Immunology Quiz: Antibody Function and Superantigens

Adaptive Immunity and Immunization

• Adaptive immunity is the third line of defense, and is a product of B and T lymphocytes.
• Immunocompetence is the ability of the body to interact with a wide spectrum of foreign substances.
• Molecules that stimulate response by T and B cells are called Antigens.
• Specific immunity is characterized by antibodies that function only against the antigen in response to.
• Lymphocytes are programmed to recall their first encounter with an antigen and respond rapidly to subsequent encounters.

Overview of Specific Immune Responses

• The specific immune response has separate but related activities:
  • Development and differentiation of the immune system
  • Lymphocytes and antigen processing
  • Cooperation between lymphocytes during antigen presentation
  • B lymphocytes and the production and actions of antibodies
  • T lymphocyte responses

Development of the Lymphocyte System

• Lymphocytes arise from the same stem cells but differentiate into two distinct cell types:
  • T cells mature in the thymus gland.
  • B cells mature in specialized bone marrow sites.
• Matured cells settle in lymphoid organs and provide constant defense against infection.

Contact with Antigens and Antigen-Presenting Cells (APCs)

• Foreign cells bear molecules called antigens that are recognized and engulfed by antigen-presenting cells (APCs).
• Dendritic cells are APCs that present processed antigen to helper T cells. In most responses, T helper cells receive the processed antigen from the APC and go on to activate B and other T cells.

Activation of T Cells

• An activated T cell forms memory cells and differentiates into helper cells (T_H) or cytotoxic cells (T_C).
• Cell-mediated immunity is triggered when the whole T cell acts directly to destroy the microbes, rather than by secreting molecules into the body fluids.

B-Cell Responses

• A B cell, activated by T helper cells, undergoes a surge in cell division, producing memory cells, which trigger rapid recall to the antigen and plasma cells that secrete antibodies (proteins).

Humoral Immunity

• Antibodies circulate in blood, extracellular fluid, and lymph, providing hormonal immunity.
• Antibodies react specifically with the antigen and enhance the immune response.

Development of the Immune Response System

• Cell receptors or markers confer specificity and identity of a cell.
• Major functions of cell receptors include:
  • Perceiving and attaching to nonself or foreign molecules
  • Promoting the recognition of self molecules
  • Receiving and transmitting chemical messages among other cells of the system
  • Aiding in cellular development.

Major Histocompatibility Complex (MHC)

• MHC is a set of cell surface proteins.
• Receptors are found on all cells except red blood cells (RBCs).
• The MHC (HLA) system recognizes self and non-self molecules.
• The MHC gene family is divided into two main groups:
  • MHC Class I genes
  • MHC Class II genes

Functions of MHC Groups

• MHC genes code for markers that display unique characteristics.
• This unique characteristic allows recognition of self and non-self molecules and regulates immune reactions.
• Required for T lymphocytes to interact with pathogens.
• MHC class I molecules are found on all nucleated human cells (except red blood cells).
• MHC class II molecules are found on some types of white blood cells.

Lymphocyte Receptors

• B-cell receptors bind free antigens.
• T-cell receptors bind processed antigens together with MHC molecules on cells that present antigens to them.
• Antigen molecules are diverse in their chemical structure exhibiting potentially billions of uniquely different structures and shapes.
• Sources of antigens include microorganisms and chemical compounds in the environment.

Origin of Diversity and Specificity in the Immune Response

• Lymphocytes use 500 genes to generate a tremendous variety of specific receptors.
• Undifferentiated lymphocytes undergo a continuous series of divisions and genetic changes during embryonic and fetal development. This then generates hundreds of different cell types each with unique receptor specificity.

Development of Lymphocytes

• In the bone marrow, lymphocytic stem cells either develop into B cells or T cells.
• B cells remain in the bone marrow while T cells migrate to the thymus gland to mature.
• Mature T and B cells migrate to secondary lymphoid tissues; these tissues will constantly be supplied with B and T cells

Proliferative Stage of Lymphocyte Development

• Lymphocyte specificity exists in the genetic makeup before an antigen has ever entered the system.
• Lymphocytes with receptors that recognize self-molecules are eliminated (clonal deletion).
• Each surviving lymphocyte is specific for a single antigen molecule making an enormous pool of mature but naïve lymphocytes.
• Naïve lymphocytes are ready to further differentiate in response to various immune stimuli in the body's "home" organs.

