Immunology: Clonal Selection and Antibody Structure

Clonal Selection and Adaptive vs. Innate Immunity

• Clonal selection is a fundamental process of adaptive immunity. It involves the activation of specific lymphocytes (B and T cells) whose receptors match a specific antigen. This leads to clonal expansion of these activated cells, resulting in a large number of effector cells, and memory cells that can quickly respond to later encounters with the same antigen.
• Innate immunity, on the other hand, provides a rapid, non-specific response to pathogens through various processes like phagocytosis, inflammation, and the complement system. It does not have memory of specific antigens, meaning responses are not improved with repeated exposures to particular pathogens.

Immunoglobulin (Antibody) Structure and Diversity

• Antibodies (immunoglobulins) are Y-shaped proteins made of four polypeptide chains (two heavy and two light).
• The variable regions of the heavy and light chains form the antigen-binding sites.
• Different binding specificities arise through variations in the amino acid sequences of these variable regions. This genetic diversity allows for enormous antibody diversity to recognize many different pathogens.
• Antibodies bind to pathogen structures like surface proteins, polysaccharides, and toxins, but also the virus capsid, cell walls, and components of bacteria (e.g. flagella).

B Cell Development and Antibody Production

• B cells develop from hematopoietic stem cells in bone marrow, undergoing maturation and selection processes.
• Key events in development include rearrangement of immunoglobulin genes, expression of surface IgM, and negative selection to prevent self-reactive B cells.
• B cells differentiate into plasma cells, which secrete antibodies, after receiving signals from T helper cells (specifically activated T helper cells), and B cells that become memory B cells—a crucial component in the memory response.
• Memory B cells differentiate from activated B cells and are responsible for faster, higher antibody production during secondary exposure to the pathogen compared to a primary infection.

Antibody Classes and Isotype Switching

• Different antibody classes (isotypes) like IgG, IgA, IgM, IgE, and IgD, have distinct functions (e.g., IgG in blood, IgA in mucosal surfaces, IgM in early immune responses).
• Isotype switching involves a change in the constant region of the antibody, influencing its function without changing the antigen-binding specificity.
• Antibody isotype switching does not involve the generation of new antigen specificities.

Memory B Cell Response

• Memory B cells exhibit faster activation and higher antibody production upon second/later exposure to a pathogen compared to primary responses.
• This rapid response is due to the increased numbers of memory B cells and their immediate differentiation into plasma cells, leading to a stronger immune response.

ELISA Assays

• ELISA (enzyme-linked immunosorbent assay) is used to detect specific antibodies or antigens.
• In tests to detect exposure, a capture antibody is placed on the surface and a labelled antibody is used in conjunction with a substrate. In tests to detect the presence of a pathogen, a known antigen is used on the surface and the labelled antibody is specific for that particular pathogen antigen.
• Rapid diagnostic tests (e.g. urine test) differ from ELISA in speed and complexity.

Antigen Recognition by Antibodies and T Cells

• Antibodies recognize and bind to the entire antigen, whereas T cells recognize specific peptide fragments presented by MHC molecules on the surface of other cells (antigen presentation).
• T cells are key in coordinating immune responses. Their function varies depending on the type of T cell—helper T cells, and cytotoxic T cells.

MHC I and MHC II

• MHC I presents intracellular peptides to cytotoxic T cells, triggering their destruction.
• MHC II presents extracellular peptides to helper T cells, activating a wide range of immune responses.

Immune Response to Extracellular and Intracellular Pathogens

• Immune response to extracellular pathogens involves phagocytosis, complement activation, and antibody production targeting the pathogen directly.
• The immune response to intracellular pathogens, targeting virus infections inside cells or intracellular bacteria involves a complex interplay of cytotoxic T cells to destroy affected cells, with a more important role from helper T cells to amplify the intracellular response.

ABO Blood Group Antigens

• ABO blood group antigens are carbohydrate molecules on red blood cells.
• Individuals develop antibodies against ABO antigens not present on their own cells through exposure to these antigens in the environment.
• Individuals with type O blood lack the A and B antigens and therefore do not produce antibodies against them, making them universal donors.

Inflammation, Septic Shock, and Anaphylaxis

• Inflammation is a localized response to infection or injury, whereas septic shock is a systemic inflammatory response, and anaphylaxis is a life-threatening systemic allergic reaction.

Allergic Symptoms and Anaphylaxis

• Allergic reactions involve the IgE-mediated activation of mast cells and basophils, leading to the release of inflammatory mediators and symptoms.
• Anaphylaxis is a severe, potentially life-threatening allergic response involving the rapid release of mediators.

Penicillin and Pentadecylcatechols

• Penicillin and pentadecylcatechols can induce an immune response due to their specific chemical structures or components that react with immune components.

Pathogen Adherence

• Pathogens adhere to host cells through specific structures like pili and adhesins.
• Mutations in adhesion proteins affect host cell binding, impacting pathogen colonization but they don't eliminate the production of adhesive structures.

Bacterial Toxins

• Bacterial toxins, varying in their structure, have various mechanisms of secretion and targets within the host, some affecting cell signaling pathways, causing cell toxicity, or disruption of cellular functions.

Immune Evasion Mechanisms

• Extracellular pathogens resist immune surveillance through various means, like hiding within tissues or producing toxins or inhibiting the complement system.
• Intracellular pathogens employ mechanisms like preventing phagosome-lysosome fusion (to hide from innate immunity) and inhibiting cytotoxic T lymphocytes and other adaptive immune responses.

Anitgenic Variation and Antibiotic Resistance

• Antigenic variation is a mechanism pathogens use to avoid immune recognition by changing their surface antigens.
• Antibiotic resistance in pathogens is linked to genetic mutations or selective pressures in using antimicrobials.

Explore the concepts of clonal selection in adaptive immunity and the structure of antibodies. Understand how specific lymphocytes respond to antigens and how innate immunity differs by providing a rapid response. This quiz covers crucial immunological principles.