Cells of the adaptive immune response Flashcards
Which cells give rise to the cells of the adaptive immune system?
Self-renewing multipotent haemaotpoietic stem cells
Which developmental pathway leads to the development of the cells of the adaptive immune system?
Lymphoid developmental pathway
What are the two features of the adaptive immunity?
Shows immunological memory
Highly antigen specific
What are the two types of lymphocytes?
B cells
T cells
Features of B cells
Differentiate further into plasma cells
Release antibodies
Develop in the bone marrow directly from the common lymphoid progenitor
Features of T cells
Stem cells leave the bone marrow and travel via the blood to the thymus to differentiate into T cells
How can we distinguish between B and T cells
Via cell markers
What are the T cell markers?
TCR - for antigen and MHC, recognises antigen
CD3 - all cells, interact with TCR and send intracellular signals upon activation
CD4/8 - once the T cells have matured
What do CD4 T cells interact with?
MHC II
What do CD8 T cells interact with?
MHC I
What are the B cell markers?
BCR - B cell receptor for antigen, transmembrane version of antibody
IgA and IgB - similar to CD3 on T cells
CD19
How can cell markers be useful?
Help differentiate between cells in a tumour - if cancer expresses CD19 on its surface = B-cell derived
Look for immunodeficiencies
Specificity of lymphocytes
Lymphocytes are specific
One lymphocyte per antigen
Since there are so many antigens = antigen-specific lymphocyte number is low at first
Not enough present to eliminate the pathogen
To overcome the problem, once lymphocytes are activated by specific antigen they
Proliferate - enough cells to fend off infection and memory cell created
What are the two types of TCR present on T cells?
Alpha beta TCR
Gamma delta TCR
What is TCR type is more common?
Alpha beta TCR
What is the role of alpha beta TCRs?
Better understood than gamma delta
Recognise processed antigens in form of peptide on MHC
Which T cell types contain alpha beta TCRs?
Helper
Regulatory
Cytotoxic
What is the role of the gamma delta TCRs?
Directly bind to antigens
Kill infected or stressed cells
Involved in immune regulation
Recognise lipids present on CD1
What is the role of the CD4/8 surface molecules?
Establishes bond between TCR and MHC
Binds to MHC non-poplymorphic parts
Which cell types drive differentation of T cells?
Dendritic cells
What is the name of a T cell that has not differentiated yet?
Th0 cells
Process by which dendritic cells activate T cells
DC use TOLL like receptors to recognise PAMPs
DCs can determine whether a pathogen is gram positive or gram negative
In response to what PAMPs bind, dendritic cells will
Change expression of molecules on CSM
Produce different concentrations of cytokines
What types of cells do Th0 cells become upon activation with cytokines?
Th1 - cell mediated immunity, help CTT and macrophages
Th2 - humoral immunity, help the production of cytokines, help B cells in the production of antibodies
What is the relationship between Th1 and Th2 cells?
Can inhibit each other
By production of cytokines
What is the relationship between Th1 cells and macrophages?
Macrophages interact with Th1 cells to activate them
Th1 cells interact with macrophages to stimulate them
Bidirectional stimulation
How do macrophages activate Th1 cells?
Via the release of cytokines like IL-12
Via cell-to-cell contact using CD40 receptors -> CD40 on macrophages interact with CD40L on Th1 cells
Peptide presentation via MHC on macrophages binds to TCR on Th1
How do Th1 cells stimulate macrophages?
Release of cytokines like gamma interferon
What is the role of cytotoxic T cells?
Kills virus-infected and unhealthy cells by inducing apoptosis
How do cytotoxic cells recognise target cells?
TCR binds to peptide sequences on MHC I
What are the two mechanisms by which CTT cells destory target cells?
Fas/ Fas ligand mechanism
Granzyme perforin mechanism
Describe the Fas/Fas ligand mechanism
Fas is expressed on CSM of infected cells
Fas Ligand is expressed on CD8 T cells
Fas molecule releases apoptotic signal on binding with Fas ligand
Describe the Granzyme perforin mechanism
Perforin molecules made by CD 8+ T cells produce pores on the surface of infected cells
Granzymes insert into the cell through these pores and set up state of apoptosis
How does apoptosis affect cells?
Causes membrane alterations in infected cells that are recognised by phagocytic cells
How do B cells recognise antigens?
Recognise antigen directly
B cells can be helped in seeing the antigen by follicular dendritic cells
DC have Fc and complement receptors that allows to bind to immune complexes of antigen and antibody
DC shows antigen in these immune complexes to the BCR - not essential, but enhances
What features in B cells allows them to make lots of antibodies?
Contain lots of RER
What is the difference in antigen presentation by MHC I and MHC II molecules?
MHC I - express enodgenous antigens. Assembly and presentation of peptides (8-10 a.a)
MHC II - express exogenous antigens. Assembly and presentation of peptides (15 a.a)
How do MHC I molecules present endogenous antigens?
Proteasome break down proteins of antigen and form peptides
MHC molecules are made in the ER
Proteasome is made in the cytoplasm
Joining the two together via TAP1 and TAP2
MHC I and peptides transported through the trans-Golgi vesicle to the CSM
How doe TAP proteins work?
Transporters associated with antigen processing
Form pores in the membrane of the ER and take up peptides from the cytoplasm
Describe the process of exogenous antigen presentation by MHC II
Molecules/ proteins or whole organisms are taken up from outside the cell
Via phagocytosis or endocytosis
Molecules end up in endosomes - contain proteolytic enzymes that break down proteins
MHC II taken into vacuole which fuse with the endosome containing the antigen
In what form is MHC II present in the vacuoles?
MHC II is bound to an invariant chain that stops it from binding to peptides in the ER
When vaculoles with the MHC bind with the endosome containing the antigen, the invariant chain is removed to except a small residue called CHIP which remains on MHC II
Antigen replaces CLIP and fuses with cell membrane
What is the name of MHC in humans?
HLA
Which HLA molecules are found on cells of the body?
HLA-A, -B, -C
Which HLA molecules are found on cells of the immune system?
HLA-DP, -DQ, -DR
