Antigens, Epitopes, and Immunogens

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Questions and Answers

What is the term for the specific part of an antigen that binds with B-cell receptors (BCR) and T-cell receptors?

  • Antigen
  • Paratope
  • Immunogen
  • Epitope (correct)

Which of the following is a characteristic of immunogens?

  • Self-antigens that do not stimulate the immune system
  • Large antigens that induce an immune response by binding with immune receptors (correct)
  • Antigens that require a carrier molecule to induce an immune response
  • Small antigens that cannot induce an immune response on their own

What distinguishes a hapten from an immunogen?

  • Haptens can induce an immune response by themselves, while immunogens cannot.
  • Haptens are large and complex, while immunogens are small and simple.
  • Haptens require conjugation with a carrier molecule to induce an immune response, while immunogens do not. (correct)
  • Haptens cannot bind to immune receptors, while immunogens can.

What is the primary characteristic of tolerogens?

<p>They are self-antigens that do not typically stimulate an immune response. (D)</p> Signup and view all the answers

Which molecular size is generally more immunogenic?

<p>Proteins greater than 10 kDa (C)</p> Signup and view all the answers

How does complexity influence immunogenicity?

<p>Complex proteins with diverse epitopes are more likely to induce an immune response. (B)</p> Signup and view all the answers

What aspect of an antigen's structure is crucial for its immunogenicity regarding immune system interaction?

<p>Conformation and accessibility (A)</p> Signup and view all the answers

Which of the following chemical properties is most likely to make a substance a good immunogen?

<p>Protein (B)</p> Signup and view all the answers

Which type of antigen activates B cells without the help of T cells?

<p>T-cell independent antigen (B)</p> Signup and view all the answers

Which type of antigen requires T cell help for B cell activation?

<p>T-cell dependent antigens (B)</p> Signup and view all the answers

What is the primary function of immunoglobulins?

<p>To mediate humoral immunity (A)</p> Signup and view all the answers

Where are antibodies primarily produced in the body?

<p>Lymphoid tissue and bone marrow (D)</p> Signup and view all the answers

Which form of immunoglobulin is expressed on the surface of B cells as a B cell receptor (BCR)?

<p>Membrane-bound IgM and IgD (C)</p> Signup and view all the answers

Where are secreted immunoglobulins typically found?

<p>Plasma and mucosal interstitial fluids (D)</p> Signup and view all the answers

What is the basic structure of an antibody molecule?

<p>Four polypeptide chains in a Y shape (B)</p> Signup and view all the answers

Which region of the antibody contains the hypervariable regions that determine its specificity?

<p>Variable domain (C)</p> Signup and view all the answers

What type of bond connects the heavy and light chains in an antibody molecule?

<p>Disulfide bond (B)</p> Signup and view all the answers

Which region of the antibody molecule includes the site of antigen recognition and binding?

<p>Fab region (D)</p> Signup and view all the answers

What characterizes the Fc region of an antibody?

<p>It tends to crystallize in solution and mediates effector functions. (C)</p> Signup and view all the answers

What is the role of the hinge region in an antibody molecule?

<p>Flexible region that lies between Fab and Fc to accommodate different Ag (A)</p> Signup and view all the answers

How are immunoglobulin classes determined?

<p>Differences in the constant domains of the heavy chain (D)</p> Signup and view all the answers

Which immunoglobulin class is associated with mucosal immunity?

<p>IgA (A)</p> Signup and view all the answers

What is the primary role of IgD?

<p>B cell receptor (C)</p> Signup and view all the answers

Which immunoglobulin class is involved in allergic reactions and parasitic infections?

<p>IgE (D)</p> Signup and view all the answers

Which immunoglobulin class is the most abundant in serum and involved in opsonization?

<p>IgG (C)</p> Signup and view all the answers

What is the secreted form of IgM?

<p>Pentamer (C)</p> Signup and view all the answers

What is the main characteristic of monoclonal antibodies?

