Lymphopoiesis-Chapter 8

What must functional T cells be able to do?

Functional T cells must be able to recognize foreign antigen along with MHC molecules.

Why can mature lymphocytes be T cell and B cell?

Gene rearrangement and site of formation

What does the variable region of the antibody depict?

Gives the antibody its unique fingerprint to pair with a homologous antigen

B cells are usually larger or smaller than T cells?

T cells are small and B cells are large

Where are lymphocytes produced?

in the bone marrow B-cells in humorous, T-cells are cell mediated but mature in Thymus

Where does antigen- dependent activation of B cells take place?

in the primary follicles of peripheral lymphoid tissue

Why are CD40 and MHC II important?

interaction between B cells and T cells

What happens to a B cell when it is stimulated by an antigen? What is the half life of these cells?

it undergoes transformation to a blast stage, which eventually forms memory cells and antibody-secreting plasma cells. This is known as "antigen dependent phase" of development. 6 wks

Is a small or large lmpphcoyte most common?

small

Where do immature B cells go to develop?

the spleen (marginal zone B cells)

Lymphocytes in secondary tissue organs travel through the tissue and return to the bloodstream by way of the .....

thoracic duct

Where do T cells develop there identifying characteristics?

thymus

Where do T cells differentiate?

thymus

Differentiation of a pro- B cell into Pre- B cells take happens when?

upon successful rearrangement of heavy-chain genes.

Where is CD25 found and what does it do?

•Activated B cells exhibit identifying markers, including CD25, which is found on both activated T and B cells and acts as a receptor for interleukin- 2 (IL-2), a growth factor produced by T cells.

Thymocytes are called double positive cells when what?

•At this second stage, when thymocytes express both CD4 and CD8 antigens, they are called double-positive cells.Only double-positive T cells with functional TCR receptors will survive this positive selection process

Plasma cell

•B cells that have transformed to produce antibodies •Function: the synthesis and excretion of antibodies •Not normally found in the circulating blood •Reside in the lymph nodes, BM, GI tract •Arise at the end of B cell differentiation

Cytotoxic T cells

•CD 8+ cells, termed T-cytotoxic cells, represent ~ 1/3 of peripheral T cells. They recognize antigen and MHC class I proteins.

What is teh function of CD3?

•CD3, the complex that serves as the main part of the T-cell antigen receptor (TCR), consists of eight noncovalently associated chains, six of which are common to all T cells. Two chains, the alpha (α) and beta (β) chains, contain variable regions that recognize specific antigens

T helper or inducer cells

•CD4+ cells, termed T-helper or inducer cells, represent ~ 2/3 of peripheral T cells. They recognize antigen and MHC class II protein.

What tends to happen to diseased and cancerous cells?

•Diseased and cancerous cells tend to lose their ability to produce MHC proteins. •NK cells are thus triggered by a lack of MHC antigens, sometimes referred to as recognition of "missing self." •If an inhibitory signal is not received at the same time as the activatory signal, then NK cells release substances called perforins and granzymes.

What do early thymocytes lack?

•Early thymocytes lack CD4 and CD8 markers, which are important to their later function; hence, they are known as double-negative thymocytes.

atypical lymphocytes

•General characteristics of atypical lymphocytes: -1. usually the overall size is increased (16-30 microns) -2. the nucleus may be enlarged -3. the nucleus may be lobulated or folded -4. chromatin patterns vary, but usually dense -5. one to three nucleoli may be present -6. cytoplasm is frequently abundant -7. may have vacuoles in the cytoplasm -8. cytoplasm color may range from gray to light blue to dark blue -9. may have azurophilic granules

Laboratory identification of B and T cells

•Laboratory identification of T and B lymphocytes utilizes flow cytometry. •CD2, CD3, CD4,CD7, and CD8 are recognized on T cells. •CD19, CD20, CD22, and surface immunoglobulin are recognized on B cells.

What are thymocytes and where do they come from?

•Lymphocyte precursors called thymocytes enter the thymus from the bone marrow. •Early precursors enter the thymus at the corticomedullary junction and migrate to the outer cortex.

Where are memory cells found?

•Memory cells (see Fig. 2-7) are also found in germinal centers and have a much longer life span than a resting B cell.

Where do natural killer cells come from?

•NK cells arise from the common lymphocyte precursor (CLP) and differentiate into a T/NK cell that can become a T cell or an NK cell. •T/NK cells in the bone marrow respond to IL-15 and become NK cells. •T/NK cells in the thymus become T cells.

antibody dependent cell cytotoxicity

•NK cells can also recognize and lyse antibody-coated cells through a process called antibody-dependent cell cytotoxicity. •Binding occurs through the CD16 receptor for IgG. •Any target cell coated with IgG can be bound and destroyed.

Natural killer cells

•NK cells lack specificity in their response; this is essential to their function as early defenders against pathogens. •This gives time for the acquired response of specific T and B cells to be activated.

NK cells possess which markers?

