Bacterial Infection Flashcards
Time scale of infection
0-12h innate. 12h - 7 days adaptive
PAMPs
pathogen-associated molecular patterns. recognised by PRR
PRRs
pattern recognition receptors that recognise PAMPs, e.g. TLR
TLR
toll-like receptors (type of PRR)
Effector functions of complement cascade
C3a and C5a bind to receptors on the cell surface of a mast cell, promoting degranulation and release of histamine to vasodilate. C5a can also act as a chemoattractant to bring in neutrophils and macrophages
recognition of bacterium by phagocyte
Direct: PAMPs recognised by PRR (e.g. TLR). Indirect: C3b recognised by C3bR and antibody-antigen complex recognised by antibody receptors (e.g. FcR)
TLR4
Homodimer (2 TLR4 molecules form a pair) and recognise lipopolysachharide (gram -ve bacteria)
TLR5
flagellin (motile bacteria)
TLR1/2
Heterodimer of 1 subunit of TLR1 and 1 subunit of TLR2. Recognise peptidoglycan and triacyl lipopeptides (bacteria)
TLR7, TLR8
Recognise ssRNA (viruses)
TLR10
recognise NK
TLR3
recognise dsRNA of viruses
TLR signalling
Recognition of bacterial molecule by TLR. Dimerisation of TLR which brings together two signalling domains. Signal down either a MyD88 pathway of TRIF pathway. MyD88 pathway activates NFkB transcription factor whereas TRIF pathway activates IRFs (interferon regulatory factors). Switch on genes within the phagocyte that produce cytokines or iterferons
Cytokines prduced due to TLR activation
IL-1 activates endothelial cells (fever). IL-6 activates antibody-producing B cells. TNF-a activates endothelial (fever) and neutrophils.
Interferons produced due to TLR activation
IFN-a and IFN-b promote CD4+ and CD8+ T cell responses in antiviral responses.
Phagocytosis after TLR activation
Bacteria get ingested into phagosome, might escape into the cytosol. Or phagosome fuses with lysosome to form phagolysosome (toxic) to break up the bacteria, exocytosis of debris.
If bacteria is in cytosol of phagocyte
Enter the MHCI pathway where they a processed by the proteasome and form a complex with MHCI at cell surface. Activate CD8+ T cells to kill the host cell by releasing perforin and granzymes and granulin. Important for diseases where bacteria live in host cells e.g. salmonellosis, tuberculosis, listerosis.
When bacteria is within the phagolysosome of the phagocyte
Bacterial proteins enter endocytic pathway with MHCII and are presented on phagocyte cell surface. Activate CD4+ T cell which releases cytokines. IL-17 and TNF lead to inflammation. IFN-gamma activate macrophages. Various other cytokines promote antibody production.
opsonisation
coat antigen with antibodies to enhance phagocytosis.
agglutination
enhances phagocytic and by clumping bacteria, there’s less infectious units to deal with. e.g. Ab 1E2 can but 5F6 cannot.
neutralisation
blocks adhesion of bacteria/viruses to mucosa. blocks active site of toxin. e.g. Diphtheria antitoxin (1981 onwards) - raised in horses and serum used to treat disease BUT foreign protein may cause serum sickness - not used anymore due to unrpredictable
inflammation
disruption of cell by complement/reactive protein attracts phagocytic and other immune cells
complement
cell lysis
ADCC
antibody attaches to target cell and cause destruction by non specific immune cells.
