How do we eliminate pathogens that live inside cells Flashcards

1
Q

what are the cells responsible for eliminating pathogens that live inside cells

A
  • cytotoxic T cells

- NK cells

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2
Q

How do we eliminate pathogens that live inside cells

A

kill the cell

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3
Q

what are the pathogens that live inside the cell

A
  • bacteria such as TB

- all viruses

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4
Q

what responses lead to death of the cell

A
  • cell mediated response (means it uses cells)

- humoral immune response ( responds directly into the body fluids)

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5
Q

what are the cytoplasmic cells

A
  • cytotoxic T cells these are cells that cause death

- NK cells

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6
Q

what are the vesicular cells

A

T cell dependent macrophage activation

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7
Q

what are the intracellular bacteria that cause disease

A

Chlamydia pneumoniae- Respiratory infections
Legionella pneumophila- Legionnaire’s Disease
Listeria monocytogenes - Listeriosis
Neisseria meningitidis - Meningitis
Salmonella typhi - Typhoid fever
Mycobacterium tuberculosis - TB

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8
Q

what are the viruses that cause disease

A
Influenza		Common cold virus
HIV			HPV (Cervical cancer) 
Hepatitis B		Rabies
Hepatitis C		Ebola
Mumps		Measles
Rubella		Herpes
Chicken pox		Polio
Smallpox
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9
Q

why do all viruses live inside cells

A

because they use the genetic machinery to make the virus

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10
Q

what cells do you use to kill the infected cells

A
  • cytotoxic T cells CD8
  • NK cells
  • macrophages
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11
Q

what is the basis of the immune response

A

There is a cut in the skin
Dendritic cells- long processes that all them to crawl through
When dendritic cell picks up bit of pathogen that is dead via toll like receptors becomes activated stops moving and processes stuff
Goes through the afferent lymphatic
Afferent lymphatic is the draining lymphatic
Leads into the lymph nodes
Efferent lymphatic is not draining lymphatic
Places protein on MHC
Looks for T cell receptors that recognise that specific pathogen from the specific protein
CD8 + T cells found and becomes activated and clonally expand
Happens over the period of a week
Go out as a clone and go to the infection where the infection is
Can then deal with the infected cells once you get there
T cell receptors have a TCR and the CD8 co-receptor
- B cell receptor can recognise any soluble molecule in the fluid whereas a T cell receptor can only recognise protein in the context of the MHC molecule
- The cell that is infected has MHCI receptors
- They kill virally infected cells and tumour cells
- MCH1 – every nucleated cell in the body presents to CD8, MCH11 restricted to the immune system presents to CD4
- MCH1 – not on red blood cell, so when a parasite such as malaria gets in it is difficult to get into it, cannot recognise infected blood cells very easily
- Viruses binds to the cell and injects DNA into the cell, cell makes viral protein
- It detects DNA and RNA that shouldn’t be in it, regulates type I interferon
- Cell infected with virus warns other cells, chops up protein and put some of the protein onto MHC class I
- T cell TCR receptor binds to MHC CLASS I that has the infected protein
- Kills the cell the cell dies by apoptosis

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12
Q

How do you recognise cytotoxic T cells

A

Recognise CD8 on the surface by binding an antibody, shows up flourscent light in laser as only cell that has CD8 on the surface

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13
Q

cytotoxic T cells can…

A

can kill repeatedly

- They can kill multiple times, unlike neutrophils which can kill you and then die in the process

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14
Q

how does apoptosis work

A
  • A programmed chain of events that is triggered in the cell
  • Nuclear blebbing
  • Alteration in cell morphology
  • Cell membrane remains intact
  • Shedding of small membrane vesicles
  • DNA is fragmented by controlled digestion by nuclease enzymes
  • Apoptotic bodies are removed by phagocytic cells such as macrophages
  • Necrosis – cell breaks down and releases the virus leads to inflammation
  • Chemotherapy and radiotherapy- induce wrong kind of apoptosis
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15
Q

why does the cell use apoptosis

A
  • Induce a type of cell death that doesnt make the inflammation worse
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16
Q

what do cytotoxic T cells have

A

they have lytic granules (these are modified lysosomes) they contain two powerful agents which are perforin and granzymes

