Summary

This document contains lecture notes on the Immune System, covering anatomy, physiology, and functions. It includes details on the Lymphatic System, including components and functions, lymphatic vessels, lymphatic tissues and organs (including the Thymus and Spleen), lymphocytes and their classification, and innate immunity, cytokines, and inflammation.

Full Transcript

21: Immune System Anatomy and Physiology in Context Chapter 21 21.1 Lymphatic System Chapter 21: Immune System General Function of the Immune System 1.Protect against foreign threat (RECOGNIZE) 2.Differentiate these foreign threats as non-self and engage (RESPOND) 3.Make s...

21: Immune System Anatomy and Physiology in Context Chapter 21 21.1 Lymphatic System Chapter 21: Immune System General Function of the Immune System 1.Protect against foreign threat (RECOGNIZE) 2.Differentiate these foreign threats as non-self and engage (RESPOND) 3.Make second response a more effective response (REMEMBER) 21.1.1 The Lymphatic System Components and Functions COMPONENTS FUNCTIONS Collection of organs, Returns excess interstitial fluid capillaries, vessels and tissues to the venous system Contains fluid (lymph) that Absorbs fats from the digestive circulates through vessels tract and returns them to the venous system for processing Contains lymph nodes and by the liver nodules Produces and matures many immune cells 21.1.2 The Lymphatic System: Lymphatic Vessels Vessels begin as fenestrated capillaries, composed of a single layer of endothelium attached to a basement membrane Lymph is transported through progressively bigger vessels, through lymph nodes, until it reaches the vena cava Larger lymphatic vessels contain one-way valves and smooth muscle 21.1.3 Lymphatic Tissues and Organs: The Thymus ANATOMY FEATURES Flat, bi-lobed organ located in superior mediastinum above heart Enlarges during childhood, then starts to atrophy as we enter our 20s Each lobe is comprised of lobules held together by areolar connective tissue Each lobe consists of a 21.1.4 Bone Marrow Is the Site of Leukopoiesis Leukopoiesis begins in the bone marrow Maturation may occur in the bone marrow, or continue in another organ, depending on the cell type 21.1.5 Lymphatic Tissues and Organs: Lymph Nodes LYMPH NODES: follicles consisting of lymphatic and non-lymphatic cells surrounded by a network of lymphatic capillaries Each is supplied by afferent lymphatic vessels and drained by efferent lymphatic vessels Outermost cortex: B- lymphocytes, macrophages, dendritic cells Paracortex: T- lymphocytes, dendritic cells 21.1.6 Lymphatic Tissues and Organs: The Spleen ANATOMY FEATURES Filters blood, stores erythrocytes, removes defective erythrocytes/ platelets, recycles iron Lies between 9th and 11th rib on left side of body Contains red pulp and white pulp Red pulp contains macrophages, erythrocytes, 21.1.7 Lymphocytes and Classification Contain a single, large nucleus, a small amount of cytoplasm, and a wide range of proteins expressed on their surface B lymphocytes: develop in bone marrow T lymphocytes: begin development in bone marrow but complete it in thymus Classified by surface proteins referred to Image courtesy of Dr. Triche in the Public Domain as Cluster of Differentiation (CD) markers 21.1.8 Lymphocytes: T Cells and the T Cell Receptor Cytotoxic T cells (TC) The T cell receptor Designed to destroy virus-infected and tumor cells Releases perforin, granzymes and granulysin Memory T cells (TM) Expresses CD8 on its surface Carry the memory of antigen exposure after the antigen has left the body Regulatory T cells (TR) Maintain immunological tolerance Block T cell-mediated immune responses at the end of the response window Other T cell types Natural killer T cells, mucosal-associated invariant T cells, gamma delta T cells 21.1.9 Lymphocytes: B Cells Memory B cells Carry the memory of previous exposure to antigen Generated after exposure to antigen by cytokine