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BMS2052 (2)
Lecture 5

Lecture 5 Notes

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Biomedical Sciences
John Bertram

Lecture 5 Notes: Learning objectives:  To understand the major types of host defences against bacterial infection  To understand the strategies that pathogenic bacteria use to evade these defences To cause disease, most pathogens must: 3) Evade host defences 4) Multiply and disseminate Evasion of host defences: Soluble factors:  Complement: part of innate and adaptive immune response  Antibodies (Ab) So the way they avoid this is to avoid complement fixation, destroy antibodies or avoid detection by antibodies (by capsule) Professional phagocytes:  Macrophages  PMNs – polymorphonuclear leukocytes So they avoid phagocytosis and/or kill phagocyte When a pathogen enters the body, C3B will bind to complement receptors on phagocytes, which results in opsonisation (bacteria is completely coated in that protein) of pathogens. This results in the C3 convertase, which results in the membrane-attack complex, which leads to lysis of certain pathogens and cells. Structural regions of an antibody molecule:  3 important Ab types in microbiology: IgA (short term, allergies), IgG (responsible for long term memory), IgM (short term, unstable) Avoid complement fixation:  Use a capsule to prevent activation of complement   Bind antibody by Fc end (portion of an antibody which binds phagocytes and helps facilitate phagocytosis) thus the variable region of the antibodies is exposed to pathogens which makes it impossible for phagocytes to bind to them  Destroy antibodies:  specific proteases that cleave IgA o IgA functions as a dimer o IgA protease cleaves at the hinge (J chain) thus destroying the antibody Avoid detection by antibodies: Remain inside host cells:  Strategy used by many viruses/ some bacteria  Key is not to display antigens on cell surface  Microbe must be able to survive in harsh intracellular environment Host mimicry:  N. meningitidis: meningococcal disease  Capsule of meningitidis type B is composed of sialic acid  Human cell surface sugars (gangliosides) contain sialic acids  Poor immune response to capsule b (even if vaccinated) Coat with host proteins:  Coat with Ig  Bind Fc end of antibody using an Fc receptor  Colonise a privileged site (with poor access for antibodies):  Inside cells  Skin  Central nervous system: meningococcal enters here and as it is a sterile environment there are no immunoglobulins, and so it can freely replicate  Gall bladder  Cyst (parasites) Antigenic/phase variation:  Change the structure of cell surface proteins  New antibodies have to be made to adjust to new cell shape Phagocytosis:  By professional phagocytes: macrophages and neutrophils  Phagocytosis is facilitated by opso
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