Generation of Diversity in the T-Cell Repitoire Flashcards
T and B cells recognise what differently?
antigens
what does antigen processing generate?
antigenic peptides
where can antigen processing take place?
lysosomes, and there is also a non-lysosomal mechanism of antigen processing
when can the TCR bind to antigenic peptides?
only when the peptides are in complex with MHC molecules on APC’s
how many types of MHC are there?
2 types of MHC (I and II)
-they interact with CD8 or CD4 T cells
what is an antigen?
any molecule that can bind specifically to an antibody
antibodies are normally immunogenic - will initiate an immune response in the host
what is an epitope?
a small portion of an antigen (could be a small peptide), it is a target for TCR’s and antibodies
adaptive immune reactions occur to specific epitopes as opposed to the entire antigen itself
immune reactions occur to specific epitopes and infection can induce polyclonal T or B cell response
how do B cells and T cells differ in the way they recognise antigens?
T cells cannot recognise native antigens – they must be processed into peptides and presented on surface of APC’s by MHC molecules
B cells will recognise and process native antigens, and undergo clonal expansion
B cell clonal expansion?
B cells proliferate and make multiple clones of the same cell, which all produce the same antibody
if an APC is fixed what is the consequence?
it will not induce cell activation
what do uptake mechanisms do?
the direct the antigen into intracellular vesicles for exogenous antigen processing
examples are:
- phagocytosis
- pinocytosis
- membrane Ig medicated uptake
- complement receptor mediated uptake
- Fc receptor mediated phagocytosis
Which immune cells recognise and process antigen?
APC’s!!!!
monocytes
macrophages (terminally differentiated monocytes)
dendritic cells
B cells
macrophages vs dendritic cells?
both rare in peripheral blood - enriched in mucosal tissues
highly phagocytic cells – induce strong T-cell responses and inflammation. Important for protection against Mycobacterium tuberculosis
Macrophages better-equipped to kill pathogens (higher NO production)
DCs better at migrating to lymph nodes (via CCR7) and presenting antigen to T- cells
how are dendritic cells specialised for their function?
these cells have has multiple dendrites - extensions of the cell membrane which increase the cell surface interaction with the environment
these cells are enriched in mucosal tissues because these are exposed to the environment
B-cells
Highly abundant in blood and mucosal tissues
Receptor-mediated internalisation of antigens, as opposed to phagocytosis
Primary function is making antibodies, but still very good at antigen presentation
Possibly main inducer of T-cell immune response to pathogens, such as Neisseria meningitidis
Endogenous antigen processing - the steps
LHS slide 17
UPTAKE
Antigens/pathogens already present in cell cytoplasm
DEGRADATION
Antigens undergo proteolytic degradation in cytoplasm
ANTIGEN-MHC COMPLEX FORMATION Peptide antigens transported to ER, enter via TAP and loaded onto MHC class I molecules
PRESENTATION
Transport and expression of antigen-MHC complexes on the surface of cells for recognition by CD8 T cells
eliminated by death by cytotoxic T cells
why do we need endogenous antigen processing - isn’t exogenous processing sufficient
Macrophages have well-developed lysosomal systems
They are specialised for motility, phagocytosis and the introduction of particles to the lysosomal system
Most cell types do not have lysosomal systems developed as well as macrophages
Viruses can infect most cell types
A non-lysosomal mechanism to process antigens for presentation to T cells is required
Non-lysosomal antigen processing requires what?
protein synthesis
antigens from inactive viruses and infectious viruses - how are they processed?
ANTIGENS FROM INACTIVE VIRUSES ARE PROCESSED VIA THE EXOGENOUS PATHWAY
ANTIGENS FROM INFECTIOUS VIRUSES ARE PROCESSED VIA THE ENDOGENOUS PATHWAY
Exogenous antigen processing? (RHS slide 17)
antigens are endocytosed into the cell, in the endosome they are broken down into peptides
loaded onto MHC class II molecules, recognised by CD4 T cells
eliminated by antibodies and phagocyte activation by T helper cells
comparison of MHC class I and II?
class I expressed on all nucleated cells, class II expressed on APCs and activated T-cells
class I binds short peptides, class II binds long peptides
class I presents to CD8 T cells, II presents to CD4 T cells
class I presents antigens from the cytosol, class II presents antigens from phagosomes and endosomes
The T-cell receptor:
- what does it bind to?
- how does it exist?
T cell receptor binds to peptide MHC complexes, cannot recognise peptide alone
Exists in a TCR complex with accessory molecules such as CD3
T cell receptor and B cell receptor - similarities and differences
Similarities to B cell receptor/antibody:
Belongs to Ig superfamily
Fab-like fragment (peptide binding site for antibody)
Large diversity
Single specificity
Differences to B cell receptor/antibody:
Lower affinity Cannot be released (remains on cell surface) No Fc fragment, so no cellular functions Single binding site rather than 2 B cell receptor/Ab: 5 classes T cell receptor: 2 classes
Mechanisms which generate B-cell and T cell receptor diversity?
before antigen stimulation: somatic recombination
after antigen stimulation (BCR only): somatic hypermutation
