1. Immunoglobulins
Unit III

5. Epitope :An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells
Paratope : The paratope is the part of an antibody which recognises an antigen, the antigen-binding site of an antibody. It is a small region (of 15–22 amino acids) of the antibody's Fv region and contains parts of the antibody's heavy and light chains.

14. Forces of Interaction Between Epitope and Paratope

15. Antibody Structure
Antibodies can also be divided into two regions based on their function
Fab (fragment, antigen binding) region.
Tip of the antibody
Binds the antigen
Fc (fragment, crystallizable) region
Base of the antibody
Can bind cell receptors, complement proteins and other molecules
Antibodies can also be divided into two regions based on their functions. The tip of the “Y”, consisting of one constant and one variable domain from each heavy and light chain of the antibody, contains the region that binds the antigen. It is for this reason that we call it the Fab (fragment, antigen binding) region. The base of the “Y”, composed of two heavy chains, plays a a role in modulating immune cell activity. This region is called the Fc (Fragment, crystallizable) region. The Fc region can bind to cell receptors, complement proteins, as well as to other immune molecules, thereby initiating different physiological effects including opsonization, cell lysis, and degranulation. 15

16. Each heavy and light chain has a constant and variable region
Each heavy chain and light chain has two regions, the constant and variable region. The constant region is identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. The variable region of the heavy chain is located at the tip of the chain. It differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone.
Each heavy and light chain has a constant and variable region
The variable region binds the antigen in a “lock-and-key” manner 16

19. Factors Influencing Immunogenicity of an Antigen
Foreignness :The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic.
Size: There is not absolute size above which a substance will be immunogenic. However, in general, the larger the molecule the more immunogenic it is likely to be.
Chemical Composition: In general, the more complex the substance is chemically the more immunogenic it will be. The antigenic determinants are created by the primary sequence of residues in the polymer and/or by the secondary, tertiary or quaternary structure of the molecule.
Physical form: In general particulate antigens are more immunogenic than soluble ones and denatured antigens more immunogenic than the native form.
Degradability: Antigens that are easily phagocytosed are generally more immunogenic. This is because for most antigens (T-dependant antigens, see below) the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC).

20. HAPTEN
A hapten is a small molecule that can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself.
(In general, only large molecules, infectious agents, or insoluble foreign matter can elicit an immune response in the body.)
Once the body has generated antibodies to a hapten-carrier adduct, the small-molecule hapten may also be able to bind to the antibody, but it will usually not initiate an immune response; usually only the hapten-carrier adduct can do this.
Sometimes the small-molecule hapten can even block immune response to the hapten-carrier adduct by preventing the adduct from binding to the antibody, a process called hapten inhibition.
The mechanisms of absence of immune response may vary and involve complex immunological mechanisms, but can include absent or insufficient co-stimulatory signals from

23. Antibody Classes: Structure
© New Science Press Ltd. 2003

28. Distribution of Immunoglobulin isotypes in the body

29. The Immunoglobulin Superfamily a few examples

30. B-Cell Receptor

31. Affinity and Avidity
Affinity: the strength of binding between a single binding site and a single ligand.
Avidity: the strength of binding between a molecule and a complex ligand, e.g. if there are multiple binding sites then the avidity may be increased by increasing the number of binding sites or by increasing the affinity of those binding sites.

32. Affinity and Avidity, continued
IgM is produced early in an immune response when the affinity for antigen often is low; as an immune response continues, antibody affinity is improved, this is combined by “class switching” to the use of smaller molecules (IgG, IgE and IgA). The increased affinity compensates for the decrease in number of binding sites in maintaining the overall avidity for antigen.

33. © New Science Press Ltd. 2003

36. Antibody Isotype Immature B-cells only express surface IgM
As it matures, it expressed both IgM and IgD
After reaching maturity, the B-cell is ready to interact with antigen and produce antibody
As antibodies are formed, some undergo isotype switching and produce IgE, IgA or IgG
The Assignment: Isotypes
Antibody isotype changes during development and with activation of the B-cells. Immature B-cells that have never been exposed to antigen are known as naïve B-cells and express only cell surface bound IgM. As the B-cell begins to reach maturity, it expresses both IgM and IgD. After reaching maturity, the B-cell is ready to interact with circulating antigen. Once an antigen is bound, the B-cell becomes activated and begins to divide and differentiate into the antibody factory, a plasma cell. In this activated form, the B-cell can now secrete antibody, allowing it to circulate in your blood and serum.
Some antibodies from the daughter cells of activated B-cells undergo isotype switching, whereby we get production of IgE, IgA or, most commonly, IgG. 36

37. Antibody Isotype IgM – 1st class of circulating antibody
- found in pentameric form
IgG - most abundant antibody
IgA - located in the mucous membranes
- found in dimeric form
IgD - found on surface of B-cells
- probably involved in memory cell formation
IgE - involved in allergies, i.e. trigger release of
histamine 37

38. Immunoglobulin Isotypes or Classes
I. IgG
Structure: Monomer
Percentage serum antibodies: 80%
Location: Blood, lymph, intestine
Half-life in serum: 23 days
Complement Fixation: Yes
Placental Transfer: Yes
Known Functions: Enhances phagocytosis, neutralizes toxins and viruses, protects fetus and newborn.

