BIO 432 Spring 2005                                                            Name___________________

Introduction to Immunology

Exam 1

 

        Before beginning, please verify that you have 7 pages.

        Please read each question carefully before answering.

 

Short Answer

 

1. (6 points) Our modern understanding of immune system function or the Clonal Selection Theory resulted from debates brought about by the supporters of two earlier theories- the Selective Theory championed by P. Ehrlich, and the Instructional Theory, championed by L. Pauling. Outline the three main tentants of the Clonal Selection Theory.

 

1. individual lymphocytes express a membrane receptor specific for a specific antigen

 

1. Repeptor Specificity is determined before thelymphocyte is exposed to antigen

 

1. Binding of antigen to the receptor changes the lymphocyte causing it to proliferate into a clone of cells with similar immunologic specificity

 

 

1. (6 points) Complete the following table

 

Antigen-Binding Molecule	Cellular Expression	Types of Antigen Recognized
Immunoglobulin	(Mature) B cells	Soluble, hydrophobic antigens
Class I MHC	Nearly all cells	Endogenously processed antigen
Class II MHC	Antigen presenting cells	Exogenous antigen acquired through endocytosis or phagocytosis

 

 

1. (14 points) Lymph nodes are important secondary lymphoid organs that serve as sites of interaction between immune cells and antigen. What is the function of primary follicles in lymph nodes? How do these structures change following antigen recognition and presentation by a dendritic APC?

MAIN POINTS: Function of the primary follicle is to provide a site whereT and B cells readily trap and interact with pathogens and mount and immune response.   Primary follicles contain resting mature B cells or unstimulated B cells surrounded by follicular dendritic cells some T helper cells Follicular dendritic cells and T helper cells act as antigen presenting cells to resting B cells Following antigen presentation B cells migrate to the center of the primary follicle and form a secondary follicle with a germinal center, surrounded by a ring of B cells, helper T cells , macrophages, and follicular dendritic cells Activated B cells proliferate in the germinal center (clonal expansion) and generate many plasma (antibody secreting) and memory B cells

 

 

 

 

 

 

 

 

 

 

 

 

 

Which lymphocyte would be expected to be activated in this lymph node if it is in a normal mouse with a viral infection?

 

                                    T_c or CTL

 

How might the structure and function of the lymph node change in a mouse born without a thymus?

            . In mice or humans born without a thymus, there would be no mature T cells . Lymph nodes have thymus independent and thymus dependent regions. Thymus- independent region or the cortex , does not contain many T cells so would be relatively unaffected by the lack of a thymus. The thymus-dependent region or the paracortex, is heavily populated with T cells and would be smaller in size with fewer cells in animals without a thymus. These animals would display a decreased humoral response and lack a cell-mediated immune response.

 

1. (14 points)

 

Cell Type	Development	Primary Function
Natural Killer Cell	Lymphoid origin	Granular lymphocyte that is cytotoxic to tumor cells and virally infected cells, uses ADCC
Dendritic cells (not follicular-they do not arise in the bone marrow)	Cells named for their long, extending processes; derived from both myeloid and lymphoid progenitor cells	Non-lymphoid antigen presenting accessory cell; express Class II MHC
Tissue Macrophages	Myeloid cell that develops from a monocyte as it migrates into tissue	Phagocytic antigen presenting cells, enhance inflammatory response
B lymphocyte	Lymphoid cell that matures in the bone marrow	Antibody production, source of memory B cells

 

 

1. (8 points) While working in the kitchen cutting chicken you cut your finger with a knife. One hour later, you notice that the cut is a reddish color and feels warm and swollen. Given what you know about the immune response, you are sure that your body is beginning to fight some bacterial infection.
1. Emigration is a fundamental component of the inflammatory response. What is the purpose of emigration and what are the three main steps of this process?

Emigration allows immune cells to move to the site of infection

1.     Margination

1.     Extravasation/Diapedesis

1.     Chemotaxis

                                                              

                                                              

 

1. Which are the first granulocytes to emigrate to the site of infection during leukocytosis?

Neurotrophils

 

 

 

1. (14 points) Activation of T_h lymphocytes in the adaptive immune system plays an important role in developing a memory response to specific immunogens. What are the components of the ternary complex that must be formed between an APC and a T_h cell for activation of the T_h response?
1. T cell receptor
2. class II MHC
3. antigenic peptide

CD4 is also required for binding and activation.

 

 

Would you expect denaturation of the epitope prior to antigen presentation to change the T_h cell response?

