BLD 434 Quiz 3

Define the following terms [including what cell(s) the term applies to, as appropriate]: CR2

(CD21) is part of the B cell co-receptor complex which is activated by C3d: ligand binding components of complex that binds

Define the following terms: double-negative thymocyte

(DN thymocyte) immature T cell at a very early stage of development in the thymus that expresses neither CD4 nor CD8. T-cell receptor gene rearrangement up to the pre-T-cell receptor stage occurs in double-negative thymocytes.

Define the following terms: double-positive thymocyte

(DP thymocyte) T cell at an intermediate stage of development in the thymus. It expresses both CD4 and CD8. The final steps of T-cell receptor gene rearrangement to produce an aß T-cell receptor gene occur in double-positive thymocytes.

List the 4 cell types that are minimally required to allow a T-dependent antibody response to occur in a secondary lymphoid tissue and the relative physical location of each cell within the secondary lymphoid tissue.

- Dendritic Cells (DC): These must activate the naive B cell in order for it to interact with a T cell -T-Follicular Helper Cells: Presents and activates an antibody response in the B cell; causes class switching, somatic hypermutation, and massive proliferation -B cells: The cell which is activated and presents a finished antibody. -Follicular Dendritic Cells (FDC): Presents antigen to the B cell and provides cytokines necessary for the proliferation of B cells.

List the cell(s) that are normally located in the dark zone, light zone and mantle zone of a germinal center (include centroblasts, centrocytes, FDC and T helper cells in your list).

-Light zone: FDCs interact with B cells and CD4 Tfh cells (centrocytes in OUTER region of light zone) -Dark zone: centroblasts -Mantle zone: unactivated B cells

Define "thymic involution" and when it occurs.

-When thymus atrophies and fills with fat as we age. - So the thymus is most active when we are young, and the majority of T cell repertoire is completed by age 30 -Does NOT appear to hinder T cell immunity

Identify the three functions that leukocyte adhesion molecules must perform prior to successful activation of a naïve T lymphocyte by an APC.

1. rolling through secondary lymphoid tissue venules 2. tight binding and extravasation by diapedesis 3. T cell and dendritic cell interaction in secondary lymphoid tissue (DOUBLE CHECK)

2) Properly order the cell stages that occur during B cell development (immature B cell, naïve mature B cell, pre-B cell, pro-B cell, stem cell) and identify characteristics of each that place it into that particular category (e.g. pre-B cell has transient expression of pre-BCR, rearranged Ig heavy chain, begins V-J rearrangement of light chain, expresses VpreB, lambda 5, Ig alpha, and Ig Beta proteins).

1.) Stem Cell: has the ability to become any progeny it would like 2.)Pro-B Cells: VDJ heavy chain rearrangement 3.) Pre-B Cells: VJ light chain rearrangement 4.) Immature B Cell: have surface expression of productivity rearranged mu heavy plus rearranged light chain (surface IgM) 5.) Naive Mature B Cells: have both light and heavy chains expressed have not been activated by antigen 6.) Mature B Cell: an antigen activated naive B cell

10) State the average half-life of a B lymphocyte after it exits the bone marrow and enters circulation.

100 days (DOUBLE CHECK)

Describe the two ways that foreign antigen can reach the secondary lymphoid tissues to activate an adaptive immune response.

1st: L-selectin binds to ICAM-1 and CD34 --> these are low-affinity interaction that allow cell to roll along 2nd: binds to chemokine on the glycocalyx layer 3rd: this causes a conformational change and the activation of LFA-1 which makes a firm adherence to ICAM-1 4th: this firm adherence blood cell to tether to the surface allowing diapedesis or extravasation to occur 5th the cell now in the lymph node follows the chemokine gradient

Identify the normal proportion of alpha-beta to gamma-delta T cells produced after birth.

90% (or more) become alpha-beta T cells 10% become gamma-delta Because delta is inside the alpha chain loci Alpha-beta allows for proliferation, so more cells trying to do alpha-beta rearrangement

Define the following terms [including what cell(s) the term applies to, if appropriate]: pluripotent

A cell that is able to develop into many different types of cells or tissues in the body.

3) Explain why it is advantageous for a pre-B cell to undergo a burst of proliferation following signaling through the pre-BCR.

