Medicina

COURSE: Medical Microbiology, MBIM 650/720 TOPIC: Immunoglobulins: Structure & Function I & II Lecture # 4 Lecture # 5

FACULTY:

Dr. Mayer

TEACHING OBJECTIVES: 1. To discuss the general properties of all immunoglobulins 2. To describe the basic structure of immunoglobulins 3. To relate immunoglobulin structure with function 4. To define immunoglobulin hypervariable and framework regions5. To define immunoglobulin classes and subclasses, types and subtypes 6. To describe the structures and properties of immunoglobulin classes REQUIRED READING: Roitt et al. Immunology,5th Ed., pp 6-7, Chapter 6 Murray et al. Medical Microbiology, 3rd Ed., pp 92-95 KEY WORDS: Immunoglobulin, Valence, Heavy chain, Light chain, Variable region, Constant region, Hinge region, Domain, Hypervariableregion, Framework region, Groups & subgroups, Fab & Fc, F(ab')2, Type & subtype, Class & subclass, Opsonin, J chain, Secretory component

Fig 1

IMMUNOGLOBULINS: STRUCTURE AND FUNCTION I. DEFINITION A. Immunoglobulins (Ig) - Glycoprotein molecules which are produced by plasma cells in response to an immunogen and which function as antibodies. The immunoglobulins derive their name from the findingthat when antibody-containing serum is place in an electrical field the antibodies, which were responsible for immunity, migrated with the globular proteins (Figure 1).

II.

GENERAL FUNCTIONS OF IMMUNOGLOBULINS A. Ag binding - Immunoglobulins bind specifically to one or a few closely related antigens. Each immunoglobulin actually binds to a specific antigenic determinant. Antigen binding byantibodies is the primary function of antibodies and can result in protection of the host. 1. Valency - The valency of antibody refers to the number of antigenic determinants that an individual antibody molecule can bind. The valency of all antibodies is at least two and in some instances more.

B.

Effector Functions - Often the binding of an antibody to an antigen has no direct biologicaleffect. Rather, the significant biological effects are a consequence of secondary "effector functions" of antibodies. The immunoglobulins mediate a variety of these effector functions. Usually the ability to carry out a particular effector function requires that the antibody bind to its antigen. Not every immunoglobulin will mediate all effector functions. 1. 2. Fixation of complement - lysis ofcells, release of biologically active molecules Binding to various cell types - phagocytic cells, lymphocytes, platelets, mast cells, and basophils have receptors that bind immunoglobulins and the binding can activate the cells to perform some function. Some immunoglobulins also bind to receptors on placental trophoblasts. The binding results in transfer of the immunoglobulin across the placenta andthe transferred maternal antibodies provide immunity to the fetus and newborn

III.

BASIC STRUCTURE OF IMMUNOGLOBULINS The basic structure of the immunoglobulins is illustrated in the Figure 2. Although different immunoglobulins can differ structurally they all are built from the same basic unit.

Fig 2 A. Heavy and Light Chains - All immunoglobulins have a four chain structure as theirbasic unit. They are composed of two identical light chains (23Kd) and two identical heavy chains (50-70Kd) Disulfide bonds 1. Inter-chain - The heavy and light chains and the two heavy chains are held together by inter-chain disulfide bonds and by non-covalent interactions The number of interchain disulfide bonds varies among different immunoglobulin molecules.

B.

2.

Intra-chain - Withineach of the polypeptide chains there are also intra-chain disulfide bonds.

C.

Variable (V) and Constant (C) Regions - After the amino acid sequences of many different heavy chains and light chains were compared, it became clear that both the heavy and light chain could be divided into two regions based on variability in the amino acid sequences. 1. 2. Light Chain - VL (110 aa) and CL (110...