BIO 432                                                                      Name________________________

Introduction to Immunology

Exam 1

 

        Before beginning, please verify that you have 8 pages.

        Please read each question carefully before answering.

 

 

I.               Short Answer (52 points):  General Concepts in Immunology and Cells;

Organs of the Immune System; Antigenicity and Immunogenicity

 

A.   (6 points) Discuss the difference between the two arms of the immune system- innate and adaptive immunity by addressing the differences in the following characteristics:

a.     Response time

b.     Specificity for antigen recognition

c.     Response to repeat infection

 

 

 

The above table is  from your textbook and contains the information that should have been covered in this question.

 

 

 

 

 

 

B.    (5 points) Collaboration of innate immunity and the adaptive immune response yields a strong defense against infection.  Discuss how the subclass of pattern recognition receptors, the Toll-like receptors, link innate immunity to the adaptive immune response.

 

Toll-like receptors supply infmration to the immune cell about the precise nature of the pathogen.  Toll-like receptors are either soluble or cell-associated receptors that recognize

 

 

 

 

 

 

 

 

 

C.    (12 points) Phagocytosis is an important function of innate immunity and is a necessary precursor to antigen presentation by antigen-presenting cells.  Use the illustration from your text shown below to answer the following questions:

5.
 

4.
 

3.
 

2.
 

1.
 
  1. List and briefly describe the five steps of phagocytosis.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  1.  Which cells of the innate immune system are phagocytic?
 

 

 

 

 

D.   (8 points)  The adaptive immune response depends on the function and interaction of lymphocytes and antigen-presenting cells.  Provide the following information for lymphocytes listed above by completing the table:

 

 

B lymphocyte

T lymphocyte

Location of Origin

 

 

Site of Maturation

 

 

Receptor used for Antigen Recognition

 

 

 

Name two of the three types of antigen presenting cells.

1.

2.

 

                                                                                                                                                                                                                                               

  1. (12 points) Antigen presentation to resting T cells results in activation and clonal expansion of T cells.  Answer the following questions concerning T cell activation and function.

 

1.     Two membrane adhesion molecules on T cells regulate the type of MHC molecules recognized by T cells.  What are these two adhesion molecules?

 

 

 

2.     It is usually the case that T helper cells and T cytotoxic cells express only one of the membrane adhesion molecules listed above.  Indicate which of these adhesion molecules is most often expressed by T helper cells or T cytotoxic cells.

 

 

 

 

3.     Which class of MHC proteins is usually recognized by T helper cells and which is usually recognized by T cytotoxic cells?  How does the mode of antigen entry into an antigen presenting cell influence the antigenic peptide-MHC complex that is presented on the surface of the antigen presenting cell?

 

 

 

 

 

 

 

4.     Briefly describe the specific functions of T helper cells and T cytotoxic cells once they are activated by an antigen presenting cell or stimulatory cytokines.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  1. (5 points)  White blood cells (leukocytes) differentiate from both myeloid and lymphoid progenitors.   Specific combinations of extracellular (ex. cytokines in HIMs) and intracellular (ex. genes) mechanisms control the specific cell type derived during differentiation. Differentiated leukocytes are functionally diverse. 

Place the number (s) of the leukocyte that is best described by each statement.

           

                        1. Natural killer cell

                        2. Neutrophil

                        3. Basophil

                        4. Dendritic cell

                        5. Macrophage

 

 

 

_______          granulocyte that binds IgE with its high affinity Fce

receptor

 

_______          participates in ADCC by recognizing decreased levels of class I MHC on target cell

 

_______          antigen presenting cell whose phagocytic activity can be enhanced dramatically by an opsonin

 

_______          granulocyte possessing a bilobed nucleus and is the primary cell type involved in leukocytosis

 

_______          differentiates from either a myeloid and lymphoid progenitor and functions as an antigen presenting cell when mature

 

 

 

I.  ( 4 points)  During inflammation, a Langerhans cell has recognized and phagocytosed an invading bacterium.  This Langerhans cell migrates to the nearest lymph node, differentiates into a mature dendritic cell, and activates a nearby T helper cell with its peptide-class II MHC complex.  Describe how this activated T helper cell might influence the structure and function of a nearby primary follicle.

