lecture 15: effector cells and immune tolerance

Question 1

clonal selection

Answer 1

selective expansion of lymphocytes that interact with antigen
eg: a B cell that is specific for native antigen is activated and undergoes extensive cell division

Question 2

how do only B cells bearing the correct BCR receive T cell help

Answer 2

–> one of the signals required to get help (cytokines) will only be activated if the B cell is able to present peptide to the CD4

Question 3

Example of B cell specific for tetanus toxin

Answer 3

• B cell binds to tetanus toxin which stimulates a signal in the B cell (signal 1) also stimulates endocytosis (dragging in the antigen and process it, peptide will mostly be loaded onto MHC2)
• one of these peptides generated from the digestion of the protein should be enough to activate some CD4

Question 4

cytotoxic T lymphocytes

Answer 4

• derived from CD8 effector cells
• Naive CD8 t cells are triggered to become cytotoxic by recognising MHC I and getting help from a CD4 cell

Question 5

what are the two signals required to produce a cytotoxic t cell

Answer 5

1. dendritic cell
2. helper cell

Question 6

how do cytotoxic lymphocytes function

Answer 6

• CTLs evolved their mechanism of death to accomodate virus world
• CTLs kiss of death is not simple lysis of targets
• it requires activation of apoptotic (programmed cell death) pathways in target cells
• CTLs are serial killers of tumour cells. this means they can engage, disengage and kill more virus infected cells

Question 7

activation of CTLs

Answer 7

• recognition is based on MHC I and peptide, all cells in our body that are nucleated have MHC I
• so all cells should have the potential to present a virus peptide if they’re infected
• CTL are already activated so they don’t need co-stimulation they just need a signal to trigger and release their cytotoxic granules on the target cell

Question 8

CTLs weapons

Answer 8

1. perforin and granzyme
   - perforin forms a polymeric, cylindrical structure in lipid bilayer of target cell
   - granzyme enters target cells, via perforin pore
   - granzyme is a protease that cleaves target cell proteins initiating programmed cell death (apoptosis)
2. CD95 ligand (CD95L)
   - binds to CD95 on target cell initiating programmed cell death
   - apoptosis does not result in release of cell contents
   - to avoid detection, many viruses have ‘learnt’ how to down regulate MHC-I

Question 9

protease def

Answer 9

an enzyme that breaks down proteins by cleaving the peptide bonds between amino acids

Question 10

Natural killer (NK)

Answer 10

–> NK cells detect altered MHC expression
- NK respond to “missing self”
- low or absent expression of MHC-I triggers NK activation leading to killing of target cells
- if CTL encounters target cell with MHC-I = no killing
- if CTL encounters target cell without MHC-II = killing

Question 11

activating receptor in NK cells

Answer 11

can activate NK cells, weak compared to inhibition

Question 12

inhibitory receptor in NK cells

Answer 12

• stronger than activating signal

Question 13

inhibitory and activating signals role in NK cells

Answer 13

• -ve signal is dominant but if there is missing MHC the activating signal is still strong enough to activate NK
• NK receive kill and dont kill signals, it is the balance of these signals which determine the fate of the target cell

Question 14

immune tolerance

Answer 14

immune systems ability to recognise and not attack the bodies own tissues
- effector cells often work together to provide optimal immunity for the body

Question 15

neonatal tolerance

Answer 15

• infants are immunocompromised and hardwired for tolerance
• central tolerance expecially active at neonatal
• a wave of regulatory T cells (tregs) are produced early in life
• tregs secrete immunosuppressive cytokines

Question 16

central tolerance

Answer 16

developing T/B cells that recognise the bodies own proteins are eliminated

Question 17

central tolerance: B cells

Answer 17

Auto reactive immature B cell (leaving bone marrow stromal cell) = death
deletional tolerance = zapped lymphocytes, not permanent bc there is always a new wave of lymphocytes coming out of thymus

Question 18

central tolerance: T cells

Answer 18

positive selection –> just right T cell (moderate signal)
negative selection –> autoreactive T cell (strong signal)

Question 19

peripheral tolerance

Answer 19

• lack of co-stimulation provided by DC leads to immune tolerance
• if they encounter t cells which react with peptides, they are producing the t cells
• so they switch off so there is no co stimulation
• ‘Danger’ activated DC provide two signals required for T cell activation

Question 20

mast cells

Answer 20

–> granulated immune cells found in tissues
- distributed throughout mucosal surfaces and skin
- what the body is trying to do it expel the parasite

Question 21

formation of mast cell

Answer 21

1. antigen binds
2. forms/activates B cell
3. B cell makes IgE to antigen
4. mast cell binding fragment to IgE
5. IgE sensitises tissue mast cells by binding to surface IgE receptor sites
6. subsequent exposures to antigen
7. antigen cross-links two antibody molecules
8. release of allergic mediators (histamines, serotonin etc.)
9. allergies (hay fever, asthma)

Question 22

hypersensitivity

Answer 22

an exaggerated adaptive immune response that occurs in an individual on a second or subsequent contact with an antigen

Question 23

Type 1 hypersensitivity

Answer 23

Eg = an allergy
- the initial exposure to an allergen = sensitization
- allergic reactions occur when an individual who has produced IgE antibody in response to the initial exposure to an antigen subsequently encounters the same allergen