L10: Evassion of Host Defences in Infection Flashcards
Name the 4 clear mechanisms used by pathogens to evade host defence mechanisms
- concealment of Ags
- antigenic variation
- immunosuppression
- interference with effector mechanisms
Explain how pathogens use concealment of Ags to evade defence mechanisms
- 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
Given an example of a diease that uses concealment of Ags to evade defence mechanism
Herpes zoosler virus
Explain how pathogens use antigenic variation to evade defence mechanisms
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
How does the influenza virus use antigenic variation to evade defence mechanisms?
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
Explain the cell biology/ structure of the influenza virus
- is an RNA virus with -ve sense segmented genome
- major surface Ags are haemagluttin & neuraminidase
How does strep. pneumonia use various antigenic types to evade host defences?
Ab to the capsule opsonises the bacteria and protects it
Explain the cell biology/ structure
Gram +ve surrounded by thick polysaccharide capsule which protects it from phagocytosis
How do vaccines for strep. pneumonia work?
- 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 - 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
How does trypanosmoa use gene switching to evade host defences?
- 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
Explain the cell biology/ strucuture of trypanosmoa
- protozoa parasite that cause African sleeping sickness
- patients undergo bouts of parasitemia
Explain how immnuosuppresin is used to evade host defences?
Via
- infection of immune cells e.g. HIV-T cells
- induction of Treg cells e.g. chronic infection of H.pylori
How are Treg cells used in immunosuppresion?
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
How does leishmania affect T cells?
Leishmania cna hide and survive in macropahes and increase expression of T reg cells and decrease the immune response
Name another virus that causes immunosuppresion and explain its implications
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
How can interference with effector mechanisms allow pathogens to evade host defences?
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
What can cause infectious disease pathology?
- 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
Explain the role microbes play in rheumatic fever in initiating autoimmune response
Abs to spretoccoal M protein may cross-react with heart muscle
Explain the strucuture of the ebola virus
Its a filovirus- enveloped, non segmented -ve stranded RNA with filamentous particle
What disease can ebola lead to?
Haemorrhagic fever
How does ebola affect host defences?
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
How does the induction of cytokine secretion by macrohpages play a role in pathogenesis
Sheds glycoprotein from virus, binds macrophages and dendritic cells leading to cytokine release and increase in vascular permeability
How can infected macrophages result in cell death>
Infected macrophages express abundant tissue factor which initiates coagulation casacade
- disseminated intravasculuar coagulation
