Host- Pathogen Responses - Weapons of Mass Infection Flashcards
What does LD 50 mean
lethal dose amount of an agent that will kill 50% of animals in a test group, describes virulence
If an animal has a higher lethal dose (LD50) is it more or less virulent?
less because a higher amount is needed for the same effect
What is the ID 50?
number of pathogen cells or visions required to cause active infection in 50% of inoculated animals, higher ID50 means it’s less infective does not consistently correlate with virulence
primary pathogens vs opportunistic pathogens
primary pathogens –> cause disease in healthy host
opportunistic pathogens –> cause disease in compromised hours or following entry into unprotected sites (usually harmless or can be fought off pretty easily except for exceptional cases or a loss of homeostatic balance)
What is an infection how does it happen?
any time where a non local microorganism is established and growing, it doesn’t always mean disease, some can even enter a latent state during infection where the organism can’t be found by culture
What is immunopathogensis?
“friendly fire” by our immune system contributes to pathology and disease by causing major damage (symptoms)
Infection cycles
Horizontal transmission:
direct (handshaking, kissing etc.), indirect (sharing contaminated objects or space)
fomites: inanimate objects (pathogen lives there for a while and infects people who come in contact, like doorknobs and utensils)
Vertical transmission:
from mother to fetus during pregnancy or birth
What are the steps to pathogenesis
Infection process:
1. exposure
2. adherence
3. invasion (through epithelium)
4. multiplication (growth and production of virulence factors and toxins)
Disease process
toxicity (toxin effects are local or systemic) or invasion (further growth at original and distant sites)
Portals of Entry
mouth, respiratory tract, conjunctiva and mucous membranes, wounds, injuries and skin lesions and parenteral route (direct into bloodstream)
Septicemia
blood borne systemic infection, can lead to inflammation septic shock etc,
bacteremia
bacteria in blood not always harmful
invasiveness
ability of a pathogen to grow in host tissue in large enough quantities that it’s a problem and inhibits host function
Types of virulence factors
adherence: adhesion, capsule, fimbriae, pili, flagella etc.
Invasion: enzymes, cytolytic exotoxins
Growth and toxicity: virulence plasmid, exotoxins, endotoxins, antiphagocytic proteins immune inhibitors, T3SS and effector proteins
What is an adhesin
glyco or lipoprotein on pathogen surface that allow it to bind to host cell by interacting with receptors on host cell membrane
ex. pili, flagella, fimbraie
How do pili (fimbriae) attach
Type I: adhere to carbs on host mb
static attachment growing from outer mb of gram -ve
Type IV: twitching motility
dynamic attachment that assemble and disassemble , grow from inner mb of gram -ve bacteria
What are non-pilus adhesins
S. pyogenes: M protein (binds to fibronectin)
B.pertussis: pertactin (binds to integrin)
P.areuginosa: MAM7 (binds to phospholipids and fibronectin)
- can bee why some people are more susceptible: receptor availability, immunocompetence, person-person differences in receptor structures are possible
How do capsules contribute to pathogenicity?
no capsule no pathogenicity
sticky and has receptors for attachment
protect the bacteria phagocytosis
they inhibit opsonization because they block bacterial receptors from opsonins
- block antibody/complement interaction
- reduce entry into endocytic pathways by lessening antigen presentation (hiding the bacteria)
- mimics self molecule, preventing antibody/complement response
How do biofilms contribute to infections
- play a role in chronic infections by enabling persistent adherence, resistance to host defences and tolerance to Abx agents
Enzymes as virulence factors
pathogens often have to break down host tissues, this is often done through enzymes that attack host cell like hyaluronidase which breaks down host tissues,
other examples are coagulase and streptokinase used by S.aureus which clots itself to avoid immune system or S. pyogenes to dissolves the clot to release pathogen into blood stream
Exotoxins
proteins produced and secreted by bacteria which kill host cells and unlock their nutrients
ex: ab toxins, cytolysis and
superantigens
mostly gram positive bacteria can. be both, proteins, cell specific, heat labile, low LD50
Cytotoxin
protein that bacteria produce that usually inhibits protein synthesis and will kills cells, or cause cell injury
hemotoxins
Toxins that destroy red blood cells, disrupt blood clotting, cause hemolysis
endotoxin
- LPS of gram -ve bacteria
- lipoteichoic acid on gram +ve
hyperactive the host immune systems to harmful levels
Effector Proteins
proteins that have a function that will help the bacteria manipulate the host to its advantage (invasion, immune evasion)
they can help with colonization, invasion, cytotoxicity, immunity, they carry out the virulence strategy
Cytolysins
exotoxins that disrupt host cell membranes
2 mechanisms:
pore-forming proteins: insert themselves into membranes by binding cholesterol and membrane receptors
ex. hemolysins and leukocidins or streptolysin S which is indiscriminate
Phospholipase enzymes: hydrolyse phospholipids into fatty acids
AB toxins general mechanism
A subunit toxicity associated factor
B subunit binds host cell, delivers “A” subunit
Cholera toxin
AB5 exotoxin, made by V. cholerae, disrupts signalling
1. Bs bind to intestinal cell membrane and trigger endocytosis of cholera toxin complex
- As ADP-ribosylate a host cell target that leads to sharp increase is second messenger cAMP
- cAMP activates ion transporters which push ions out making the cell hypotonic and water leaves leading to watery diarrhea
Diphteria Exotoxin
produced by Corynebacterium diphtheria that blocks protein synthesis
- destroys healthy tissues in respiratory system
-causes thick gray psuedomembrane coating that makes it very hard to breathe and swallow
-can get into blood stream and damage other systems heart, kidneys nerves
Neurological Exotoxins
Botulinum toxins and tetanus toxins
- disrupt transport
B causes loss of contraction
T constant state od contraction
Endotoxins
- only made by gram -ve
- lipid A a part of the LPS is the endotoxin part,
- general systemic symptoms of inflammation and fever
-heat stable
-high LD50 - immunopathogenic
- less immunogenic (less good for vaccines essentially) –> maybe cause they are so immunopathogenic
can lead to toxic shock and systemic infections
Septic shock: induced by pathogen associated molecular patterns other than endotoxins
Type II secretion system
- homologous to Type 4 pili
- secretion structures extend and extract like pili using polymerization and depolymerization
- protein is secreted into the periplasm gets folded than secreted out via an outer membrane pore
Type III secretion system
- homologus to flagellar synthesis mechanism
- bacterial pathogens use them to insert their receptor into target cells
–> inject toxin(effectors) into eukaryotic host cells - secretion is triggered by cell-cell contact bwt host and bacterium
- genes located within pathogenicity island
