Lymphatic & Immune System PDF 2024

Lymphatic and Immune System Dr. Dalal Almuaili Nov 2024 Today’s lecture Lecture Overview: Lymphatic System: Function, structure, and distribution Immune System: Definition, function, and distinctions between innate and adaptive immunity Learning Objective...

Lymphatic and Immune System Dr. Dalal Almuaili Nov 2024 Today’s lecture Lecture Overview: Lymphatic System: Function, structure, and distribution Immune System: Definition, function, and distinctions between innate and adaptive immunity Learning Objectives: Understand the role of the immune system in overall physiology Understand the source of lymph and its role in immune system function Describe the histological structure and functions of lymph nodes and spleen Explain the structure and function of the thymus Describe and contrast the innate and adaptive immune responses Dr. Dalal Almuaili  Why do we divide the human body into different physiological systems? To allow us to Study >>> Understand >>> Identify/Predict/Prevent/Solve problems Dr. Dalal Almuaili Background Immunology originated by studying the body’s defense against infection to address questions including: How does the body defend itself? How does the body eliminate a threat? How does the body develop long-lasting immunity? In 1908, the Nobel prize was awarded to two scientists. Paul Ehrlich for his contributions towards understanding immunity. Ilya Ilyich Mechnikov for his contribution towards describing phagocytosis The immune system is now appreciated in maintaining homeostasis under many other circumstances. Dr. Dalal Almuaili The Lymphatic and Immune System What makes up the lymphatic system? Lymphatic vessels Lymph nodes Lymph What makes up the immune system? Immune cells Lymphoid organs Primary lymphoid organs: Thymus, Bone marrow Secondary lymphoid organs: Lymph nodes, Spleen, Tonsils, Peyer’s patches Dr. Dalal Almuaili  Lymph Vessels Drained by the right lymphatic duct Drained by the thoracic duct Lymph vessels are a one-way network that allow lymph to move towards the heart. Source: Human Anatomy & Physiology, 11the by Elaine Marib & Katja Hoehn Collecting vessels have thinner walls, more internal valves. Largest collecting vessels unite to form lymphatic trunks. Trunks are drained by two large Lymphatic Collecting Lymphatic Lymphatic Lymphatic capillaries Trunks Ducts ducts. Vessels Dr. Dalal Almuaili Function of the Lymphatic System 1. What is Lymph? Lymph is the fluid contained within the lymphatic vessels. Lymph contains interstitial fluid, proteins, pathogens, absorbed fat 2. What is the function of the lymphatic system? Supports the immune system in its role in the body’s defense. Dr. Dalal Almuaili Components of the immune system Immune cells Granulocytes Eaters Parasite destroyers Allergic Scouts reactions Eaters Dr. Dalal Almuaili Components of the immune system Immune cells-continued. Lymphocytes Effector Antibody Killers cells producers Dr. Dalal Almuaili Lymphoid organs Primary lymphoid organs Red bone marrow, and thymus B and T cells originate in the red bone marrow, T-cells then migrate and mature in the thymus, while B-cells mature in the bone marrow. Secondary lymphoid organs Lymph nodes, Spleen, Mucosa Associated Lymphoid Tissue (MALT) including Tonsils, and Peyer’s patches. Site of first interaction between antigens and immune cells. Dr. Dalal Almuaili Thymus Capsule Site of T-cell maturation, lacks B-cells. T-cells become immunocompetent. Histological features: Capsule: outer layer Cortex: site of immature T-cells Medulla: site of mature T-cells Source: Hill et al, 2019 Dr. Dalal Almuaili Lymph node Hundreds of lymph nodes along lymphatic vessels Large clusters near body surface: inguinal, axillary, and cervical regions Sites of antigen interaction with immune cells Known for their “cleansing” function through phagocytosis of microorganisms Histological structure: Capsule Cortex: Includes germinal centres full of lymphocytes. Medulla: Includes macrophages and lymphocytes Lymph travels into nodes through afferent vessels, Source: Essentials of Human and from the nodes through efferent vessels. Anatomy & Physiology, 13the by Elaine Marib & Suzanne Keller Dr. Dalal Almuaili Spleen Located in the left side of the abdominal Capsule cavity beneath the diaphragm Site of lymphocyte proliferation Filters blood Histological features: Capsule Red pulp: Mostly macrophages; site of RBC Source: https://precisionary.com/ filtration White pulp: Mostly lymphocytes; site of immune function Dr. Dalal Almuaili The main role of the immune system To distinguish SELF from NON-SELF To recognise and eliminate threat How can the immune system recognise self and foreign cells? The immune system is made up of cells that express receptors, those receptors bind to corresponding ligands (antigens) on different cells and molecules and those ligands indicate whether they are “self” (or harmless) or non-self (or harmful). Dr. Dalal Almuaili Antigens vs antibodies Antigens are any molecule than can elicit (initiate) an immune response. Antibodies are proteins produced by the immune system with specificity to the antigen that initiated their production. Receptors are expressed on the surface of cells Ligand and also would only bind to specific ligands. Receptor There are several important families of receptors Antigen including PRRs (to be discussed later). Ligands are any portion of a molecule that binds Antibody to a receptor. Dr. Dalal Almuaili The origin of immune cells Immune cells can be categorized into two main groups depending on their location: Circulating immune cells Tissue-resident immune cells Most of circulating immune cells originate in the bone marrow Most tissue resident immune cells expand from precursor cells that are seeded in their tissues during embryonic development from the yolk sac or fetal liver. Dr. Dalal Almuaili Pathogens and the microbiome Pathogens are microorganisms that can cause disease. There are four categories of pathogens: Viruses Bacteria Fungi Parasites The microbiome refers to the microenvironment of