17
Q

how does the cytotoxic T cell kill a infected cell

A
  • Perforin forms pores in the membrane and granzymes bind to proteins in the membrane
  • Perforin forms a pore in cell membranes, as they are hydrophobic,
  • Calcium ions go through these pores and change the charge
  • This destabilises the membrane and this enables the proteins to flip, these proteins are attached to the granzymes
  • A lot of inactive proteins in the cells and they become activated and activates something else
  • Eventually start to chop up the cell
  • Enzymes chop up viral proteins
  • Cytotoxic effector molecules are released in a precisely focused manner
  • CD8 cell come along to any cell in that tissue, then using molecules will make a non specific adhesion, then see if the cell has MHC1, sees if the mHC1 has viral protein attached to it, if it does not have the viral protein then it is released, if it does then it binds to it
  • This gives a shoot to secrete things in
  • The apparatus and granules in the cell line up with the shoot, Golgi, microtubules
  • Secrete stuff into the tube
  • This kills the cell
  • Can kill the cell in 40 minutes
  • Can get tissue damage so it has lots of regulatory factors
  • LFA1 and ICAM1binds to target cells
18
Q

why are natural killer cells called natural killer cells

A

because they can kill cancer cells naturally without doing anything to the cell

19
Q

what immune system are NK cells part of

A

innate immune system

20
Q

what kind of cell are NK cells

A
  • lymphocytes
21
Q

how do natural killer cells kill infected cells

A

same method as cytotoxic T cells using perforin and granzymes

22
Q

what don’t NK cell have

A
  • They do not have antigen specific receptors such as BCR and TCR therefore they cannot recognise cells that have disease in them
23
Q

how are NK cells activated

A
  • activated by cytokines

- NK cells release IFN- gamma, NK cells can kill 20-100x more efficiently

24
Q

How do NK cells avoid killing normal cells

A
  • use the missing self hypothesis
25
Q

how does the NK cells recognise self from non self

A
  • Recognition of self – no killing by NK cells

- Recognition of missing self – killing by NK cells (missing – doesn’t answer or is not self)

26
Q

why are NK cells a problem for organ transplant

A
  • Problems for organ transplant – NK cells are killed to stop rejection
  • NK cells – cause rejection on the operating table
    recognise the organ as non self
27
Q

How do NK cells influence infertility

A
  • Infertility treatment – women who have trouble getting pregnant have over active NK cells – NK cells kill babies – graft from the partner, half of someone else – NK cells normally try to kill it but they are stopped trying to get into the placenta,
  • Kills NK stem cells before they try to get pregnant
28
Q

describe how the missing self hypothesis of NK cell killing works

A
  • MCH1 – groove needs to be filled, cell fills it with self-proteins
  • NK cell comes along and sees if the MHC1 from the body is expressed,
  • Inhibitory receptors bon NK cell stops the cell from killing self (doesn’t care about the protein but does care about if there is MHC on the surface), activating receptors allow it to kill missing self
  • If virus peptides are in MHC1 NK still goes away because it has MHC1 receptor
  • CD8 – does recognise viral MHC1 and kills it NK cell doesn’t need to worry
  • Viruses have mutated and these downregulate MHC1 no longer on the surface, but then the NK cell recognises that there is no MHC1 on the surface so it kills it because the self is missing
  • Tumours don’t have MHC1 that’s why NK cells kill them
  • Tumours can grow faster and divide quicker without having MHC class I so some tumours don’t have MHC class I on the surface
29
Q

extracellular diseases

A
  • parasites
  • protozoa
  • fungi
  • prokaryote
30
Q

intercellular disease

A
  • viruses

- prion

31
Q

which pathogens affect intracellular structures

A
Myobacterium tuberculosis 
Campylobacter jejuni
 Streptococcus pneumoniae
Staphylococcus aureus
Streptococcus porci
32
Q

what cells eliminate pathogens inside cells

A

cytotoxic T cell
natural killer cells
macrophages

33
Q

what does the CD8 mean

A

express the CD8 glycoprotein on the surface of the cell

34
Q

what cells does MHC I attract

A

CD8 cells

35
Q

what attract NK cells

A

When cells are infected with a pathogen they release interferons
Interferons are signaling molecules that alert nearby cells of the presence of infection and trigger an immune response
Interferons activate NK cells turning them into effector NK cells
interferes such as IL-2 - cytokines which activate nK cells

36
Q

2 types of receptors on NK cells

A
  • activating receptor

- inhibitory receptor