Antigen recognition by T cells Flashcards
What is the difference between where B and T cells work?
Bcells- remove pathogens outside body cells
T cells- remove pathogens inside body cells
What things do T cells remove?
intracellular
virus
bacteria
malignant cells
How do B cells recognise antigens?
directly through their surface immunoglobin receptors
What happens when a B cell gets activated?
Proliferation- make lots of identical B cells that can recognise the antigen
differentiate to plasma cells or memory cells
How do the antibodies work to get rid of the microbes?
neutralization- prevents binding antogen to receptor
opsonization- more likely phagocytosis
complement activation- lysis of microbes
What are the types of T cells?
alpha beta T cell receptor T cells
gamma-delta T cell receptor T cell
What kind of antigens do alpha beta T cell receptor T cells recognise?
peptide antigens -they need to be cell bound and bound to the major histocompatibility complex of antigen presenting cells (ie the peptides cannot be soluble)
What kind of antigens do gamma-delta T cell receptor T cells recognise?
non-peptide antigens
recognize mostly lipid antigens that are bound to different types of MHC molecules
What do antigen presenting cells do?
process antigens into peptides (onlny alpha beta T cell receptor T cells)
What do the peptides do?
- bind to MHC molecules of the antigen presenting cells
- peptide-MHC complex is presented on the surface of the antigen presenting cell
- t lymphocytes scan it with their receptors
- if they recognize the peptide MHC-complex, they get activated and proliferate
What do CD4+ T helper cells recognise?
CD4+ T helper cells recognize peptides displayed by MHC II molecules
What do CD8+ T helper cells recognise?
and CD8+ cytotoxic T cells recognize peptides displayed by MHC I molecules (peptides combined with MHC I)
What is MHC restriction of antigen recognition by T cells?
T cells can only see antigens only when combined with MHC
What are antigen presenting cells?
dendritic cell
macrophage
b cell
How do CD8+ T lymphocytes work?
need to be activated
when activated, they can recognise antigens on ALL nucleated cells
fight viruses e.g. hepatitis
What does naive mean?
havent been activated
are still in the secondary lymphoid organs
How are dendritic cells antigen presenting cells?
these are the only cells that can activate naïve T cells (CD4+ or CD8+)
How are macrophages APCs?
present antigens to previously activated naive T cells and activate them (activate effector T cells)
usually these are Th1 cells
this also leads to co activation of macrophages which allows them to kill the antigen
How are B cells APCs?
present antigens to previously activated naïve T cells and activate them (activate effector Tcells)
occurs in germinal centres in the lymph nodes and spleen
leads to co activation of B cells, and leads to production of antibodies
What is a germinal centre?
areas of B cell proliferation
Where are dendritic cells present?
skin, mucosa, airways, gut
What do dendritic cells detect?
microbes present in tissue and capture them
Where are naive T cells?
in spleen and lymph nodes
What does a dendritic cell do?
- detect pathogen
- take up by phagocytosis
- transport microbe from tissue to lymph node or spleen (where naive T cells are- antigens need to be presented here)
once pathogens are detected, they are taken up by phagocytosis - whilst transporting- they process microbes into peptides and present antigens to naive T cells
Why do dendritic cells transport microbes to lymph nodes/spleen?
this is where naive T cells are
antigens need to be presented here
What is the priming of the adaptive T cell mediated immune response?
is the link between the innate and adaptive immune system
What are the 2 signals needed to activate the T cell?
Signal 1= not enough to activate T cell
Signal 2= stong costimulatory signal by B7 family, CD80 and CD86 ACTING on CD28 receptors on T cells
THEN T cell activated and proliferates
What is the third signal needed to help T cells differentiate after being activated?
cytokine release=
Th1= bacterial infection (IL12)
Th2= parasitic infection (IL4)
CD8+ cytotoxic lymphocytes= viral infection
What does Th1 cooperate with?
macrophages- to eliminate bacteria
What does Th2 cooperate with?
B cells and mast cells- to eliminate parasites and allergies
What do macrophages do?
Macrophages phagocytose microbes and present antigens to effector CD4+ T cells in particular Th1 cells
What does IFN-gamma leads to a switch to?
IgG
What does IL4 lead to a switch to?
IgE
What are cytotoxic CD8+ T cells specialised to do?
-recognize viral antigens and mutated proteins (from cancerous cells) presented in combination with MHC I – eliminate these cells that are infected with a virus or are malignant
How does a T cell recognise antigen?
T cell receptor recognises a complex (MHC MOLECULE PLUS PEPTIDE FROM PATHOGEN)
Tcell has groves that allows it to interact with the amino acid residues
What is the structure of the T cell receptor?
2 chains
most common T CEL= alpha and beta
Less common T cell= gamma and delta
each chain has constant and variable domain
3 hypervariable domains (contact with antigen peptides)
How are different T cell receptors generated?
rearrangement of gene segments - cutting light and heavy chain genes by RAG (in immunoglobins)
What is MHC 1?
- these bind and present peptides to CD8+ T cells
- composed of an alpha chain and a short beta 2 macroglobulin chain
- present in all nucleated cells
What is MHC II?
- bind and present peptides to CD4+ T cells
- they are composed of an alpha chain and a beta chain
- present on only the professional antigen presenting cells like dendritic cells and macrophages
MHC present antigens to what?
alpha beta T cells
not gamma delta
What are human MHC molecules also called?
HLA
What is the function of CD4 and CD8 receptors?
make sure that MHC I binds to cytotoxic cells, and MHC II binds to helper cells
What are CD4 and CD8 receptors coupled to?
tyrosine kinase receptors
they decrease the threshold for T cell activation as they are coupled to tyrosine kinases−and thus the T cells need to make contact with fewer peptide-MHC complexes
How do you eliminate exogenous bacteria?
- phagocytes and eliminate
2. antibodies eliminate (neutralisation, opsonisation, and complement activation)
How is an antigen presented to CD4+ T cells?
- bacteria taken in phagosome
- fuse with lysosome- break down bacteria
- put peptides from bacteria with MHC II (so CD4+ can recognise)- MHC II (protein exported fromgolgi fuses with the phagolysosome)
- Low pH in phagolysosome so invariant chain breaks down but CLIP remains (fragment on chain) in groove
- another MHCII molecule (HLA- DM) has high CLIP affinity and takes it
- now groove is free peptide from bacteria can bind
- when peptide fits, MHCII is stabilised
- travels to plasma membrane
- CD4 recognises it
How are viruses taken up?
Proteins derived from virus are tagged with ubiquitin so that they can be recognized by lytic complexes called proteasome
What doe proteasomes do?
proteasomes take up ubiquitinated proteins and breaks them down into peptides
there will be peptides from these viral proteins present in the cytosol•these peptides need to get into the endoplasmic reticulum where the MHC I is synthesized
What is TAP?
transporter in the membrane of the endoplasmic reticulum
which takes up these viral peptides from the cytosol and transports them into the lumen of the endoplasmic reticulum
Why cant viral proteins bind to MHC II?
the invariant chain blocks the groove for MHC II, and thus viral proteins in the ER cannot bind to MHC II
MHCI doesnt leave ER until binds to viral protein
What can mycobacterium tuberculosis do?
block expression of MHC II
What does Neisseria meningitidis do?
lowers expression of MHCI and MHCII
What does herpes simplex virus do?
produces proteins which bind to and inhibits TAP transporters which transport viral peptides into the ER to bind to MHC I
What does adenovirus do?
produce proteins which binds to MHC I molecules and prevent it from leaving the ER to the plasma membrane