All daughter cells can skip the mu heavy chain rearrangement to get as many developing pre-B cells as possible to increase chances of getting a viable B cell after light chain rearrangement. Has a viable heavy chain;To get as many developing pre-B cells as possible to increase chances of getting a viable B cell after light chain rearrangement..

8) Compare and contrast B-1 and B-2 B cells in regards to: which is produced primarily in a fetus, self-renewal capacity, spontaneous Ig production, major isotype secreted, relative level of somatic hypermutation, and ability to respond to carbohydrate and protein antigens.

Antigens they respond to: - B-1: carbohydrates - B-2: proteins

9) Define receptor editing and whether it is allowed on heavy chains, light chains, or both.

B cells that express self-molecules have to opportunity to edit their light chains in order to avoid negative selection. Its only light chain nothing else

7) Identify the two CD markers that when used in combination, can identify B-1 B lymphocytes (note: you need to differentiate B cell from T cell).

B-1 B lymphocytes: CD19 as well as CD5 + so CD5 differentiates B-1 from B-2 lymphocytes which is a T cell marker So CD19 is what differentiates B-1 lymphocytes from t cells

Define the following terms [including what cell(s) the term applies to, if appropriate]: BAFF

B-cell activating factor in the TNF family, a cytokine that promotes B-cell survival. primarily from FDC provides life-saving signal to B cell

Define the following terms [including what cell(s) the term applies to, if appropriate]: primary lymphoid follicle

B-cell area in a secondary name for lymphoid tissue in the absence of an immune response. It contains resting B lymphocytes. Also known as primary follicle. See also secondary lymphoid follicle.

12) Identify the cell that provides necessary periodic survival signals to a naïve B lymphocyte, where this cell is located, and what molecule it produces that provides the survival signal.

BAFF: primarily from FDC provides life-saving maturation signal to B-Cell Lymphotoxin (LT): provides maintenance signal for FDC. Access to a primary follicle controls the homeostatic size of the B lymphocyte pool + FDC: a meshwork of cells that form the scaffolding of B cell follicle --> essential for maintaining the homeostatic size of the B lymphocyte pool: If too many cells the FDC prevents cell from getting lifesaving signal

Identify the 2 main effector T cells and the important role that each has in the immune system.

CD 8+ cytotoxic T cells—produce cytokines CD 4+ T helper cells—activate granulocytes & macrophages, antibody response, T effector cells (DOUBLE CHECK)

List the 3 CD proteins that form the B cell co-receptor complex, and the functions of each of the proteins (if known).

CD19: signaling component that transduces the signal CD21 (CR2): ligand binding component of the complex that binds to CD3 CD81: protein that holds B Cell complex to BCR

Identify the functions of CD40 ligand (CD40L) in regards to effector T cell functions.

CD40 ligand: transmembrane protein on T cells that is the ligand for CD40 on B cells and triggers their proliferation and differentiation, and their ability to switch isotype. A defective CD40 ligand gene is one cause of hyper-Ig syndrome, in which only IgM antibodies are made.

Describe the difference between central tolerance and peripheral tolerance in regard to T cells, and whether each is achieved by either anergy or apoptosis.

Central tolerance: is the deletion of self-reactive T lymphocytes in the thymus by the negative selection (induces apoptosis). • Crucial to prevent autoimmunity, refer back to AIRE. - solid phase Peripheral tolerance: is the induction of anergic T-cells. Self-reactive T cells that escape negative selection in the thymus can be made anergic in the periphery. - They are not deleted, but they are made unresponsive to antigen stimulation.• - Can't respond to IL-2, the primary T cell growth factor.• Doesn't occur in Thymus! ANERGY induction for T cells=self antigen within MHC in the periphery (cell bound NOT soluble)ANERGY induction in B cells=clonal anergy is in response to soluble antigen

6) Explain why Ig light chain rearrangement has a higher rate of success than Ig heavy chain rearrangement. (Make sure you list two reasons, not just one!)

DON'T KNOW DOUBLE CHECK Heavy chain rearrangement has only 2 chances: V-DJ on the 1st and V-DJ on the 2nd chromosome. Light chain rearrangement has 4 chances. Kappa on 1st and 2nd and then Lambda on 1st and 2nd.

Define the following terms [including what cell(s) the term applies to, as appropriate]: DC

Dendritic cells (DC) are professional antigen presenting cells, uniquely able to induce naïve T cell activation and effector differentiation

Describe the function of dendritic cells and macrophages in the thymus (note: they are different).

