Human Anatomy and Physiology: The Lymphoid and Immune Systems PDF

Human Anatomy and Physiology Elaine N. Marieb and Suzanne M. Keller The Lymphoid and Immune Systems Learning Objectives 1. Distinguish between primary and secondary lymphoid organs 2. Define immunity 3. Describe the components of the first and second lines of the innat...

Human Anatomy and Physiology Elaine N. Marieb and Suzanne M. Keller The Lymphoid and Immune Systems Learning Objectives 1. Distinguish between primary and secondary lymphoid organs 2. Define immunity 3. Describe the components of the first and second lines of the innate immunity 4. Describe the adaptive immunity, the function of T cells and B cells the relationship between an antigen and an antibody 5. Explain the functions of antibody-mediated (Humoral) immunity and cell-mediated (Cellular) immunity and how both are important for the adaptive immunity Lymphatic System: Lymphatic Organs and Tissues The lymphatic system functions to: 1. Drain excess interstitial fluid 2. Transport dietary fats 3. Carries out immune responses Lymphoid organs and tissues are classified into two groups based on their functions; 1. Primary lymphoid organs: Red bone marrow and Thymus 2. Secondary lymphoid organs and tissues: Lymph nodes, Spleen & Lymphoid nodules Figure 21.8 Lymphoid organs (Marieb et al, 2019) All lymph nodes are illustrated in the next slide’s figure Lymphatic System: Primary Lymphatic Organs and Tissues 1. Primary lymphoid organs: where stem cells divide and become immunocompetent, include: Red bone marrow (B cells) Thymus gland (site of T cells maturation) Lymphatic System: Thymus (Lymphoid organ) The thymus: Bilobed structure, from the inferior neck into the superior thorax Location of T-lymphocyte maturation Hormonal secretion: thymosin & thymopoietin Prominent in newborn and early childhood, starts to atrophy after puberty Different from other lymphoid organs; no follicles because it lacks B cells (not directly fight antigens) Lymphatic System: Secondary Lymphatic Organs and Tissues 2. Secondary lymphoid organs and tissues: where most immune responses occur, including: Lymph nodes Spleen Lymphoid nodules, mucosa-associated lymphatic tissue (MALT) (Tonsils, Peyer’s patches, and appendix)  Lymphatic System: Lymph nodes (Lymphoid tissue) Lymph nodes have two protective functions: Lymph nodes are present throughout the body, 1. Cleansing the lymph: macrophages act as a filter & usually clustered in groups early alert system 2. Immune system activation: B-cell division, (follicular cortex), T-cell surveillance, phagocytic activity Slow fluid flow by the sinuses, fewer efferent vessels (exits) Swell with antigen accumulation (pain) and metastasizing cancers (no pain) Lymphedema: is build-up of fluid, edema in soft body tissues, a consequence of lymph system damage due to tumors or surgical removal of lymphatic nodes/vessels  Lymphatic System: Spleen (Lymphoid organ) The Spleen, Soft, blood rich organ, the size of a fist Consist of two components: White pulp (lymphocyte suspended on reticular fibers) and Red pulp (aged RBCs and macrophages) Functions of Spleen: 1. Lymphocyte activation and proliferation. 2. Blood cleansing by extracting defective red blood cells and platelets. Also, Debris, and foreign matter in blood removal by splenic macrophages 3. RBC production in the fetus (ceases after birth) 4. Stores platelets, monocytes, and iron Splenectomy: surgical procedure to remove your spleen Lymphatic System: Lymphatic nodules Lymphatic nodules, mucosa-associated lymphatic tissue (MALT) are egg-shaped masses of lymphatic tissue that are not surrounded by a capsule. Scattered throughout the connective tissue of mucous membranes lining the gastrointestinal, urinary, and reproductive tracts and the respiratory airways 1. Tonsils; located around the entrance to the pharynx “throat” 2. Peyer’s patch; located in the walls of the small intestine (distal part) 3. Appendix; located in the walls of this small tube structure which branch off the first part of the large intestine  The Immune System Immunity Immunity or resistance is the ability to ward off damage or disease through our defenses Vulnerability or lack of resistance is termed susceptibility The immune system has two intrinsic systems: 1. Innate (mostly nonspecific) defense system 2. Adaptive (specific) defense system Innate Immunity: First line of defense Innate Immunity: Second line of defense Includes cells and chemicals Necessary if microorganisms invade deeper tissues nonspecific cellular and chemical means 1. Phagocytes (neutrophils and macrophages) Adherence of phagocytes to pathogen (phagocytosis) Facilitated by opsonization 2. Natural killer (NK) cells 3. Inflammatory response: macrophages, mast cells, WBCs, and inflammatory chemicals 4. Antimicrobial proteins: interferons and complement proteins 5. Fever 1. Phagocytes Macrophages: develop from monocytes to become the chief phagocytic cells: Free macrophages walk through tissue spaces, E.g.: alveolar macrophages Fixed macrophages are permanent residents of some organs, E.g.: Kupffer cells (liver) and Microglia (brain) Neutrophils: Become phagocytic on encountering infectious material in tissues 2. Natural Killer Cells Natural Killer cells are large granular lymphocytes, NOT phagocytic cells Target cells that lack “self” cell-surface receptors (MHC) Natural Killer cells directly contact the target cells and induce; 1. Apoptosis (programmed cell death) in cancer cells and virus- infected cells 2. Secrete potent chemicals that enhance the inflammatory response 3. Inflammation: “Tissue Response to Injury” Inflammation clears the injured place from pathogens, dead tissue cells and other debris Inflammation is triggered whenever body tissues are injured by: physical trauma intense heat irritating chemicals infected by bacteria, viruses and fungi Beneficial effects of inflammation: 1. Prevents the spread of damaging agents 2. Disposes of cell debris and pathogens 3. Alerts the adaptive immune system 4. Sets the stage for repair 3. Inflammatory Response Inflammatory chemicals and their functions : Must know Only for General Knowledge Must know 3. Inflammatory Response: Steps for phagocyte mobilization 1. Leukocytosis: release of neutrophils from bone Phagocyte Mobilization marrow in response to leukocytosis-inducing factors from injured cells 2. Margination: neutrophils cling to the walls of capillaries in the inflamed area – Cell Adhesion Molecules (CAMs) 3. Diapedesis/Emigration: neutrophils squeeze between capillary cells 4. Chemotaxis: inflammatory chemicals (chemotactic agent) promote positive chemotaxis of neutrophils 4. Antimicrobial Proteins: Interferons The Interferons mechanism against viruses Interferons (IFNs) and complement proteins enhance innate defenses by 1. Attacking microorganisms directly 2. Stopping the microorganisms’ ability to reproduce Interferons are not specific Viral-infected cells are activated to secrete IFNs IFNs enter neighboring cells Neighboring cells produce antiviral proteins that block viral reproduction  4. Antimicrobial Proteins: Complement System Major mechanism for destroying foreign substances not specific A group of 20 plasma proteins. Include C1 through C9, factors B, D and P plus regulatory proteins. Activated complement 1. Amplifies all aspects of the inflammatory response and Promotes phagocytosis 2. Kills bacteria and certain other cell types by cell lysis Membrane Attack 3. Enhances (complement) both innate Complex Figure 21.6 Complement and adaptive defenses activation 5. Fever Fever is a systemic response to invading microorganisms When Leukocytes and macrophages exposed to foreign substances; they secrete pyrogens. (Pyrogens reset the body’s thermostat upward) Benefits of moderate fever: 1. Causes the liver and spleen to sequester iron and zinc (needed by microorganisms) 2. Increases metabolic rate, which speeds up tissue repair  AMPs like dermcidin, defensins, and thrombocidin Note: AMPs are short peptides that have a broad spectrum of antimicrobial activity. Examples of AMPs are dermcidin (produced by sweat glands), defensins and cathelicidins (produced by neutrophils, macrophages, and epithelia), and thrombocidin (produced by platelets).  The adaptive immune: Third line of defense The adaptive immune is a specific defense system is composed of two separate overlapping arms: 1. Humoral (antibody-mediated) immunity 2. Cellular (cell-mediated) immunity It acts by: 1. Protects against infectious agents and abnormal body cells 2. Amplifies the inflammatory response 3. Activates complement When it fails, AIDS and cancer result Effect of Antigens on the adaptative immune response Antigens are substances that trigger adaptive defenses and provoke an immune response Most are large, complex molecules not normally found in the body: non-self Antigens can be complete or incomplete: Complete antigens: (1) Immunogenicity is ability to stimulate proliferation of specific lymphocytes and release antibodies, (2) Reactivity is the ability to react with activated lymphocytes and released antibodies such as foreign proteins, polysaccharides, lipids, and nucleic acids/pollens & grains/ bacteria, fungi, and viruses. Incomplete antigens (Haptens): immunogenic when attached to body proteins, such as: poison ivy, animal dander, detergents, and cosmetics Antigenic Determinants (Epitopes) Antigenic determinants, epitopes are certain parts of an entire antigen that are immunogenic Antibodies and lymphocyte receptors bind to them Most naturally occurring antigens have numerous antigenic determinants that: 1. Mobilize several different lymphocyte populations 2. Form different kinds of antibodies against it Antibodies and the adaptative immune response Antibodies are Immunoglobulins, gamma globulin portion of blood plasma Proteins secreted by plasma cells Capable of binding specifically with antigen detected by B cells Inactivate antigens by forming antigen-antibody (immune) complexes The adaptive immunity Adaptative immunity has the following components: 1. B lymphocytes (B cells) - humoral immunity 2. T lymphocytes (T cells) - cell-mediated immunity Non-antibody producing cells 3. Antigen-presenting cells (APCs): do not respond to specific antigens, play essential auxiliary roles in immunity The adaptive immunity: B- Cells and T-Cells How lymphocytes develop, mature, and get activated? The adaptive immunity: B-Cells and T-Cells B-cells and T-cells originate from red bone marrow B cells mature in the red bone marrow T cells mature in the thymus When both types of cells mature, they become: Immunocompetence; they are able to recognize and bind to a specific