22: bacterial pathogenesis Flashcards
How do we resist microbes?
physical barriers, limits nutrient availability, innate and adaptive immunity
How do pathogens evade restriction?
adhere/invade host tissue, secrete toxins/effectors, steal host nutrients, SEC
What is a primary pathogen?
always cause disease
What is an oppurtunistic pathogen?
cause disease only in compromised host or following entry into unprotected sites
What is lochs postulate?
- microbe only found in disease but is absent from healthy individuals
- microbe is isolated from diseased host and grown in pure culture
- microbe in new host, same disease occurs
- same strain of microbe is isolated from dead host
What must a pathogen do to cause disease?
enter host, find unique niche, SEC defenses, multiply, transmit susscebtibilty via virulence factors
Whats a pathogenicity island?
virulence genes in pathogens clustered in islands with unique GC/AT ration, linkage to tRNA gene or association with gene homology to plasmid
horizontally transferred via transduction and conjugation
What are lochs molecular postulates?
inactivation of virulence genes should be associated w? decrease in pathogenesis
replacement of gene should restore pathogenicity
Microbial attachment
adhesion via adhesion protons cell attachment, bind to specific host factor (pilus or nonpilus proteins)
chemical defenses of mucosal colonization:
lysozyme: modify pG to be resistant to it
antimicrobial peptides: bacteria change charge of membrane to repe positively charged defension, prevent pores
obtain nutrients: specific receptors (lactoferrin, transferrin) to harvest essential molecules
adaptive immunity:
antibody degradation (iGA protease) or antigenic variation(type 4 pilus)
Portals of entry: skin
pathogen invasion via damaged skin
portals of entry: mucus membrane
entry through damaged epithelium
-forced uptake: use of type 3 secretion system to induce uptake in non phagocytotoxic cells
-M cell transcytosis: antigen/bacteria taken up by M-cell, exit M-cell for macrophage uptake
SEC: subvert
effectors/toxins employed to block signaling pathways or to remove key immune cells
What are toxins?
secreted into extracellular place
- can damage cellular membranes via pore
- can inhibit protein synthesis via iron starvation
What are effectors?
proteins injected into host cell via type 3 ss
enteropathic e.coli attaches via type 1 pilus. inject TirA effect which binds to intimin on membrane, Air phosphorylated, actin polymerization, pedestal formation
SEC: evade
mask MAMPS to avoid immune detection
- capsular polysaccharide: barrier to MAMP, protect from PRR and toll receptors
- on glycosyl chains of gram -
SEC: counteract
shields used to render host useless: antibodies and ROS
phagocytes can break down ROS
FC region and receptor: aid in linking antibodies at FC region
antibodies link bacteria and macrophage
immune evasion of yrsenia pestis
gamma proteobacteria, g- rod with LPS in outer membrane is a MAMP that binds to PRR TLR4 to induce inflammation
- lipid A core of LPS is conserved in g-, sensed by TLR4
temp dependency of yrsenia pestsis
hexa acetylated when in host but tetra acetylated in host, TLR4 cannot recognize it so it goes undetected
Yrsenia and lysozyme
When sensed by lysozyme, yrsenina resists it and kills macrophage, enters lymphoid tissue, develops T3SS
-> T3 needly protein binds to formyl peptide receptor on phagocytes and uinhects w effectors, blocks cytokine production and disrupts actin polymerization-> no phagocytosis
