Adaptive immunity 1 Flashcards
Where do lymphocytes come from and how do they differentiate?
Multipotent stem cell in bone marrow -> common lymphoid progenitor cell –> differentiate into B cells, T cells or NK cells.
Migrate to thymus -> mature into CD4 or CD8 cells. CD4 T helper cells can further sub-divide based on cytokines they produce -> Th1, Th2, Th17 + regulatory T cells.
What are the differences between T and B cells?
B cells (except plasma cells) express protein CD19 T cells express CD3 -> divide into CD4 or CD8
Which cells guide T and B cell maturation and what are their features?
development occurs in specialised micro-environments.
B cell maturation guided by stromal cells in bone marrow.
T cell maturation driven by interactions with stromal cells in specific compartments of cortex + medulla of thymus.
B cells produced throughout life in bone marrow.
T cells produced in thymus -> involutes after puberty. reduces capacity for adults to produce new T cells but can be derived from liver + intestine.
Life expectancy of naïve B cell is approx 5 days.
Naïve T cells lasts years.
B + T cells display vast diversity of antigen receptors.
What are the stages of development for B cells?
Originate from common lymphoid progenitor in bone marrow.
Pro-B cell emerges + has undergone genetic rearrangement of its DJ segments -> differentiation to pre-B cells -> first expression of pre B cell receptor on cell surface.
Immature B cells undergo positive + negative selection –> only positively selected B cells released into peripheral blood.
Failure at either step -> apoptosis
What are the stages of development for T cells?
T cell precursors migrate to thymus -> 4 stages of differentiation (express neither CD4 nor CD8).
DN4 cells express pre T cell receptor -> transiently go through immature single positive phase before becoming double positive for CD4 + CD8 -> undergo positive + negative selection -> released into peripheral blood as CD4 or CD8 T cells.
Summarise the common stages of B and T cell development
1st phase: generation of unique antigen receptor through genetic rearrangement of V(D) + J segments.
2nd phase: refinement of antigen receptor repertoire. receptor challenged with self antigen. cells that recognise “self” selected for further development (positive selection). receptors that bind too strongly to self antigen are deleted (negative selection).
3rd phase: encounter with foreign antigen in lymph nodes or spleen -> clonal selection + expansion –> development of effector + memory lymphocytes.
What are the B cell antigens?
B cells, unlike T cells, can recognise native antigen + sometimes produce full immunological response without T cell help.
But for majority of antigens, B cells need to interact with T cells to become fully activated.
Thymus independent -> polysaccharides, lipids or nucleic acids characterised by repeating motifs, allow for B cell receptor cross-linking, don’t need helper T cells.
Thymus dependent -> majority, proteins, don’t contain repeating epitopes. depend on helper T cells for antibody production.
Outline T cell independent responses?
Simple, repetitive antigens
Secrete mostly IgM antibodies
Modest affinity
No memory (plasma cells are short-lived)
B cells activated by direct BCR cross-linking
B cells still require second activation signal -> often via TLR receptor engagement.
Naïve B cells express both IgM + IgD on surface. Activation with T-independent antigens -> B cell commonly secrete IgM. not capable of class switching to produce different immunoglobulin isotypes as it requires T cell help.
Compare how antigens are recognised by T cells and B cells
B + T cells generate diverse array of antigen receptors via V(D)J recombination.
B cell receptor -> 2 heavy chains, 2 light chains, “Y shaped” antigen receptor on surface, can be secreted as antibody.
T cell receptor -> alpha chain + beta chain heterodimer.
Antigen engagement of both BCR + TCR results in cell signalling regulated by B cell co-receptor complex (Igalpha, Igbeta) + CD3 complex respectively.
B cells can recognise native antigens.
T cells can only bind processed peptide antigens presented to them in context of MHC.
Give examples of the reciprocal ligand/receptor expression interaction between B cells and T cells
CD40 on B cell + CD40 ligand on T cell
CD80 / CD86 on B cell + CD28 on T cell
Outline the T-dependent B cell response
Via 3 signal process:
1st -> antigen binds to BCR. antigen internalised + processed into peptides in lysosomes -> bound to MHCII -> MHCII/antigen complexes shuttled to cell membrane + displayed on cell surface. CD4+ T cell receptor recognises antigen + binds to MHCII -> 1st activation signal to T cell.
T cell signal 2 -> CD80 and/or CD86 on B cell binds to CD28 on T cell -> increased T cell activation + up regulation of CD40 ligand on surface -> B cell signal 2.
Signal 3 -> T cell produces more cytokines, further activating B cell.
B cell proliferates + undergoes somatic hypermutation to improve affinity of B cell receptor for antigen -> production of immunoglobulin-secreting plasma cells + memory B cells.