antigen Self-tolerance; unresponsive to self-antigens Naive (unexposed) B and T cells are exported to lymph nodes, spleen, and other lymphoid organs The adaptive immunity: T-Cells T cells mature in the thymus under negative and positive selection pressures: 1. Positive selection: selects T cells capable of binding to self-MHC proteins (MHC restriction) 2. Negative selection: prompts apoptosis of T cells that bind to self-antigens displayed by self-MHC , to ensure self-tolerance The adaptive immunity: B-Cells B cells mature in red bone marrow Self-reactive B cells: eliminated by apoptosis (clonal deletion) or undergo receptor editing. i.e. rearrangement of their receptors. They are inactivated (anergy) if they escape from the bone marrow  Adaptive immunity: Antigen-Presenting Cells (APCs) Antigen-presenting cells (APCs) engulf antigens and present fragments of antigens to be recognized by T cells (activate naive T cells) Three Major types: Dendritic cells: in connective tissues and epidermis Macrophages: in connective tissues and lymphoid organs B cells (do not activate but present antigen to T helper cells) Humoral Immunity Response In humoral immunity, antibodies are produced and target extracellular antigens, circulate in blood or lymph Antigen challenge First encounter between an antigen and a naive immunocompetent lymphocyte, usually occurs in the spleen or a lymph node B cell activation: B cell is activated when antigens bind to its surface receptors Stimulated B cell grows to form a clone (identical cells with same receptors) Most clones become plasma cells that produce antibodies, the rest become Memory B cells Immunological Memory 1. The Primary Immune Response: Occurs on the first exposure to a specific antigen, Lag period: three to six days, peak levels of plasma antibody are reached in 10 days, antibody levels then decline 2. Secondary Immune Response: Occurs on re- exposure to the same antigen, sensitized memory cells respond within hours, Faster, More prolonged and More effective response, antibody levels peak in 2 to 3 days Humoral Immunity types Active Humoral Immunity Occurs when B cells encounter antigens and produce specific antibodies against them, it is acquired in two ways: 1. Naturally acquired response to a bacterial or viral infection 2. Artificially acquired response to a vaccine of dead or attenuated pathogens Passive Immunity Naturally acquired antibodies delivered to a fetus via the placenta or to infant through milk Artificially acquired injection of serum, such as gamma globulin, the protection is immediate but ends when antibodies naturally degrade in the body  Types of Antibodies : Very Important Antibodies proteins, also called immunoglobins (Igs) are secreted in response to an antigen by effector B cells.  Antibody Targets and Functions The Defensive mechanisms (Disabling Antigens) used by antibodies act by: 1. Neutralization 2. Agglutination 3. Precipitation 4. Complement activation (triggers cell lysis), functions: Molecules released from activation amplify the inflammatory response, promote phagocytosis by Opsonizing pathogen, and thus recruits more and more defensive elements  Cellular Immune Response Cellular immunity consists of T lymphocytes that direct adaptive immunity or attack target cells directly. There are two major types of T-cells based on the glycoprotein (CD4 or CD8) presented on the cell surface 1. CD4 cells become helper T cells (TH) when activated 2. CD8 cells become cytotoxic T cells (TC ) that destroy cells harboring foreign antigens 3. Other cell types, Regulatory T cells (Treg) (present CD4) and Memory T cells (present CD4 OR CD8) MHC Proteins and T-cell Activation MHCs (major histocompatibility complex) are antigens presented on the cell surface of infected cells with foreign material. MHCs act as “flags” to alert the immune system. Two types of MHC proteins are important to T cell activation: 1. Class I MHC proteins: displayed by all nucleated cells except RBCs 2. Class II MHC proteins: displayed by APCs (dendritic cells, macrophages and B cells) For the maturation of T cells to be either CD4 or CD8 cells, they required different MHC; CD4 cells bind to APCs that display MHC class II, then they become TH cells CD8 cells are activated by antigen fragments linked to MHC class I of APCs, then they become Tc cells Roles of Helper T (TH) Cells and Cytotoxic T (TC) Cells Helper T play a central role in the adaptive immune response, once primed by APC presentation of antigen, they: Help activate T and B cells Induce T and B cell proliferation Activate macrophages and recruit other immune cells Without TH, there is NO adaptive immune response Cytotoxic T directly attack and kill other cells, activated TC cells circulate in blood and lymph and lymphoid organs in search of body cells displaying antigen they recognize Cytotoxic T Targets: Virus-infected cells Cells with intracellular bacteria or parasites Cancer cells Foreign cells (transfusions or transplants)  Lethal Two-hit method TC cell and NK cells releases perforins and granzymes by exocytosis Perforins: create pores through which granzymes enter target cell Granzymes: stimulate apoptosis Regulatory T (Treg) cells Dampen immune response by direct contact or by inhibitory cytokines such as IL-10 and TGF-β Important in preventing autoimmune reactions Summary