Dendritic cells contribute to negative selection by presenting antigen to T-cells in the thymus. A T-cell with either too much or no binding will then subsequently die by apoptosis. Macrophages remove the cells that die via apoptosis

Describe how adhesion molecules (aka,homing receptors) differ on effector T lymphocytes compared to naïve T lymphocytes.

Effector T cells lose L-selectin expression and gain VLA-4 to home to inflamed blood vessel endothelium instead of HEV of secondary lymphoid tissues Also increase CD2 and LFA-1 to bind target cells expressing low levels of their ligands (LFA-3 and ICAM-1) Naive T cell home to secondary lymphoid tissue Effector T cells home to a site of infection

For the following cytokines, identify the cell(s) that produces it and its main function: IFN-gamma

IFN-y: Produced by CD8 T cells, Th1, Tfh - Activates macrophages to clean up debris

Identify what cytokine is needed in high concentration to activate a naïve CD8+ T cell to a Tc, and which cell can aid the APC in this activation process.

IL-2 activate a naive CD8+ T cell to a Tc, dendritic cells aid the APC in this activation process. (double check)

Describe the importance of IL-2 in T cell responses and how the 3 immunosuppressive drugs (Cyclosporin A and Rapamycin) short-circuit this signal.

IL-2 induces T cell proliferation Cyclosporin A and FK506- inhibit IL-2 receptor Rapamycin- inhibits signaling through IL-2 receptor; blocks response

Identify the cortex and medulla of the thymus and what cell lineages can be found in each.

In the outer section - Cortex: (yellow section) -- from the ectoderm - Cortical epithelial cell (thymic origin) - thymocyte (bone marrow origin) - macrophage (bone marrow origin) - dendritic cell (bone marrow origin) the inner section - Medulla (orange section): from the endoderm - medullary epithelial cells (thymic origin) - thymocyte (bone marrow origin) - macrophage (bone marrow origin) Corticomedullary junction: - dendritic cell (bone marrow origin)

Define "linked recognition" and identify the cells that participate in linked recognition.

Maximal activation of B lymphocytes by T helper cells requires linked recognition -BOTH B AND T CELLS MUST BE SPECIFIC FOR THE SAME ANTIGEN IT IS ANTIGEN SPECIFIC RESPONSE WHERE TFH HELPS B CELL REQUIREMENTS: AS LONG AS T CELL PEPTIDE IS A PORTION OF THE B CELL COGNATE THESE CELLS CAN INTERACT AND HELPER CELL IS LICENSED TO HELP THE B CELL Tfh cell recognizes a peptide derived from B cell's antigen(MHC class II). Naive B cell and Tfh cell exchange signals that begin the process of B cell activation. Tfh secretes cytokines that trigger isotype switching and engagement of CD40L to activate somatic hypermutation and affinity maturation Linked recognition occurs when a B cell is activated by a T cell that responds to the SAME cognate antigen at the B cell (i.e. the T cell and B cell must be specific for the same antigen) Note: Tfh cells activate naïve B cells for antibody production and this is then linked recognition is key

16) List the 3 main options for what a B lymphocyte can do functionally (what it can become) after it is activated by antigen (hint: look at Fig. 6.23 in Parham)

Memory cell Centrocyte Centrobalst - Continue to act with T cell and become a memory cell that are saved for later infections - Become an IgM antibody secreting plasma cell that enters the medulla of the LN - Become an IgG antibody secreting plasma cell that enters the germinal center and undergoes somatic hypermutation (DOUBLE CHECK)

4) List when RAG-1 and RAG-2 are expressed during B cell development (i.e. what stages?).

Necessary for somatic recombination of BCR (and TCR) and recognize recombination signal sequences (RSS's) and make the dsDNA cuts to initiate recombination - Pro-B Cell for heavy chains - Pre-B Cell for light chain (the turned off to avoid erroneous cuts) (DOUBLE CHECK)

Identify what receptor/ligand interaction triggers commitment of an uncommitted lymphoid progenitor to the T lymphocyte lineage and where this interaction occurs.

Notch1 receptor on lymphoid progenitor binding to delta-1 ligand in thymus (double check)

Describe how "strength of TCR binding" is important for positive and negative selection.

