Describe the different natural/physical barriers of the body that limit bacterial entry/infections (including AMPs)
body surface: first line of defence
physical and chemical
bacteria-killing enzyme Lysozyme (tears & salvia)
AMPs (Anti-microbial peptides): membrane disruption, pore formation, intracellular toxicity
-> bacteriostatic or bactericidal effects
Describe what is meant by the term inflammation with respect to bacterial infections
innate response of the body to acute bacterial infections
-> non specfic
-> mediated by
soluble factors including complements
phagocytic cells
Know what TLRs are, and what bacterial components they recognise
Toll-like receptors
bind to specific bacteria surface components
causes secretion of cytokines
attraction of phagocytic cells to infection site
bacterial components
bacterial lipids (TLR1/2/4/6)
bacterial DNA (TLR9)
bacterial proteins (TLR5/10)
Briefly describe the anti-bacterial properties of neutrophils and macrophages
neutrophils
macrophages
high antibacterial activity
short lived (3-4 days)
long lived (months)
normally only present in blood
different types w. different locations
tissue - RES
circulating - Monocytes
attraction by several soluable factors
attracted to site of infection
early accumulation
mature into phagocytic macrophages in tissue
major defence against extracellular bacteria (traps/nets to catch bacteria)
IFN and TNF generation which causes chemoattraction and change to endothelium of blood vessels
Describe the process of phagocytosis
phagocytosis
specific form of endocytosis
recognition
change of cell structure to engulf bacterium
phagosome: phagocytic vesicle around bacterium
production of enzymes by lysosome and bumped into phagosome
killing of bacteirum and digestion
Describe oxygen- vs. non-oxygen-dependent anti-bacterial activity in phagocytes
oxygen dependent
oxygen independent
respiratory burst during phagocytosis -> O2 consumption increase
not as effective as oxygen dependent ones
production of oxygen damaging radicles to damage bacterial membrane
damage bacterial membranes (BPI, defensins)
ROIs (Reactive oxygen intermediates); RNIs (Reactive nitrogen intermediates)
damage peptidoglycan (bacterial cell wall - Lysozyme)
toxic compounds kept in compartments (phagosomes) inside cell
damage bacterial proteins (Proteases, elastase)
deprive bacteria of nutrients (Lactoferrin, Vitamin B12 binding proteins)
Describe what opsonins are and their importance in phagocytosis
chemicals produced in response to bacterial infection
-> receptor clustering and triggers phagocytosis
=> attraction of phagocytes and bacteria getting recognised by phagocytes
=> innate opsonins: enhance uptake by phagocytes through acute phase proteins/complement components
=> acquired opsonins: specific immunoglobins
Briefly describe the compliment cascade and name the 3 pathways
recognition and phagocyotsis of oposonised microbes
series of > 20 proteins circulating in blood and tissue fluids
-> activation through recognition of bacteria
sequentially activated by enzyme cascade (cleavage and next)
3 pathways
classical pathway
alternative pathway
MBL pathway
Know how compliment enhances clearance of pathogenic bacteria work
result of C3b binding to bacterial cell surface
-> recognised by complement receptors (CR) on phagocytic cells
-> enhances engulfment of opsonised particles
=> intracellular microbial killing
Understand how adaptive immunity modulates anti-pathogen
responses
> 7 days for effective development
removal of persistent/chronic bacterial infections\
specific and prevent re-infection
mediated by CD4 T-cells
help B cells to produce antibodies to specific protein/structures
-> extracellular bacteria clearance & their product neutralisation
help strengthen/increase cellular response through increase in killing mechanisms within macrophages
-> intracellular bacteria clearance
Describe the main immune cell types involved; TH1, TH2 and B cells, and how these promote anti-infection responses
TH1
promoting activation of macrophages and killing cells intracellular
-> attraction and activation of macrophages
-> increase in cytokines
-> specific upregulation of activities
=> IFN, TNF, IL-12
TH2
promoting humoral or antibody response
-> proliferation and secretion of antibodies by B-Cells
-> forming of Granulomas (“wall” of B-cells around bacteria, not killing it)
=> IL4/5/6/10
B cells
through matching antigen activation -> engulfment -> antigen fragments bound to its unique MHC molecules -> attraction of help from mature matching T-cells -> multiply B-cells and mature into plasma cells -> lock onto matchin antigens and clearance by complement cascade
-> bacteriolysis, opsonization, ADCC, agglutination, neutralisation, secretion blockade
Describe the role of antibodies in protective anti-bacterial responses
depending on bacterial location
inhibit interaction btw. bacterial adhesins and host reception
mucosal surface
gut
neutralising antibodies (prevent toxins from binding)
effective antibody (depending on previous exposure -> vaccination basis!)
Understand how the gut microbiota modulates anti-infection
responses (direct and in-direct)
competition for nutrients -> faster microbiota than pathogen
direct killing of pathogen through anti-microbial microbiota
competition for niches -> colonisation resistance
strengthening of epithelial barriers
SCFAs
cytokines
muscosal and systemic immune compartments (tolerance and specific response)
Last changeda year ago
