M3 Online: Antibody and Antigens

This information is from the online module

M3: Features of Biologic Antigens

Q: What is the basic definition of antigen?

Q: What recognize and bind to the antigen?

Antigen: substances that are recognized by immune system

All functions of antibodies depend on their ability to specifically bind antigens

M3: Features of Biologic Antigens

Q: Is it only the antibody that the antigen can bind to or there is another one?

An antigen is any substance that can be bound by antibody or by T cell receptor (TCR)

M3: Features of Biologic Antigens

Q: Which features does the antibodies can recognize of an antigen?

• lipids

• simple sugars

• nucleic acids

• proteins

• All above

• complex carbohydrates

All above

M3: Features of Biologic Antigens

Q: Which features does the TLR can recognize of antigen

• simple sugars

• complex carbohydrates

• proteins

• nucleic acids

• peptides derived from proteins

• lipids

• All above

ONLY peptides derived from proteins

M3: Features of Biologic Antigens

Q: Can all antigens activate lymphocytes? What are they called?

Not all antigens can activate lymphocytes, only some which are called immunogens

M3: Features of Biologic Antigens

Q: It is known that small chemicals itself cannot activate B cells because they are not immunogenic. In order to generate antibodies, what does the small chemicals need?

The small chemicals need to physically attached(coupled) to larger protein (which itself is an an immunogen)

M3: Features of Biologic Antigens

Q: When both the small chemical and protein are conjugated together, they are known to act as an immunogen. What are the names for the small chemical and the larger protein?

• Hapten

• antibody

• carrier

• immunogen

• globulin

Hapten: small chemical

Carrier: the large protein to which it is conjugated

M3: Features of Biologic Antigens

Q: What is a antigenic determinant or epitope?

It is where an antibody only bins a portion of a macromolecule since they are generally bigger than antigen-binding region of antibodies

M3: Features of Biologic Antigens

INFORMATION ON TYPE OF EPITOPES

• Since macromolecules can contain multiple epitopes, it is known that they can be repeated and each can be bound by an antibody. This is called polyvalency or multivalency. The spatial arrangement of different epitopes influences antibody binding.

M3: Features of Biologic Antigens

INFORMATION ON TYPE OF DETERMINANTS

• Nonoverlapping determinants are when epitopes that are well separated can be bound by two or more antibodies and do not influence each other

• Overlapping determinants are when epitopes are close together, the binding of antibody to the first epitope causes steric hinderance, preventing binding of the second

  • the binding of the first antibody can also cause conformational changes that affect the binding of second antibody

• The formation of some epitopes depends on primary structure of protein, while other epitopes depend on the tertiary structure

M3: Features of Biologic Antigens

INFORMATION OF TYPES OF DETERMINANTS

• Linear determinants: epitopes formed by several adjacent amino acids (USUALLY SIX)

• Conformational determinants: formed when amino acids are spatially juxtaposed in folded protein. Denaturing destroys these epitopes.

• Neoantigenic determinants: formed upon post-translational modification as glycosylation or phosphorylation

just info

M3: Structure and Chemical Basis

Q: Define affinity and avidity. Which definition it belongs to?

• Strength of binding between an antibody and an epitope

• Overall strength of attachment; it can be greater than ___

• AFFINITY: strength of binding between an antibody and an epitope

• AVIDITY: overall strength of attachment; it can be greater than affinity

M3: Structure and Chemical Basis

INFORMATION

• a monovalent interactions results when epitopes are spaced wide apart on surface of a microbe.

• although affinity of antibody for antigen may be high, this is a LOW avidity interaction

• a bivalent or polyvalent interaction results when epitopes are closer together and both antigen binding sites on an IgG molecule (bivalent) or all 10 antigen-bindings on IgM are engaged. This is a high avidity interaction

M3: Structure and Chemical Basis

INFORMATION

• polyvalent antigens are biological significance because effector functions of antibodies are optimallly tiggered

• formation of antigen-antibody complex is also function of relative concentrations of antigen and antibody

• formation of large immune complexes can cause inflammation and disease

  • at correct amounts of antibody to antigen—called zone of equivalence, a network of attached molecules if formed

  • increasing antigen (zone of antigen excess) or increasing antibody (zone of antibody excess) can dissociate immune complexes

M3: Structure—Function Relationships in Antibody

Features Related to Antigen Recognition—SPECIFICTY

• Antibodies are very specific for antigen.

• They can distinguish two linear epitopes by difference of a single amino acid or different chemical isomers

• Some antibodies can bind to different but a structurally-related antigen This is called a cross-reaction and is basis for disease

M3: Structure—Function Relationships in Antibody

Features Related to Antigen Recognition—DIVERSITY

• an individual can make a lot of number of structurally distinct antigens—up to 10^11—each with different specificity

• ability of antibodies in a given individual to bind large number of antigens reflects antibody diversity

• collection of antibodies with different specificities represents the antibody repertoire

• genetic mechanism for this diversity is random recombination of a set of inherited germline DNA sequences into functional genes that encode antibody heavy and light chains

M3: Structure—Function Relationships in Antibody

Features Related to Antigen Recognition—AFFINITY MATURATION

• tight binding between antigen and antibody is needed to activate B cells

• this binding achieved by generation of high affinity binding antibodies

• mechanism for making high affinity antibodies are called somatic mutation, involves changes in V region of an antibody during T cell dependent humoral immune responses to protein antigens

  • B cells that produce higher affinity antibodies preferentially bind to antigen and re selected to become dominant B cell population made in response to that antigen (survival of the fittest)

• overall process of affinity maturation increases antibody binding from Kd ranging 10^-7 to 10^-9M during a primary response to a Kd of 10^11 M or less during a secondary antigen response

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M3: Structure—Function Relationships in Antibody

Features Related to Effector Function

• Many effector functions of antibody are mediated by Fc portion of molecules.

• Antibody isotypes that differ in Fc regions perform distinct functions

  • IgG coats microbes and helps phagocytosis because its Fc portion binds to Fc receptors expressed on neutrophils and macrophages

  • C1q complement protein initiates classical complement pathway by binding to Fc portions of IgM or IgG

• Various effector mechanism are only activated when antibody binds antigens and not by free antibody

• changes in isotype of antibodies influence how and where these responses work to eliminate antigen

  • after stimulation with antigen, a B cell produces antibodies of different isotype but with same V domains (antigen-binding site)

M3: Structure—Function Relationships in Antibody

• Naive B cells produce IgM and IgD and upon further antigen activation (ex: microbe recognition) they undergo isotype switching in which C region of heavy chain is changed

  • isotype switching enables original B cell (that made IgM/IgD) to produce IgG with same antigen specificity to eradicate a bacterial infection or IgE to eliminate a parasite

• heavy chain C region determines tissue distribution of antibody molecules

• As B cells are activated these lose expression of membrane-bound antibody and express secreted antibody

• IgA is secreted through mucosal epithelia and is major antibody found in mucosal secretions and breast milk

• Neonatal IgG secreted from mothers help protect infants from infection

• The transfer of maternal IgG is mediated through placental and intestinal expressed Fc receptors