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Moravec_Lymphatic-System-Slides.........
- 1. The Lymphatic System TissueFluid and the Immune Response
- 2. Functions • drain excesstissue fluid – not all fluid returns to bloodstream • extra enters the lymphatic vessels • immune response – responds to eliminate pathogens from the body • innate and adaptive responses • major structures include: – lymphatic vessels, lymph nodes, spleen, thymus
- 3. Lymphatic Structures • lymphaticvessels • lymphoid tissues/organs – primary or central • bone marrow and thymus – secondary or peripheral • lymph nodes, spleen, mucosal
- 4. Lymphatic Vessels • similarstructure to veins – thin with valves • unlike veins, they are a “one-way street” – originate as capillaries in the tissues – end at the veins
- 5. Lymph • lymph istissue fluid that has entered the lymphatic vessels – excess tissue fluid • functions: – transports proteins and other molecules to the bloodstream – moves foreign particles to lymph nodes
- 6. Thymus • located behindthe sternum – larger in children • site of T cell maturation – migrate from bone marrow
- 7. Lymph Nodes • locatedalong lymphatic pathways – absent in the central nervous system • functions: – filter/remove potentially harmful particles before they enter bloodstream – immune surveillance (monitoring of fluids by immune cells)
- 8. Spleen • located inupper abdominal cavity • similar to lymph node • red pulp (majority of spleen) – site of red blood cell disposal • white pulp – houses lymphocytes – site of antigen presentation
- 9. Mucosa Associated LymphaticTissue (MALT) • Lymphatic tissue in the mucosal membranes throughout the body – Contains T cells, B cells, and macrophages – Can encounter antigens passing through the mucous membranes
- 10. • Found inseveral locations in the body – Lungs, digestive tract, nasopharynx, skin, breast, salivary glands
- 11. Cells of theImmune System • broken into two broad groups: – myeloid • mostly in innate immune system – lymphoid • adaptive immune system
- 12. Myeloid Cells • macrophage –engulf and kill invading microorganisms – can help induce inflammation – can activate other immune cells • mast cells – play a role in allergic responses – respond to parasitic worms – can induce inflammation
- 13. • granulocytes – neutrophils •most numerous • phagocytic • role in bacterial infection – eosinophils and basophils • defense against parasites • contribute to allergic response – can be more damaging than helpful
- 14. • dendritic cells –can take up and degrade pathogens – main function is antigen presentation • activate cells of adaptive immunity – a bridge between innate and adaptive responses
- 15. Lymphoid Cells • naturalkiller cells (NK) – not part of the adaptive immune system…but come from lymphoid lineage – not antigen specific • can recognize and kill some abnormal cells – ex: tumor cells and some viruses • thought to keep viruses at bay until adaptive response kicks in
- 16. • B lymphocytes(B cells) – antigen-specific receptors • B cell receptors (BCRs) – once activated divides to form plasma cells • produce antibodies – secreted form of BCRs
- 17. • T lymphocytes(T cells) – three categories • helper T cells – provide signals which initiate responses from other cells • cytotoxic T cells – kill cells which are infected with a virus or other pathogen • regulatory T cells – suppress immune activity and help control immune response
- 18. The Immune System •cells and biochemicals responsible for the surveillance and destruction of non-self – innate response • quick, non-specific – adaptive response • slower, specific
- 19. Cytokines and Chemokines •chemical signaling molecules – cytokines • proteins secreted which affect behavior of nearby cells • pro-inflammatory, regulatory, or growth factors – chemokines • proteins secreted which attract cells to an area • migrate due to a density gradient • cells have receptors that bind chemokines
- 20. Innate Immune Response •macrophages – recognize pathogens through receptors – engulf and degrade pathogens • can present antigens from the pathogen on the surface – secrete cytokines and chemokines
- 21. • inflammation (heat,redness, swelling, pain) – recruits proteins and cells to infected areas • macrophages and neutrophils – increases lymph flow • brings microbes and antigen presenting cells (antigen presenting cells – APCs) to lymphoid tissues – can recruit effectors of adaptive immunity later on
- 22. • complement – pathogenscan trigger activation of complement proteins – activation begins a cascade which can result in destruction of the pathogen – can also promote inflammation
- 23. Innate Immune Recognition •PAMPs (Pathogen Associated Molecular Patterns) – cells (macrophages, neutrophils, dendritic cells) have receptors that recognize simple molecules and regular molecular patterns • pattern recognition receptors (PRRs) – PAMPs are present on microorganisms but not body cells
- 24. Innate and Adaptive •innate response initiates adaptive response – macrophages engulf pathogens and present antigens to lymphocytes – dendritic cells triggered to activate T cells – adjuvants • bacterial extracts used in vaccines • initiate an innate response…which in turn activates the adaptive response – leads to successful vaccination to the purified protein (antigen)
- 25. Adaptive Immune Response •initiated by APCs (antigen presenting cells) – primarily dendritic cells (but also macrophages) • engulf pathogens, degrade, then move the antigen to the surface of the cell – dendritic cells also have costimulatory molecules • stimulate T cells to proliferate and differentiate • B cells usually also require a helper T cell – occurs in secondary lymphoid tissues/organs
