16 - Immunological Memory Flashcards
Linked recognition
T cells and B cells must recognise antigens contained within the same molecular complex in order to interact
Immunological memory
- Does not require repeated exposure to original antigen
- Memory cells may be sustained by cytokines produced in response to infection with other, unrelated pathogens
Naive T cells in lymph nodes
Naive T cells activated in the T cell rich area of lymph node by DC become follicular T helper cells, express CXCR5 and move towards B cell zone where they attach to activated B cells via linked recognition
Primary focus
- Formation takes about 5 days
- B cells activated in the primary foci move to adjacent follicles to become germinal centre (GC) B cells, or the medullary cords of LN to become plasma cells in situ
- Surviving GC B cells that have undergone class switching and affinity maturation will become either high affinity memory B cells or long lived plasma cells
Plasma cells in situ
Secrete antibody for a few days, then undergo apoptosis
high affinity memory B cells/long lived plasma cells
Become resident in bone marrow where they continue to secrete antibodies into the blood for months - years
Memory B cells
- Divide very slowly
- Express surface Ig but do not secrete antibody
- May differentiate into plasma cells, allowing long term production of antibody
Repeated immunisation
Leads to increasing affinity of antibody due to somatic hypermutation and selection by antigen in germinal centers
Memory B cells during secondary exposure
During secondary exposure to antigen, antibodies persisting from primary immune response immediately bind to pathogen to initiate phagocytosis and complement pathway
Primary response
- Following activation of naive cells
- Consists of antibodies derived from diverse population of precursor B cells specific for different epitopes
- Low affinity with few somatic mutations
- Isotype is IgM class switching to IgG
Secondary response
- Mediated by memory cells
- Derived from high affinity B cells which have undergone significant clonal expansion
- High affinity antibodies with extensive somatic mutation
- Isotype is IgG and IgA
- More intense and effective response
How do naive T cells home to lymph nodes
Through binding of L selectin (CD62L) to sulphated carbohydrates (e.g. CD34) displayed on surface of HEV
How can naive T cells be identified
CD45RA
How can effector T cells be identified
CD45RO
Receptors expressed on the surface of effector T cells and their ligands
- Lose expression of L selectin
- Express LFA-1 which binds to ICAM-1
- Express VLA-4 which binds to VCAM-1
Signals required for T cell survival
Restimulation with IL-7, IL-15 and with self antigens presented by MHC
what do naive T cell differentiate into
Effector T cell or memory T cell
Why are elderly more susceptible to infection
- Capacity to produce naive cells is lost with age, must rely on memory cells
- Problem when new strain arises
Memory T cells
- TCR does not undergo class switching or somatic hypermutation
- Identified via expression of cell surface molecules
Marker of T cell activation
CD69
Marker of activated T cell
CD44
Two types of memory cells that CD4 and CD8 cells differentiate into
- Effector memory cells (Tem)
- Central memory cells (Tcm)
Effector memory cells (Tem)
- Rapidly differentiate into effector T cells after restimulation, and secrete large amounts of IFN-gamma, IL-4, IL-5
- Lack chemokine receptor CCR7
- Express high levels of integrins such as LFA-1
- Specialised for rapidly entering inflamed tissues
CCR7
(required for entry of naive T cells into HEV, therefore Tem cells are excluded from lymph nodes
Central memory T cells (Tcm)
- Express CCR7 and can enter lymphoid tissue, as do naive T cells
- On stimulation with antigen, rapidly lose expression of CCR7 and differentiate into Tem cells
Further differentiation of Tem cells
Further differentiate into Th1 or Th2 cells, determining the cytokines these cells produce
CD4 T cells
- Promote the maintenance of CD8 memory cells
- In absence of MHC class 2 proteins, CD4 T cells fail to develop in thymus
Tissue resident memory (TRM) T cells
- Major immune compartment that surveys peripheral tissues for reinfection
- Activated CD8 and CD4 T cells enter dermis and other peripheral tissues (via CXCR3)
- induction of CD69 expression on T cells leads to their retention in dermis
Original antigenic sin
When individuals who have been infected with one variant of influenza virus are infected with a second or third variant, they make antibodies only against epitopes that were present on the initial virus
Tools for measuring antigen specific T cells
- Tetramers are reagents used in flow cytometry to identify and track antigen specific T cells
- The combination of MHC class 1 and antigen peptide must be known (synthesised)
- This MHC/peptide complex is labeled with a fluorophore, and added to the T cells being analysed
- Attachments of the tetramer to a T cell indicates the presence of an antigen specific T cell
- Detection of other markers (e.g. CD45RO) indicates effector or memory phenotypes