Positive selection: selects cells with a T cell receptor able to bind MHC class I or II molecules with at least a weak affinity --> This eliminates (by a process called "death by neglect") those T cells which would be non-functional due to an inability to bind MHC. Negative selection: destroys thymocytes with a high affinity for self peptides or MHC --> This eliminates cells which would direct immune responses towards self-proteins in the periphery.

Describe the purpose of "positive selection" and "negative selection", comparing these processes in B and T lymphocytes.

Positive: the process in the thymus that selects for developing T cells with receptors that recognize peptide antigens presented by self-MHC molecules. Only cells that are positively selected are allowed to continue their maturation. Negative: process in the thymus whereby developing T cells that recognize self antigens are induced to die by apoptosis. + Developing B cells are positively selected when the pre-B receptor binds its ligand. + Developing T cells are positively selected for their ability to bind MHC as well as peptide + Both immature B and T cells are negatively selected if they bind self-antigen (DOUBLE CHECK)

For the following cytokines, identify the cell(s) that produces it and its main function: GM-CSF

Produced by Th1 - Produces neutrophils - secreted by Th1 cells to stimulate greater production of monocytes and neutrophils from the bone marrow myelopoiesis

For the following cytokines, identify the cell(s) that produces it and its main function: TNF-alpha

Produced by Th1 - inflammatory cytokine

For the following cytokines, identify the cell(s) that produces it and its main function: IL-10

Produced by Treg -Anti-inflammatory and prevents tissue destruction

For the following cytokines, identify the cell(s) that produces it and its main function: TGF-beta

Produced by Treg - Anti-inflammatory

Define the following terms: single-positive T cell

T cell at a late stage of development in the thymus, characterized by the cell-surface expression of a T-cell receptor and either the CD4 or the CD8 co-receptor.

Discuss what factors (minimally, the 3 mentioned in class) can influence the choice of a naïve CD4 T cell to a functional subset choice (Th1, Th2...), and which of these factors appears dominant.

T cell subset choice is influenced by: 1. TCR affinity 2. APC co-stimulatory molecules 3. Concentration of Ag 4. Cytokines in vicinity (most dominant!) (DOUBLE CHECK)

Compare and contrast T-dependent and T-independent B lymphocyte antibody responses. Be sure to identify the subsequent characteristics of these two responses in regards to the main antibody isotype produced, whether isotype switching and/or affinity maturation occur, whether the B cell activation is antigen-specific vs. polyspecific, and whether a memory response is induced.

T-dependent: main antibody isotype produced: any antibody whether isotype switching and/or affinity maturation occur: isotype switching and affinity maturation occurs whether the B cell activation is antigen-specific vs. polyspecific: whether a memory response is induced: yes T-independent: main antibody isotype produced: IgM whether isotype switching and/or affinity maturation occur: no somatic hypermutation, minimal isotype switching whether the B cell activation is antigen-specific vs. polyspecific: B-1 (CD5+) B cell response responding to carbohydrates and lipid molecules that are a part of the cell wall of bacteria whether a memory response is induced: no protective memory

List the proteins that compose the pre-TCR.

TCR-beta + pTalpha + CD3 complex + zeta chain + CD4 + CD8

What cytokines do Th1, Th2, Th17, TFH and Treg secrete and what transcription factors are responsible for activating this secretion in each cell type?

TFH: - go to the follicle and interact with bcells and activate them to undergo isotype switching and affinity maturation Treg: - produce anti-inflammatory cytokines which suppress these effector T cells (Th1, Th2, Th17) - they build our tolerance to environmental stimuli like pollen and make sure that the effector T - could get out of control and cause pathology Th1, Th2, Th17: - carry out function by secretion of different cytokines that then act on other effector cells within the immune system to carry out their function

Identify where TFH versus Th1, Th2, and Tc reside following activation in the secondary lymphoid tissue.

Tfh STAYS in the secondary lymphoid tissue and migrates to B cell follicle (right next to T cell zone) Th1, Th2, and Tc LEAVE the secondary lymphoid tissue and migrate to the site of infected/inflamed tissue and interact with other cells

Define Treg and describe their cellular characteristics and the role they play in tolerance. How do they carry out this role

Treg are a subset of CD4+ alpha beta T cells - CD25+ (IL2Ralpha) - express FoxP3 transcription factor - Secrete cytokines (IL-10 and TGF-beta) that suppress normal T cell activation multiple subsets of Treg appear to exist-central Treg arises in the thymus and "iTreg" that are educated and differentiate in secondary lymphoid tissue ***Treg exerts peripheral tolerance

Compare and contrast linked recognition and the two-signal hypothesis. Include the cells involved in both, the cell receptors critically important on each cell, and the overall goal of each. For each, state what will happen if the process is not satisfied?

