Microbial immune evasion mechanisms

Question 1

What do virulence factors promote?

Answer 1

→Colonisation and adhesion
→To establish infection

→Promote Tissue Damage
→Growth, Transmission e.g. toxins

Question 2

What aspect of immunity have pathogens evolved to overcome or avoid?

Answer 2

→Natural defences - mucosal layers, skin,
→Innate immunity
→Adaptive Immunity

Question 3

How do microbes evade the complement system through negative binding?

Answer 3

→coating with non-fixing IgA instead of IgG
→Capsule blocks C3b binding
→Capsule prevents C3b receptor access
→sIgA proteases

Question 4

How do microbes evade the complement system through disruption of regulation?

Answer 4

→Factor H sequestration

→Factor H regulates complement

Question 5

How do microbes evade the complement system through expelling MAC?

Answer 5

→C5a proteases , blebbing

Question 6

How do microbes evade phagocytosis?

Answer 6

→kill cell - leucocidins
→prevent opsonisation
→protein A (binds Fc portion of IgG) - blocks ability of antibody to bind to Fc receptors
→capsules have PAMPs not recognized by phagocyte

Question 7

How do intracellular pathogens evade killing?

Answer 7

→Promote own uptake (safe) - CR3; mannose lectin receptors
→Prevents reactive species- produce catalases/peroxidases
→Inhibit Phagosome-lysosome fusion
→ Escape Phagosome-lysosome to cytoplasm
→Dysregulation of apoptosis

Question 8

Mechanisms that enable life inside macrophages

Answer 8

→Directs phagocytosis via CR3 – no reactive species
→Actin rearrangement - +ve engulfment
→Type 3 secretion systems – prepares cell- phagocytosed in a safe way
→Resists digestion and ROIs in PLs - SOD, catalase
→Escape into cytoplasm from lysosome
e.g. Listeria
→Inhibits PL fusion maintains early endosome
→ Blocks acidification e.g. mycobacteria
→Controls antigen presentation
Stops CTLs or P activation

Question 9

What is protein A?

Answer 9

→mimics of Fc receptor which sequester antibodies in the wrong way
→Access to surface antigen by specific antibody blocked

Question 10

What are the ways the microbe evade adaptive immunity?

Answer 10

→Concealment of antigen
→Immunosuppression
→Antigenic variation
→Persistence/latency/reactivation

Question 11

What type of bacteria is Streptococcus?

Answer 11

→Gram positive

→Commensal of upper respiratory tract

Question 12

What is the mechanism of Strep?

Answer 12

→Have capsules to avoid detection

Question 13

What conditions does Strep cause?

Answer 13

→Pneumonia;
→Otitis media;
→meningitis

Question 14

Describe pathogenic mechanisms of Strep

Answer 14

→aerosol
→Colonisation of nasopharynx 
(adhesins; receptor NAc-hex-gal )
→Inhalation into lungs
→By-passes defences: surfactants, pneumolysin 
→Reaches lung

Question 15

What happens when Strep reaches the lungs?

Answer 15

→Escapes phagocytosis (capsules)
→Inflammation -Lung damage
(teichoic acids; pneumolysin)
→Damage to endothelial cells
(inflammation; pneumolysin)

Question 16

How many serotypes of Strep?

Answer 16

→more than 80

→due to capsules

Question 17

How do surfactants prevent bacteria evasion?

Answer 17

→prevent bacteria from reaching epithelial lining of the lung
→Facilitate expelling of bacteria through mucus

Question 18

How do viruses evade adaptive immune reponse?

Answer 18

→Latency
→reduce antigenic presentation
→reduce MHC presentation
→Mutation of epitopes

Question 19

How do viruses reduce antigenic presentation?

Answer 19

→by binding to TAP - inhibits peptide transfer to MHC

Question 20

Example of virus which reduces MHC expression

Answer 20

→Cytomegalovirus (CMV)

Question 21

How do mutations of epitopes help viruses evade adaptive respnse?

Answer 21

→B cells - neutralisation escape

→T cells - CD8+ escape mutants of HIV

Question 22

What is phase variation?

Answer 22

→ON/OFF of an antigen at low frequency
→occurs - during course of infection in an individual host
→ during spread of microbe through a community

Question 23

What can structures on viruses undergo to allow for persistence and infection?

Answer 23

→Phase variation

→Antigenic variation e.g. pilins (or both phase and antigenic)

Question 24

What type of virus is influenza?

Answer 24

→RNA virus with envelope

Question 25

Compare HA and NA on influenza

Answer 25

→HA=binding to the host receptor protein,

→NA gene= a receptor destroying enzyme, is involved in release of the virus from the host cell

Question 26

How many types of HA?

Answer 26

→18

→Segmented –ve ssRNA genome

Question 27

How many types of NA?

Answer 27

→11

→8 segments, at least 10 genes

Question 28

What is antigenic drift?

Answer 28

→mutation + selection
→Changes and mutations along with poor RNA polymerase without proofreading means more changes in HA and NA
→epidemics

Question 29

What is antigenic shift?

Answer 29

→gene reassortment
→When two diff viruses coexist in host they can exchange and recombine gene segments making new strains of virus
→pandemics