Block D Lecture 2: Immunity to Pathogens

Question 1

What is a parasite?

Answer 1

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)

Question 2

What is one way a host-parasite association may occur?

Answer 2

Due to the host being injured
(Slide 3)

Question 3

What are 2 examples of unicellular parasites?

Answer 3

Leishmania
Toxoplasma
(Slide 3)

Question 4

What is leishmaniasis caused by?

Answer 4

Protozoa (unicellular) parasites from over 20 leishmania species
(Slide 4)

Question 5

What is known to transmit leishmaniasis?

Answer 5

Over 90 species of sandfly
(Slide 4)

Question 6

What are the 3 main forms of leishmaniasis?

Answer 6

Visceral
Cutaneous
Mucocutaneous
(Slide 4)

Question 7

What is the fatality rate in untreated cases of visceral leishmaniasis?

Answer 7

> 95%
(Slide 4)

Question 8

What is the most common form of leishmaniasis?

Answer 8

Cutaneous
(Slide 4)

Question 9

What 2 things does cutaneous leishmaniasis cause?

Answer 9

Skin lesions and ulcers
(Slide 4)

Question 10

What is mucocutaneous leishmaniasis?

Answer 10

Partial or total destruction of mucous membranes of the nose, mouth and throat
(Slide 4)

Question 11

What is crucial in healing cutaneous leishmaniasis?

Answer 11

Cell-mediated immune responses
(Slide 5)

Question 12

What happens in healing cutaneous leishmaniasis?

Answer 12

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)

Question 13

What happens in Non-healing cutaneous leishmaniasis?

Answer 13

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)

Question 14

What 2 things are important in healing toxoplamosus?

Answer 14

Cell-mediated immune response and humoral response
(Slide 9)

Question 15

What is toxoplasmosis caused by?

Answer 15

Toxoplasma parasite
(Slide 9)

Question 16

What cells can the toxoplasma parasite live in?

Answer 16

Any cell
(Slide 9)

Question 17

What are the main mediators of toxoplasmosis?

Answer 17

Cytotoxic (CD8+) T cells producing IFN-gamma
(Slide 9)

Question 18

What role does IgA play in protecting against toxoplasmosis?

Answer 18

Protecting gut mucosa
(Slide 9)

Question 19

What happens to toxoplasma parasites coated in IgG?

Answer 19

They are killed inside macrophages following phagolysosome fusion
(Slide 9)

Question 20

What 2 things must the body increase in order to expel gut nematodes?

Answer 20

Increased mucous production
Increased peristalsis (contraction and relaxation of muscles in the gastrointestinal tract)
(Slide 10)

Question 21

What response does the body use to expel gut nematodes?

Answer 21

A cell-mediated Th2-dependent response
(Slide 10)

Question 22

What needs to infect host cells in order for a virus to replicate?

Answer 22

An “obligate parasite”
(Slide 12)

Question 23

What does an “obligate parasite” infecting host cells to replicate cause?

Answer 23

Damage to host cells known as “cytopathic effects”
(Slide 12)

Question 24

How does a virus often stop the infected host cell from completing its function?

Answer 24

As it hijacks the host cells machinery to make more viruses
(Slide 12)

Question 25

Why does a virus often kill the host cell?

Answer 25

As it ruptures to release new virus particles or virions (Slide 12)

Question 26

What 3 things must an immune response against a virus do?

Answer 26

Kill virus particles - known as virions Clear virus infected cells Neutralise viral toxins (Slide 12)

Question 27

What 3 things make up the innate response against viruses?

Answer 27

Type-1 interferon (IFN) Natural Killer (NK) cells Dendritic cells (Slide 13)

Question 28

What 2 things make up the adaptive immune response to a virus?

Answer 28

T cells (both CD4+ and CD8+) B cells (Slide 13)

Question 29

What are the 2 different types of Type-1 Interferons?

Answer 29

IFN-α and IFN-ß (Slide 14)

Question 30

What does cytokine production in a virus infected cell induce?

Answer 30

The cell to shutdown some of its protein-making functions and increase its RNA-cutting enzymes (Slide 14)

Question 31

What are 2 ways some viruses try to evade immune response?

Answer 31

By switching off MHC-1 expression or inhibiting the processing pathway (Slide 15)

Question 32

How much does IFN-α increase the activity of natural killer cells?

Answer 32

20-100 fold (Slide 15)

Question 33

What do activated natural killer cells produce?

Answer 33

IFN-gamma (Slide 15)

Question 34

What induces T cells towards the Th1 phenotype?

Answer 34

IFN-gamma (Slide 15)

Question 35

What type of cytotoxicity do natural killer cells carry out?

Answer 35

Antibody-dependent cell-mediated cytotoxicity (Slide 15)

Question 36

How are natural killer cells activated by altered self cells?

Answer 36

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)

Question 37

What do cytotoxic T cells produce on activation?

Answer 37

Granules (Slide 18)

Question 38

How do cytotoxic T lymphocytes recognise infected cells?

Answer 38

It recognises the viral peptide-MHC class I receptor complex with it's TCR (Slide 18)

Question 39

What is MHC-1 expression increased by?

Answer 39

IFN-α (Slide 18)

Question 40

What triggers cytotoxic T cell killing?

Answer 40

Recognition of specific viral antigen on MHC-I (Slide 19)

Question 41

What do the intracellular granules activated by cytotoxic T cells activate?

Answer 41

Apoptosis (Slide 19)

Question 42

What are neutrophil extracellular traps (NETs)

Answer 42

Release of DNA webs decorated with all 5 histones and neutrophil derived granular proteins with antimicrobial activity (Slide 24)

Question 43

What can neutrophil extracellular traps (NETs) cause?

Answer 43

Immobilisation of bacteria at the site of infection (Slide 24)

Question 44

What is NETosis?

Answer 44

A specialised type of apoptosis caused by neutrophil extracellular traps (NETs) (Slide 24)

Question 45

What is tuberculosis caused by?

Answer 45

Mycobacterium tuberculosis (Mtb) (Slide 28)

Question 46

What type of pathogen is mycobacterium tuberculosis?

Answer 46

Intra-macrophage (Slide 28)

Question 47

What is important in limiting the ability of the mycobacterium tuberculosis to invade macrophages?

Answer 47

Innate immunity (Slide 28)

Question 48

What 2 cells release TNF-α to induce apoptosis of macrophages infected with tuberculosis?

Answer 48

Natural killer and cytotoxic T cells (Slide 28)

Question 49

What are 3 ways to limit tuberculosis?

Answer 49

Macrophage stimulation - to kill bacterium Apoptosis of infected macrophage Granuloma - multicellular structures to limit mycobacterium tuberculosis growth (Slide 28)

Question 50

What do macrophages infected with virulent (severe) mycobacterium tuberculosis (Mtb) secrete more of?

Answer 50

IL-10 (Slide 29)

Question 51

What 2 things result from macrophages infected with virulent Mtb secreting more IL-10?

Answer 51

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)