Immuno II

• Adaptive defenses are reviewed and compared with innate defenses in this lecture.
• The roles of B and T lymphocytes, antigens, and antigen-presenting cells in adaptive immunity are also examined.

Lecture Goals

• Understand the difference between humoral and cellular immunity and know which cells are responsible for each.
• Know what antigens are, why they are important, and how the body recognizes self versus non-self.
• Know the steps of the immunocompetent cycle.
• Understand the steps involved in humoral immunity and B-cell cloning.
• Understand the different types of humoral immunity, including active vs. passive and natural vs. artificially acquired.
• Describe structure of an immunoglobulin (Ig), know the different classes of Igs, and explain how they differ.
• Understand the mechanisms of how antibodies work and the strategies employed to destroy antigens once bound.
• Understand the mechanisms of how antigen-presenting cells (APCs) operate.
• Understand the mechanisms of how cytotoxic and helper T cells operate.

Overview of Adaptive Immunity

• Adaptive immunity requires priming before it can take effect.
• In the 1800s, experiments showed that animals surviving bacterial infections developed protective factors in their blood to defend against future attacks by the same pathogen.
• Serum containing antibodies can protect other animals not previously exposed.
• Injecting lymphocytes also offered protection.

Types of Adaptive Immunity

• Humoral immunity involves antibodies produced from lymphocytes that circulate in the body's fluids (blood, lymph).
  • This targets extracellular pathogens such as bacteria, toxins, and free viruses with B cells.
• Cellular immunity involves lymphocytes directly defending the body.
  • This targets cellular pathogens such as cells infected with pathogens, cancer cells, and foreign graft cells with T cells.

Adaptive vs. Innate Immunity

• Adaptive defenses uses B and T lymphocytes, whereas innate defenses involves diverse cells, processes, and structures like NK cells, phagocytes, antimicrobial proteins, inflammatory chemicals, and physical barriers.
• Adaptive immunity is specific, recognizing and targeting identified pathogens or foreign substances like antigens, while innate immunity is nonspecific in identifying friend or foe.
• Adaptive immunity is slow to mobilize, while innate immunity is fast and always ready.
• Adaptive immunity has memory, reacting strongly to successive encounters of the same antigen, whereas innate immunity usually has no memory.
• Adaptive immunity is systemic (body-wide) and not restricted to the initial infection site, while innate immunity is largely restricted to the initial infection site, except for fever.

Antigens

• Antigens are substances that can provoke an immune response, including any foreign cells.
• Antigens not normally present in the body are recognized as 'non-self,' triggering an immune response.
• Self-recognition/self-antigens are molecules on the surface of cells.
• Major histocompatibility complex (MHC) class I proteins are found on all nucleated cells in the body.
• MHC class II proteins are found on antigen-presenting cells.
• Antigens have "antigenic determinants" where antibodies or lymphocyte receptors bind.

Immunocompetence of Lymphocytes

• Before lymphocytes can respond to antigens, they must become immunocompetent.
• Lymphocytes (B cells, T cells) originate from red bone marrow.
• B and T cells mature in primary lymphoid organs, displaying receptors that can recognize antigens, which makes them immunocompetent.
  • B cells mature in the bone marrow.
  • T cells mature in the thymus.
• Lymphocytes circulate in blood and secondary lymphoid organs.

Humoral Immune Response (B-Cell Cloning)

• Immunocompetent B-cells encounter and bind to antigens.
• B-cells clone themselves.
• Most clone cells differentiate into plasma cells (effector B cells), but some clone cells become memory cells.
• Plasma cells secrete antibodies into plasma during the primary immune response, where antibody levels peak around day 10.
• If memory cells are re-exposed to the same antigen later, a secondary immune response occurs, which is more rapid, larger, and prolonged.

Humoral Response

• The first exposure to an antigen is the primary immune response.
  • Antibody production begins in about 3-6 days, with antibody levels peaking around day 10.
• The second exposure to the same antigen induces a secondary immune response.
  • The secondary immune response is faster, larger, and more prolonged.

Types of Humoral Immunity

• Active humoral immunity can be either naturally or artificially acquired.
  • Occurs through infection or vaccination.
  • Both result in the formation of memory B cells and provide long-term protection.
• Passive humoral immunity can be either naturally or artificially acquired.
  • Occurs through antibodies passed from mother to fetus or infant, or injection of gamma globulin.
  • Ready-made antibodies are introduced into the body and do not create memory B cells.
  • Provides short-term protection where protection from the mother lasts several months, while exogenous antibodies last weeks.

Antibodies (Immunoglobulins or Igs)

• Antibodies are secreted by plasma cells (effector B cells) in response to an antigen.
• An antibody monomer has four polypeptide chains linked by disulfide bonds, forming a T or Y shape.
  • Includes 2 heavy (H) chains and 2 light (L) chains.
  • C (constant) region.
  • V (variable) region.
  • The V regions of H and L chains combine to form two antigen-binding sites in a monomer.

Antibody Classes

• Include 5 major classes IgD, IgG, IgE, IgA, and IgM
• IgD, IgG, and IgE are monomers, IgA is a dimer, and IgM is a pentamer.
• Dimers have 4 antigen-binding sites, and pentamers have 10.

Antibody Functions

• Antibodies inactivate antigens and tag them for destruction.
• Strategies to achieve this include:
  • Neutralization: Blocking the harmful effects of the antigen.
  • Agglutination: Clumping together antigen particles.
  • Precipitation: Making soluble antigens insoluble.
  • Complement activation: Triggering the complement system to enhance phagocytosis or cell lysis.

Cellular Immunity: T Lymphocytes (T cells)

• Two types of T cells exist including helper T and cytotoxic T.
• Cytotoxic T cells (TC) directly kill body cells that are infected by viruses or bacteria, cancerous or abnormal, or foreign (transplanted cells).
• Helper T cells (TH) release chemicals that help activate TC cells and B cells.

Cellular Immunity: Antigen-Presenting Cells (APCs)

• APCs have MHC class II proteins on their cell surfaces.
• APCs engulf antigens and present fragments to T-cells to initiate an immune response.
• Examples of APCs include dendritic cells, macrophages, and B cells.

T-Cell Activation

• T-cells activate by double recognition, where they must recognize both the foreign antigen displayed and self (MHC I or MHC II).
• TH cells bind to antigens on APCs and also recognize self (MHC II).
• TC cells bind to antigens on body cells and also recognize self (MHC class I proteins).

Cellular Immunity: Helper T cells (TH)

• TH cells bind to antigens on APCs and also recognize self (MHC II).
• Macrophages release interleukin-1, which stimulates TH cells to release interleukin-2 (IL-2).
• IL-2 stimulates the activation and proliferation of TC and B cells. -TC cells then attack infected cells. -B cells engage in antibody production.

Cellular Immunity: Cytotoxic T cells (TC)

• Infected/cancerous cells display abnormal antigens.
• TC cells bind to abnormal antigens on body cells and also recognize self (MHC class I proteins).
• TC cells release perforins and granzymes to kill off infected cells after recognizing the target.

Clinical Connections

• Organ transplants require tissue similarity to prevent T cells, NK cells, and antibodies from attacking the new organ, often involving immunosuppressive and anti-inflammatory drugs.
• Immunodeficiencies result in immune cells and/or antibodies behaving abnormally.
• Autoimmune diseases involve a loss of ability to distinguish self from non-self, leading the body to produce antibodies against its own cells.
  • In HIV/AIDS, helper T (TH) cells are destroyed. -Multiple Sclerosis (MS) destroys the white matter of the brain and spinal cord. -Type-1 diabetes destroys pancreatic cells that produce insulin.