TBL10 Adaptive Immunity Flashcards
Children with __________ have disrupted development and maturation of functional B and T cells, resulting in defective antibody response and improper B cell activation.
SCID (Severe combined immunodeficiency)
There are two types of adaptive immunity (one mediated by each type of lymphocyte):
1)
2)
1) Humoral (B-cell)
2) Cell-mediated (T-cell)
B lymphocytes are derived from multipotent _________ stem cells in the bone marrow, through a process known as ________ to give rise to the common lymphoid progenitor cell which then differentiate and commit further to give small lymphocytes.
haematopoietic stem cells; haematopoeisis
B cells are produced in the (red/white) marrow, from the differentiation of haematopoietic stem cells before migrating into circulation and into secondary lymphoid organs.
red marrow
The development of B cells in the bone marrow begins near the ________ (thin vascular membrane of connective tissue that lines the inner surface of the body tissue) where the committed lymphoid progenitors interact with _________ cells. This leads to proliferation and maturation into immature B cells.
begins near the endosteum where the committed lymphoid progenitors interact with stromal reticular cells
B cell development begins with interaction of protein _____ on the committed lymphoid progenitor cells with the protein ___ on the bone marrow _____ cells.
Protein VLA-4/CAMs on the lymphoid progenitor cell interacting with protein V-CAM1 on the bone marrow stromal cell
B-cell development:
Upon interacting with the bone marrow stromal cells, the ______ (Stage) B-cell is formed. It then begins to experience upregulation of ___ gene (CD117), binding to ____ on the stromal cell.
This leads to proliferation and growth of early pro B-cells into ________.
Heavy chain recombination starts.
Upon interacting with the bone marrow stromal cells, the early pro-B-cell is formed. It then begins to experience upregulation of Kit gene (CD117), binding to stem cell factor (SCF) on the stromal cell.
Early pro-B cells –> Late pro-B cells
B-cell development:
Late pro B-cells then begin to transform into ____-B cells by expressing the precursor receptor of B-cells.
The ____ chain of BCR is formed at this stage, giving rise to primitive version of BCR.
pre-B cells with pre-B cell receptors
Heavy chain of BCR is formed, light chain is not.
B-cell development:
Naive B cells are formed when the ____ chain of the BCR is formed after the pre-BCR.
They will then detach from CAMs and begin to circulate.
light chain of BCR
___________ phase of B-cell development refers to the B cell generation and maturation that occur in the ________ in the absence of antigen.
whereas __________ phase refers to the activation and differentiation of B cells that occurs in the __________ organs, that require antigen stimulation.
Antigen-independent phase: occurs in the bone marrow
Antigen-dependent phase: occurs in the secondary lymphoid organs AFTER the maturation of B cells (naive)
B cells undergo _____________ to generate a huge diversity of B cell receptors. This occurs (before/after) antigen stimulation.
VDJ recombination; BEFORE antigen stimulation (i.e. they have not yet encountered the antigens)
The BCR is composed of a membrane-bound antibody (mIg) and di-sulfate linked heterodimers, Ig alpha and Ig beta, which are involved in ________.
signal transduction
The Ig alpha and Ig beta of the BCR have cytoplasmic tails that bear intracellular _______-based activation motif (ITAM) which signals downstream to induce production of cytokines or inflammatory markers.
tyrosine
The BCR has ____ heavy chains and ___ light chains, both of which have variable and constant regions.
2 heavy and 2 light chains
The ____ region on the BCR is responsible for antigen binding and has a large variability.
variable
Kappa light chain is coded for by gene on chromosome ___; lambda light chain is coded for by gene on chromosome ___ and heavy chain is coded for by gene on chromosome ___.
Kappa light chain: chromosome 2
Lambda light chain: chromosome 22
Heavy chain:
chromosome 14
VDJ recombination (BCR gene rearrangement) occurs in the _______ during B cell maturation.
bone marrow
Mature B cells emerging from the bone marrow already have the receptors ___ and ___ on their surfaces.
IgM and IgD
(i.e. IgM first followed by IgD when mature B cell exits bone marrow)
Fully mature B cells co-express BOTH.
____ signals B cells that are to be activated in response to repetitive multivalent antigens, and bind to basophils and mast cells to produce antimicrobial factors.
IgD
The heavy chain gene starts rearranging at the (stage)-B cell during B cell maturation.
It finishes rearrangement by (stage)-B cell.
Light chain gene starts rearranging during (stage)-B cell and finishes by the time the immature B cell is formed.
Heavy chain gene starts rearrangement at early pro-B cell, ends by large pre-B cell.
Light chain gene starts rearrangement by small pre-B cell, and ends by immature B cell.
The immature B cell only has Ig__ whereas the mature B cell has both Ig_ and Ig__.
Immature B cell: IgM only
Mature B cell: both IgM and IgD
B cells also express various cell surface proteins during maturation. (at different stages of development)
CD19, CD25, Kit, IL7 (growth and proliferation of B cells)
The antigen-dependent phase occurs in the _________ and the basis of adaptive immune response is ______ selection of B and T lymphocytes.
secondary lymphoid organs; clonal selection
B cells either differentiate into ______ cells which circulate in the body for a long time, forming the basis for immunological memory; or _______ cells which secrete huge amounts of antibodies to provide immune response.
memory cells and plasma cells
Naive B lymphocytes cannot be activated by antigen alone. They are either activated by microbial constituents or ______ cells.
T-helper cells
Microbial constituent-mediated activation only leads to the production of ____. This is thymus independent with no production of _______.
IgM; no production of memory B cells
T-helper cell-mediated activation of B lymphocytes leads to the production of all Ig classes and _______ cells.
memory cells
In T-helper cell-mediated activation, B cells act as _________ cells which internalise the antigen and process it into peptides to present them on the MHC class __ molecules to T-cells.
antigen presenting cells; MHC Class II molecules
T helper cells recognise the antigen and secrete _______ that induce the entry of B cell into the cell cycle, undergoing clonal expansion. B cells then differentiate into plasma or memory B cells.
Lymphokines
IL2, IL4 and IL5
Activated T cells expresses ____ receptor, which binds to the ____ on naive B cells.
CD28 on T cells bind to the ___ on naive B cells, providing co-stimulation for T helper cells.
CD40 ligand on T cells bind to CD40 on B cells;
CD28 on T cells bind to B7 on B-cells for costimulation
Binding of antigen to the BCR will trigger B cell movement to the interface of the secondary lymphoid organ between the follicle and the T cell zone to interact with ______.
T-cells
B-cells, during proliferation at the periphery of the follicle, will differentiate into 3 main types of B cells:
1) Plasma cells (effector cells)
2) Memory B cells
3) Germinal center B cells
Germinal center B cells continue to divide rapidly, hypermutate their BCR variable regions and interact with __________ cells bearing antigen and TFH cells.
GC B cells then decide between proliferation and death depending on their BCR affinity for foreign and self-antigens.
interact with dendritic follicular cells (presents intact antigen to B cells)
________ affinity selection of B-cells is when the foreign antigen is displayed in small amounts on follicular dendritic cells bound with complement C3d.
Positive affinity selection