signaling Plasma B cells Long-lived, non-proliferating antibody-secreting cells Arise after exposure to antigen Other B cell types Plasmablasts Follicular B cells Marginal zone B cells Regulatory B cells 21.1.10 Positive and Negative Selection of Lymphocytes Positive selection: ensures lymphocytes are able to respond to antigen Negative selection: removes lymphocytes that bind strongly to self antigens 21.1.11 Outcomes of Negative Selection of Lymphocytes Receptor editing: change the lymphocyte receptor so it no longer recognizes self antigens Anergy: change the lymphocyte so it is no longer capable of an immune response Apoptosis: clonal deletion and cell death Ignorance: continue 21.2 Innate Immunity Chapter 21: Immune System 21.2.1 Overall Flow of Innate Immunity 21.2.2 Physical Barriers: The Skin ANATOMY FEATURES First line of defense against foreign threats Epidermis: Waterproof, chemically resistance to bacterial enzymes Glands: Maintain surface pH of 3-5, blocking the growth of most microorganisms Mucosal membranes contain anti-pathogenic substances 21.2.3 Cytokines Affect Both the Innate and Adaptive Immune Systems Act in an autocrine, paracrine and endocrine manner Produced by a broad range of immune cells Overproduction of cytokines can lead to sickness and death 21.2.4 VIDEO: Diapedesis Please insert the following video: Diapedesis – Medical Animation by Arc Solutions https://www.youtube.com/watch?v=R8VzquHdwZw 21.2.5 Innate Immune Cells (1): Granulocytes and Mast Cells Most abundant Comprise ~1% of leukocyte leukocytes First responders to Release histamines at NEUTROPHI BASOPHILS site of infection LS site of infection Release anti- Responsible for microbial enzymes symptoms of allergies and “NETS” Release histamine, Comprise ~6% of heparin and other MAST EOSINOPHI leukocytes compounds CELLS LS Also release Also responsible for histamines symptoms of allergies Highly effective against parasites 21.2.6 Innate Immune Cells (2): NK Cells ANATOMY FEATURES Able to induce apoptosis in virus- infected and cancer cells Release granules containing powerful proteases and perforin Also secrete ɑ-defensins (anti- microbial peptides) People with an impairment in NK Image courtesy of The National Institutes of cell development display a Health in the Public Domain heightened incidence of blood cancer 21.2.7 VIDEO: NK Cells Killing Cancer Cells Please insert the following video: Natural killer cell(White blood cells) killing cancer cells https://www.youtube.com/watch?v=Va1jaBGwoT8 21.2.8 Innate Immune Cells (3): Macrophages ANATOMY PROCESS OF MACROPHAGE PHAGOCYTOSIS 1. Macrophages drawn to site by chemotaxis 2. Physical interaction between macrophage and foreign threat 3. Macrophages produce pseudopodia that extend around foreign threat 4. Pseudopodia fuse foreign threat within a vesicle forming a phagosome 5. Phagosome is internalized, fuses with lysosome 6. Proteases and toxic chemicals in Image courtesy of Librepath under CC BY-SA 3.0. lysosome kill foreign threat 7. Parts of the foreign threat are exposed 21.2.9 VIDEO: Phagocytosis by Macrophages Please insert the following video: Macrophage engulfs foreign cell https://www.youtube.com/watch?v=w0-0Bqoge2E 21.2.10 Proteins Involved in Innate Immunity: The Complement System Complement: refers to a family of over 30 soluble and cell- bound proteins Most components are produced in the liver in inactive forms 3 separate pathways all converge to produce C3 and C5 convertase activities 21.2.11 The Membrane Attack Complex Opens Pores on Target Cells 21.2.12 Inflammation Is a Stereotypic Innate Immune Response 21.3 Adaptive Immunity Chapter 21: Immune System 21.3.1 A Comparison of Innate and Adaptive Immunity ADAPTIVE IMMUNITY ntibody Mediated Immunity Cell Mediated Immunity MHC ll MHC l TH T TR TM C Plasma cells 2nd Response Memory B cells HUMORAL IMMUNITY CELLULAR IMMUNITY 21.3.2 Components of Adaptive Immunity: Antigens ANATOMY FEATURES Antigen = anything that can trigger an adaptive immune response The immune system recognizes epitopes – discrete sites on macromolecules Any molecule has the ability to act as an antigen, but some are more potent than others  Proteins are most potent, followed by sugars 21.3.3 Components of Adaptive Immunity: Antibody Structure Can be kappa or lambda Defines isotype o antibody Variabl e region Consta nt region 21.3.4 The Various Isotypes of Antibodies * There are 4 versions of IgG and 2 versions of IgA. IgM is secreted on the surface of B cells as a monomer, but is secreted as a pentamer. cross present passed Ig D & IgE placenta in through binds to mast and neonates body cells, basophils, protect fluids protection fetus against worms, hives 21.3.5 Functions of Antibodies in Adaptive Immunity Antibody interaction with antigen triggers the following: ANTIGEN ANTIGEN ANTIGEN NEUTRALIZATION AGGLUTINATION PRECIPITATION Covering and Clumping of antigens Bringing antigens blocking the surface into larger complexes out of solution, of the antigen more readily making them more recognized by easily recognized by COMPLEMENTmacrophagesLYMPHOCYTE macrophages ACTIVATION RECRUITMENT AND Through Fc region; ACTIVATION leading to cell lysis and attraction of other leukocytes 21.3.6 VIDEO: B Cell Activation and Antibody Production Please insert the following video: Specific immunity, antibodies https://www.youtube.com/watch?v=Ys_V6FcYD5I 21.3.7 How Antibodies Recognize So Many Antigens: VDJ Recombination Each region is made up of small gene segments with multiple copies Segments are combined in a random fashion, generating many possibilities Other modifications are also made (removal of bases from ends, addition of extra bases) to even further increase variability 21.3.8 Major Histocompatibility Complex (MHC) Types and Structures Individuals inherit one copy of each MHC gene from each parent, so the MHC for each individual is unique Critical means through which cells communicate about what is self versus non-self Expressed on Only the surface of expressed on all cells, macrophages, except B cells and erythrocytes dendritic cells Docks with Docks with CD8 protein CD4 protein on the on the surface surface of TC of TH cells cells Interaction Interaction leads to clonal with CD8 growth of T 21.3.9 How Antigens Are Presented on Antigen-Presenting Cells (APCs) Foreign proteins are internalized, processed and their fragments transported to the cell surface as part of the MHC MHC I: presents peptides from the cytosol MHC II: presents peptides from endocytotic vesicles 21.3.10 Steps of Humoral-Mediated Immunity and Antibody Production 21.3.11 Primary Versus Secondary Antibody Responses Primary phase starts with IgM, while secondary phase starts with IgG Difference in primary and secondary response is due to presence of memory B cells in secondary response Antibodies are more rapidly produced in 21.3.12 Cell-Mediated Immunity: Activation of Cytotoxic T Cells 21.3.13 Cell-Mediated Immunity: Activation of Helper T Cells 21.3.14 FOCUS ON DISEASE: Autoimmune Diseases CAUSES (in general): unknown, but may include molecular mimicry, triggering of an immune response that bypasses TH cell involvement, or a deficiency in TR cells TREATMENTS: immunosuppressive drugs, removal of thymus, plasmapheresis 21.4 Aging and the Immune System Chapter 21: Immune System 21.4.1 Aging-Related Changes in the Immune System Tissues and organs related to immunity decrease in size and become less responsive to the presence of pathogens Elderly are more likely to have to take immunosuppressive drugs for other conditions (e.g., chemotherapy for cancer) Inability to produce and mature new T lymphocytes due to replacement of thymus tissue with adipose tissue Fewer antibodies and memory B cells are produced, reducing vaccine effectiveness Accumulation of damage caused by autoimmune diseases that developed earlier

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