3.3

Adaptive Immunity

General Features

  • Innate vs. Adaptive Immunity:

    • Innate immunity: first line of defense, non-specific.

    • Adaptive immunity: specific response to pathogens, involves lymphocytes (B cells and T cells).

  • Recognition of Non-Self:

    • Proteins from other organisms can be recognized as foreign through specific receptors.

    • Major Histocompatibility Complex (MHC) proteins play a vital role in presenting these proteins to the immune system.

Antigens

  • Definition: Substances that provoke an immune response.

  • Complete Antigens:

    • Immunogenic: Stimulate specific lymphocytes to multiply.

    • Reactive: Interact with activated lymphocytes and antibodies.

  • Incomplete Antigens (Haptens):

    • Typically not immunogenic by themselves but can react with antibodies when bound to larger carriers.

Cell Surface Receptors

  • Types:

    • T Cell Receptors (TCRs)

    • B Cell Receptors (BCRs)

    • CD Markers (CD4 for T helper cells and CD8 for cytotoxic T cells)

    • MHC Proteins (Type I and II)

  • Function:

    • These receptors are essential for recognizing antigens and initiating immune responses.

Major Histocompatibility Complex (MHC) Proteins

  • Function:

    • Distinguish self from non-self antigens.

    • MHC Class I presents endogenous antigens, while MHC Class II presents exogenous antigens to T cells.

  • Genetic Variation:

    • MHC genes show significant variation among individuals, which is crucial for the diversity of immune responses.

Antigen Presentation

  • MHC I Proteins:

    • Found on all nucleated cells, present intracellular (self) antigens.

    • Interactions with cytotoxic T cells for self/foreign discrimination.

  • MHC II Proteins:

    • Present primarily on antigen-presenting cells (APCs) like macrophages, dendritic cells, and B cells.

    • Interact with helper T cells to activate adaptive immunity.

Importance of Antigen Presentation

  • Essential for identifying infected or cancerous cells and triggering immune responses.

  • If a cell does not present MHC I, it can be targeted by natural killer (NK) cells for elimination.

Immune Cell Types

  • Agranular Leukocytes:

    • Lymphocytes: B cells (antibody production), T cells (kill infected cells), NK cells (destroy abnormal cells).

  • Granulocytes:

    • Neutrophils, eosinophils, basophils. Major contributors to innate immunity.

Adaptive Defenses

  • B Lymphocytes:

    • Differentiate into plasma cells (produce antibodies) and memory cells (provide lasting immunity).

  • T Lymphocytes:

    • Helper T cells (CD4) and cytotoxic T cells (CD8).

  • Lymphocyte Maturation:

    • B cells mature in bone marrow; T cells mature in the thymus. Both undergo selection processes to ensure self-tolerance.

Lymphocyte Selection**

  • Positive Selection: Weeding out T cells that do not recognize self-MHC proteins.

  • Negative Selection: Eliminating self-reactive T cells that could cause autoimmune disease.

Conclusion

  • Adaptive immunity relies heavily on the specific interactions between antigens and lymphocyte receptors, leading to effective and targeted immune responses against pathogens.

  • Continuous research is vital for understanding and enhancing these mechanisms for therapeutic advances.

General Features

  • Innate vs. Adaptive Immunity:

    • Innate immunity: Acts as the body’s first line of defense against pathogens, characterized by a fast, non-specific response that includes physical barriers like skin, mucous membranes, and cellular responses such as phagocytosis.

    • Adaptive immunity: Involves a specific response tailored to individual pathogens, characterized by a slower onset (days to weeks) and the involvement of lymphocytes, specifically B cells and T cells, which adapt and enhance their response upon repeat exposure.

Antigens

  • Definition: Antigens are molecules or molecular structures that are recognized by the immune system, specifically by antibodies, B cells, or T cells, provoking an immune response.

  • Complete Antigens:

    • Immunogenic: Such antigens can stimulate specific lymphocytes to undergo proliferation and differentiation, leading to a robust immune response.

    • Reactive: They have the ability to interact with previously activated lymphocytes and antibodies, ensuring that the immune response is effective against previously encountered pathogens.

  • Incomplete Antigens (Haptens):

    • Typically, these small molecules are not immunogenic on their own but can elicit a response when attached to a larger carrier protein, thus highlighting the importance of size and complexity in immune recognition.