 

            No

 

 

Given that the T_h response leads to the production of immunoglobulin, which type of T_h response (T_h 1 or T_h 2) was activated?

 

            T_h2

 

Which immunoglobulin isotype(s) is the first to be expressed following the T_h response?

            IgM, (also IgM and IgD)

 

 

Which feature of immunoglobulin structure determines immunoglobulin isotype?

 

            Heavy chain expression

 

 

What genetic mechanism(s) is employed following the T_h response to improve the affinity of the immunoglobulin for the antigenic epitope?

 

                        Somatic Hypermutation, SHM

 

1. Fill-in-the-Blank (14 points, 2 points each)

Please place the term on the line that is best described by the definition to its right.

 

A. IgA                               immunoglobulin that is secreted as a dimmer by the polymeric Ig receptor through transcytosis

 

B. Toll Like Receptor        soluble or cell-associated membrane associated pattern recognition receptors that recognize conserved pathogen-associated molecular patterns

 

C. Granuloma                   dense, macrophage-rich mass of cells formed at the site of adjuvant injection

 

D. Peyer’s Patch               secondary lymphoid organs located in the gastrointestinal tract

 

E. Opsonins                      molecules (antibodies or protein fragments) that bind to the surface of microbes and increase the efficiency of phagocytosis

                                         

F. Stromal cells                 the group of nonhematopoietic cells supporting growth and differentiation of hematopoietic stem cells by providing a HIM

 

G. Avidity                          strength of multiple interactions between a multivalent antibody and antigen

 

8. (12 points) Normally functioning RAG proteins are required for V(D)J recombination. What is the purpose of V(D)J recombination?

To form functional exons encoding heavy and light chains of immunoglobulin molecules

(Also begins the process of generating diverse antigenic specificity of the population of B cells)

 

What is the primary function of RAG proteins in lymphocytes? At which stage of V(D)J recombination are functional RAG proteins required?

 

RAG- recombination activating genes recognize RSS sequences by following the 12/23 rule

                        Stage: Cleavage

 

Researchers observed that V(D)J recombination is developmentally ordered. Describe the developmental pattern of V(D)J recombination (ie. allelic exclusion), its basis and importance for B cell function.

                        Heavy chain locus is rearranged first, D_H to J_H then V_HD_HJ_H

                        Light chain is rearranged after heavy chain

 

                        All options for rearrangement are exhausted before proceeding to another locus. Antigen receptor genres are expressed from only a single chromosome at a time (allelic exclusion). Importance: Lymphocytes do not express receptors of different antigenic specificities.

                 

 

9. (12 points) Illustrated below is standard Scratchard plot demonstrating the results of an equilibrium dialysis experiment analyzing the affinity of an antibody you have designed to measure the amount of a novel performance enhancing hormone in the blood.

r

 

 

Which sample of antisera consists of a monoclonal antibody/immunoglobulin?

            A

 

 

What is the valency of the monoclonal antibody?

            2

 

 

Which regions of the antibody contribute to the functional valency of the antibody? How many of these regions are present in this antibody?

            Complementarity Determining Regions (CDRs), 12

 

 

Given that other experiments indicate that this antibody exists as a monomer in serum, is found highly concentrated in blood serum and appears to cross the placenta, which immunoglobulin isotype is likely to be represented by Plot A?

 

            IgG

 

What is most probable shape of the antibody binding site of this immunoglobulin if its epitope is a drug?

                                    Pit or Hole

Bonus ( 10 points)

1. (2 points) What is the significance of the periarteriolar lymphoid shealth?

 

Site of immune reactions in the spleen, populated by helper T cells and primary follicles

 

2. (2 points) Which is the only antibody class that is not secreted?

 

IgD

 

3. (4 points) You are analyzing the immunoglobulin response to immunization in mice by examining the sequence of rearranged immunoglobulin V genes in B cell clones you have obtained. In one clone, you have derived the putative IgH V, D and J germline gene segment usage by sequence comparison. Shown are the coding regions of the segments (RSSs would be lost after V(D)J recombination). Align the germline gene segments (top) to the rearranged gene (bottom) and explain how the coding junctions present might have been formed. Explain any difficulties you have in determining your answer and describe any additional features you observe in the sequence. Note: only the top strand of DNA is shown.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

4. (2 points) NK cells are important mediators of ADCC. Which Fc receptor expressed on the surface of NK cells binds the Fc region of IgG to stimulate ADCC?       

CD16 or FCgRIII