Two signal: - T cells must receive a minimum of 2 signals to respond to antigen ( a signal from MHC is not enough) 2 signals needed: - primary signals through TCR binding cognate peptide/MHC - Co-stimulatory signal through co-stimulatory molecules located on APC. Binds to CD28 on T cell DOUBLE CHECK

Define the following terms [including what cell(s) the term applies to, as appropriate]: cognate pairs

a CD4 effector T cell bound via its antigen receptor to its target cell (either a macrophage or a B cell). Also used for other pairs of interacting cells, one of which is. lymphocyte

Define the following terms [including what cell(s) the term applies to, if appropriate]: Pre-BCR

a developing B cell that has rearranged its heavy-chain genes but not its light-chain genes. It expresses an immunoglobulin-like receptor called the pre-B-cell receptor. Pre-B cells develop from pro-B cells; if they survive, they develop into immature B cells. See also large pre-B cell; small pre-B cell.

Define the following terms [including what cell(s) the term applies to, if appropriate]: CAM (cell adhesion molecule)

a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each other and to their surroundings.

Define the following terms [including what cell(s) the term applies to]: cell-mediated immunity

any adaptive immune response in which antigen-specific effector T cells dominate. it is defined operationally as all adaptive immunity that cannot be transferred to a naive recipient by serum antibody.

13) Explain what cell interaction triggers isotype switching and somatic hypermutation.

are triggered by T cell interaction. T helper Cells present Ag to a B cell and stimulate the B cell's maturation

Define the following terms [including what cell(s) the term applies to, if appropriate]: germinal center

area in secondary lymphoid tissue that is a site of intense B-cell proliferation, selection, maturation, and cell death. Germinal centers form around follicular dendritic cell networks when activated B cells migrate into lymphoid follicles. The cellular and morphological events that form the germinal center and take place there are called the germinal center reaction.

For the following cytokines, identify the cell(s) that produces it and its main function: IL-21

autocrine growth factor for Th17 but for Tfh: recruiting into the germinal center and interacting with antigen-activated B cells support their process of somatic hypermutation and isotype switching

For the following cytokines, identify the cell(s) that produces it and its main function: IL-4

autocrine growth factor for Th2 Cells keeps the activated - Produced by Th2 - Helps to activate basophils, mast cells, eosinophils, and B cells

Define the following terms [including what cell(s) the term applies to]: co-stimulatory molecule

cell-surface protein on an antigen-presenting cell that delivers signals to an interacting naive lymphocyte that are required in addition to the antigen-binding signal for the lymphocyte to respond. Co-stimulator molecules include the B7.1 and B7.2 proteins on professional antigen-presenting cells, which engage molecules CD28 and CTLA4 on T cells. CD40 ligand on T cells serves a co-stimulatory role when it binds to CD40 on B cells.

Define the following terms [including what cell(s) the term applies to]: CD28

co-stimulatory receptor on T cells that interacts with B7 co-stimulatory molecules to promote T-cell activation.

For the following cytokines, identify the cell(s) that produces it and its main function: IL-2

cytokine produced by activated T cells that is essential for the proliferation of activated T cells and the development of an adaptive immune response Produced by CD8 T cells and TH1 - Maintains own activation. Autocrine cytokine

Define the following terms [including what cell(s) the term applies to]: CTLA-4

cytotoxic T-lymphocyte-associated protein 4, a high-affinity inhibitory cell-surface receptor on T cells that interacts with B7 co-stimulatory molecules.

Identify what cell(s) express CTLA-4, and what its function is.

cytotoxic T-lymphocyte-associated protein, a high-affinity inhibitory cell-surface receptor on T cells that interacts with B7 co-stimulatory molecules. It terminates T cell response

Define the following terms [including what cell(s) the term applies to]: B7

either of the B7.1 or B7:2 proteins, which are co-stimulatory molecules present on the surface of professional antigen-presenting cells such as dendritic cells. With other related proteins, they form the B7 family of co-stimulatory molecules.