<p>They are identical antibodies produced by a single clone of cells. (D)</p> Signup and view all the answers

How are monoclonal antibodies produced?

<p>Using hybridoma technology (D)</p> Signup and view all the answers

In hybridoma technology, what is the purpose of fusing B cells with myeloma cells?

<p>To provide immortality and produce large amount of antibodies (C)</p> Signup and view all the answers

What is a key application of monoclonal antibodies in research and clinical settings?

<p>To identify phenotypic markers on cells (D)</p> Signup and view all the answers

How are monoclonal antibodies used in immunodiagnosis?

<p>To detect specific antigens or antibodies (A)</p> Signup and view all the answers

What is a therapeutic application of monoclonal antibodies?

<p>Immunosuppression and prevention of graft rejection (E)</p> Signup and view all the answers

Which of the following statements accurately describes a key difference between monoclonal and polyclonal antibodies?

<p>Monoclonal antibodies are produced from a single B cell lineage, recognizing a single epitope on the antigen, whereas polyclonal antibodies are derived from multiple B cell lineages, recognizing different epitopes on the same antigen. (D)</p> Signup and view all the answers

Imagine a scenario where researchers are developing a new therapeutic antibody to target a specific cancer cell marker. They aim to enhance the antibody's ability to recruit cytotoxic T cells to the tumor site. Which part of the antibody would they most likely engineer to improve this function?

<p>The Fc region, to enhance binding to Fc receptors on cytotoxic T cells. (B)</p> Signup and view all the answers

A researcher is investigating a novel antigen that is a small, chemically defined molecule. They find that this molecule can bind to B cell receptors but does not elicit an antibody response on its own. To generate antibodies against this molecule, the researcher should:

<p>Conjugate the molecule to a larger protein carrier before injecting it into an animal. (D)</p> Signup and view all the answers

A biotechnology company is developing a novel monoclonal antibody for treating rheumatoid arthritis, an autoimmune disease. They engineer the monoclonal antibody to have high affinity for TNF-$\alpha$, a key inflammatory cytokine. However, during clinical trials, patients developed severe hypersensitivity reactions shortly after receiving the antibody. What is the most likely cause?

<p>The monoclonal antibody is cross-linking IgE on mast cells and basophils (B)</p> Signup and view all the answers

You are designing a diagnostic test for a new viral infection. You have two potential antibodies: one IgG and one IgM, both specific for the viral antigen. Knowing the kinetics of antibody responses, which antibody would be MOST useful for detecting an acute, early-stage infection?

<p>IgM, because it is the first antibody produced during an immune response and indicates a recent infection (D)</p> Signup and view all the answers

A patient presents with a suspected immune deficiency. Lab tests show normal levels of B cells but significantly reduced levels of IgG, IgA, and IgE, while IgM levels are elevated. All the subclasses of IgG are tested and the patient is deficient in all the IgG's. The IgM pentamers appear normal and testing shows that antibodies are functional. What is the most likely underlying cause?

<p>A defect in heavy chain class (isotype) switching (A)</p> Signup and view all the answers

An avid researcher is studying the process by which B lymphocytes switch from producing IgM antibodies to IgG antibodies during a T-dependent immune response. He hypothesizes that T follicular helper (Tfh) cells are absolutely required in this process. To test this hypothesis, the researcher designs an experiment where he incubates activated B cells with antigen plus or minus Tfh cells. To measure the production of IgG by individual B cells irrespective of their antigen specificity, she should use:

<p>Flow cytometry to examine the fraction of B cells that have acquired the IgG isotype (C)</p> Signup and view all the answers

Flashcards

What is an Antigen?

A substance recognized by the immune system.

What is an Epitope?

The smallest part of an antigen, that binds with B cell receptors (BCR) and T cell receptors.

What are Immunogens?

Large antigens with epitopes capable of binding with immune receptors and inducing an immune response.

What are Haptens?

