Relationship Between CellMediated and Humoral Immunity 1 Antibody

Relationship Between Cell-Mediated and Humoral Immunity 1. Antibody Production T-Dependent Antigens: – Antibody production requires assistance from T helper cells. – A macrophage cell ingest antigen and presents it to TH cell. – TH cell stimulates B cells specific for antigen to become plasma cells. – Antigens are mainly proteins on viruses, bacteria, foreign red blood cells, and hapten-carrier molecules. T-Independent Antigens: – Antibody production does not require assistance from T cells. – Antigens are mainly polysaccharides or lipopolysaccharides with repeating subunits (bacterial capsules). – Weaker immune response than for T-dependent antigens. 1

Humoral Response to T Dependent Antigens 2

Relationship Between Cell-Mediated and Humoral Immunity 2. Antibody Dependent Cell Mediated Cytotoxicity – Target cell is covered with antibodies, leaving Fc portion sticking outwards. – Natural killer and other nonspecific cells that have receptors for Fc region are stimulated to kill targeted cells. – Target organism is lysed by substances secreted by attacking cells. – Used to destroy large organisms that cannot be phagocytosed. 3

Destruction of Large Parasites by ADCC Antibody-dependent cellmediated cytotoxicity (ADCC): Represents the relationship between innate (cells eg. Eos) and acquired (Ab) immunity 4

Overview of the Immune Response 5

A prototype antibody molecule Light chain Disulfide bonds Heavy chain 6

ENZYME DIGESTION OF IMMUNOGLOBULINS Fragment “antigenbinding” Papain Fragment crystallizable Pepsin 7

IMMUNOGLOBULIN CLASSESTHE BASIC SUBUNITS MONOMER PENTAMER MONOMER DIMER MONOMER WHEN ACTING AS B-CELL RECEPTOR FOR ANTIGEN 8

THE PENTAMERIC Ig. M MOLECULE FIRST LINE OF DEFENCE LOW AFFINITY-HIGH AVIDITY 9

IMMUNOGLOBULIN-THE BASIC UNIT 10

CH 3

CH 2 CH 3

CH 1 CH 2 CH 3

VH 1 CH 2 CH 3

VH 1 CH 1 VL CH 2 CH 3

VH 1 CH 1 VL CH 2 CH 3 CL

VH 1 CH 1 VL CH 2 CH 3 CL

VH 1 CL VL CH 2 Elbow Hinge CH 3

Fv Fv Fv Flexibility and motion of immunoglobulins Fb Fb Elbow Fb CH 2 3 C H 3 CH 2 Hinge Fv Fv

Fv VH 1 CH 1 Fb VL CL Fab CH 2 Elbow Hinge Fc Carbohydrate CH 3

The Immunoglobulin Fold COOH S S NH 2 Unfolded VL region showing 8 antiparallel b-pleated sheets connected by loops.

Domain A protein domain is a conserved part of a given protein sequence and (tertiary) structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. 22

Domain Structure of Immunoglobulins Domains are folded, compact, protease resistant structures Fab Fc S S VL S S H 3 C C L CH 2 Heavy chain C domains a, d, e, g, or m Pepsin cleavage sites Papain cleavage sites CH 1 S VH S F(ab)2 - 1 x (Fab)2 & 1 x Fc - 2 x Fab 1 x Fc Light chain C domains k or l

The Structure of Immunoglobulins 2 heavy (H) chains (~50 k. D) 2 light (L) chains (~25 k. D) Total mw >150 k. D Effector function is determined by the constant regions of the H chains. The 5 classes of immunoglobulins are determined by the H chain constant region. . 24

Greek letters are used to name the heavy and light chain constant regions g, m, a, d, e for the heavy chains k, l for the light chains (k: l = 2: 1 human; 20: 1 mice; For example; lk 1: 20 bovine) dg The heavy chain determines the class of the Ig, thus Ig. G Ig. D If the heavy chain is g the class is Ig. G (and g 1 for Ig. G 1, etc. ) If the heavy chain is m the class is Ig. M If the heavy chain is a the class is Ig. A If the heavy chain is d the class is Ig. D If the heavy chain is e the class is Ig. E Q: What is the isotype of this Ig? A: Ig. A ? ? Different heavy chains provide different functions and distribution; there is no known difference in function for k and l l a Q: what is the name of heavy and light chains that are not labeled? A: a and l 25

Heavy and light chains are disulfide linked (interchain disulfide bond) Heavy chains are disulfide linked (interchain disulfide bond) Each immunoglobulin domain has an intrachain disulfide bond 26

Different way to depict an Ig molecule Y 27