Identify whether B cells, alpha-beta T cells, and gamma-delta T cells each undergo positive and/or negative selection.

gamma-delta T cells: do not undergo positive and/or negative selection alpha-beta T cells: undergo positive and/or negative selection B-cells: undergo positive and/or negative selection because B cells.

5) Identify what percent of developing B lymphocytes successfully make it through each major step of somatic recombination during development (heavy chain rearrangement, light chain rearrangement).

heavy chain rearrangement: 66% or 2/3 light chain rearrangement: 85% percent of cells are successful at going all the way through development to create an immature B cell with a mature/complete BCR on its cell surface: 50% or 1/2 (Double Check)

14) Describe the outcome when a B cell interacts with antigen in the lymph node.

if a mature B cell binds antigen in the T cell area, it will be stimulated by CD4+ T helper cells to proliferate and differentiate: Plasma cells secrete large amounts of antibody. Other activated B cells move to primary follicle, forming a secondary follicle containing a germinal center this will continue proliferation as well as isotype switching and somatic hypermutation

Define the following terms [including what cell(s) the term applies to]: humoral immunity

immunity that is mediated by antibodies and can therefore be transferred to a nonimmune recipient by serum

Define the following terms [including what cell(s) the term applies to, if appropriate]: Btk

is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies

Define the following terms [including what cell(s) the term applies to, if appropriate]: centroblast

large dividing B cell present in germinal centers. Somatic hypermutation occurs in these cells, and antibody-secreting and memory B cells derive from them.

15) Identify the main function of a plasma cell and the 4 locations where it may reside in the body.

main function is to produce antibodies 4 locations : Red pulp of spleen, Bone marrow, LN medulla, GALT (double check)

Define the following terms [including what cell(s) the term applies to, as appropriate]: FDC

non-lymphoid cell characteristics of follicles in secondary lymphoid tissues. It has long branching processes that make intimate contact with B cells and have Fc and complement receptors that hold antigen:antibody: complement complexes on their surfaces for long periods. These cells are crucial in selecting antigen-binding B cells during antibody responses.

Define the following terms [including what cell(s) the term applies to, if appropriate]: centrocyte

nondividing B cell in germinal centers. Centrocytes have undergone isotype switching and somatic hypermutation.

Identify the four major proteins found in Tc lytic granules and the functions of each protein. Indicate which protein polymerizes to form the pore, and which activate caspases.

perforin (make a pore) granzyme (activate caspases) granulysin (make a pore) serglycin (make a pore)

Identify whether a pre-T cell, pro- T cell, and mature T cells would be a double-negative thymocyte, a double-positive thymocyte, or a single positive T cell.

pro-T cell: Double-negative thymocytes pre-T cell: Double-positive thymocytes Mature T cells: Single positive T cell

Define the following terms [including what cell(s) the term applies to, if appropriate]: negative selection

process in the thymus whereby developing T cells that recognize self antigens are induced to die by apoptosis.

For the following cytokines, identify the cell(s) that produces it and its main function: IL-5

produced by Th2 - its a eosinophill growth factor - feeds back to the bone marrow and upregulates the production of eosinophils and activates them

For the following cytokines, identify the cell(s) that produces it and its main function: LT

produced by cytotoxic T cells and Th1 Cells PURPOSE?? (DOUBLE CHECK)

Define the following terms [including what cell(s) the term applies to, as appropriate]: immune complex(es)

protein complex formed by the binding of antibodies to soluble antigens. The size of immune complexes depends on the relative concentrations of antigen and antibody. Large immune complexes are cleared by phagocytes bearing Fc and complement receptors. Small soluble immune complexes tend to be deposited on the walls of small blood vessels, where they can activate complement and cause damage.

Define the following terms [including what cell(s) the term applies to, if appropriate]: surrogate light chain

protein that mimics an immunoglobulin light chain and is an essential factor in immunoglobulin biosynthesis. It is made up of two subunits, VpreB and 25, and is produced by pro-B cells. Together with the u heavy chain it forms the pre-B-cell receptor in pre-B cells.

