Lec 28 - Defences of pathogens against the host Flashcards
Give the 5 internal defences that host systems (humans) have
- phagocytes
- cytokines and inflammatory response
- complement
- B and T cell activation
- antimicrobial peptides
Describe the 7 ways in which microbes interfere with phagocytosis
- anti phagocytic structures eg production of thick outer layer slime coat (seen as mucoid colonies when plated out) that prevent phagocytes engulfing. capsule NOT immunogenic therefore doesn’t bind complement/antibodies
- production of toxins to directly kill the phagocyte
- induction of phagocyte apoptosis - IpaB production by Salmonella and Shigella which enter the phagocyte cytosol and induce apoptosis by activation of caspase 1. Yersinia produce Yop proteins which bind to and inhibit anti-apoptic signallig
- prevention of the lysosome fusing with phagosome
- escape for the phagolysosome - Shigella produces IpaB to escape into cytoplasm and lyse phagolysosome membrane
- prevention of lysozyme enzymes eg catalase (H202 > water) , Superoxidedismutase (O2- > H202), globins (NO > nitrate)
- prevention of opsonisation - production of protein that binds to the opsonising antibody
What are cytokines and what are the 2 different types?
PRO INFLAMMATORY
- produced by host cells in response to bacterial products
- increase bacteriacidal property of T cells
- recruit other cells of the immune system
- eg IL-1/8, TNFa
ANTI - INFLAMMATORY
- have the opposite effects as pro-inf
- IL-6/10
How does M.tuberculosis interfere with cytokine secretions?
- produces iL-6 - stops T cell activation
- IL-10 inhibits macrophage activation
- contributes to the generation of T suppressor cells
What are the 2 main ways of interfering with the complement system?
- having a direct effet on complement activitiy
- preventing complement binding
How is complement prevented to bind?
- Gram +ve have thick peptidoglycan layer
- sugar molecules eg sialic acid bind to LPS groups of G-ve bacteria (non-immune activating)
- thick capsule (sialic acid)
- secreted polysaccharide layer
How are the activities of complement targeted by microbes?
- secreted bacterial protease that directly binds to and breaks down complement
- prevention of MAC
- breadown of C3b complement on the surface of cells
Give the 4 main ways that interfere with T or B cell activation
- antigenic phase variation
- antigenic disguise
- induction of T cell apoptosis (H. pylori)
- interefering w/ IFN releas from T cells
how is antigenic disguise carried out?
PRODUCTION OF IMMUNOGLOBULIN BINDING PROTEINS
- eg S. aureus protein A binds to the Fc region of IgG and prevents interactions w/ complement and phagocytes
MOLECULAR MIMICRY
- E. coli K1 capsule and S. pyogene hyalouronic acid capsule
- both aim to mimic host sugars and prevent immune response
Give an example of phase (antigenic) variation , draw a diagram
- flagella synthesis
What are antimicrobial peptides and describe how they work to kill bacteria
- produced by most cells in response to bacterial products
- net positive charge (Lys/Arg residues) - CAMPS (Cationic Antimicrobial Peptides) so bind to -vely charged hydrophillic heads
- insert into microbial membranes and forms pores
- result in loss of ions and therefore loss of PMF
- in severe cases, large chunks of membrane are lost and can get influx of CAMPs which bind to -vely charged DNA and protein which result in cytoplasmic components being glued together
Why is it hard for bacteria to evolve a defence against CAMPS?
non specific nature , innate immune system
What are the 4 ways in which bacteria can resist CAMP action?
- reduced the -ve charge of the membrane to prevent CAMPs binding. eg addition of lys / arg (like S. aureus). however charge can’t be reduced too much
- secrete peptidases to break down CAMPs
- can actively take up CAMPs combined w/ increase in intracellular peptidase conc eg H. influenzae have Sap transporter
- increase peptide binding proteins @ surface to sequester CAMPs therefore and prevent entry of them into the cell
