immunity to pathogens - block d

Question 1

Parasite

Answer 1

An organism (parasite) benefits at the expense of another organism usually of different species (host). This host-parasite association may eventuate to the injury of the host. The host does not benefit from the association

Question 2

Parasitic diseases

Answer 2

Unicellular (protozoa)

Malaria (Plasmodium)

Leishmaniasis (Leishmania)

Toxoplasmosis (Toxoplasma)

Sleeping sickness (Trypanosoma)

Multicellular (worms)

Question 3

Leishmaniasis

Answer 3

caused by a protozoa parasite from over 20Leishmaniaspecies

over 90 sandfly species are known to transmitLeishmaniaparasites

There are 3 main forms of the disease:

Visceral – untreated, is fatal in 95+% of cases

Cutaneous – most common, causes skin lesions and ulcers

Mucocutaneous – partial or total destruction of mucous membranes of the nose, mouth and throat

Question 4

Cutaneous leishmaniasis - Healing

Answer 4

Leishmania major or Leishmania mexicana

Cell-mediated immune responses important

Macrophage/Dendritic cell produce IL-12 activates a macrophages to kill the intramacrophage parasite

IFN-g from NK cells, Th1 cells activates macrophages

Activated macrophages – produce microbicidal products
e.g., superoxide, nitric oxide, enzymes - kill intracellular parasites

Question 5

Cutaneous leishmaniasis – Non-healing

Answer 5

No activation of macrophages

Th2 dependent

IL-4 drives a Th2 response.

Th2 cells produce IL-4/IL-13.

IL-4/IL-13 inhibit a Th1 response by inhibiting IL-12 production or preventing IL-12Rb2 expression.

IL-4/IL-13 inhibit IFN-g production and activity

Question 6

Toxoplasmosis – Toxoplasma gondii

Answer 6

Cell-mediated immune response most important but humoral responses may also have an effect

Parasite can live in any cell

CD8+ T cells producing IFN-gamma- main mediators of resistance

In AIDS patients, dormant tissue cysts in the brain reactivate resulting in encephalitis

IgA may play role in protecting gut mucosa

IgG coated parasites are killed inside macrophages following phagolysosome fusion

Question 7

Multicellular parasites – Gut nematodes

Answer 7

Need to expel parasites from the gut

Increased mucus production

Increased peristalsis

Immunity cell-mediated – Th2 response – need IL-4 production e.g., Trichuris

Question 8

Immunity to Viruses

Answer 8

an ‘obligate parasite’- needs to infect host cells to replicate

causes damage to the host cells – ‘cytopathic effects’

often stops the infected cell completing its function -
virus hijacks the machinery to make more viruses

often kills the host cell as it ruptures to release new virus particles or virions

Question 9

Virus immune response

Answer 9

Kill virus particles - virions

Clear virus infected cells

Neutralise viral toxins

Question 10

Immune response to viruses

Answer 10

Innate response – not antigen-specific

Type-I interferon (IFN)
NK cells
Dendritic cells

Adaptive response – antigen-specific
T cells - CD4+ (‘helper’) and CD8+ (‘cytotoxic’)
B cells – specific antibody

Question 11

Type-I interferon

Answer 11

Two different types – IFN-a and IFN-b (distinct from IFN-g)

Recognised the ability of heat-killed influenza to interfere with growth of live virus in eggs - isolated the protein responsible for interfering with virus replication = interferon

Cytokine production is induced in a virus-infected cell (can be produced by most cell types upon infection)

Induces cell to shutdown some of its protein-making functions and increase its RNA-cutting enzymes

Question 12

Natural Killer (NK) Cells

Answer 12

Some viruses try and evade immune response by switching off MHC-I expression or inhibiting the processing pathway (Tc may not work but NK cells will)

Increase activity 20-100-fold in response to IFNa
Activated NK cells produce IFNg - helps activate macrophages to remove virus, induces T cells towards Th1 phenotype

Kill using the same mechanisms as CTL – apoptosis
Can also carry out antibody-dependent cell-mediated cytotoxicity

Question 13

Activated by recognition of ‘altered-self’

Answer 13

Altered surface proteins on infected cell might suggest infection - direct killing by NK cell by inducing apoptosis

Reduced levels of MHC-I might allow virus-infected cell to evade cytotoxic T cell - recognised by NK cells as it does not express sufficient MHC-I to switch NK cell off

Question 14

Antibody responses

Answer 14

Antibodies produced by plasma b cells

Can bind to virus proteins - target for uptake/destruction by phagocytic cells, block viral proteins - preventing invasion of target cells

Question 15

Cytotoxic T lymphocytes

Answer 15

Activated ‘effector’ CD8+ CTL migrate through tissues looking for infected cells

CTL contain several killing molecules - produces granules on activation

Recognise infection via T cell receptor – recognises antigen presented by MHC-I molecules

MHC-I expressed by all cells - expression increased by IFNa

Question 16

Phagocytes

Answer 16

Phagocytic cells can remove bacteria using: phagocytosis , toxic products e.g., TNF-alpha, superoxide, NO, neutrophils most numerous in the body

Site of bacterial infection can have a different effect – aim to keep the bacteria localised and increase influx of protective immune cells

Question 17

Neutrophil extracellular traps (NETs)

Answer 17

Neutrophils can produce traps – immobilise bacteria at the site of infection

Special cell death program – specialised type of aopotosis called ‘NETosis’

Release of DNA webs decorated with all five histones and neutrophil-derived granular proteins with antimicrobial activity e.g., elastase, myeloperoxidase (MPO), and the bactericidal/permeability-increasing protein

Question 18

Antibodies

Answer 18

Bind to bacterial toxins – neutralise effects, stop toxin reaching its active site

Act as an opsonin – clumped bacteria easier to be taken up by phagocytes

Question 19

Mycobacterium tuberculosis

Answer 19

Causes tuberculosis – primarily lung disease

Intra-macrophage pathogen

Innate immunity important in limiting ability of bacterium to invade macrophages

Need macrophage stimulation to kill bacterium – IFN-gamma important (Tc or Th1 cells) – NO, reactive nitrogen intermediates important

Apoptosis of infected macrophage – NK/Tc release TNF-alpha can induce apoptosis

Granuloma can form – multicellular structures that limit growth of Mtb

Question 20

Mycobacterium tuberculosis (Mtb) immune evasion mechanisms

Answer 20

Macrophages infected with virulent Mtb secrete more IL-10 - IL-10 down regulates activity of macrophages – less NO, reactive oxygen intermediates etc., – switches off macrophage killing mechanisms

IL-10 induces the release of TNFR-2 – and soluble TNFR-2 forms a complex with TNF-α and downregulates the TNF-α induced apoptosis of macrophages – causing survival of Mtb infected macrophages