Lymphatic and Immune System PDF

SECTION 2 | BIOLOGY CHAPTER 19 | THE LYMPHATIC SYSTEM Unlike the circulatory system, the human lymphatic system is not a closed circuit. It consists of a network of blind-ended tubules, meaning they are open at one end FUNCTIONS The lymphatic system ha...

SECTION 2 | BIOLOGY CHAPTER 19 | THE LYMPHATIC SYSTEM Unlike the circulatory system, the human lymphatic system is not a closed circuit. It consists of a network of blind-ended tubules, meaning they are open at one end FUNCTIONS The lymphatic system has the following main functions: Drain excess interstitial uid Lymphatic tubules begin at capillary beds and drain the excess interstitial uid that is produced as blood leaks out of the vasculature due to excess hydrostatic pressure The drained uid is called lymph, and is pumped by smooth muscle contractions and released back into systemic circulation via the subclavian vein Like veins, lymphatic tubules have valves to prevent back ow If the lymphatic system did not exist, blood volume would gradually decrease as all our plasma leaked into the interstitial space Mount immune defence Before the lymph is reintroduced into systemic circulation, it passes lymph nodes, which contain B and T cells that can trigger the adaptive immune response Absorbs fat from food Fats in the small intestine interact with lipoproteins and form chylomicrons, which are absorbed by lymph vessels called lacteals located within intestinal villi The fats are released into the systemic circulation via the subclavian vein, and absorbed by tissues in the body at capillary beds LYMPHATIC TISSUE Primary lymphatic tissue includes the thymus, spleen, and lymph nodes Thymus – Location where T cells from the adaptive immune system mature Spleen – Filters blood and houses immune cells for early detection of pathogens Lymph Nodes – Collects lymph from lymphatic vessels and houses immune cells Secondary lymphatic tissue refers to MALT (mucosa-associated lymphoid tissue) MALT describes small, interspersed regions of lymphoid tissue in the tonsils, appendix, small intestine, thyroid, breast, lung, skin, any many other tissues Regional MALT tissue is named after the tissue it resides in. For example, BALT stands for bronchus- associated lymphoid tissue PATHOLOGIES Lymphoedema – Swelling (edema) of tissue due to the insu cient clearance of uids by the lymphatic system 125 fl fl fl ffi fl fl  SECTION 2 | BIOLOGY CHAPTER 20 | THE IMMUNE SYSTEM TYPES OF IMMUNITY HIGH-YIELD Components of the immune system can be categorized in three di erent ways: Humoral vs Cell-Mediated Humoral immunity is mediated by molecules in bodily uids such as antibodies and complement proteins. In contrast, cell-mediated immunity involves leukocytes (aka “white blood cells”) Innate vs Adaptive Innate immunity describes the body’s non-speci c defences against pathogens, which does not require previous exposure to an antigen. Examples include: Anatomic barriers (skin, cilia, blood-brain barrier, etc.) Chemical or enzymatic defences (low pH of skin, lysozyme in tears, etc.) Mutualistic skin microbiota outcompeting harmful bacteria The complement system The interferon response The in ammatory response Non-speci c immune cells (granulocytes, NK cells) Adaptive immunity describes the body’s speci c defences against pathogens, which is acquired after exposure to an antigen. The adaptive immune response increases with additional exposures. Examples include: B cells, T cells, and antibodies Professional antigen-presenting cells (B cells, macrophages, dendritic cells) Active vs Passive Active immunity results from an antigen triggering the adaptive immune system and antibodies being produced (i.e. infection or immunization). In contrast, passive immunity results from antibodies naturally or arti cially acquired from another source (i.e. newborn infants acquiring antibodies via breast feeding, or an ebola patient getting injected with puri ed antibodies from another previously sick victim) CELLS OF THE BLOOD Antigen Presenting Cells (APCs) – A cell that presents antigens on MHC I to cytotoxic (CD8+) T cells. All cells have MHC I, so all cells are APCs Professional Antigen Presenting Cells – A cell that presents antigens on MHC II to helper (CD4+) T cells. Includes B cells (most common), macrophages, and dendritic cells Leukocytes – A category of cells known as “white blood cells,” that includes all lymphoid cells (B cells, T cells, NK cells) plus some myeloid cells (granulocyte cells and macrophages). All cells involved in the immune response are leukocytes 126 􀋂 fl fi fi fi fi fl fi ff  SECTION 2 | BIOLOGY Lymphocytes – A category describing cells that all originated from a common lymphoid progenitor during hematopoiesis. Includes B cells, T cells, and NK cells MNEMONIC All the cells with a letter in their name (“B”, “T”, “NK”) are lymphoid Natural Killer (NK) Cells – Cytotoxic lymphocytes that destroy virus-infected or cancerous cells via perforin (which forms pores in the cell membrane) and granzyme (which triggers apoptosis) B Cells – Lymphocytes containing antibodies on the cell membrane that bind to antigen epitopes. Once bound, the B cell phagocytoses the antigen and presents a fragment on MHC II. A helper T cell binds and activates the B cell, which undergoes clonal expansion and di erentiates into plasma cells and memory B cells. B cells mature in the bone marrow and are professional APCs Plasma Cells – Produce high volumes of antibodies with variable regions that are complementary to the same epitope that initially activated the B cell. These antibodies hinder pathogen mobility, trigger opsonization (enhanced phagocytosis), and activate the complement system Memory B Cells – Contain identical surface antibodies to the B cell that was initially activated. They serve as a “reserve” force of cells to mount a faster and stronger immune response incase the body is exposed to a pathogen with the same epitope in the future. This is the basis for immunological memory and the adaptive immunity T Cells – Lymphocytes containing T cell receptors (TCRs) on the cell membrane. T cells mature in the thymus Helper (CD4+) T Cells – Activated when its TCR binds with a professional APC’s MHC II, an antigen, plus a CD28 co-stimulatory protein. Once activated, the helper T cell undergoes clonal expansion and di erentiates into e ector helper T cells E ector Helper T Cells – Release T cell cytokines (such as interleukin) that cause B cell antibody class switching and increased cytotoxic T cell activation. As their name describes, they “help” B cells become activated. Further di erentiated into Th1 and Th2 cells Cytotoxic (CD8+) T Cells – Activated when its TCR binds with an infected or cancerous APC's MHC I, plus an antigen. Upon activation, di erentiates into e ector cytotoxic T cells and some mature further into memory cytotoxic T cells E ector Cytotoxic T Cells – Binds with APCs that present the same antigen and kills them via perforin and granzyme Memory Cytotoxic T Cells – Recognizes the same antigens as the cytotoxic T cell that was initially activated. They serve as a “reserve” force of cells to mount a faster and stronger immune response in the future Regulatory T Cells – Immune suppressive T cells that down-regulate the induction and proliferation of e ector T cells. This regulates the immune system, maintaining tolerance to self-antigens to prevent autoimmune disease 127 􀉢 ff ff ff ff ff ff ff ff ff SECTION 2 | BIOLOGY Myelocytes – A category describing cells that all originated from a common myeloid progenitor during hematopoiesis. Includes red blood cells, platelets, granulocytes, and macrophages Erythrocytes/Red Blood Cells – The most abundant cell in blood, which carries four oxygen molecules via a porphyrin ring and one iron molecule. They are anucleate cells (contain no nucleus) and are not involved in immunity Thrombocytes/Platelets – Fragments of cytoplasm from megakaryocytes that functions to prevent bleeding by forming a blood clot. They are anucleate cells and not involved in immunity Granulocytes – Phagocytic myelocytes that destroy antigens at the site of injury. They are characterized by the presence of granules in the cytoplasm and multi-lobed nuclei. Neutrophils – The most abundant leukocytes in blood and often the rst responders to in ammatory cytokines. They are specialized to phagocytose and kill bacteria via oxidative/respiratory burst (the release of toxic reactive oxygen species). Neutrophil counts are elevated during acute in ammation and is the main component of pus Eosinophils – Mainly responsible for allergic and asthmatic responses. Eosinophil counts are elevated during allergic responses or parasitic infections Basophils – Similar responsibilities