How do we eliminate pathogens that live inside cells Flashcards
what are the cells responsible for eliminating pathogens that live inside cells
- cytotoxic T cells
- NK cells
How do we eliminate pathogens that live inside cells
kill the cell
what are the pathogens that live inside the cell
- bacteria such as TB
- all viruses
what responses lead to death of the cell
- cell mediated response (means it uses cells)
- humoral immune response ( responds directly into the body fluids)
what are the cytoplasmic cells
- cytotoxic T cells these are cells that cause death
- NK cells
what are the vesicular cells
T cell dependent macrophage activation
what are the intracellular bacteria that cause disease
Chlamydia pneumoniae- Respiratory infections
Legionella pneumophila- Legionnaire’s Disease
Listeria monocytogenes - Listeriosis
Neisseria meningitidis - Meningitis
Salmonella typhi - Typhoid fever
Mycobacterium tuberculosis - TB
what are the viruses that cause disease
Influenza Common cold virus HIV HPV (Cervical cancer) Hepatitis B Rabies Hepatitis C Ebola Mumps Measles Rubella Herpes Chicken pox Polio Smallpox
why do all viruses live inside cells
because they use the genetic machinery to make the virus
what cells do you use to kill the infected cells
- cytotoxic T cells CD8
- NK cells
- macrophages
what is the basis of the immune response
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
How do you recognise cytotoxic T cells
Recognise CD8 on the surface by binding an antibody, shows up flourscent light in laser as only cell that has CD8 on the surface
cytotoxic T cells can…
can kill repeatedly
- They can kill multiple times, unlike neutrophils which can kill you and then die in the process
how does apoptosis work
- 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
why does the cell use apoptosis
- Induce a type of cell death that doesnt make the inflammation worse
what do cytotoxic T cells have
they have lytic granules (these are modified lysosomes) they contain two powerful agents which are perforin and granzymes
how does the cytotoxic T cell kill a infected cell
- 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
why are natural killer cells called natural killer cells
because they can kill cancer cells naturally without doing anything to the cell
what immune system are NK cells part of
innate immune system
what kind of cell are NK cells
- lymphocytes
how do natural killer cells kill infected cells
same method as cytotoxic T cells using perforin and granzymes
what don’t NK cell have
- They do not have antigen specific receptors such as BCR and TCR therefore they cannot recognise cells that have disease in them
how are NK cells activated
- activated by cytokines
- NK cells release IFN- gamma, NK cells can kill 20-100x more efficiently
How do NK cells avoid killing normal cells
- use the missing self hypothesis
