How pathogens evade the immune response

Question 1

Give examples of ways pathogens evade the immune response

Answer 1

Secreted modulators or toxins
Modulators on the pathogen surface
Hide from immune surveillance
Antigenic hypervariability
Subvert or kill immune cells/phagocytes
Block acquired immunity
Inhibit complement
Inhibit cytokines/interferons/chemokines
Modulate apoptosis/autophagy
Interfere with TLRs
Block antimicrobial small molecules
Block intrinsic cellular pathways

Question 2

How do pathogens evade immune response by secreting modulators or toxins?

Answer 2

Ligand mimics (virokines)
Receptor mimics (viroceptors)

Question 3

Give examples of modulators on the pathogen surface that evade the immune response?

Answer 3

Complement inhibitors
Coagulation regulators
Immune receptors
Adhesion molecules

Question 4

How can pathogens hide from immune surveillance?

Answer 4

Latency - avoid phagolysosomal fusion
Infect immunopriviledged tissues to evade regonition

Question 5

Describe how antigenic hyperavailability allows pathogens to evade the immune response

Answer 5

Antigenic drift and shift
Express error-prone replicase
Escape from antibody recognition
‘outrun’ T cell recognition via strain to strain variation

Question 6

What is antigenic shift and antigenic drift?

Answer 6

Antigenic drift:
- point mutations in the genes that code for the surface proteins of the pathogen
- small gradual changes
- makes existing immunity less effective

Antigenic shift:
- when 2 different viral strains exchange DNA (reassortment)
- creates a new subtype
- makes immune response ineffective

Question 7

How do pathogens subvert or kill immune cells?

Answer 7

infect and kill immune cells
inhibit NK cell killing pathways - avoid phagolysosomal fusion
alter immune cell signalling, effector functions, or differentiation
Express superantigens - replicate within and overrun immune cells

Question 8

How do pathogens block acquired immunity?

Answer 8

Downregulate MHC-I or -II
Block antigen presentation
Prevent induction of immune response genes

Question 9

How do pathogens inhibit complement?

Answer 9

Soluble inhibitors of complement cascade
viral Fc receptors - avoid complement deposition and MAC attack

Question 10

How do pathogens inhibit cytokines/interferon/chemokines?

Answer 10

Inhibit ligand gene expression - block inflammatory pathway
Ligand/receptor signalling inhibitors - activate alternative pathways
Block secondary antiviral gene induction
Interfere with effector proteins

Question 11

How do pathogens modulate apoptosis/autophagy?

Answer 11

Inhibit or accelerate cell death
Block death signalling pathways
Scavenge free radicals - alter apoptotic signalling pathways
Downregulate death receptors or ligands
Inactivate death sensor pathways

Question 12

How do pathogens interfere with TLRs?

Answer 12

Block or hijack TLR signalling:
- alter TLR ligands to decrease recognition
- bind to TLR to dampen inflammation
- inject effectors to inhibit downstream inflammation signalling

Question 13

What are virokines and viroceptors

Answer 13

Proteins produced by viruses which mimics cytokines and receptors to act as decoys

Question 14

What is the function of bacterial capsules

Answer 14

Covers proteins on the surface of pathogens to disguise them from the immune response

Question 15

What is viral latency?

Answer 15

e.g., herpesvirus
Replication can be shut off to prevent detection by immune response - replication can be restarted at times of stress when immune response is damaged

Question 16

How can pathogens attack the immune system?

Answer 16

Infect and kill immune cells - don’t look for pathogens within themselves
Downregulate/inhibit immune effector molecules - e.g., switching off production of cytokines
Inhibit cell signalling pathways/apoptosis