Immunology (Spring 2005)



Immunology (Spring 2005)

Midterm 1: Answer Key

1) Antigenic determinants (epitopes) on imunonoglobulins may be of three types. Name and briefly describe them. (6 points)

a) -Isotypic Determinanat (1): Class/Isotype of Ab (1) (e.g. IgM, IgD, Ig G, etc.).

b) -Allotypic Determinant (1): Subtle amino-acid differences found between individuals of the same species (1).

c) -Idiotypic Determinant (1): Unique Variable Heavy-chain and Variable Light-chain combination found on every single AB (1).

2) Which immunoglobulin isotype is predominantly secreted through mucous membranes? How does the secretory component facilitate this process? (4 points)

a) -IgA (1): Dimeric Ab with a secretory component

b) -Secretion: Aided by Poly Ig receptor (1), which binds to the secretory component at the J-chain region (1), and it is this interaction that facilitates transport across the mucous membranes (1).

3) Primary and secondary immunization with native protein can induce antibody production and a T-cell mediated response as part of a secondary immune response. However, secondary immunization with denatured protein induced a secondary T-cell mediated response, but no secondary antibody response. Why? (6 points)

a) -Denatured proteins may not be recognized by the B-cell receptor, if the Ab was initially generated against native protein, because denatured proteins do not retain the unique 3-dimensional structure that the Ab receptor was generated to recognize (3).

b) -In contrast, denatured proteins can still be recognized by T-cell receptors because of the recognition mechanism involved: T-cell receptors need processed antigen coupled to an MHC molecule for activation. Therefore, the 3-dimensional structure of a protein is not relevant, and denaturing a protein does nothing to impair this mechanism, as the protein must be processed anyway (3).

4) Name the 7 mechanisms important for the generation of antibody diversity. (7 points)

a) -Genetic diversity, with multiple gene segments coding for Ab’s (1).

b) -Combinatorial differences in V-D-J and V-J joining (1).

c) -P-nucleotide addition after cleavage of hairpin turn (1).

d) -N-nucleotide addition, especially at CDR3 (1).

e) -Flexible joining at coding regions (1).

f) -Somatic Hypermutation (1).

g) -Association of Heavy and Light chains (1).

5) Trace the path a B-cell may take starting with early development (i.e. where will it be present) to the formation of plasma cells. You can mention 4 different stages. Be specific about the locations at different stages of development and activation/differentiation? (4 points)

a) -Pro B-cell(Pre B-cell(Immature B-cell(Mature B-cell(Activated B cell(Plasma/Memory B-cell

b) -Development/differentiation in bone marrow; activation and formation of plasma cell in secondary lymphoid tissue/lymph nodes/periphery.

1 point for each correct B-cell maturation stage, matched with the location in which this takes place. Any 4 stages in the right order from above are acceptable.

6) What is the consequence of a strong interaction between developing T-cells in the thymus and self-antigens? What may happen to the individual if certain self-antigens are not present in the thymus? (4 points)

a) -T-cells interacting strongly with self-antigens in the thymus during development will die (2).

b) If certain self-antigens are not present in the thymus during development, T-cells that recognize these self-antigens are not selected to die and can initiate an autoimmune attack when these antigens are encountered later on in life (2).

7) You immune system will normally not respond to foreign proteins if injected alone. However, a T-cell response to the same foreign protein can be induced when it is presented with the gram-negative bacterial cell wall component LPS. What are the key host receptors that are important for host responses to these bacterial structures? Which key cells expressing these receptors are important for activation of T-cells and how? (6 points)

a) -Toll-like receptors (2); full credit will also be given if you just mention TLR2 or TLR4.

b) -Dendritic cells are the crucial APC involved in the activation of T-cells upon antigenic challenge by LPS (2). Interaction of LPS with dendritic cells causes changes crucial to T-cell activation, the most important of which are the upregulation of MHC molecules and B7, resulting in a vigorous T-cell response (2).

If you mention macrophages for part (b), you will get 1 point instead of 2, since dendritic cells are more important than macrophages in this response.

8) How are the following different? (3 points each)

a) Antigen and Immunogen

An antigen is a molecule that can be recognized by, and bind to, an antibody molecule. An immunogen is a molecule that can be recognized by and bind to an antibody molecule, and induce a humoral or cell-mediated immune response (3)

b) Polyclonal and monoclonal antibodies against the same antigen

A polyclonal antibody represents a heterogeneous mixture of antibodies that can recognize more than 1 epitope on the antigen. A monoclonal antibody represents a homogenous mixture of antibodies that is specific for only 1 epitope on the antigen (3).

c) “Normal” Antigen and Superantigen

A “normal” antigen will induce an immune response by binding to and activating a specific B-cell, or by activating a T-cell by binding to the T-cell receptor and a MHC molecule. A superantigen induces an immune response by activating only T-cells, and it does so by binding to the conserved region of the TCR and an MHC molecule. As a superantigen binds to the conserved region of the TCR, this causes a far more potent immune response compared to a “normal” antigen (3).

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