L12- Immunological Memory Flashcards
What is the immunological memory for patients who received vaccinia vaccine (cowpox) for the treatment of smallpox?
Vaccinia-specific T cell and antibody responses last for up to 75 years after original immunisation.
Immunological memory does not require repeated exposure to the original antigen so how is it sustained in the body for so long?
Memory cells may be sustained by cytokines produced in response to infection with other, unrelated, pathogens
Only T helper cells are involved in humoral immune response. T or F?
True
Only the T cell dependent antigens led to cell mediated immunity. T or F?
True
Can the humoral immune response eliminate tumour cells?
No. Only cell mediated immunity can eliminate tumor cells and thus can provide immunity against cancer
How is the humoral immune response mediated?
Antigen binds to the B cell receptor and:
- sends a signal into the B cell to activate it
- Is internalized and processed into peptides that activate helper CD4+ T cells
- Signals initiated by the bound antigen and from the helper CD4+ T cell (in the form of the co-stimulatory CD40 ligand CD40L, and cytokines) induce the B cell to proliferate and differentiate into plasma cells secreting specific antibody or memory cells
What are the 3 main functions of the antibody secretion by plasma cells?
Neutralisation- antibody prevents bacterial adherence
Opsonization- antibody promotes phagocytosis
Complement activation- antibody activates complement, which enhances opsonization and lyses some bacteria
What is linked recognition?
B cells can only be activated by helper CD4+ T cells that respond to the same antigen– this is called linked recognition
What is the role of the helper T cell in humoral immunity?
Helper T cells s-mulate the prolifera-on and then the differentiation of antigen‐binding B cells
The CD4+ T cell must have been activated previously by a dendritic cell (DC) that ingested, processed and presented that same antigen. T or F?
True
Naïve T cells activated in the T cell‐rich area of LN by DC become _________ express _______ and move towards B cell zone where they attach to activated B cells via linked recognition
follicular T helper cells
Expressing CXCR5
How long does clonal expansion take?
~5 days
Explain in detail how memory cells are created
- Naïve T cells activated in the T cell-rich area of LN by DC become follicular T helper (F TH ) cells, express CXCR5 and move towards B cell zone where they attach to activated B cells via linked recognition
- A primary focus of clonal expansion forms (takes about 5 days).
B cells activated in primary foci move to adjacent follicles to become germinal centre (GC) B cells, or the medullary cords of the LN (or the red pulp of the spleen) where they become plasma cells in situ that secrete antibody for a few days, then undergo apoptosis
• 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, which become resident in bone marrow where they continue to secrete antibodies into the blood for months-‐years
Memory B cells may differentiate into plasma cells, this would allow long-‐term production of antibody after the original antigen was cleared from the host
How can you tell memory B cells apart from plasma cells?
Memory B cells divide very slowly if at all, and express surface immunoglobulin but do not secrete antibody (or do so at very low rate)
Primary response (following activation on of naïve cells) consists of antibodies made by plasma cells derived from a diverse population of precursor B cells specific for different epitopes of the antigen and with B cell receptors with a wide range of affinities for the antigen. These antibodies are of low affinity overall, with few somatic mutations.
What happens at a secondary response?
The secondary response (mediated by memory cells) derives from high-affinity B cells which have undergone significant clonal expansion.
• Memory B cell receptors and antibodies have high affinity for the antigen and show extensive somatic mutation – the quality of the antibody response is radically altered such that it is more intense and more effective.
Where do memory B cells first arise from and where do they migrate to?
Arise from the germinal centre reaction
• Populate the spleen and lymph nodes as well as circulating through blood
Memory B cells express markers from naïve B cells. What are they?
– CD27: binds CD70, expressed on dendritic cells
– Increased MHC class II
– Increased B7
• Increased MHCII and B7 allows memory B cells to initiate interactions with helper CD4+ T cells at lower doses of antigen than naïve B cells – B cell differentiation and antibody production start earlier after antigen recognition than in the primary response
Memory B cell phenotype: CD19+CD27+
What class switching occurs with memory B cells?
Have switched from IgM to IgG, also IgA and IgE
Naïve T cells - T cells which developed in the bone marrow, matured in the thymus, and have not yet encountered the antigen that can be recognized by their T cell receptor (their cognate antigen) ‐ home to lymph nodes through the binding of….
L-selecitin (CD62L) to sulphated carbohydrates (such as CD34) displayed by various proteins on the surface of high endothelial venules (HEV)
After encounter with antigen, many differentiated effector T cells lose expression of L‐selectin and become….
They than leave lymph nodes 4-5 days later and now express …… and increased levels of ………
lose expression of L‐selectin and become CD62L–ve.
They than leave lymph nodes 4-5 days later and now express VLA-4 and increased levels of LFA-1
The molecules VLA-4 and LFA-1 on effector T cells bind to what?
These molecules bind with ICAM‐1 and VCAM‐1, respectively, on vascular endothelium at sites of inflammation.
The isoform of the naïve T cell marker CD45RA. What is the isoform of effector cells?
What does this change do?
CD45RO
The change of isoform sensitises effector T cells to stimulation by specific antigen.
- The effector T cell phenotype is CD45RO+CD62L-
Why do effector T cells change there surface molecules?
Allows them to home in on sites of infection.
Naïve T cells have L-selectin (CD62L) to bind to sulphated carbohydrates on the lymph node surface.
After encounter with antigen, many differentiated effector T cells have to leave the lymph node so must remove the anchor. They become CD62L-ve. They express VLA-4 and increased levels of LFA-1.
These effector T cells are now able to bind to ICAM-1 and VCAM‐1, on vascular endothelium at the sites of infection.
Effector cells also express CD45RO which sensitises effector T cells to stimulation by specific antigen.
The T cell receptor (TCR) does not undergo class switching or somatic hypermutation. Instead what happens?
Instead, memory T cells are often identified via expression of cell surface molecules.