•NK cells possess CD16, a receptor for the Fc portion of IgG. The other main surface antigen on NK cells is CD56

Natural killer cells

•Natural killer cells are a small percentage of lymphocytes that do not express the markers of either T cells or B cells. •These large, granular lymphocytes make up 5 to 10 percent of the circulating lymphoid pool found mainly in the spleen and peripheral blood. •They have the ability to mediate cytolytic reactions and kill target cells without prior exposure to them. •

Where do you find plasma cells?

•Plasma cells are not normally found in the blood but are located in germinal centers in the peripheral lymphoid organs.

What to T regs do?

•T regs play an important role in suppressing the immune response to self-antigens. •They may do so by producing interleukins such as IL-10 and transforming growth factor B, which switch off the immune response.

What do TH2 cells do?

•Th2 cells produce a variety of interleukins, including IL-4, IL-5,IL-10, and IL-13. •The essential role of the Th2 cells is to help B cells produce antibody against extracellular pathogens.

What does a functional B chain do?

•The appearance of a functional β chain on the cell surface sends a signal to suppress any further β chain gene rearrangements. •Signaling by the β chain also triggers the thymocyte to become CD4-positive (CD4+) and CD8-positive (CD8+).

Where do large double negative thymocytes proliferate?

•These large double-negative thymocytes actively proliferate in the outer cortex under the influence of interleukin-7. •Rearrangement of the genes that code for the antigen receptor known as TCR begins at this stage (see Fig. 2-9).

How long do memory cells stay activated?

•They remain in an activated state for months or years, ready to respond again to the initial antigen.

What is the lifespan of a mature B cell?

•Unless contact with antigen occurs, the life span of a mature B cell is typically only a few days.

What happens when B cells are activated?

•When B cells are activated in this manner, they transform into blasts that will give rise to both plasma cells and so-called memory cells.

What is the significance of IgD to B cells?

•may prolong the life span of mature B cells in the periphery.

Why do mature B cells remain in the spleen?

•to respond quickly to any bloodborne pathogens they may come into contact with.

What is a region of the heavy chain called?

Fc fragment, determines the class

Thynocytes that express gamma and delta chains lack what?

CD4 and CD8; •They populate the skin, intestinal epithelium, and pulmonary epithelium. •They are capable of recognizing antigens without being presented by MHC proteins. •They may behave like NK cells.

What are some early surface markers of T cell maturation?

CD44 and CD25

What can the earliest B-Cell precursors can be recognized by what surface molecule?

CD45R

Antigen-Independent Phase

B-cell precursors go through development process that prepares them for their antibody production and restricts types of antigens to hich the cells can respond.

T reg cells contain what?

CD4 and CD25 antigens

What do B cell receptors contain?

Antibodies that contain 2 heavy chains and 2 light chains

Secondary tissues have what type of antigen cells? "Reactive"

Antigen dependent

Where are antigen independent cells formed? "naive"

Bone marrow

What are primary lymphoid tissues in humans?

Bone marrow and thymus

All mature B cells exhibit which two immunoglobulins?

IgM and IgD

Where does lymphopoiesis occur?

Secondary tissues (Lymph nodes, spleen, tonsils and peyer's Patched os the intestine)

What are secondary lymphoid tissues in the human?

Lymph nodes, spleen, tonsils and peyer's Patched os the intestine

What control NK cell activity?

NK-cell activity is based on a balance of inhibitory and activatory signals•NK cells are stimulated by exposure to cytokines such as interleukin-12, interferon gamma, and interferon beta. •The inhibitory signal is based on recognition of MHC class I protein, expressed on all healthy self cells.

What are B Cells derived from?

Multipotential progenitor cells

Where are mature lymphocytes seen?

Peripheral blood

What are plasma cells?

Plasma cells are spherical or ellipsoidal cells between 10 and 20 μm in size with abundant cytoplasmic immunoglobulin and little to no surface immunoglobulin

What is the end result of B-Cell?

Produce unique antibody molecule, consists of 2 identical light chains and two identical heavy chains

What happens to pro B cell when under the influence of Growth factors and cytokines?

Rearrangement of genes, code for heavy and light chains of an antibody

What is the function of lymphocytes?

Regulate immune system -antigen and antibody interactions

What interacts with pro-b cells to secrete molecules necessary for development

Stromal cells

Which lymphocyte is the majority in circulating blood?

T lymphocytes

What type fo lymphocyte makes up the majority in circulation?

T-cells: 60-80%

What do TH1 cells do?

Th1 cells produce interferon gamma (IFN-γ) and tumor necrosis factor-beta (TNF-β), which protect cells against intracellular pathogens

•One subset of NK cells has high levels of CD56 and little/no CD 16. What do these do?

These produce cytokines to support antibody production

•The second subset of NK cells has some CD56 and high levels of CD16. What do these do?

These produce cytokines to support cytotoxic activity

When does the pre B stage begin? What happens to the B cells? Where do the mu (heavy) chains accumulate?

When synthesis of the heavy chain part of the antibody molecule occurs; •Pre-B cells lose the CD43 marker as well as c-Kit and TdT. In the cytoplasm