Microbial Immune Evasion Flashcards
What are virulence factors?
β components that drive pathogenic processes
What is virulence?
β the degree to which a pathogen causes disease
What 3 things do virulence factors mainly do?
β promote adherence or receptor binding
β allow bacteria to colonise
β promote tissue damage - toxins
What are the 5 roles of the complement?
β Activate, promote and regulate the inflammatory process β increase phagocytosis by opsonization β increasing vascular permeability β mast cell degranulation β lysis of cell membranes
How does the complement activate, promote and regulate the inflammatory process?
β Releasing factors that chemo attract effector cells like macrophages and neutrophils
How does the complement increase phagocytosis by opsonization?
β binding to the surface of bacteria and viruses allowing them to be phagocytosed by macrophages
Why is complement sometimes unable to bind to bacteria?
β They have polysaccharide capsuled on their surface and endotoxins
β they donβt allow the early stages of the complement cascade to bind to their surfaces
What happens if bacteria can bind to factor H?
β it can stop the complement activating on the surface
How do some bacteria stop C3B binding?
β they coat themselves in non-fixing IgA
What is C3B ?
β a powerful opsonin which allows opsonisation into macrophages
When is C5A released?
β after the complement is activated
What is C5A?
β a chemoattractant
What are 3 intracellular pathogens?
β mycobacterium tuberculosis
β listeria
β salmonella
What is used by bacteria to avoid phagocytosis?
β capsules
What is protein A?
β binds antibodies the wrong way round
β they have Fc receptors that bind the antibody by the Fc region not the epitope
How does staph damage immune cells?
β they produce extracellular toxins that damage the membrane of white cells
βthey prevent opsonization by complement
How does M.tuberculosis prevent phagocytosis?
β blocks the phago-lysosome formation and stops acidification of the endosome
How does Listeria prevent phagocytosis?
β escapes the phago-lysosome into the cytoplasm
How do some bacteria neutralise the ROS made in the phago-lysosome?
β some bacteria produce catalases and peroxidases
How do microbes make Fc receptors?
β they have proteins on their surface that encode mimics of the Fc receptors
Why are microbe Fc receptors effective?
β Even if the immune system generates antigen specific antibodies the Fc receptors will bind the antibodies the wrong way round
β they can no longer be phagocytosed and killed
What are the 4 ways pathogens conceal antigens?
β hide inside cells
β privileged sites
β block MHC antigen presentation
β Surface uptake of host molecules - CMV
What virus blocks MHC antigen presentation?
β Herpes
What are 4 ways that pathogens cause immunosuppression?
β Decreased MHC
β downregulate receptors like interferon gamma, apoptosis, cytokine switch, IgA proteases
β Antigenic variation
β Persistence/latency/reactivation
What pathogen is the common cause of lobar pneumonia?
β Streptococcus pneumoniae
How is streptococcus pneumoniae breathed in?
β through the nasopharynx
How does streptococcus pneumoniae prevent antibody degradation?
β by secreting IgA proteases
What disease does streptococcus pneumoniae often follow and why?
β A viral infection because it will have damaged the structure of the defense mechanisms in the respiratory tract
What are the main defense mechanisms against streptococcus pneumoniae?
β Surfactant and mucus in the lungs
How does streptococcus pneumoniae invade the lungs?
βproduces IgA proteases which cleave antibodies
β Induces and switches on the genes for pneumolysin which is a toxin that lyses the membranes and causes pores in pneumocytes of the lungs
How many serotypes of streptococcus pneumoniae are there?
β 80-90
How can streptococcus pneumoniae escape phagocytosis?
β they have capsules
What are 4 ways that pathogens can evade the immune system?
1) Latency
2) decreased antigen presentation
3) decreased MHC expression
4) mutation of epitopes
What 2 pathogens can become latent and why?
β VZV, HSV
β if the virus were to infect everybody at the same time then the virus would die out
Where do latent viruses usually affect and why?
β Nerve cells
β they have very little immune surveillance so they can exist undisturbed
Which virus decreases antigen presentation and how?
β HPV
β binds to the TAP protein and blocks antigen transfer to MHC molecules
Which virus decreases MHC expression?
β CMV
Why do viruses mutate epitopes?
β so the B cell antibodies canβt work
β they evade the immune cells
What is antigenic diversity?
β Genetically stable and alternative forms of antigens in a population of microbes
What is antigenic variation?
β Successive expression of alternative forms of an antigen in a specific clone or its progeny
How is antigenic variation done?
β Pathogens can switch antigens on or off at low frequency
What kind of an infection is gonorrhoea?
β Inflammatory and pyogenic infection of the anterior urethra
Where does gonorrhoea infect?
β mucosal surfaces with a columnar epithelium
β urethra, cervix, rectum , pharynx, conjunctiva
What are the 4 symptoms of gonorrhoea?
β Dysuria
β Redness
β swelling
β pain on urination
What are the 9 pathologies that can occur as a result of gonorrhoea?
β Destruction of mucosa β prostatitis β orchitis β strictures β ovaritis β fistulas β PID β proctitis β sterility
What are three disseminated infections that can occur as a result of gonorrhoea?
β Arthritis
β Endocarditis
β Meningitis
Which structures of gonorrhoea can undergo phase variation?
β Capsule β pilus β outer membrane β Opa β Inner membrane
What are the two components of the influenza virus?
β Haemagglutinin
β Neuraminidase
How many haemagglutinin types are there?
β 15
How many neuraminidase types are there?
β 9 types
What kind of genome does the influenza virus have?
β segmented negative ssRNA genome
β 8 segments, 10 genes
What causes epidemics?
β Antigenic drift
What is antigenic drift?
β as the virus replicates itself it has errors
β if there is a mutation then antibodies do not recognise it
What causes pandemics?
β Antigenic shift
What is antigenic shift?
β Two viruses infecting a single cells
β they undergo recombination of the genome
β There are combinations that are new and the population has not seen before
What are the 6 ways that viruses avoid the adaptive immune system?
β MHC mimics - block killing by NK cells
β downregulate MHC
β Block antigen processing by TAP
β induce immune suppression by decreasing cell mediated immunity and CD4+ cells
β host mimicry
β cytokine binding mimics and binding proteins
What are the 2 ways that viruses avoid innate immunity?
β Latency reactivation
β Rapid growth and transmission prior to adaptive immunity
What are the 3 ways that bacteria avoid the adaptive immune system?
β Inhibition of antigen presentation
β superantigens and inappropriate immune activation
β induction/inhibition of apoptosis
What are the 4 ways that bacteria avoid the innate immune system?
β Prevent opsonin binding
β C3a and C5A proteases, anti-inflammatory and anti chemoattractant
β inhibits opsonisation
β inhibits complement activation