as eosinophils, but also mediates histamine release to stimulate local blood vessel dilation Mast Cells – Same responsibilities as basophils, except residing in tissue instead of blood Macrophages – Phagocytic myelocytes that destroy pathogens throughout the body. They are professional APCs. Monocytes are the precursors to macrophages. Like neutrophils, monocytes kill bacteria via oxidative/respiratory burst Dendritic Cells – Phagocytic myelocytes or lymphocytes that destroy pathogens in tissues that interact with the external environment (nasal membrane, lungs, intestines, skin, etc.). Once activated, they migrate to the lymph nodes where they present antigens on MHC II to helper T cells. Dendritic cells are professional APCs Innate Immunity Adaptive Immunity Granulocytes B cells Eosinophils Plasma Cells Basophils Dendritic cells T cells Neutrophils Macrophages Helper T cells Mast cells Cytotoxic T cells NK cells Regulatory T cells Neither Red blood cells Platelets 128 fi fl fl  SECTION 2 | BIOLOGY CELLS OF THE BLOOD SUMMARY HIGH-YIELD Cell Name Main Function Location Kills infected/cancerous cells via Circulates in blood and migrates to NK Cell granzyme and perforin tissue Matures in bone marrow; circulates in Produce antibodies once activated; B Cell blood and migrates to 2° lymphoid Present antigens to helper T cell tissues Activates B cells; kills infected/ Matures in thymus; circulates in blood T Cell cancerous cells; immunesupression and migrates to 2° lymphoid tissues Contains hemoglobin which carries Matures in bone marrow, spleen, and Red Blood Cells oxygen with a porphyrin ring and Fe2+ liver; circulates in blood Activated by thrombin to form blood Released by megakaryocytes into blood; Platelets clots; triggers coagulation cascade stored in spleen Phagocytoses and kills bacteria via Matures in bone marrow; circulates in Neutrophils oxidative burst blood; migrates into tissues Mediates allergic/asthmatic and Matures in bone marrow; circulates in Eosinophils parasitic response blood; migrates into tissues Same as eosinophils, except releases Matures in bone marrow; circulates in Basophils histamine to dilate vessels blood; migrates into tissues Same as eosinophils, except releases Mast Cells Resides in tissues histamine to dilate vessels Phagocytose pathogens; present Macrophages Circulates in blood; resides in tissues antigens to helper T cell Phagocytose pathogens; present Resides in tissues that contact external Dendritic Cells antigens to helper T cell environment; migrates to lymph nodes Legend Myeloid Cell Involved in Innate Immunity Professional APC (MHC II+) Lymphoid Cell Involved in Adaptive Immunity LINES OF DEFENCE The immune system is described as having three “lines of defence”: Fist Line of Defence – Physical barriers, which are non-speci c (skin, mucociliary escalator, gastric acid, lysozyme, symbiotic bacteria, etc.) Second Line of Defence – The innate immune system, which is non-speci c (complement system, interferon response, in ammatory response, phagocytic cells, NK cells, etc.) Third Line of Defence – The adaptive immunes system, which is speci c and has memory (B cells, T cells, antibodies) 129 􀋂 􀋅 􀐩 􀀛 􀀝 􀙦 􀀛 􀀛 􀀛 􀐩 􀐩 􀀝 􀀝 􀙦 􀀝 fl 􀀝 􀀝 􀋅 􀙦 􀙦 􀀝 􀙦 􀀝 􀙦 􀀝 􀙦 􀙦 􀐩 􀐩 􀋅 􀋅 fi fi fi  SECTION 2 | BIOLOGY T AND B CELL MATURATION Each T cell has a T cell receptor (TCR) with speci city to a di erent epitope. The variety of TCR speci cities is due to alternative splicing of introns in the genes coding for the TCR’s variable region In the thymus, developing T cells undergo di erent types of selection: Negative Selection – T cells with TCRs that are high in self-reactivity are eliminated Positive Selection – T cells with TCRs that are low in self-reactivity are kept Cells that interact well with MHC I become cytotoxic (CD8+) T cells Cells that interact well with MHC II become helper (CD4+) T cells Goldilocks Selection – T cells with TCRs that are intermediate in self-reactivity become regulatory T cells B cells mature in a similar process to T cells, except they do not undergo goldilocks selection nor become CD8 or CD4 positive ANTIBODIES/IMMUNOGLOBULINS Unlike T cells, B cells secrete their surface receptors as antibodies/immunoglobulins (Ig) The antibodies secreted by a particular B cell are identical and all recognize the same antigen epitope Antibodies destroy pathogens by attaching to their