Small antigens that can bind to immune receptors but cannot induce an immune response on their own, unless conjugated with a large carrier molecule.

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What are Tolerogens?

Self-antigens that do not normally stimulate an immune response.

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What are T-independent antigens (TI)?

Activate B cells directly, without T cell help.

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What are T-dependent antigens?

Require T cell help to activate B cells.

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What are Immunoglobulins (Igs)?

Glycoproteins that mediate humoral immunity.

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What are Membrane-bound Ig?

Expressed on B cell surfaces (IgM and IgD); binds antigen to initiate B cell response.

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What are Secreted Ig?

Found in plasma and mucosa; includes various antibody isotypes with diverse functions.

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What is the basic structure of Antibodies?

Y-shaped molecules made of 4 polypeptide chains: 2 identical heavy and 2 identical light chains.

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What is the Fab Region?

Region of an antibody that contains the whole light chain + VH + CH1; involved in antigen recognition and binding.

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What is the Fc Region?

Region of an antibody that contains the remaining heavy chains; involved in effector and biological function.

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What are Ig classes (isotypes)?

Subdivisions of immunoglobulins (IgG, IgA, IgM, IgE, IgD) based on heavy chain structure.

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What is Heavy chain class (isotype) switching?

Switch from one Ig isotype to another after B cell activation.

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What are Monoclonal Antibodies?

Identical monospecific antibodies derived from a single parent cell clone.

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What is Hybridoma technology?

A technology used to produce monoclonal antibodies by fusing B cells with myeloma cells.

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Study Notes

  • A 27-year-old pregnant woman in her first trimester has a pink continuous maculopapular rash and enlarged posterior auricular lymph nodes
  • Positive Measles IgG, negative Cytomegalo-virus IgM, and positive rubella IgM
  • Diagnosis and potential fetal effects are needed

Antigens

  • Antigens are substances recognized by the immune system
  • Antigens can be simple or complex
  • Antigens can be carbohydrates, lipids, proteins, nucleic acids, or phospholipids
  • B cells recognize any biological antigen
  • T cells recognize peptide antigens presented on MHC

Epitopes

  • Epitopes are the smallest part of an antigen that binds with B cell receptors (BCR) and T cell receptors
  • If an antigen contains multiple epitopes, it is called a multivalent antigen
  • Paratope is the part of the antibody that recognizes the epotope

Immunogens

  • Immunogens are large antigens with epitopes allowing binding with an immune receptor and induce an immune response
  • Not all antigens are immunogens

Haptens

  • Haptens are small antigens with epitopes capable of binding with an immune receptor but without inducing an immune response
  • Haptens can produce an immune response when conjugated with a large carrier molecule like a protein
  • This results in an immune response against epitopes of both the hapten and the carrier

Tolerogens

  • Tolerogens are self-antigens (MHC) that normally do not stimulate the immune system

Factors Influencing Immunogenicity

  • Size matters, proteins greater than 10 KDs are more immunogenic
  • Complex proteins with numerous and diverse epitopes are more likely to induce an immune response compared to simple peptides

Conformation and Accessibility

  • Epitopes must be accessible to the immune system to be effective
  • Proteins are good immunogens
  • Carbohydrates, steroids, and lipids are not

Type of Antigens

  • T-cell independent antigens (TI) can activate B cells without T cell help
  • Examples include polysaccharides like Pneumococcal polysaccharide and LPS
  • T-cell dependent antigens require T cell help for B cell activation
  • Examples include proteins like microbial proteins, non-self proteins or altered-self proteins

Immunoglobulins

  • Immunoglobulins (Igs) or antibodies, are glycoproteins that mediate humoral immunity
  • Antibodies are produced in lymphoid tissue and bone marrow

Production and Distribution of Antibodies

  • In the lymph node, antigen stimlulation of B cells with the help of T helper cytokines leads to B cell proliferation and differentiation into plasma cells which secrete antibodies that enter circulation to the site of infection
  • Mature B cells in the bone marrow express membrane bound antibodies (B cell receptors)