Cell Surface Receptors

  • Types:

    • T Cell Receptors (TCRs): Unique receptors found on T cells that recognize specific antigens presented by MHC proteins, crucial for T cell activation.

    • B Cell Receptors (BCRs): Membrane-bound immunoglobulin molecules on B cells that bind directly to antigens, initiating B cell activation and antibody production.

    • CD Markers: Specific proteins found on T cells, with CD4 identifying helper T cells and CD8 marking cytotoxic T cells, playing vital roles in their respective immune functions.

    • MHC Proteins: Comprise two classes, Class I and Class II, essential for antigen presentation to T cells, facilitating an effective adaptive immune response.

  • Function:

    • These receptors are critical for recognizing antigens and triggering subsequent immune responses, ensuring the specificity of the adaptive immune system.

Major Histocompatibility Complex (MHC) Proteins

  • Function:

    • MHC proteins distinguish self from non-self by presenting processed peptide antigens to T cells, thus acting as a vital communication medium between innate and adaptive immunity. MHC Class I molecules present endogenous antigens (from within the cell), activating CD8+ cytotoxic T cells, whereas MHC Class II molecules present exogenous antigens (from outside the cell) to CD4+ T helper cells, activating them and enhancing immune responses.

  • Genetic Variation:

    • MHC genes exhibit significant polymorphism among individuals, which is essential for the diversity of immune responses across populations, enhancing the ability to combat a wide array of pathogens.

Antigen Presentation

  • MHC I Proteins:

    • These proteins are expressed on all nucleated cells and are crucial for presenting intracellular antigens to cytotoxic T cells, which monitor for signs of infection by recognizing atypical peptides.

  • MHC II Proteins:

    • Primarily found on antigen-presenting cells (APCs) like macrophages, dendritic cells, and B cells. They present processed extracellular antigens to helper T cells, facilitating their activation and subsequent orchestration of adaptive immune responses.

Importance of Antigen Presentation

  • This process is essential for the immune system's ability to detect and respond to infected or malignantly transformed cells in the body. If a cell fails to present MHC I, it can trigger a targeted immune response initiated by natural killer (NK) cells, which are crucial for eliminating abnormal cells.

Immune Cell Types

  • Agranular Leukocytes:

    • Lymphocytes:

    • B cells: Responsible for the production of antibodies, which neutralize pathogens and mark them for destruction.

    • T cells: Subdivided into helper T cells (CD4+), which modulate immune responses, and cytotoxic T cells (CD8+), which directly kill infected or cancerous cells.

    • NK cells: These cells play a critical role in the innate immune response, targeting and simplifying tumor cells or virus-infected cells without prior sensitization.

  • Granulocytes:

    • Comprising neutrophils (key players in innate response against infections), eosinophils (primarily involved in combating parasitic infections and allergic responses), and basophils (which release histamine and mediate inflammation).

Adaptive Defenses

  • B Lymphocytes:

    • Upon activation, they differentiate into plasma cells, which produce high-affinity antibodies, and memory cells, which confer long-lasting immunity against previously encountered pathogens.

  • T Lymphocytes:

    • Helper T cells (CD4) assist in activating B cells and other immune cells while cytotoxic T cells (CD8) are involved in the direct killing of infected cells.

  • Lymphocyte Maturation:

    • B cells mature in bone marrow, whereas T cells mature in the thymus gland, the latter undergoing rigorous selection processes to ensure self-tolerance and efficacy in recognizing foreign antigens.

Lymphocyte Selection

  • Positive Selection:

    • This process involves selecting T cells that can adequately recognize self-MHC proteins, ensuring a functional repertoire of T cells capable of responding to pathogens without attacking healthy tissue.

  • Negative Selection:

    • Self-reactive T cells, which could potentially lead to autoimmune diseases if allowed to persist, are eliminated during this phase, thus maintaining immune tolerance.

Conclusion

  • The success of adaptive immunity relies heavily on the precise interactions between antigens and lymphocyte receptors, leading to effective and targeted immune responses against pathogens. The ongoing research into these mechanisms is crucial for developing advanced therapeutic strategies to enhance immune protection and combat diseases, including autoimmune disorders, cancers, and vaccine development.