Define the following terms [including what cell(s) the term applies to, if appropriate]: LT

provides maintenance signal for FDC

Identify the general role of selectins and integrins in lymphocyte trafficking.

rolling through secondary lymphoid tissue venules (low affinity): - Naive Tcell: L-selectin - Target: + CD34 + GlyCAM-1 + MAdCAM-1 Tight Binding and extravastion by diapedesis: - Naive Tcell: LFA-1 - Target: + ICAM - 1 + ICAM - 2 T cell and APC interaction in secondary lymphoid tissues - T cell: + LFA-1 + ICAM-3 + CD2 - APC: + ICAM -1 and ICAM-2 + LFA-1 and DC SIGN + LFA-3

Define the following terms [including what cell(s) the term applies to, if appropriate]: anergic

state of nonresponsiveness to an antigen. People are said to be anergic when they cannot mount delayed-type hypersensitivity reactions on challenge with an antigen. T and B cells are said to be anergic when they cannot respond to their specific antigen.

Define the following terms [including what cell(s) the term applies to]: "two-signal hypothesis"

states that a T cell must receive a minimum of two signals to respond to antigen: 1. primary signal through the TCR binding cognate peptide/MHC I or II 2. a costimulatory signal through costimulator molecules on APC surface (usually B7)

Define the "two-signal hypothesis" and identify the ligand/receptor proteins that provide the second signal, including specifically what cells these ligands and receptors are expressed on.

states that a T cell must receive a minimum of two signals to respond to antigen: 1. primary signal through the TCR binding cognate peptide/MHC I or II 2. a costimulatory signal through costimulator molecules on APC surface (usually B7) B7 on APC binds to CD28 of naive T Cells

Describe the role of subcapsular sinus macrophages, FDC, and medullary sinus macrophages in filtering antigen from lymph fluid.

subcapsular sinus macrophages pick up antigen on CR2 and hold it for B cells to interrogate; FDC can hold antigen in the primary follicle for b cells to interrogate medullary sinuses macrophages are highly phagocytic and clean efferent lymph entirely before it exits the lymph node, this prevents further infection downstream (problems here often lead to sepsis).

Define the following terms [including what cell(s) the term applies to, as appropriate]: CR1

target opsonized C3b for cleavage by Factor 1

Define the following terms [including what cell(s) the term applies to, if appropriate]: plasma cell

terminally differentiated B lymphocyte that is dedicated to the synthesis and secretion of antibodies.

Define the following terms [including what cell(s) the term applies to, if appropriate]: polyspecific antibody (polyspecificity)

the ability to bind to a range of different antigens, a property shown by some antibodies. It is also known as polyreactivity.

Identify what cell(s) mediate (carry out) negative selection of T cells.

the cells: - thymic dendritic cells - alpha-beta T cells

Identify what cell(s) mediate (carry out) positive selection of T cells.

the cells: - thymic epithelial cells - Double positive thymocytes

Define the following terms [including what cell(s) the term applies to, if appropriate]: clonal deletion

the elimination during lymphocyte development of immature lymphocytes that bind to self antigens. It is the main mechanism that produces self-tolerance.

Define the following terms [including what cell(s) the term applies to, if appropriate]: secondary lymphoid follicle

the lymph nodes, spleen, and mucosa-associated lymphoid tissues. These are the tissues in which immune responses are initiated. The highly organized tissues such as lymph nodes and spleen are also known as secondary lymphoid organs. Also known as peripheral lymphoid tissue.

Define the following terms [including what cell(s) the term applies to, if appropriate]: self-tolerance

the normal situation whereby a person's immune system does not respond to constituents of his or her body. The circulating lymphocyte population in an individual is thus said to be self-tolerant.

Define the following terms [including what cell(s) the term applies to, if appropriate]: clonal anergy

the presence of antigen-specific B cells in an unresponsive state, can be achieved by a number of mechanisms.

Define the following terms [including what cell(s) the term applies to, if appropriate]: RAG-1/RAG-2

the recombination proteins that form the enzymatic complex that carries out V(D)J recombination.

Define the following terms: pT alpha

the surrogate a chain that combines with the TCRB chain to form the pre-T-cell receptor.

Identify the AIRE protein, what cell expresses it, and whether it is important in positive or negative selection.

transcription factor that causes several hundred tissue-specific genes to be transcribed by a subpopulation of epithelial cells in the thymus, and which thus enables the developing T-cell population to become tolerant of antigens that normally occur only outside the thymus.

Define the following terms [including what cell(s) the term applies to, if appropriate]: PAX-5

transform Common lymphoid progenitor --> pro B cell