Block D Lecture 2: Immunity to Pathogens Flashcards
What is a parasite?
An organism which benefits at the expense of another organism (usually of a different species) called a host with the host not benefitting from the association
(Slide 3)
What is one way a host-parasite association may occur?
Due to the host being injured
(Slide 3)
What are 2 examples of unicellular parasites?
Leishmania
Toxoplasma
(Slide 3)
What is leishmaniasis caused by?
Protozoa (unicellular) parasites from over 20 leishmania species
(Slide 4)
What is known to transmit leishmaniasis?
Over 90 species of sandfly
(Slide 4)
What are the 3 main forms of leishmaniasis?
Visceral
Cutaneous
Mucocutaneous
(Slide 4)
What is the fatality rate in untreated cases of visceral leishmaniasis?
> 95%
(Slide 4)
What is the most common form of leishmaniasis?
Cutaneous
(Slide 4)
What 2 things does cutaneous leishmaniasis cause?
Skin lesions and ulcers
(Slide 4)
What is mucocutaneous leishmaniasis?
Partial or total destruction of mucous membranes of the nose, mouth and throat
(Slide 4)
What is crucial in healing cutaneous leishmaniasis?
Cell-mediated immune responses
(Slide 5)
What happens in healing cutaneous leishmaniasis?
Macrophages and dendritic cells produce IL-12 to activate macrophages to kill the parasite
Interferon-gamma from NK cells and Th1 also activate macrophages
The activated macrophages then produce microbicidal (agent that kills microbes) products
(Slide 5)
What happens in Non-healing cutaneous leishmaniasis?
Macrophages are not activated
IL-4 drives a Th2 response instead
Th2 produce IL-4 / IL-13 which inhibit a Th1 response by inhibiting IL-12 production or expression of IL-12Rß2 expression and they also inhibit IFN-gamma production and activity
(Slide 7)
What 2 things are important in healing toxoplamosus?
Cell-mediated immune response and humoral response
(Slide 9)
What is toxoplasmosis caused by?
Toxoplasma parasite
(Slide 9)
What cells can the toxoplasma parasite live in?
Any cell
(Slide 9)
What are the main mediators of toxoplasmosis?
Cytotoxic (CD8+) T cells producing IFN-gamma
(Slide 9)
What role does IgA play in protecting against toxoplasmosis?
Protecting gut mucosa
(Slide 9)
What happens to toxoplasma parasites coated in IgG?
They are killed inside macrophages following phagolysosome fusion
(Slide 9)
What 2 things must the body increase in order to expel gut nematodes?
Increased mucous production
Increased peristalsis (contraction and relaxation of muscles in the gastrointestinal tract)
(Slide 10)
What response does the body use to expel gut nematodes?
A cell-mediated Th2-dependent response
(Slide 10)
What needs to infect host cells in order for a virus to replicate?
An “obligate parasite”
(Slide 12)
What does an “obligate parasite” infecting host cells to replicate cause?
Damage to host cells known as “cytopathic effects”
(Slide 12)
How does a virus often stop the infected host cell from completing its function?
As it hijacks the host cells machinery to make more viruses
(Slide 12)
Why does a virus often kill the host cell?
As it ruptures to release new virus particles or virions
(Slide 12)
What 3 things must an immune response against a virus do?
Kill virus particles - known as virions
Clear virus infected cells
Neutralise viral toxins
(Slide 12)
What 3 things make up the innate response against viruses?
Type-1 interferon (IFN)
Natural Killer (NK) cells
Dendritic cells
(Slide 13)
What 2 things make up the adaptive immune response to a virus?
T cells (both CD4+ and CD8+)
B cells
(Slide 13)
What are the 2 different types of Type-1 Interferons?
IFN-α and IFN-ß
(Slide 14)
What does cytokine production in a virus infected cell induce?
The cell to shutdown some of its protein-making functions and increase its RNA-cutting enzymes
(Slide 14)
What are 2 ways some viruses try to evade immune response?
By switching off MHC-1 expression or inhibiting the processing pathway
(Slide 15)
How much does IFN-α increase the activity of natural killer cells?
20-100 fold
(Slide 15)
What do activated natural killer cells produce?
IFN-gamma
(Slide 15)
What induces T cells towards the Th1 phenotype?
IFN-gamma
(Slide 15)
What type of cytotoxicity do natural killer cells carry out?
Antibody-dependent cell-mediated cytotoxicity
(Slide 15)
How are natural killer cells activated by altered self cells?
Altered surface proteins on infected cell might suggest infection resulting in a direct killing by an NK cell by inducing apoptosis (such as reduces levels of MHC-I)
(Slide 16)
What do cytotoxic T cells produce on activation?
Granules
(Slide 18)
How do cytotoxic T lymphocytes recognise infected cells?
It recognises the viral peptide-MHC class I receptor complex with it’s TCR
(Slide 18)
What is MHC-1 expression increased by?
IFN-α
(Slide 18)
What triggers cytotoxic T cell killing?
Recognition of specific viral antigen on MHC-I
(Slide 19)
What do the intracellular granules activated by cytotoxic T cells activate?
Apoptosis
(Slide 19)
What are neutrophil extracellular traps (NETs)
Release of DNA webs decorated with all 5 histones and neutrophil derived granular proteins with antimicrobial activity
(Slide 24)
What can neutrophil extracellular traps (NETs) cause?
Immobilisation of bacteria at the site of infection
(Slide 24)
What is NETosis?
A specialised type of apoptosis caused by neutrophil extracellular traps (NETs)
(Slide 24)
What is tuberculosis caused by?
Mycobacterium tuberculosis (Mtb)
(Slide 28)
What type of pathogen is mycobacterium tuberculosis?
Intra-macrophage
(Slide 28)
What is important in limiting the ability of the mycobacterium tuberculosis to invade macrophages?
Innate immunity
(Slide 28)
What 2 cells release TNF-α to induce apoptosis of macrophages infected with tuberculosis?
Natural killer and cytotoxic T cells
(Slide 28)
What are 3 ways to limit tuberculosis?
Macrophage stimulation - to kill bacterium
Apoptosis of infected macrophage
Granuloma - multicellular structures to limit mycobacterium tuberculosis growth
(Slide 28)
What do macrophages infected with virulent (severe) mycobacterium tuberculosis (Mtb) secrete more of?
IL-10
(Slide 29)
What 2 things result from macrophages infected with virulent Mtb secreting more IL-10?
IL-10 downregulates activity of macrophages - so less NO etc produced - switching off macrophage killing mechanisms
IL-10 induces release of TNFR-2 which forms a complex with TNF-α and downregulates TNF-α induced apoptosis of macrophages - causing survival of Mtb infected macrophages
(Slide 29)
