CHAPTER 6.2 - STAGES OF B AND T CELL DIFFERENTIATION Flashcards
Derived from a multipotential progenitor cell particularly, the lymphoid-myeloid progenitor
PRO-B CELL
IL-7 is necessary
PRO-B CELL
CD 24, CD19 and CD45R are the present surface markers
PRO-B CELL
Rearrangement of genes on chromosome 14 coding for the heavy chain
PRO-B CELL
When synthesis of the heavy chain part of the antibody molecule occurs, it begins
PRE-B CELL
Mu chains in cytoplasm (IgM) are prominent
PRE-B CELL
first heavy chains synthesized
IgM
Rearrangement of genes coding for light chains
o Kappa = chromosome 2
o Lambda = chromosome 22
PRE-B CELL
1st expressed Ab on the surface: IgM
IMMATURE B CELL
Monomer
IgM
This indicates that rearrangement of the genetic sequence coding for light chains on either chromosome 2 or 22 has taken place by this time. Completion of light chain rearrangement commits a cell to produce an antibody molecule with specificity for a particular antigen or group of related antigens.
IMMATURE B CELL
CD21 (Epstein-Barr virus) and CD 35
IMMATURE B CELL
2nd on the surface: IgD
MATURE B CELL
Released in the bone marrow
MATURE B CELL
Naïve B cell – encountered not Ag
MATURE B CELL
When activated by an Ag. CD25 appears which is a receptor for lI-2 to enhance proliferation of lymphocytes
ACTIVATED T CELL
Result of Ag stimulation and transformation of activated B cells
PLASMA CELLS
B cell surface markers disappears
PLASMA CELLS
Abundant cytoplasmic Ig which are excreted in the blood stream as ANTIBODIES/ IMMUNOGLOBULINS
PLASMA CELLS
Early thymocytes lack CD4 and CD8 markers
– T helper T cells
o CD4
– Cytotoxic T cells
o CD8
Large thymocytes actively proliferate in the outer cortex under the influence of interleukin-7.
DOUBLE NEGATIVE STAGE
Rearrangement of the genes that code for the antigen receptor known as TCR begins at this stage
DOUBLE NEGATIVE STAGE
The combination of beta chain with CD3 forms the pre-TCR receptor.
DOUBLE NEGATIVE STAGE
Signaling by the Beta chain also triggers the thymocyte to become CD4 positive and CD8 positive.
DOUBLE NEGATIVE STAGE
– the complex that will serve as the main part of the T cell antigen receptor (TCR)
CD3
thymocytes express both CD4 and CD8 antigens
DOUBLE POSITIVE STAGE
rearrangement of the genes coding for the alpha chain
DOUBLE POSITIVE STAGE
CD3-αβ receptor complex (TCR) is expressed
DOUBLE POSITIVE STAGE
process takes place that allows only doublepositive cells with functional TCR receptors to survive
T cells must recognize foreign anti gen in association with class I or class II MHC molecules
class I –
CD8
class II –
CD4
Any thymocytes that are unable to recognize selfMHC antigens die without leaving the thymus.
Positive selection
process, whereby the surviving cells recognize MHC determinants along with foreign antigen.
Negative selection
The T cells are responsible for cell-mediated immunity, which involves production of cytokines that serve as regulatory factors for the immune response.
Negative selection
Have single –positive expression of the surface markers
MATURE T CELL TYPES
- CD4+ / T-helper cells
Activation of Tc and delayed hypersensitivity
Th1
Produce: interferon gamma (IFN-γ) and tumor necrosis factor-beta (TNFβ)
Th1
Activation of B cell
Th2
Produce: IL-4, IL-5
Th2
: used for IL-2 receptor in ACTIVATED T CELL
CD25
: Promotes further proliferation of lymphocytes in ACTIVATED T CELL
IL-2
Secretes lymphokines
SENSITIZED T CELL
Produced by T lymphocyte
lymphokines
maturation stages of B cells
B CELL DIFFERENTIATION
– bone marrow derived lymphocytes
B lymphocytes
precursor cell in antibody production
B lymphocytes
T CELL DIFFERENTIATION
(?)of circulating lymphocytes in the peripheral blood are (?), and these become differentiated in the thymus.
60 to 80 percent
T cells
T CELL DIFFERENTIATION
is also needed and critical for growth and differentiation
Interleukin 7
Lymphocyte precursors called (?) enter the thymus from the bone marrow.
thymocytes
T CELL DIFFERENTIATION
A significant selection process occurs as maturation takes place, because it is estimated that approximately (?) of the cortical cells die intrathymically before becoming mature T cells.
97 percent
Much more strict compared to B cell differentiation
T CELL DIFFERENTIATION
Similar to Pro-B cell with the need of IL-7
DOUBLE NEGATIVE STAGE
important when interacting with an antigen
Positive selection
takes place among the surviving double-positive T cells with functional TCR
Negative selection
Strong reactions with self-peptides send a signal to delete the developing T cell by means of apoptosis, or programmed cell death.
Negative selection
Most T cells that would be capable of an autoimmune response are eliminated
Negative selection
This selection process is very rigorous
Negative selection
Thymus checks if the double positive thymocytes are capable of reacting to self-molecules (came w/ BM function)
Negative selection
Only (?) of the doublepositive thymocytes in the cortex survive
1-3 %
– released from the thymus → peripheral blood or SLO
CD4 and CD4
has encountered Ag; another surface marker (CD25) will be visible
ACTIVATED T CELL