commensal microorganisms Known to have little to no damage to the tissue, and often benefit the human body. (How?) Dr. Dalal Almuaili 1. Activation of Immunity There are 2 broad types of immune responses against threats: Innate immune response Fast non-specific immune response Adaptive immune response Slower specific immune response Dr. Dalal Almuaili The story of an innate immune response Initiate inflammation Kill pathogen Dr. Dalal Almuaili Principles of innate immunity Macrophages, dendritic cells, and neutrophils are very important innate immune cells. Macrophages are long lived cells. They are known for their ability to engulf and kill threatening microorganisms. They are also important for the subsequent adaptive response because it produces signals that activate and recruit other immune cells. Granulocytes are short lived cells. The majority of immune cells in an innate response are neutrophils and are very important for their phagocytic role. Dendritic cells can also engulf microorganisms but their main role is to produce signals that activate T-cells as part of the adaptive immune response. Macrophages, dendritic cells, and neutrophils are also important “scouts”. Dr. Dalal Almuaili Innate recognition and effect Macrophages, neutrophils and dendritic cells express receptors that can help them recognise pathogens. There are several types of receptors: PRRs (pattern recognition receptors) recognise molecules common to most pathogens known as pathogen-associated-molecular-patterns (PAMPs). PRRs are activated in response to binding to PAMPs, subsequently they induce effector function. Effector functions are how immune cells eliminate pathogens. Activated innate immune cells can act on the pathogen directly AND can release “signals” that lead to inflammation. Inflammation is the process of recruiting immune cells into the site of infection to destroy the pathogen. (eg. NK-cells, more macrophages and neutrophils) Dr. Dalal Almuaili Antigen presenting cells (APC) Antigen presenting cells bridge the innate and adaptive immune response. Antigen presenting cells include: Dendritic cells Macrophages T-cells As the name suggests, they circulate and capture antigens, then transport and present them to the adaptive immune cells. There are several pathways of antigen processing depending on the type of pathogen and required immune response. The processing of extracellular antigens is through MHC II The processing of intracellular antigens is through MHC I Dr. Dalal Almuaili Major Histocompatibility Complex (MHC) MHC is a group of proteins present on the surface of all antigen presenting cells. They have the key role of presenting antigens to the adaptive immune cells. There are two main types of MHC; MHC I and MHC II. The type of MHC dictates which immune cells are activated, and therefor controls the type of immune response that proceeds. Dr. Dalal Almuaili  MHC I MHC II Expressed on all nucleated cells Expressed on all antigen presenting cells Intracellular antigens Extracellular antigens Present Ag’s to cytotoxic T-cells Present Ag’s to helper T-cells Initiate target cells lysis Initiate B-cell activation and antibody production Dr. Dalal Almuaili MHC I Dr. Dalal Almuaili MHC II Dr. Dalal Almuaili The story of the adaptive immune response Dr. Dalal Almuaili Principles of adaptive immunity The main adaptive immune cells are lymphocytes. Lymphocytes (eg T-cells and B-cells) have receptors that recognise and bind to specific antigens. What are antigens? Any molecule that can elicit an immune response. The adaptive immune response can generate immunological memory. What is the advantage of immunological memory? The immune system becomes capable of initiating a faster and more powerful immune response against the pathogen on second and future exposures. Dr. Dalal Almuaili Adaptive immunity: memory and antibody development The adaptive immune response starts with their receptors (T-cell receptor and B-cell receptor) recognizing a specific pathogen antigen. This then activates some B-cells to differentiate into plasma cells (effector cells), while some B-cells will differentiate into memory cells. plasma cells secrete antibodies specific to that antigen. Upon subsequent exposure to the same pathogen: Memory cells will be ready to differentiate into effector cells. Dr. Dalal Almuaili Innate vs adaptive immune response Innate immunity takes place in response to FIRST exposure to the pathogen. Adaptive immunity develops during first exposure and takes full effect later in response to subsequent exposure to the pathogen. Innate immunity Adaptive immunity Fast (minutes-hours) Slow (days) Moderate response Strong response No to little antibodies High antibody titer Less sensitive and less specific More sensitive and specific Dr. Dalal Almuaili Consequences of immune activation 1. Antibodies 2. Other effector mechanisms Dr. Dalal Almuaili The role of antibodies in host defense 1. Neutralisation of bacterial toxins, and viral particles 2. Opsonisation marking a target and making it more visible to phagocytes 3. Complement activation Complement are a group of proteins that can eliminate pathogens. Dr. Dalal Almuaili Other effector mechanisms of immunity In response to the activation of an immune response, the immune system can eliminate and remove pathogens in different ways 1. Cell mediated immunity The immune system can activate cells (CD8 T-cells, and NK cells) to directly kill target cells. This is essential in fighting intracellular pathogens 2. Release of cytokines Cytokines are proteins that are used to communicate messages within the immune system. They can activate cells, recruit more immune cells, and enhance an immune response. 3. Complement activation Complement can be activated without antibodies. Dr. Dalal Almuaili Resources Human Anatomy & Physiology, 11the by Elaine Marib & Katja Hoehn Janeway’s immunobiology. Chapter 1 All unreferenced figures created with BioRender.com Contact info [email protected] Room 3-77 Office hours: Sundays, Mondays 9:00 to 1:00 (appointment advised) Dr. Dalal Almuaili