Definition of antigen?
-any molecule capable of binding specifically to antigen receptor on B or T lymphocytes
What type of molecule is an antigen?
-can be carb, lipid, or nucleic acid
When an antigen is a protein, what deals with it? how?
-must be processed and presented by a major histocompatibility complex
-done by antigen presenting cells
When an antigen is a carb, lipid, or nucleic acid, what deals with it?
-better if conjugated to protein
What antigens are better?
bigger and more complex ones
Definition of immunogen?
any agent capable of inducing an immune response by T or B lymphocytes
Difference between antigens and immunogens?
-all immunogens are antigens, but not all antigens are immunogens
-immunogens actually generate an immune response -antigens can generate a response
What 7 factors determine immunogenicity?
1. the chemical nature of the antigen, doesn't have to be linear, T cells only process linear, B cells can do both
2. the antigens size
3. the antigens usual presence in the body (self vs non self)
4. antigen dose, route and timing of administration
5. whether the antigen is easily phagocytosed
6. whether antigen is efficiently presented to T cells on MHC
7. the maturity of the immune system and specific lymphocytes
What does immunogenicity depend on?
the immune system as well as the antigen
Epitope definition? Linear or nonlinear? how many amino acids long?
-part of an antigen that directly interacts with the antigen receptor on lymphocytes
-linear for T lymphocytes
-conformational or linear for B lymphocytes
-5 to 7 amino acids long for antibody, longer for T cells
What happens to proteins that have several epitopes?
they are recognized by different B cells and induce a polyclonal antibody response
What happens in a polyclonal response?
several clones of B cells each make different antibodies, all able to bind to the same antigen but at different epitopes- multivalent antigen
Epitopes on multivalent antigens?
they may have multiple identical epitopes or multiple different epitopes
Cross reactivity of epitopes?
epitopes may be shared by closely related antigens so that antibody made to tetanus toxoid binds to tetanus toxin
What are antibodies (immunoglobulins)? How are they made?
-variable, antigen specific proteins made by B cells
secreted when B cells are:
-stimulated by relevant antigen
-get help from T cells
-differentiate into plasma cells
-facilitate class switching
What is the structure of immunoglobulin?
Two heavy chains:
-composed of 3-4 globular constant (C) domains (regions)
-one variable (V) domain
-can be one of 5 classes: mew, delta, epsilon, alpha, gamma
Two light chains:
-composed of one V and one C domain (region)
-can be either kappa or lambda
What are the fragments of immunoglobulins?
Fab -antigen binding portion
Fc (crystallizable) -biologic activity
What cleaves the fragments of immunoglobulins?
Papain -cleaves into 2 Fab and 1 Fc fragment
Pepsin -cleaves into one F(ab)2 and one Fc
What is the hinge region of immunoglobulins?
-links Fc and Fab portions of the immunoglobulin molecule
-allows for flexibility
-molecular ball and socket joint
What is the variable domain of immunoglobulins? where is it present? function? regions?
-present in heavy and light chains
-contains highly variable region called hyper variable, also known as complementarity determining regions (CDR)
-contains less variable framework region
What is the immunoglobulin superfamily? What are the 6 in the family?
-a family of closely related cell surface and secreted molecules
3. Class I MHC
Roles of Immunoglobulin?
-serve as a B cell surface receptor
-serve as a secreted molecule
What are the 5 classes of immunoglobulins (Ig)? What makes them different?
1. IgG- has gamma heavy chain constant region
2. IgM- has mew heavy chain constant region
3. IgD- has delta heavy chain
4. IgA- has alpha heavy chain
5. IgE- has epsilon heavy chain
What is the secreted form of IgA? Functions? Half life?
-sometimes monomer or trimer
What is the secreted form of IgD? Functions? Half life?
-naive B cells antigen receptor
What is the secreted form of IgE? Functions? Half life?
-defense against helminthic parasites, immediate hypersensitivity
What is the secreted form of IgG? Functions? Half life?
-antibody dependent cell mediated cytotoxicity
-feedback inhibition of B cells -23 days
What is the secreted form of IgM? Functions? Half life?
-naive B cell antigen receptor (monomeric form)
What genes make the different classes of immunoglobulins?
all classes are made from the same gene
What is the only time we have two classes of immunoglobulins on the same cell surface? why? what determines which one is secreted?
-IgM and IgD
-have not encountered the antigen yet
-whatever antigen attaches to the cell surface, that Ig is secreted
What chromosomes are the genes encoding kappa and lambda light chains, as well as, the heavy chains on?
-kappa light: chromosome 2
-lambda light: chromosome 22
-heavy chain (all): chromosome 14
What are the encoded sections of the heavy chain (V) region gene?
What are the encoded sections for the light chain (V) region gene?
What is the structure of IgA dimer?
-dimerized via J chain
Structure of IgM pentamer?
pentamerized via J chain
What are 7 biologic properties of IgG?
2. Agglutination and formation of precipitates
3. passage through placenta
4. activation of complement via classical path
5. neutralization of toxin
6. immobilization of bacteria
7. neutralization of viruses
Opsonization process in IgG?
-binds epitopes on microorganisms via Fab
-binding of phagocytic cells via Fc receptor
Agglutination and formation of precipitates in IgG?
-particulate antigens (bacteria) can agglutinate with IgG
-soluble multivalent antigens can precipitate
What passes through placenta to fetus (IgG)?
-transfer of immunity from mother to fetus
-only Ig that passes mother to child adds protection at birth
Activation of complement in IgG?
-results in lysis of cell bearing antigen
-certain complement components act as opsonins and direct phagocytes to antigen
-certain complement components are chemotactic (pro inflammatory)
Immobilization of bacteria in IgG?
IgG antibodies to cilia of flagella cause clumping
Neutralization of viruses in IgG?
antibodies to viral coat antigens preven viral attachment
Biologic properties of IgA?
-tears, saliva, colostrum, sweat, mucus
-prominent role in mucosal immunity
Biologic properties of IgM?
-activation of complement- more efficient than IgG because of IgM pentameric structure
-isohemagglutinin- naturally occurring antibodies against the ABO blood group antigens
What is the strength of binding (avidity) between IgG and IgM with complement?
IgM very strong due to pentameric structure
Biologic property of IgD?
B cell maturation
Biologic properties of IgE?
-reaginic antibody (allergy)
-immunity against parasitic infection
What are the multiple sources of therapeutic agents as antibodies?
-chimeric (mouse variable domains + human constant domains)
-humanized (mouse CDR + human)
-human (made in mice)
3 examples of therapeutic agents as antibodies? What does it treat? Target?
1. Rituximab (chimeric)- treats B cell malignancies -target: CD20 B cell surface marker
2. Omalizumab (humanized)- treats severe cases of allergy -target: IgE
3. Adalimumab (human)- treats rheumatoid arthritis -target: TNF-alpha