 

 

 

 

 

 

 

 

II. 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. _______________       mucous membrane lining the inner surface of the eyelids

 

B. ______________         term used to describe the migration of a phagocyte   through the endothelial cell wall tissue

 

C. _____________           developmental process leading to the generation of red and

                                          white blood cells

 

D. _____________           secondary lymphoid organ functioning in filtering dead or

                                          damaged erythrocytes  and antigen from the blood

 

E.______________           the ability of an antigen to induce a humoral or cell-mediated immune response

 

F. ______________          low molecular weight molecule that can be immunogenic

                                          when conjugated to a suitable carrier

 

G.______________          substances when mixed with antigen and injected into an

                                          organism enhance immunogenicity of the antigen

 

 

 

III. Short Answer  (34 points): Antibody Structure and Function; Organization and Expression of Immunoglobulin Genes

 

  1. (6 points) Immunoglobulin structure contains two heavy and two light chains.  Please answer the following questions concerning immunoglobulin structure.

 

What are the five classes of heavy chains?

 

                               

 

What are the two classes of light chains?

 

                                            

 

What two forces stabilize an immunoglobulin fold domain?

 

 

 

                  Which immunoglobulin heavy chain(s) lacks a hinge region?

 

 

  1. (4 points) What is the significance of complementarity determining regions

(CDR’s)?   

                                                

 

Where are CDR’s located? 

 

 

 

How many CDRs are present on an IgG molecule?

 

 

 

 

  1. (4 points)  Why is an antibody that binds a single nucleotide unlikely to bind double-stranded DNA?

                                                       

 

 

 

 

 

  1. (4 points) During the cleavage phase of V(D)J recombination, RAG proteins function to introduce DNA double strand breakage through three main stages (synapsis, nicking and hairpin formation).   How do RAG proteins distinguish between different gene segments to generate the coding segments that will be brought together during the joining phase?

 

 

 

 

 

  1. (6 points) List the three stages of the joining phase of V(D)J recombination. 

 

1.

2.

3.

 

Coding joints formed during the joining phase are formed through “imprecise joining”.  Discuss one benefit and one drawback to “imprecise joining”.

 

 

 

 

 

 

  1. (6 points) Below is a list of all sources contributing to antibody diversity.   Fill in the table below and indicate by writing “yes” or “no” across from the source whether each source contributes to antibody specificity.

 

            Sources                                                              Impact antigenic specificity?

            Multiple V, D and J segments                                                Yes

            Combinatorial rearrangement                                      Yes

            Junctional diversity (N,P, exonuclease)                      Yes

            Random H and L chain pairing                                   Yes

            Somatic Hypermutation (SHM)                                 Yes

            Allotypic variation                                                     No

            Class switch recombination (CSR)                             No

            Alternative RNA splicing                                           No

 

            Which of the above occur after antigenic stimulation?

 

                        SHM, CSR, and Alternative RNA splicing

 

  1. (4 points) What two primary forces help ensure that the B cell receptors on a given B cell have only one antigenic specificity?

 

 

                      

 

 

 

 

 

 

IV. Bonus (10 points)

 

 

    1. (2 points)  Mammals are thought to have evolved bone marrow as the site for the generation of lymphocytes from a condition found in jawless fish such as the lamprey.  Name the site of hematopoiesis and lymphocyte generation in lamprey.  What was the first group of vertebrates to develop bone marrow as the site of lymphocyte generation?

 

 

 

 

    1. (2 points)  DiGeorge’s syndrome is a congenial defect resulting in absence of a thymus.  Briefly describe how this condition influences the function of the adaptive immune response.

 

 

IV. Bonus (10 points)

 

    1.  (2 points)  Why is the Ig-a/Ig-b heterodimer necessary for the function of a mature B cell?

 

 

 

 

 

 

 

 

 

 

    1. (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.  Note: only the top strand of DNA is shown.