immunity and infection Flashcards
infectious diseases
1) 1/3 disease burden is due to infectious diseases
2) viruses, fungal, bacterial, parasites
immunity to infection
1) immune system protects from pathogen and cancer
2) most pathogens do not overcome this
- surface barriers
- immune system
3) few potential pathogens cause diseasep
physical and physiological barrier
1) saliva and skin
- lysozyme breaks down proteoglycan in cell wall
disease caused by pathogens
1) can damage directly
- exotoxin damage surfaces of host cell
2) indirectly
- via immune response
- pro-inflammatory cytokines cause local symptoms
- epitopes can bind to heart tissue (complement mediated)
3) virus replication can destroy host cell
immune responses are specific for different compartments
1) almost all pathogens have a extracellular stage, some have intracellular
early immune response to infection
1) preexisting molecules like complement
- inflammation
cooperation between innate and adaptive
1) adaptive is activated after innate immune system
2) innate controls most infections, but need both branches to eliminate pathogens that cause disease
stages in typical infections
1) pathogen reaches physical barrier
2) innate immunity contains the infection through inflammation
3) Ag captured in secondary lymphoid tissue stimulate adaptive immune response (Ag can also be carried by DC)
4) activated TH1 and CD8+ cells migrate to site of infection
complement
1) C3 is first immediate immune defenders
2) C3 is hydrolyzed spontaneously at low rate => iC3
- alternative pathway
alternative pathway
1) iC3 can recruit serum factor B, a substrate for protease factor D
2) alternative pathway is initiated and surface bounded C3b is produced
3) C3b fixation leads to alternative C3 convertase
4) binding of another C3b subunit leads to formation of alternative C5 convertase
5) C5a attracts phagocytes and inflammatory response
—
1) it is inhibited by complement control proteins (DAF, MCP, CR1)
2) pathogens lack these control proteins, and they also attract factor P which stabilized alternative C3 convertase
other components of early response (4-96 hrs)
1) phagocytes
2) NK cells
3) interferon
phagocytes
1) both macrophages and neutrophils are
2) recognize pathogens through DC14, TLR4 and scavenger receptors
3) receptors that simulate phagocytosis
- CR1, CR3 and CR4
4) have chemicals and enzymes that destroy pathogens in phagolysosomes
macrophages
resident in most tissues and abundant in mucosal tissues
- long lived
2) antigen presentation
3) inflammatory mediators
PMN
1) abundant in blood and rapidly recruited to any site with active complement
- short lived
2) reactive chemical species
3) antimicrobial peptides
4) antibacterial enzymes
5) NETs
phagocytes and innate immunity
1) receptors are PAMPs
- LPS, teichoic acids, or G+ bacteria
2) PAMPs recognized by PRR
- TLR4 recognizes LPS
PRR on macrophage
1) CD14
- binds LPS from gram negative bacteria
2) mannose receptor
- lectin binds to some bacteria and viruses
3) scavenger receptors
- heterogenous family of receptors
4) TLR4
role of macrophages
1) PRR or complement stimulate macrophage
2) macrophages transcribe cytokine genes
- TNF alpha, IL06, IL1beta, IL-12, IL-8
3) APC
TNFalpha
1) contain infections
2) local inflammation