39. Immunoglobulin Classes
II. IgM
Structure: Pentamer
Percentage serum antibodies: 5-10%
Location: Blood, lymph, B cell surface (monomer)
Half-life in serum: 5 days
Complement Fixation: Yes
Placental Transfer: No
Known Functions: First antibodies produced during an infection. Effective against microbes and agglutinating antigens.

40. Immunoglobulin Classes
III. IgA
Structure: Dimer
Percentage serum antibodies: %
Location: Secretions (tears, saliva, intestine, milk), blood and lymph.
Half-life in serum: 6 days
Complement Fixation: No
Placental Transfer: No
Known Functions: Localized protection of mucosal surfaces. Provides immunity to infant digestive tract.

41. Immunoglobulin Classes
IV. IgD
Structure: Monomer
Percentage serum antibodies: 0.2%
Location: B-cell surface, blood, and lymph
Half-life in serum: 3 days
Complement Fixation: No
Placental Transfer: No
Known Functions: In serum function is unknown. On B cell surface, initiate immune response.

42. Immunoglobulin Classes
V. IgE
Structure: Monomer
Percentage serum antibodies: %
Location: Bound to mast cells and basophils throughout body. Blood.
Half-life in serum: 2 days
Complement Fixation: No
Placental Transfer: No
Known Functions:. Possibly lysis of parasitic worms. Pathological function is its involvement in Allergic reactions

43. Antibody Function
Antibodies are the main component of the Humoral Immune System
They bind antigen and flag them for elimination via 1 of 3 ways:
Function
Antibodies constitute the main component of the humoral immune system. They circulate freely in the bloodstream and search for harmful foreign agents. Antibodies protect the immune system from invading antigens by binding to them and flagging them for elimination via one of three ways:

44. Viruses and intracellular bacteria require a
Neutralization:
Viruses and intracellular bacteria require a
host cell in order to replicate
Antibodies prevent their entry into the cell
by binding the antigen, making it harder
for it to pass through the cell membrane.
Antibodies cannot attack pathogens hidden
within cells
Neutralization: Viruses and intracellular bacteria require a host cell in order to replicate and pass on disease. These antigens generally enter the cell either by fusing with receptors on the cell. Antibodies prevent this action by binding to the antigen, making it harder for it to pass through the cell membrane. Antibodies cannot attack pathogens within cells.

45. antigen, antibodies flag the foreign agent for destruction
Opsonization:
Upon binding to an
antigen, antibodies flag the
foreign agent for destruction
or elimination by other
immune cells, such as natural
killer cells or macrophages
Opsonization: Upon binding to an antigen, antibodies flag the foreign agent for destruction or elimination by other immune cells, such as natural killer cells or macrophages.

46. Activation of Complement: Similar to opsonisation, antibody will
flag the antigen for elimination.
However, elimination is initiated by a
cascade of proteins which collect on
the cell membrane and form a hole,
leading to cell lysis
Activation of Complement: Similar to opsonisation, antibody will flag the antigen for elimination. However, elimination is initiated by a cascade of proteins which collect on the cell membrane and form a hole, leading to cell lysis.

47. Terms
adaptive immunity: the response of antigen-specific lymphocytes to antigen, including the development of immunological memory
antibody: an antigen-binding immunoglobulin, produced by B-ells, that functions as the effector of an immune response
antigen: a foreign molecule that does not belong to the host organism and that elicits an immune response
B-cell: a type of lymphocyte that develops in the bone marrow and later produces antibodies, which mediate humoral immunity
complement: an immune response whereby a cascade of proteins attack extracellular forms of pathogens
Fab (fragment, antigen binding) region: the regions of the antibody that binds the antigen
Fc (Fragment, crystallizable region): the region of the antibody that binds to cell receptors
heavy chain: heavy chains come in a variety of heavy chain classes or isotypes, each which confers a distinct function to the antibody
humoral immunity: the type of immunity that fights bacteria and viruses in the body fluids with antibodies that circulate in blood plasma and lymph
immune system: is the name used to describe the totality of the host defence mechanism
immunoglobulin: all antibody molecules belong to this family of plasma proteins
isotype: antibody class determined by the heavy chain
light chains: smaller of the two components making up an antibody
memory B-cell: a clone of long-lived lymphocytes, formed during the primary immune response, that remains in a lymph node until activated by exposure to the same antigen that triggered it’s formation. Activated memory cells mount the secondary immune response.
naïve B-cell: a B-cell that has never bound antigen before
neutralization: when antibodies inhibit the infectivity of a virus or the toxicity of a toxin
opsonisation: is the alteration of the surface of a pathogen or other particle so that it can be ingested by phagocytes
plasma cell: a derivative of B-cells that secretes antibodies, i.e. antibody factory
variable region: regions that contains the antigen binding site