surface and hindering mobility, marking them for other cells to phagocytose. This process is called opsonization and activates the complement system Antibody Structure Antibodies consist of two large heavy chains and two small light chains connected via disulphide bonds The region that recognizes antigens is called the variable region (Fab) while the region that remains constant is called the constant region (Fc) There are ve di erent types of heavy chains that determine the antibody’s class/isotype: IgM, IgD, IgG, IgE, or IgA Variable Region Light Chain Disulphide Bonds Constant Region Heavy Chain Class/Isotype Switching When a B cell is activated by a helper T cell, the T cell secretes interleukin, a cytokine which triggers the B cell to undergo class switching The B cell rearranges its heavy chain constant region genes, converting the antibodies it secretes from IgM/ IgD to IgG, IgA, and IgE THE COMPLEMENT SYSTEM The complement system is a group of serum proteins that “complement” other immune defences. It can be activated directly by pathogens or indirectly by antibody-coated pathogens The complement proteins are part of innate immunity and have three major functions: Opsonization – Pathogens get covered by complement protein 3b (C3b), which binds to compliment receptor 1 (CR1) on phagocytes and triggers phagocytosis Cytotoxicity – Induces cell lysis through the membrane attack complex (MAC) In ammation – Complement protein 3a (C3a) induces in ammation by increasing vascular permeability and attracting phagocytes to the site of infection 130 fl fi ff ff fi fl ff fi  SECTION 2 | BIOLOGY THE INTERFERON RESPONSE Interferons are antiviral cytokines secreted by infected cells. They are an important component of innate immunity and have three major functions: Self Destruction – Kills infected cells by triggering apoptosis Warning System – Signal neighbouring cells to start preparing for a viral attack Recruit Phagocytes – Interferon gamma mobilizes macrophages and NK cells, which phagocytose infected or cancerous cells THE INFLAMMATORY RESPONSE The in ammatory response is a combination of events that occur in response to pathogen invasion (i.e. bacteria colonizes urinary tract), cellular damage (i.e. twisted ankle), or irritants (i.e. pollen). It is an important component of innate immunity Macroscopic signs of in ammation include redness, swelling, heat, pain, and loss of function. Pathologists refer to this as the ve cardinal signs of in ammation Microscopic signs of in ammation include: Histamine Release – A molecule released by basophils during allergic reactions or parasite invasion. Histamine increases capillary permeability to allow extravasation of leukocytes (migration out of the vessels and into infected tissues) Vasodilation – Occurs in response to histamine release. Increases blood ow to infected tissue, allowing faster recruitment of leukocytes Phagocyte Recruitment – Leukocytes extravasate into infected tissue and phagocytose pathogens. They follow the chemical gradient left by complement proteins PATHOLOGIES Regulatory T Cell Pathologies: Too much T cell regulation results in susceptibility to cancer, because the immune system does not adequately ght abnormal cells or small tumours Too little T cell regulation results in the immune system ghting the body, causing autoimmune disorders Acquired Immunode ciency Syndrome (AIDS) – Caused by infection by the human immunode ciency virus (HIV). The disease destroys helper T cells, weakening the immune system and making the body susceptible to opportunistic infections Type I Diabetes – An autoimmune disease where the beta cells of the pancreas are attacked. This results in an insulin de ciency Rheumatoid Arthritis – An autoimmune disease where the synovial membrane of joints are attacked. Unlike osteoarthritis, it is not caused by “wear and tear” Lupus – An autoimmune disease where various healthy tissues are attacked, including the skin, muscles, bones, heart, lungs, kidneys, and eyes In ammatory Bowel Disease (IBD) – An autoimmune disease where the lining of the intestines are attacked Hashimoto’s Thyroiditis – An autoimmune disease where the thyroid gland is attacked. This results in a thyroid hormone de ciency Asthma – A hypersensitivity disease where the bronchioles overreact to stimuli, resulting in spasms 131 fl fl fi fi fi fi fi fl fl fl fi fl fi