Chapter 20 (Part III) - Adaptive Immune System

Chapter 20 (Part III): The Adaptive Immune System

What is Adaptive Immunity?

• Definition: The last and most effective line of defense against pathogens.

• Components: Involves cells of the lymphoid lineage, specifically lymphocytes and Natural Killer (NK) cells.

• Lymphocytes: Specialized leukocytes comprising B-cells and T-cells, known for their specific capability to bind to antigens due to cell surface receptors.

  • T-cell receptors (TCRs): Present on T-cells.

  • B-cell receptors (BCRs): Present on B-cells.

• Memory: Lymphocytes retain memory of encountered antigens, allowing for stronger responses to subsequent infections.

Antigens

• Definition: Substances recognized by lymphocytes; related to pathogens or aberrant cells allowing the immune system to identify them upon future encounters.

  • Forms of Antigens: Typically peptides (proteins), but also sugars, glycoproteins, glycolipids, or metals like nickel.

• Function: Distinguishes self from foreign entities, functioning like "nationality papers" for cells.

Self Antigens vs. Immunogens

• Self Antigens: Present in host cells, recognized as non-threatening; demonstrate to the immune system that the cell is part of the organism.

• Immunogens: Antigens that provoke an immune response.

• Autoimmune Disease: Occurs when self antigens are misidentified as immunogens, leading the immune system to attack the body’s own cells.

• Immunodeficiency Disorder: Occurs when immunogens are not recognized or responded to by the immune system, reducing its efficacy.

Endogenous vs. Exogenous Antigens

• Exogenous Antigens: Arise from outside the cell, present on pathogen surfaces, require phagocytosis by antigen-presenting cells (APCs) for activation of lymphocytes.

• Endogenous Antigens: Originating within the host cell, either from pathogens within the cell or encoded by mutated/self-generated DNA, presented by MHC molecules.

Major Histocompatibility Complex (MHC)

• Definition: Glycoproteins on cell surfaces that present antigens; categorized into MHC-I and MHC-II.

• MHC-I: Found on all nucleated cells; presents endogenous antigens to demonstrate the health status of the cell (self vs. aberrant).

• MHC-II: Found on APCs (e.g., dendritic cells, macrophages, B-cells); presents exogenous antigens to helper T-cells to initiate immune response.

T-cells

• Definition: A type of lymphocyte in the adaptive immune response, available to react to specific antigens.

• Production and Maturation: Originates in bone marrow, matures in thymus.

• Types of T-cells: Including Cytotoxic T-cells (TC) and Helper T-cells (TH).

  • Cytotoxic T-cells: Recognize and kill aberrant cells via MHC-I presentation.

  • Helper T-cells: Activate other immune cells and amplify the immune response via cytokine release.

T-cell Receptors (TCRs)

• Function: Each T-cell bears many identical TCRs that specifically recognize distinct antigens, created through random DNA rearrangement prior to antigen exposure.

• Selection Process: Involves positive and negative selection of T-cells in the thymus to ensure that only functional and self-tolerant T-cells mature.

Helper T-cells

• CD4 Cells: Recognize exogenous antigens presented by MHC-II; activated by dendritic cells.

• **Functions: **Release cytokines to enhance the activation of other immune cells, including B-cells and cytotoxic T-cells.

Cytotoxic T-cells

• CD8 Cells: Target and kill cells displaying endogenous antigens via MHC-I.

• Mechanism: Releases perforins that create pores in target cells and induce apoptosis.

Natural Killer Cells

• Identify cells lacking MHC, playing a crucial role in targeting these aberrant cells, including some cancers.

Dendritic Cells

• Role: Essential in activating naive T-cells; distinguishes between endogenous and exogenous antigens due to differing presentation on MHC.

• Importance for Adaptive Immunity: They are the most effective APC, crucial for an efficient adaptive response.

Organ Transplants and Rejections

• Transplants as Foreign: Need to limit recognition by T-cells; various graft types (autograft, isograft, allograft, xenograft) differ in compatibility.

• Immunosuppressants: Used to prevent rejection but increase vulnerability to infections.

B-cells

• Function: Produce antibodies, serve as APCs with MHC-II.

• Activation: Through antigen binding; may require helper T-cell support.

• Effector Cells: Differentiate into plasma cells (antibody-secreting) and memory cells (for rapid response upon re-encountering an antigen).

Antibodies

• Definition: Secreted BCRs from plasma cells; proteins with variable and constant regions.

• Types of Antibodies: Include IgG, IgA, IgM, IgE, and IgD; differing in function and structure.

• Role: Facilitate pathogen detection, opsonization, and neutralization.

Immunological Memory

• Primary vs Secondary Response: Faster and more effective secondary responses due to the presence of memory cells, leading to less severe illness upon re-exposure.

Vaccines

• Purpose: Expose the host to antigens to prepare adaptive immunity for future infections.

• Types of Vaccines: Live-attenuated, inactivated, and subunit vaccines.

• Flu Vaccination: Recommended annually due to rapid mutations of the virus.

Hypersensitivity and Immunodeficiency Disorders

• Types of Hypersensitivity: Type I is commonly known as an allergy, involving the overproduction of IgE.

• Immunodeficiency: Refers to disorders leading to reduced immune function, such as AIDS and SCID.

Autoimmune Diseases**

• Definition: Conditions where the immune system attacks self antigens as if they were foreign, e.g., Type I Diabetes, Multiple Sclerosis.

Summary of Immune Responses**

• Viral Infections: Cytotoxic T-cells target infected cells via MHC-I, while antibodies from B-cells further neutralize pathogens.

• Bacterial Infections: Involve activation of helper T-cells recognizing exogenous antigens presented by MHC-II, enhancing response coordination.