Clonal Selection and Expansion

• The first introduction of an antigen selects a genetically unique lymphocyte clone.
• This causes the clone to rapidly expand with mitotic divisions into a larger population of lymphocytes that can react to the same single specificity antigen.

Antibody Structure and Functions

• Antibodies (Igs) are large glycoproteins with four polypeptide chains connected by disulfide bonds.
• The protein chains are in a Y-shape with two functionally distinct segments called fragments:
  • Antigen-binding fragments (Fabs) with the amino-terminal end and variable regions of the heavy and light chains: antigens bind here.
  • Crystallisable fragments (Fc) that binds to various cells and molecules within the immune system.

Antigen-Antibody Binding

• The Fab antigen-binding site is composed of hypervariable regions with extremely variable amino acid content.
• The groove of the antigen-binding site has a specific three-dimensional fit for the antigen.
• The specificity of the two Fab sites is identical for each antigen.

Antibody-Antigen Interactions

• The goal of antibodies is to bind to the antigen that initiated antibody formation.
• In the process of coating microorganisms and other particles, specific antibodies are called opsonins.
• Antibodies fill surface receptors on viruses and microbial enzymes to prevent attachment.
• Several forms of interaction between antibodies and antigens include agglutination (clumping together of cells or particles), complement fixation, and precipitation.

Functions of the Fc Fragment

• Fc fragments bind to cell membranes of macrophages, neutrophils, eosinophils, mast cells, basophils, and lymphocytes.
• Regions on the Fc portion enable antibody molecules to fix complements.
• Binding of the Fc portion in certain antibodies may cause the release of cytokines.

Classes of Immunoglobulins (Isotypes)

• Five functional classes (isotopes) of immunoglobulins (Ig):
  • IgG: monomer; produced by plasma cells; most prevalent in serum.
  • IgA: monomer in blood; dimer in mucous and serous secretions.
  • IgM: pentamer; first class synthesized after Ag encounter; serves as a receptor for antigen on B cells.
  • IgD: monomer; serves as a receptor for antigen on B cells.
  • IgE: monomer; involved in allergic responses and parasitic worm infections.

Antibodies in Serum

• Serum containing specific antibodies may be separated into 4 bands via electrophoresis; Alpha-1 (a1), Alpha-2 (a2), Beta (β), and Gamma (γ) globulins.
• Most globulins are antibodies.
• Gamma globulin (γ) is predominately composed of IgG; others are a mixture of IgG, IgA, and IgM.

Monitoring Antibody Production

• Primary response: a latent period with no measurable antibody occurs early; IgM then followed by IgG is produced; titer tapers to low levels.
• Secondary response: a latent period is lacking; rapid rise in antibody titer (mainly IgG) and sustained for several weeks; smaller amount of IgM.

Antibodies

• Originate from single clones and have a single specificity for an antigen.
• Pure preparation of antibody: formed by fusing a mouse B cell with a cancer cell to create high specificity.
• Used in diagnosis, microbe identification, and treatment.

Use of Monoclonal Antibodies for Treatment

• Trastuzumab (Herceptin) - breast cancer
• Rituximab (Rituxan) - B-cell disorders (lymphomas, leukemias)
• Omalizumab (Xolair) - asthma
• Belimumab (Benlysta) – systemic lupus erythematosus (SLE)
• Daclizumab - Multiple Sclerosis
• Ibalizumab(Trogarza) - HIV
• Erenumab(Aimovig) - Migraine
• Adalimumab(Humr) - Rheumatoid arthritis, psoriasis
• Casirivimab and Imdevimab - COVID-19

Immunity Categories by Mode of Acquisition

• Active immunity: develops when a person is challenged with an antigen stimulating production of antibodies; creates immunological memory; takes time to develop but is lasting.
• Passive immunity: preformed antibodies are donated to an individual; no immunological memory is created; acts immediately; is short-term.
• Natural immunity: acquired as part of normal life experiences.
• Artificial immunity: acquired through a medical procedure, such as a vaccine.