Forms of antibodies

  • Membrane bound Ig include IgM and IgD, expressed on B cell surfaces as BCR for Ag
  • Ig, when bound to an Ag, intiates a B cell response
  • Secreted Ig are found and function in plasma and mucosa and interstitial fludis of tissues

Antibody Structure

  • Antibodies are Y-shaped molecules composed of 4 polypeptide chains
    • Two identical heavy chains with 1 variable domain (VH) and 3 or 4 constant domains (CH)
    • Two identical light chains with 1 variable domain (VL) and 1 constant domain (CL)
  • Each variable domain (VL or VH) contains three hypervariable region - complementary determining repeats (CDR)
  • Disulfide bonds connect heavy chains with light chains and heavy chains with each other

Antibody Fragments

  • Fab (fragment antigen-binding) includes the full light chain + VH + CH1; there are two per antibody for antigen recognition and binding
  • Fc (fragment crystallizable) includes the remaining constant domains of the heavy chains for domain effector & biological function
  • Hinge region - Flexible region lies between Fab & Fc

Immunoglobulin Classes

  • Immunoglobulins are divided into five classes based on the structure in constant domains of heavy chain
    • Gamma heavy chains: IgG
    • Alpha heavy chains: IgA
    • Mu heavy chains: IgM
    • Epsilon heavy chains: IgE
    • Delta heavy chains: IgD
  • Different classes and subclasses of antibodies perform different effector functions
  • There are two types of light chains called K (kappa) and λ (lambda); an antibody has either two kappa or two lambda light chains
  • Heavy chain class (isotype) switching is the switch from one Ig isotype to another after activation of B lymphocytes

Immunoglobulin Classes Details

  • IgA
    • Subtypes include IgA1,2
    • H chain is α1 or α2
    • Serum concentration is 3.5mg/ml
    • May be monomer, dimer or trimer
    • Function: mucosal immunity
  • IgD
    • H chain is δ
    • Serum concentration in traces
    • No secreted form
    • Function: B cell receptor
  • IgE
    • H chain is ε
    • Serum concentration is 0.05mg/ml
    • Monomer form
    • Function: parasite immunity and allergy response
  • IgG
    • Subtypes include IgG1-4
    • H chain is γ(1,2,3,4)
    • Serum concentration is 13.5 mg/ml
    • Monomer form
    • Function: Opsonization, complement activation, ADCC (antibody-dependent cell-mediated cytotoxicity)
  • IgM
    • H chain is µ
    • Serum concentration is 1.5 mg/ml
    • Pentamer form
    • Function: B cell receptor, complement activation

Monoclonal Antibodies

  • Monoclonal antibodies (mAbs) are identical, monospecific antibodies produced from clones of a single parent cell
  • Antibodies obtained from the blood of an immunized host are polyclonal antibodies
  • Production involves hybridoma technology, where B cells from an immunized mouse are fused with myeloma cells
  • This produces hybridomas, which can be grown in culture to secrete large amounts of monoclonal antibodies

Production of Monoclonal Antibodies

  • Immunize a mouse with an antigen
  • B cells are isolated from the spleen of the mouse
  • Then fused with myeloma (cancerous) cells in vitro
  • Using a fusion agent
  • Poly-ethylene glycol or a virus

Monoclonal Antibody Applications

  • Identification of phenotypic markers to define clusters of differentiation (CD markers) on lymphocytes
  • Immunodiagnosis, with detection of specific antigens or antibodies in circulation or tissues
  • Tumor diagnosis using tumor-specific monoclonal antibodies for detection of tumors by imaging
  • Anti-CD3 for immunosuppression and prevention of graft rejection

Practice Questions

  • IgG is present normally at the highest concentration in the plasma
  • A molecule covalently linked to a non-immunogenic antigen to make it an immunogen is called carrier
  • The Fab portion of IgG is part of antigen recognition and binding

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