L6 - Linking Innate & Adaptive Immunity Flashcards
What happens if the adaptive immunity is activated incorrectly?
Autoimmunity and allergies
Innate immune cells decide friend from foe. How do they tell T cells?
T cells can’t recognise Ag on its own so it has to be presented by APC. This cell-cell handshake ensures correct T cells is activated
How do you present an almost infinite array of peptides?
Major histocompatibility complexes (MHC) 1 and 2. Both have peptide binding cleft where the sequence binds. Molecule attaches to cell membrane
- class 1 = only for intracellular antigens
- class 2 = only extracellular antigens
Describe the binding of MHC and peptide (class 1 vs 2)
Antigens lies in groove of MHC and T cells cn only recognise peptide when combined with MHC. In class 1 the ends are closed an in class 2 the ends are open
Describe the diversity of MHC molecules
They need to be able to present a humane array of peptides so each MHC can bind to a range but not all. The more MHC molecules the more peptides you can present.
Describe the expression of MHC alleles from parents
MHC genes are codominantly expressed from both parents.
3 MHC class 1 genes from each parent (6 in total)
3 MHC class 2 genes with 2 copies of one o them so 3-4 from each parent each of us has 6-8 MHC class 2 genes
What is the MHC haplotype
Set of MHC alleles present on each chromosome
What is the significance of MHC molecules and grafts
MHC molecules are the principle factor in defining acceptance or rejection of grafts. Foreign MHC molecules on graft activate the recipient T cells that then kill the graft. Need to match the MHC haplotypes between host and donor (tissue typing)
Are MHC genes polymorphic? What does that mean? Is it good on individual and population levels?
5000 HLA alleles in population so very unlikely that 2 individuals will have the exact same MHC haplotypes
- good on individual level → every allele is diff, present more sequeces
- good on population level → more people will produce the antigens
- good bc if have children , they will have varied MHC
- graft rejection = different haplotypes of MHC, low probability to find graft matches
Describe the experiment that showed MHC polymorphism so important u can smell it.
Females slept overnight in T shirts
- best smelling = greater number of diff MHC alleles
- less attractive = similar MHC alleles
What is the difference in extra cellular and intracellular Ag
Extra - presented by MHC class 2 to Th and Treg cells (express CD4 on surface) to coordinate immune response
Intra - presented by MHC class 1 to cytotoxic T/lymphocytes (express CD8 on their surface e) to kill cells infected w intracellular pathogens
Match CD4 and CD8 to their respective MHC
CD4 = MHC class 2
CD8 = MHC class 1
(Stabilised)
Outline key aspects of dendritic cells
They tell T cells whether or not to activate
- present in all barrier tissue
- immune sentinels similar to macrophages
- do not kill (unlike acrophages)
- express PRRs
Their role
- scan for infections
- sample environment Ag
- take Ag to lymph nodes to talk w T cells
(Macrophage stay at infection site)
What is the first phase in the life of a dendritic cell
Sampling. Takes u[p and spits out extra cellular fluid and molecules. Expresses PRRs to detect DAMPs and PAMPs. Not very good at presenting Ag
What is the second phase of a dendritic cell life cycle
“ traveller with cargo”
- takes in more antigens
- stops sampling
- carries antigens (DAMPS or PAMPs) to the lymph nodes to present them to T cells
What happens after DC is at LN
- DC takes Ag to LN
- Naive T cells circulate and interrogate DC to see if presenting an Ag they recognise
MHC on DC also presents self antigens. How does DC communicate danger to T cell to tell them to respond?
T cells require 2 signals to activate
What are the 2 signals that T cells require to activate?
Signal 1 - communicates Ag specificity so MHC-Ag interacts with TCR
Signal 2 - danger signals (PAMPs) upregulate B7 on APC via CD28 and presence of B7 on APC tells teh T cell that the Ag it is recognising comes from a microbe
What does signal 1 without signal 2 show
That the Ag the T cell is recognising is non-dangerous (e.g. self-Ag or food)
Why don’t T and B cells have 2 or more receptor?
one is pathogen specific so it activates but you dk what the second one is for. if its specific for self antigen then youve started an autoimmune disease
What is phase 3 of the dendritic cell life cycle
“Presenter”
- mature antigen presenting cell in LN
- upregulates MHC class 2
- upregulates molecules B7 or CH80/CD86) required for signal 2
What is cytotoxic T cells (CTL) and what presents antigens to it
- only intracellular
- role is to identify infected cell and kill them
- only recognises Ag presented by MHC class 1 bc it presents intracellular Ag
- MHC class 1 identified infected cells
- it kills infected cells by handshake between CTL and infected cell
Where is MHC class 1 expressed usually and why?
On all nucleated cells bc any cell can become infected
What does macrophages do as an APC
- activated Th cell goes to infection site
- macrophage asks for help by presenting Ag - Th cell responds by producing IFN y
- tells Th cell infection still present
Outline key ideas of B cell acting as an APC (T-dependent Ab response) and (T-independent Ab response)
B cells require permission from activated Th cells to gain full potential. Bcell presents the Ag it recognises to Th cell if Th recognises then it gives permission to B cell to respond.
- Full effector functions, can switch isotope (Fc region of Ab that defines effector functions), affinity maturation (can increase its afffinty for Ag)
- Limited effector functions, no isotope switching no affinity maturation, stimulated by repeating epitopes, usually against carbohydrates or non-proteins
Immune memory fo B and T cells
- easier to activate
- can be actibated by more APC types not just dendritic cells
- patrol tissues focussing on location of last infection so do not need to be activated in LN
As the infection clears, how is the immune response resolved?
Danger signal reduce - innate cells lose activation signal
Antigens reduce - innate cells no longer activate T cells, b cells no longer see Ag
Immune regulatory networks develop - Treg cells and inhibitory cytokines such as IL0
- majority of T and B cells die some become memory cells