- 26. Proliferation • once activated,naïve lymphocytes become lymphoblasts – divide to produce clones • clonal expansion – can divide 2-4 times per 24 hours for about 3-5 days • producing about 1000 cells specific to the target antigen – these cells become effector cells • B cells = plasma cells • T cells = cytotoxic or helper T cells
- 27. Immunological Memory • mostcells generated by clonal expansion die • some T and B cells are left behind – memory cells • reactivated quickly when the same antigen is encountered again • provides long-lasting immunity
- 28. Mechanisms of AdaptiveImmunity • cell-mediated immune response – T cells responsible for destruction of intracellular invaders • humoral immunity – antibodies detect pathogens in blood and other extracellular fluid (humor = body fluid) • other mechanisms are similar to those of innate immunity – macrophages, neutrophils, complement
- 29. T Cells andCell-mediated Immunity • T cells – CD4 = helper T cells – CD8 = cytotoxic T cells – recognize peptides on MHC molecules (major histocompatibility complex) • complex displayed on surface of cells • trap peptide during production and transported to surface
- 30. • MHC classI – proteins synthesized in cytosol – can display viral proteins – recognized by cytotoxic T cells
- 31. • MHC classII – expressed by APCs – derived from proteins taken in through phagocytosis/endocytosis – activate CD4 cells
- 32. • stimulated effectorcells secrete effector molecules – mainly cytokines – recruit other effectors to target area • CD8 cytotoxic T cells directly kill infected cells – recognize antigens • CD4 helper T cells can become different types of T cells
- 33. – TH1 helpcontrol bacteria in vesicles of macrophages • stimulate them to increase intracellular destruction of bacteria – TH2 promote response at mucosal surfaces • parasitic infections – TH17 promote responses with lots of neutrophils • extracellular bacteria and fungi – TFH (follicular helper) • in lymphoid follicles • aid in B cell activation
- 34. Antibodies and HumoralImmunity • antibody structure – secreted B cell receptor – two variable regions • antigen binding sites • almost infinite combination of amino acids – constant region • 4 or 5 forms • determines effector function – how the antibody will interact with immune cells to dispose of antigen
- 35. • antibody actions –neutralization • binds to antigens and blocks access to cells • important in viral infections and against bacterial toxins – opsonization • coating pathogens with antibodies – lead to phagocytosis • bacterial infections – some evade innate response because they have an outer coat – antibodies can recognize the antigens on surface – complement activation • constant regions can activate the 1st protein • coats surface and enables phagocytosis
- 36. • antibodies arefound in plasma and extracellular fluid – antibody mediated immunity is called humoral immunity • body fluids used to be known as humors
- 37. Immune Responses • primaryimmune response – T cells and B cells become activated for the 1st time – some memory cells remain • secondary immune response – if the antigen is encountered again, the memory cells can mount a more rapid attack since they are already present – this ability can be long lasting
- 38. Practical Classification ofImmunity • naturally acquired immunity – occurs after exposure to the antigen itself • artificially acquired immunity – occurs through the use of vaccines – person does not become ill from the disease • artificially acquired passive immunity – injection of gamma globulin antibodies (short-lived) • naturally acquired passive immunity – antibodies are passed from mother to fetus
- 39. Vaccines • first vaccinedeveloped in 1796 – used the cowpox virus to vaccinate against smallpox – vaccine comes from the Latin word vaccinus meaning “of cows” • mimic a natural infection – immune system responds like it normally would – left with a supply of memory T and B cells
- 40. Vaccination vs. Immunization •vaccination – giving of vaccines to prevent disease • immunization – acquiring immunity against a disease – protection against getting sick • successful vaccination results in immunization
- 41. Types of Vaccines •live attenuated vaccines – contains live microbes that are weakened so they no longer cause disease – elicits an immune response involving memory T and memory B cells – drawbacks include: • refrigeration • there is a risk of mutation of the pathogen which causes disease – diseases include measles, mumps, rubella, polio, chickenpox, shingles, flu
- 42. • inactivated or“killed” vaccines – most common type used today – contains pieces of viruses killed with heat, chemicals, or radiation – no risk of mutation (since they aren’t alive) – stimulates B cells to produce antibodies – drawbacks include: • not as potent as live attenuated • booster shots are needed – diseases include flu, hepatitis A, polio, rabies
- 43. • subunit vaccines –contain only parts of the microbes that stimulate the immune system • mainly the antigens – tend to cause fewer adverse reactions – diseases include diphtheria, hepatitis B, pertussis, tetanus • toxoid vaccines – used to combat the toxins produced by pathogens – contain inactivated toxin called toxoids – stimulate antibody production – diseases include diphtheria and tetanus