Examples of Origins of Immunity

• Getting an infection: recovering from an infectious disease and developing active resistance to reinfection.
• Mother-to-child: IgG antibodies from the mother can pass or be actively transported across the placenta to the fetus; IgA antibodies from breast milk react against microbes entering the intestine.
• Immunotherapy: a preparation of antibodies is administered to a patient at risk of infection.
• Vaccination: microbial (antigenic) stimulus to trigger the immune system to produce antibodies and memory cells.

Categories of Acquired Immunities

• Acquired Immunity
• Natural immunity: acquired though normal life experiences
• Active immunity: results when a person develops their own immune response.
• Passive immunity: results when a person receives preformed immunity.
• Artificial immunity: produced purposefully through medical procedures (immunization).

Immunization

• Useful for immunocompromised patients who cannot be vaccinated. Acts immediately; lasts 2 to 3 months.
  • Human antisera
  • Intravenous immune globulin (IVIG), gamma globulin; Ig extracted from pooled blood of donors; used in preventing measles, hepatitis A, and in replacing antibodies in immunodeficient patients
  • Specific immune globulin (SIG) from donors in a hyperimmune state after vaccination or infection by pertussis, tetanus, chickenpox, hepatitis B
• Antisera and antitoxins of animal origin: sera is produced in horses; used in diphtheria, botulism, and spider and snake bites.

Artificial Active Immunity

• Can be conferred by provoking exposure to material that is antigenic, but not pathogenic, to stimulate a primary and secondary anamnestic response to prepare the immune system for future encounters to virulent pathogens
• Response is immediate, powerful, and lasting

Principles of Vaccine Preparation

• Vaccines are prepared from:
  • Killed whole cells or inactivated viruses
  • Live, attenuated cells or viruses
  • Antigenic molecules derived from bacterial cells or viruses
  • Genetically engineered microbes or microbial agents
• Vaccines should have low toxicity/side effects; protect against naturally occurring pathogens; stimulate both antibody response and cell-mediated response; produce long-term effects creating memory cells; work with minimal doses or boosters; be inexpensive; have a relatively long shelf life; and be easy to administer.

Advantages and Disadvantages of Live Vaccines

• Advantages: Organism can multiply; long-lasting protection; usually requires fewer doses and boosters.
• Disadvantages: Requires special storage; can be transmitted to other people; can conceivably mutate back to virulent strain.

Whole Pathogen Vaccines

• Vaccines made from whole pathogens (killed or deactivated) or whole but attenuated (reduced virulence) microorganisms.
• They stimulate immunity but cannot cause the disease.

Vaccines from Microbe Parts

• Vaccines that rely on a portion of the cell of a virus; uses antigens to create immunity; exotoxins are used in tetanus and diphtheria vaccines.

Genetically Engineered Vaccines

• Purified antigen vaccines: plasmids with surface antigens are used to stimulate a response without direct contact, are used in hepatitis B, and HPV vaccines.
• Viral vector vaccines: use modified viruses to deliver genetic code to human cells mimicking viral infection. Johnson & Johnson COVID vaccine, Ebola vaccine, and trials for HIV & Zika are ongoing.
• RNA vaccines: viral RNA is inoculated into the recipient; primary means of protecting against COVID-19; vaccine against influenza is currently in clinical trials.

Development of New Vaccines

• No reliable vaccines are available for HIV or various diarrheal diseases, respiratory diseases, and worm infections.
• Companies are exploring plant-based methods for mass production of vaccine antigens.
• Tests are underway to use plants like tomatoes, potatoes, and bananas to synthesize proteins from pathogens like cholera, hepatitis, and papillomavirus.

Routes of Administration and Side Effects of Vaccines

Most vaccines are administered via injection (few oral, nasal). Some vaccines require a compound to enhance immunogenicity. Benefit outweighs risk. Possible side effects include local reaction at the injection site, fever, allergies, and rarely mutated back into virulent strain or neurological effects.

Herd Immunity

• Immune individuals do not harbor pathogens, subsequently reducing occurrence.
• This makes it less likely that a nonimmunized person will encounter the pathogen

Vaccine Protection

• Vaccines have dramatically reduced the morbidity of various diseases like measles, pertussis, mumps, rubella, smallpox, and polio (paralytic).

Test your knowledge on the immune response, specifically focusing on the roles of superantigens and antibodies. This quiz covers topics such as antibody structure and B-cell activation processes. Challenge yourself with questions that explore the intricacies of immune system functioning.