L10: Evassion of Host Defences in Infection

Question 1

Name the 4 clear mechanisms used by pathogens to evade host defence mechanisms

Answer 1

• concealment of Ags
• antigenic variation
• immunosuppression
• interference with effector mechanisms

Question 2

Explain how pathogens use concealment of Ags to evade defence mechanisms

Answer 2

• inhibit Ag presentatino by MHC class I (so CTL reognition process cannot occur)
• pathogenn is localised to a privelleged site
• uptake of host molecules (cloak-effector) where pathogen isn’t recogniseed as foreign

Question 3

Given an example of a diease that uses concealment of Ags to evade defence mechanism

Answer 3

Herpes zoosler virus

Question 4

Explain how pathogens use antigenic variation to evade defence mechanisms

Answer 4

Acheived via:

• Large # of antigenic types e.g. strep. pneumoniae
• Muation ( antigenic drift) e.g.g flu, polio, HIV
• Recombination (antigenic shift) e.g. flu
• Gene switching e.g. trypanosomes

Question 5

How does the influenza virus use antigenic variation to evade defence mechanisms?

Answer 5

Antigenic drift (causing mild epidemics):

• nuetralising Ab against haemaglutinin, block binding to cells
• mutations alter epitomes in haemagglutinin so neutralising Ab no longer binds

Antigenic shift (causing major pandemics):

• occurs when RNA segments are exchanged between viral strains in secondary host
• no cross protective immunity to virus, expressing a novel haemagglutini

Question 6

Explain the cell biology/ structure of the influenza virus

Answer 6

• is an RNA virus with -ve sense segmented genome

- major surface Ags are haemagluttin & neuraminidase

Question 7

How does strep. pneumonia use various antigenic types to evade host defences?

Answer 7

Ab to the capsule opsonises the bacteria and protects it

Question 8

Explain the cell biology/ structure

Answer 8

Gram +ve surrounded by thick polysaccharide capsule which protects it from phagocytosis

Question 9

How do vaccines for strep. pneumonia work?

Answer 9

1. Pneumovsx: polysacc vaccine (contains Ag to all 23 capsules)
   - not effective in kids <2 or with poor immune response (HIV)
   - low level respnse, just B cell IgM response
2. Prevnar 13: conjugate vaccine (contains only 13 capsule Ag)
   - bound to the diptheria toxoid which is highly immunogenic but non toxix
   - T and B cell (all Ig) response

Question 10

How does trypanosmoa use gene switching to evade host defences?

Answer 10

• correlates with changes in major surface Ag of the tryp, brought about by genetic rearrangement
• there are many inactive tryp VSG (variant-specific glycoprotein) genes but only one site for expression
• inactive genes copies into expression site by gene conversion leading to many rounds of gene conversion occuring, allowing try to vary VSG gene expressed

Question 11

Explain the cell biology/ strucuture of trypanosmoa

Answer 11

• protozoa parasite that cause African sleeping sickness

- patients undergo bouts of parasitemia

Question 12

Explain how immnuosuppresin is used to evade host defences?

Answer 12

Via

• infection of immune cells e.g. HIV-T cells
• induction of Treg cells e.g. chronic infection of H.pylori

Question 13

How are Treg cells used in immunosuppresion?

Answer 13

Treg regulates immune system by supressing differentiation and proliferation of Th1/2 cells & is immunosupressive (e.g. IL10)

• maintains tolerance of self- Ag
• helps rpevent autoimmune disease
• expresses CD4 and 25 on surface & FoxP3 (txnal factor) expressed

Question 14

How does leishmania affect T cells?

Answer 14

Leishmania cna hide and survive in macropahes and increase expression of T reg cells and decrease the immune response

Question 15

Name another virus that causes immunosuppresion and explain its implications

Answer 15

Measles: RNA virus that can lead to secondary infections
- infects dendritic cells and infected cells showed increased apoptosis, decreased T cell stimulation and decreased IL-2 production (NK and Th1 cells affected

Question 16

How can interference with effector mechanisms allow pathogens to evade host defences?

Answer 16

Via
1- molecules interfering with Ab function e.g. IgA proteases (strep. pneumoniae) & Fc binding molecules (herpes)
2- Molecules interfering with complement e.g. enzymes that breakdown C3a/5a & molecules that inhibit complement activation e.g. smallpox vius
3- Molecules binding cytokines e.g. vaccinia (smallpox, IFN-gamma)
4- Subvert responses by producing molecules with cytokine activity e.g. epstein barr virus produces VIL-10
5- Inhibition of phagocytic killing e.g. M tuberculosis

Question 17

What can cause infectious disease pathology?

Answer 17

• Direct effects of pathogen e,g, toxins
• Host responses:
  innative- LPS induces macrophage cytokine secretion, causing fever and endotoxic shock

specific- Ab/ T cel reactions may contribute to pathology e.g. skin rashes in measles due to T cell response

Question 18

Explain the role microbes play in rheumatic fever in initiating autoimmune response

Answer 18

Abs to spretoccoal M protein may cross-react with heart muscle

Question 19

Explain the strucuture of the ebola virus

Answer 19

Its a filovirus- enveloped, non segmented -ve stranded RNA with filamentous particle

Question 20

What disease can ebola lead to?

Answer 20

Haemorrhagic fever

Question 21

How does ebola affect host defences?

Answer 21

Infects immune cells, including dendritic cells and macropahges

• inhbits maturation of infected dendritic cells so they don’t present Ag effectively
• causes aapoptosis leading to reduced # of circulating T lymphocytes and NK cells & weakened immune response
• interferes with production of type I interferon and the cellular response to interferon

Question 22

How does the induction of cytokine secretion by macrohpages play a role in pathogenesis

Answer 22

Sheds glycoprotein from virus, binds macrophages and dendritic cells leading to cytokine release and increase in vascular permeability

Question 23

How can infected macrophages result in cell death>

Answer 23

Infected macrophages express abundant tissue factor which initiates coagulation casacade
- disseminated intravasculuar coagulation