Lecture 2 Flashcards
What are the 4 basic mechanisms of immune evasion by bacteria?
Disguise (through antigenic variation and surface molecules)
Hide (through invasion of host cells or biofilms)
Fool (through deregulation of the immune response)
attack (through destruction of immune components)
What are CAMPS and how do they function?
Cationic antimicrobial peptides, these are overall positively charged chains of amino acids which are attracted to the typically negatively charged bacterial membrane structures to form a pore destroying the bacteria
What are the different CAMPS?
Alpha-Defensin hNP1 Beta-Defensin hBD1 Cathelicidn LL-37 Thrombocidin TC1 Dermicidin
What cells produce alpha-defensin hNP1?
Granulocytes, Paneth cells and T cells
What cells produce beta-defensin hBD1?
Epithelia and skin
What cells produce cathelicidin LL-37?
Epithelia, skin, granulocytes
What cells produce thrombocidin TC1?
Platelets
What cells produce dermicidin?
Sweat glands
What are the four resistance mechanisms of bacteria to CAMPs?
Repulsion of CAMP by changing surface components (eg lipid A) from negative to positively charged in species like Staphlyococcus and streptococcus
Extrusion of CAMP through and efflux pump such as MtrCDE in species like Neisseria
Neutralisation of CAMP by production of a binding protein such as staphylokinase or SIC in species such as staphylococci and streptococci
Cleavage of CAMP by proteases such as PgtE Proteease produced by E.Coli
What is the classical complement pathway?
When the complement system becomes activated by antibody opsonisation
What is the alternative pathway?
…
What is the lectin complement activation pathway?
When certain lectins recognize sugars or glycproteins on the bacterial surface and opsonise the bacteria
How does complement activation result in attacks on the bacteria?
C3 is converted to C3a which forms a chemotactic gradient to attract neutophils and to C3b which can opsonise the bacteria
C5 is converted to C5a which is a chemotactic attractant of neutophils and C5b which forms part of the membrane attacking complex
What are the limitations of the membrane attack complex?
It is very good at killing gram negative bacteria but not really able to kill gram positive bacteria due to the thick peptidoglycan layer
What are the three methods of complement evasion by bacteria?
Modulation or inhibition of complement proteins
Inactivation by enzymatic degradation
recruitment or mimicking of complement regulators
What is the function of staphylococcal complement inhibitor (SCIN)?
Binds to C3 convertases to inhibit C3 conversion to C3a and C3b therefore preventing complement activation
What is the function of streptococcal inhibitor of complement (SIC)?
Binds to C5b-C7/C8 preventing the formation of the membrane attack complex
What is the function of the chemotaxis inhibitory protein of S. Aureus
Binds to C5a receptor to prevent it from forming a chemotactic gradient which would normally attract neutrophils
What is the function of staphylococcal protein A?
The protein is bound on the bacterial membrane surface and can bind the Fc region of IgG preventing opsonisation and activation of the complement system through the classical pathway
What is the function of pseudomonas protease?
Cleaves C3 in a way which prevents C3b formation so opsonisation is avoided
What is the function of the C5a Peptidase produces by streptoccus and serratia?
Cleaves C5a prevetning neutrophil chemotaxis
What is the function of Pseudomonas elastase?
Cleaves IgG and C1q preventing initiation of the classical pathway of complement activation
What are the functions of staphylokinase and streptokinase?
Both convert plasminogen to plasmin which cleaves IgG and C3b
What is the function of C4 Binding protein?
A host protein which accelerates the decay of C3 convertases and is recruited by streptoccus, E. Coli, Haemophilus Influenza, Moraxella Catarrhalis, Neisseria gonorrhoe to deregulate the immune system
What is the function of factor H?
Host protein which degrades C3b and accelartes the degradation of AP C3convertases designed to prevent the immune system from destroying the host tissue as the membrane attacking complex C3b forms is non-specific and can attack immune cells
What is the role of lipopolysaccharide in immue evasion?
Bacteria which can recruit factor H can use it to block opsonisation of sialic acid containing surfaces such as lipopolysaccharides
Lipopolysaccharides can have long side chains known as the O antigen which can be large and numerous enough to physically stop the phagocyte from reaching the receptor on the bacteria and binding to it
How can factor H be used by bacteria?
It can be recruited by staphylococcus aureus M protein to deregulate the immune system to reduce the amount of C3b present (by degrading the convertases and and cleaving existing C3b) therefore preventing the membrane attacking complex to form
How do bacterial capsules help in immune evasion?
The cover many of the bacterial proteins so the immune system cannot recognize them
They also add to antigenic variation as many different strains of the same species of bacteria
Some bacterial capsules are particularly good at disguising bacteria such as streptococcus pyogenes which makes its capsule out of a host molecule (in this case hyaluronic acid)
How can bacteria evade phagocytosis?
Blocking lysosome fusion
arresting phagosome maturation
Blocking the proton pump to prevent acidification with compunds such as UreC
Breaking down reactive oxygen species with a catalase enzyme
Use of compounds such as cytolysin and listerolysin to leave the phagosome and enter the cytosol
How does antigenic variation result in relapsing infections?
The adaptive immune system will recognize one form of an antigen and eradicate the bacteria displaying this, however before the bacteria is entirely removed it may alter the antigen resulting in a slightly different structure which the immune system will need to mount another immune response against in order to act against
How do bacteria enter non-phagocytic cells?
The uptake must be induced by the bacteria and requires extensive reorganization of actin cytoskeleton
Uses a type 3 secretion system
