Immune evasion Flashcards
Respiratory system barriers to infection
Respiratory epithelium has evolved to prevent microbes from entering the submucosal spaces
Goblet cells produce mucous. Cilia move mucous outwards, trapping and ejecting potential pathogens
Routes of infection in mouth and resp tract
True pathogens need specialised mode of entry, most often to cross mucosal surfaces and adapted characteristics to overcome normal host defences and cause infection
- Inhalation or ingestion of infective material 9e.g. saliva droplets) - measles virus, influenza virus, Varicella-zoster, epstein-barr, H.influenza
- Spores - bacillus anthracis (inhalation anthrax)
What are the defining features of a true pathogen?
Avoid immune destruction by innate and adaptive immunity long enough to replicate and spread to new host
Different pathogens adopt different strategies - at one extreme some pathogens cause acute disease, replicate and spread quickly before they are cleared by the host or kill the host - other extreme where some pathogens can survive over long periods causing chronic infections
Viral mechanisms to immune evasion - antigenic variation
A characteristic of many different pathogens. The adaptive immune system mounts an antibody response, the pathogen numbers decline. The pathogen then alters surface antigens and the immune system needs to begin all over again - virus then gains ground
Influenza virus (RNA) antigenic shift and antigenic drift
RNA polymerase will not proof-read the nascent strand - therefore new viral RNA genomes have a higher mutation rate than DNA viruses. RNA viruses more likelt mutate and evade immunity through antigenic druft
Antigenic drift - neutralising antibodies against hemagglutinin block binding to cells. Mutations after epitopes in hemagglutinin so that neutralising antibody no longer binds
Antigenic shift - occurs when RNA segments are exchanged between viral strains in a secondary host. No cross-protective immunity in virus expressing a novel hemagglutinin
Give examples of how DNA viruses have evolved diverse mechanisms to evade immune system
- Inhibition of humoral immunity - Herpes simplex
- Inhibition of inflamm response - epstein-barr virus, vaccinia
- Blocking of antigen processing and presentation - Herpes simplex
- Immunosuppression of host - epstein-barr
What are viral immunoevasins and give examples of immunoevasins
Viral encoding proteins that prevent infected host cells from presenting viral peptides in MHC class I molecules to CD8+ T-cells. CD8+ T-cells are cytotoxic T-cells that primarily recognise and kill viral infecetd cells by recognising virus particles presented in MHC class I molecules
Herpes simplex virus 1,(blocks peptide entry to endoplasmic reticulum), adenovirus (retention of MHC class I in endoplasmic reticulum)
Latency example?
Persistence and re-infection of herpes virus is an example of latency
Initial infection in skin is cleared by host immune system. Residual infection persists in nuclei sensory neurons serving the inf tissue. The virus transcribes a small part of genome that codes for LAT protein that suppresses the lytic cycle - also prolongs life of cell. When virus is re-activated by environmental factors or other consitions viral particles travel back along neurons to tissue and cause repeat infections (e.g. cold sores on lips)
Bacterial pathogen immune evasion
EC bacteria typically elicits an ILC type 3 immune response - TH17 and neutrophil
neutrophilic repsonses, drive forward opsonising and complement fixing antibodies, production of antimicrobial peptides
EC bacteria evasion mechanisms
Shielding/inhibition of MAMPs e.g. S.pneumoniae
Antigenic variation
Inhibition of opsonisation - H.influenza, S.pneumoniae
Inhibition/scavenging of reactive oxygen species (ROS) - S.aureus
Resitance to antimicrobial peptides - E.coli
Intracellular bacterial clearance
Macrophages phagocytose bacteria that have breached barriers. The phagosome fuses with the lysosome and bacterium is formally degraded
IC pathogenic bacteria - immune evasion
IC bacterial pathogens have developed mechanisms to survive inside cells macrophages
- Antigenic variation
- Inhibition of MAMP recognition/signalling
- Resistance to anti-microbial peptides
- Inhibition of fusion of phagosome with lysosome
- Survival within phagolysosome (mainly this)
- Escape from phagosome
Mycobacterium tuberculosis
M.tuberculosis is phagocytosed by macrophages but M.tb prevents fusion of phagosome and lysosome and is therefore protected. Followed by granuloma formation
M.tb resists the effects of macrophage activation. M.tb only partially eliminated by a type 1 immune response (ILC T1, TH1 CD4+ T lymphocytes and cytotoxic cd8+ T- cells). A chronic low level infection dveelops requiring TH1 to keep infection from spreading. A localised inflamm repsonse develops and a granuloma forms
What is the granuloma in TB?
Consists of a central core of infected macrophages - with fused multi nucleated giant cells and surrounded by large macrophages called epithelial cells - the core can become necrotic. The core is surrounded by T-cells, mostly CD4+ Th cells. What drives this formation and how it breaks down largely unknown.
Immune evasion in protozoa
Plasmodium and trypanosoma can escape the immune system by antigenic variation
