Microbial Immune Evasion Mechanisms

Question 1

Explain the concept of Balanced Pathogenicity

Answer 1

Properties of the microbe
(Pathogenic mechanisms):

Adhesins
Toxins
Capsule
Etc.

VS

Properties of the host
(Defensive mechanisms):

Natural barriers
Defensive cells
Complement
Immune response

Question 2

Virulence Factors - describe 3 effects

Answer 2

Promote colonisation and adhesion

• To establish infection
  e. g. adhesins

Evade host defences

Promote tissue damage

• Growth, Transmission?
  e. g. toxins

Question 3

Roles of Complement

Answer 3

induces inflammatory response
	promotes chemotaxis
	↑ phagocytosis by opsonisation
	↑vascular permeability
	mast cell degranulation
	lysis of cell membranes

Question 4

Intracellular pathogens:- example

Answer 4

Intracellular pathogens:-
e.g. Mycobacterium tuberculosis
Listeria
Salmonella

Question 5

Intracellular pathogens:- hidden from?

Answer 5

hidden from serum killing, complement, antibodies

Question 6

Phagocytosis - functions

Answer 6

kill cell - leucocidins - Staphs
prevent opsonisation - protein A (binds Fc portion of IgG) - Staphs

block contact - capsules -meningococcus, Hib

Question 7

intracellular pathogens:- function

Answer 7

Promote own uptake (safe)
- CR3; mannose lectin receptors

Prepares cell for invasion - Shigella

• ve P-L fusion
• M. tuberculosis

Escape P-L to cytoplasm - Listeria

Resist oxidative killing
- produce catalases/peroxidases

Question 8

Describe phagocytosis

Answer 8

1. Directs phagocytosis
   via CR3 – no ROI
2. Actin rearrangement - +ve engulfment
3. Type 3 secretion systems – prepares cell
4. Resists digestion and ROIs
   in PLs - SOD, catalase
5. Escape into cytoplasm
   e. g. Listeria
6. Inhibits PL fusion
   maintains early endosome
   Blocks acidification
   e.g. mycobacteria
7. Controls antigen
   presentation
   Stops CTLs or
   Pφ activation

Question 9

Effect of production of Fc receptors by microbes

Answer 9

Microbial antigen bind to antibody leading to elimination

However when microbial Fc receptors bind antibodies leads to binding specific + non-specific antibody by Fc portion

Access to surface antigen
by specific antibody blocked

Question 10

Concealment of antigen - describe

Answer 10

Adaptive immunity

• hide inside cells
• privileged sites
• block MHC antigen presentation = Herpes -ve TAP protein
• surface uptake of host molecules e.g. CMV and beta2microglobulin

Question 11

Effect of immunosuppression

Answer 11

Immunosuppression

- e.g. ↓ MHC, ↓ receptors, apoptosis, cytokine switch IgA proteases

Question 12

Streptococcus pneumoniae - pathogenic mechanisms

Answer 12

Colonisation of nasopharynx
(adhesins; receptor NAc-hex-gal, sIgA proteases) = Otitis media
(inflammation)

Inhalation into lungs

By-passes defences: surfactants sIgA proteases; pneumolysin

Reaches lung

=

Escapes phagocytosis
(capsules)

Inflammation -Lung damage
(teichoic acids; pneumolysin)

Damage to endothelial cells
(inflammation; pneumolysin)

=

pneumonia

Bacteraemia

Meningitis + septicaemia
(Inflammation and toxic shock)

Question 13

Viral Immune Evasion - describe

Answer 13

1. Latency - VZV, herpes simplex
2. ↓ antigenic presentation by binding to TAP
   - Inhibits peptide transfer to MHC
   - Herpes simplex
3. ↓MCH expression - Cytomegalovirus (CMV)
4. Mutation of epitopes
   B cells - neutralisation escape
   T cells - CD8+ escape mutants of HIV

Question 14

Intracellular pathogens - requires

Answer 14

Intracellular pathogens - requires adaptive cell mediated immunity

Question 15

Ophthalmic Zoster - presentation

Answer 15

During chicken pox VZ V becomes latent in nerve ganglia

In shingles, reactivates years later

Question 16

Ophthalmic Zoster - define

Answer 16

Shingles involving the eye. Symptoms = include a rash of the forehead with swelling of the eyelid.

There may also be eye pain, eye redness, and light sensitivity.

Question 17

Explain infection of next generation susceptibles

Answer 17

Microbes infects
susceptibles

Microbe remains
latent

Microbes reactivates (zoster)
and infects next generation
of susceptibles

Question 18

Explain immunological state of nerves

Answer 18

Nerves –
immunologically privileged site
Poor protective immunity for reactivation

Question 19

Phenotype changes - list

Answer 19

Phenotype changes - colony morphology, virulence, serotype loose flagella, change surface sugars

Question 20

Antigenic Diversity/ polymorphisms - define with an example

Answer 20

Antigenic Diversity/ polymorphisms

• genetically stable and alternative forms of antigens in a population of microbes
  e. g. serotypes of Strep.pneumoniae

Question 21

Antigenic Variation - define

Answer 21

Antigenic Variation
- successive expression of alternative forms of an antigen
in a specific clone or its progeny

Question 22

Define phase variation - when does it occur

Answer 22

• Phase variation - 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

Gonorrhoea – a sexually transmitted disease = define

Answer 23

Inflammatory and pyogenic infection of anterior urethra
Infects mucosal surfaces with columnar epithelium
- urethra, cervix, rectum, pharynx, conjunctiva

Question 24

Gonorrhoea – a sexually transmitted disease = effects

Answer 24

dysuria, redness, swelling, pain on urination, destruction of mucosa

prostatitis, orchitis, strictures, ovaritis, fistulas, PID, proctitis, sterility

Disseminated infections → arthritis, endocarditis, meningitis

Question 25

Neisseria gonorrhoeae - characteristics

Answer 25

Surface components interact with host cells Components vary at high frequency in a population of bacteria Variation to avoid immune response

Question 26

Neisseria gonorrhoeae - list cell surface components

Answer 26

``` Pilus Capsule Inner membrane Outer membrane Opa ```

Question 27

Neisseria gonorrhoeae - cell surface structures can undergo what

Answer 27

All of these structures can undergo either: Phase variation i.e. an ON-OFF switch (capsule, Opa’s) Antigenic variation e.g. pilins (or both phase and antigenic)

Question 28

Epidemics cause

Answer 28

Antigenic drift | – mutation + selection

Question 29

Pandemics cause

Answer 29

Antigenic shift | - gene reassortment

Question 30

What effects do bacterium have on the body

Answer 30

Superantigens and inappropriate immune activation Induction/inhibition of apoptosis Inhibition of antigen presentation Prevents opsonin binding C3a and C5a proteases Anti-inflammatory and anti chemoattractant Inhibits opsonisation Inhibit complement activation Ig binding proteins e.g. protein A sIgA proteases Survival inside macrophages Induction/inhibition of apoptosis

Question 31

What effects do viruses have on the body

Answer 31

MHC mimics – block killing by NK cells Downregulate MHC Block antigen processing by TAP Induce immune suppression ↓CMI, ↓CD4+ Host Mimicry Cytokine mimics and binding proteins Hide inside cells Survival inside cells Induction/inhibition of apoptosis Blockage of cell cycle progression CTL escape mutants – quasi species swarms Latency reactivation e.g. VZV, Herpes simplex Rapid growth and transmission prior to adaptive immunity e.g. colds