Microbial Immune Evasion Strategies
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Direct answer
Microbial immune evasion describes the strategies pathogens use to avoid recognition, complement attack, phagocytosis and antibody effects. The main mechanisms are antigenic variation, polysaccharide capsules, enzymes that cleave immunoglobulins, binding of host immunoglobulin and survival inside host cells. Neisseria, Staphylococcus aureus, Streptococcus pyogenes and Mycobacterium tuberculosis each illustrate one or more of these routes.
What you must remember
- Antigenic variation: switching surface proteins, as Neisseria changes its pilin through gene recombination, lets a population escape antibodies raised against earlier variants.
- Capsule: the polysaccharide capsules of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b resist phagocytosis and mask complement-activating surfaces.
- IgA protease: enzymes from Neisseria species, Haemophilus influenzae and Streptococcus pneumoniae cleave the hinge region of secretory IgA1 at mucosal surfaces.
- Protein A: Staphylococcus aureus binds the Fc region of IgG, so antibodies attach in the wrong orientation and cannot opsonise the bacterium.
- M protein: Streptococcus pyogenes uses M protein to resist phagocytosis and to limit complement deposition on its surface.
- Intracellular survival: Mycobacterium tuberculosis arrests phagosome maturation, and Listeria monocytogenes escapes into the cytoplasm using listeriolysin O.
- Molecular mimicry: group A streptococcal antigens resemble human tissue, so the immune response can injure the heart and joints, as in rheumatic fever.
A stepwise sequence of evasion at a mucosal surface
Most successful pathogens combine several strategies, so a single defect rarely clears the infection. The steps below describe a generic invader that colonises a mucosal surface, although the exact order varies between organisms.
- Attach: adhesins and pili bind the mucosal epithelium, so the organism is not swept away by secretions.
- Shield: a capsule covers the surface, masking complement-activating molecules and resisting ingestion by phagocytes.
- Cleave: IgA1 protease removes the hinge of secretory antibody, weakening the mucosal barrier.
- Block complement: surface proteins bind complement regulators or inhibit deposition of C3b, so the membrane attack complex does not form.
- Escape: the organism either prevents phagolysosome fusion or leaves the phagosome for the cytoplasm.
- Vary: antigenic variation changes the target epitopes, so antibody raised earlier no longer binds efficiently.
Each step can be reversed by a specific host defence, which explains why immunity to one organism often depends on several arms of the immune system acting together.
Where the exam tries to catch you
Immune evasion questions usually test the mechanism behind a named organism and the defence that the mechanism defeats.
- Trap: equating antigenic variation with random point mutation Correct: it is switching among stored gene variants, such as pilin or variant surface glycoprotein, which is faster than mutation alone.
- Trap: thinking IgA protease acts only in the blood Correct: it acts on secretory IgA1 at mucosal surfaces, such as the genital and respiratory tracts.
- Trap: assuming the capsule works only against antibody Correct: capsules also resist phagocytosis and mask complement activation, which is why capsular conjugate vaccines are needed in young children.
Frequently asked questions
Why does antigenic variation help Neisseria gonorrhoeae escape antibodies?
Antigenic variation helps Neisseria gonorrhoeae because pilin genes recombine to change the pilin protein, so antibodies raised against earlier variants no longer bind well. This is one reason natural infection with gonococci does not reliably produce lasting protective immunity.
Which bacteria produce IgA protease to cleave secretory antibody?
Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae and Streptococcus pneumoniae produce IgA1 protease. The enzyme cleaves the hinge region of secretory IgA1 at mucosal surfaces, reducing the antibody's ability to agglutinate organisms and block adhesion.
How does Staphylococcus aureus protein A interfere with antibody function?
Staphylococcus aureus protein A binds the Fc region of immunoglobulin G, so antibodies attach to the bacterium in the wrong orientation. Bound antibodies then fail to engage Fc receptors on phagocytes, which reduces opsonisation and clearance of the organism.
Why does Mycobacterium tuberculosis survive inside macrophages?
Mycobacterium tuberculosis survives inside macrophages because it arrests phagosome maturation and prevents fusion with lysosomes. The bacillus persists in a protected compartment, which is why cell-mediated immunity, rather than antibody, is the main defence against tuberculosis.