cells disrupting the membrane, common types are leukocidins (WBCs)
What are staphylococcus aureus toxins?
Both hemolysins and leukocidins
What are A-B toxins?
two-component toxin including A component (active) and B component (binding)
ex. corynebacterium diphtheriae, diphtheria toxin inhibits RNA translation
ex. clostridium tetani, tetanus toxin inhibits fusion of vesicle containing inhibitor neurotransmitters
ex. clostridium botulinum, botulinum toxin inhibits fusion vesicles containing excitatory acetylcholine neurotransmitters
How does the process of the diphtheria toxin work?
- Diphtheria toxins receptor binding domain (B) binds host membrane
- membrane-bound toxin (A+B) enters by endocytosis
- catalytic subunit A is cleaved but held to the B subunit by disulfide bonds. Endosome vesicle acidifies, the disulfide bonds are reduced
- the transmembrane domain facilitates passage of the catalytic A peptide through the vesicle membrane
- the catalytic A domain ADP-ribosylates elongation factor 2 (EF2). This halts protein synthesis and kills the cell
What are second-messenger toxins?
toxins that disrupt secondary messengers of cellular signal pathways (sub-class of A-B toxins)
ex. bacillus anthracis
ex. bordetella pertussis, pertussis toxin disrupts signaling pathways of immune system
ex. vibrio cholerae
Bacillus anthracis
secondary messenger
anthrax toxin disrupts signaling pathways of the immune system
Bordetella pertussis
secondary messenger
pertussis toxin disrupts signaling pathways of immune system
vibrio cholerae
secondary messenger
cholera toxin disrupts intestinal osmotic balances resulting in rapid fluid floss
Exiting the host
most pathogens are not adept to long-term survival within their host, making their escape from the host a necessity in order to find a new organism to invade
ex. vibrio cholerae, bacteria escapes by diarrhea
CVEC = conditionally viable environmental cells (cannot be cultured)
