Microbial Immune Evasion Flashcards
Describe the features of bacteria and viruses that are recognised by the immune system
The immune system identifies foreign organisms by detecting molecular patterns that are typically found in microbes, but not in host cells.
These molecular patterns are referred to as pathogen-associated molecular patterns (PAMPs)
Bacteria:
1) Lipopolysaccharide (LPS):
- Endotoxin, on the outer membrane of Gram-negative bacteria.
- Binds to TLR4 on the surface of immune cells
2) Peptidoglycan:
- Cell wall of Gram-positive bacteria and Gram-negative bacteria.
- Fragments of peptidoglycan can be recognised by TLR2 and NOD-like receptors
3) Flagellin:
- Makes up Flagellum protein, recognised by TLR5
4) Bacterial DNA:
- Contains unmethylated CpG motifs, recognised by TLR9
Viruses:
1) Viral nuclei acids:
- Double-stranded RNA; recognised by TLR3
- Single-stranded RNA; recognised by TLR7 and TLR8
- Unmethylated CpG DNA; recognised by TLR9
2) Viral proteins:
- influenza virus hemagglutinin is recognized by antibodies, and viral capsid proteins can be recognised by TLR2
3) Viral gylcoproteins:
- Heavily glycosylated proteins on the surface of viruses; recognised by C-type lectin receptors
Explain the concept of immune evasion
1) Antigenic Variation:
- Pathogens changing their surface proteins or antigens periodically to avoid being recognised by the immune system
- Meaning the immune system is always playing catch-up, trying to produce specific antibodies to new antigens
- In influenza viruses, this antigenic drift (minor antigenic changes due to point mutations) and antigenic shift (major antigenic changes due to genetic reassortment) results in new strains of viruses
2) Inhibition of Complement Activation:
- By producing proteins that bind to and inactivate the complement cascade proteins
- Staphylococcus Aureus produce Staphylococcal complement inhibitor (SCIN) that binds to and inhibits C3 convertase; preventing opsonisation
3) Resistance to Phagocytosis:
- Capsules are gelatinous laters that surround bacterial cells, preventing them from being recognised and engulfed
- Can produce proteins that prevent the fusion of the phagosome with the lysosome
4) Survival within Host Cells:
- Intracellular pathogens have evolved mechanisms to survive within host cells, using these cells as protective niches
- Some can mask their PRRs via cell-surface associated lipids (mycobacterium tuberculosis)
- Others can delay and prevent phagolysosome formation such as mycobacterium tuberculosis
5) Immunosuppression:
- Some pathogens can directly kill immune cells or interfere with their signalling pathways to suppress the immune response
- HIV infects and kills CD4+ T cells
6) Molecular Mimicry:
- Mimic host antigens to evade immune recognition
- Group A Streptococcus has similar antigen proteins resembling those found on human heart tissues, leading to autoimmune reactions
Give examples of the components of bacterial and viral pathogens that are responsible for immune evasion
Bacterial Component for Immune Evasion:
1) Capsules:
- Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitis have a polysaccharide capsule
The capsules are hydrophilic and have a negative charge, as well as mimicking host molecules, resisting phagocytosis and immune recognition
2) Protein A:
- Staphylococcus aureus produces Protein A which binds to the Fc region of IgG antibodies
- Preventing opsonisation of the bacterium and impairs phagocytosis
- Also crosslink inhibitory receptors on B cells, impeding antibody production
3) O Antigen:
- Gram-negative bacteria like Salmonella and E.coli have an O antigen as part of their lipopolysaccharide (LPS) outer membrane
- This antigen prevents the deposition of the complement on the bacterial surface, making it resistant to complement-mediated lysis
4) Secreted Proteins:
- Inhibit the complement system by binding and disrupting C3 convertases (inhibiting C3b formation = inhibition opsonisation) and preventing C5 conversion (Halting the formation of MAC)
- like Staphylococcal complement inhibitor (SCIN) produced by Staphylococcus aureus
5) Intracellular Life:
- Mycobacterium tuberculosis and Listeria monocytogenes can survive and replicate inside host cells, hiding from the immune system
- Interfere with signalling pathway to prevent the fusion of phagosome with the lysosome
Viral Pathogens:
1) Antigenic Variation:
- Influenza viruses can change the antigens on their surface to avoid detection
- This process is called antigenic drift (minor changes from small point mutations) and antigenic shift (major changes from reassortment)
2) Inhibition of Interferon Activity:
- Hepatitis C virus (HCV) inhibits interferon signalling
- Interfering with the JAK-STAT signalling pathway activated by interferon
- Also produce proteases that degrade components of this pathway, disrupting the downstream expression of antiviral genes
3) Downregulation of MHC Molecules:
- HIV and CMV reduce the expression of MHC class 1 on the surface of infected cells to void cytotoxic T cells
- HIV with Nef protein and CMV with US6 gene product
4) Latency:
- Herpes Simplex Virus (HSV) and Varicella-Zoster Virus (VZV) can establish a latent infection where the virus remains dormant within the host cell
- HSV VZV in neurons or EBV and CMV in lymphocytes
5) Inhibition of Apoptosis:
- Adenoviruses and HSV encode proteins that block apoptosis
- Adenoviral protein E1B-19K mimics Bcl-2 (a cellular protein that prevents apoptosis) and VACV protein CrmA inhibits caspase-1 (A key enzyme in the execution of apoptosis)
Define the terms ‘antigenic diversity’ and ‘antigenic variation’
Antigenic Diversity:
Refers to the variety in the surface antigens of microorganisms for the survival and escape from immune response
1) Viral Antigenic Diversity:
- Influenza exhibits antigenic drift, a slow, gradual change in the antigens due to mutation
- As well as antigen shift, a sudden, drastic change in the antigen due to reassortment of viral RNA segments
2) Parasitic Antigenic Diversity:
- Antigen switching (changing surface coat) allows parasites to avoid detection
Antigenic Variation:
1) Mechanisms of Antigenic Variation:
- Gene conversion, site-specific DNA inversions, hypermutations, or recombination of sequence cassettes result in clonal population of pathogens expressing a heterogenous phenotype
- Meaning Identical pathogens can express different antigens
2) Impact on Host Immunity and Re-Infection:
- Avoid acquired immune response by evading immune memory
Explain the impact of immune evasion on the usefulness of vaccines
