Elements of Immune System PDF

Elements of the Immune System https://www.history.com/news/the-rise-and-fall-of-smallpox What happens when microbes breach the skin barrier…? Immune response to infection  When the barriers of the skin and mucosa are breached and pathogens gain entry to the body’...

Elements of the Immune System https://www.history.com/news/the-rise-and-fall-of-smallpox What happens when microbes breach the skin barrier…? Immune response to infection  When the barriers of the skin and mucosa are breached and pathogens gain entry to the body’s soft tissues, the other defenses of the immune system are brought into play  Two ‘arms’ of immune system work together against infectious threats that breach our skin and mucosa:  innate immune response  adaptive immune response The lymphatic system The innate and adaptive immune system rely on a network of organs, vessels and tissues called the lymphatic system to function The lymphatic system moves immune cells, fluids (lymph) and proteins between blood and lymphoid organs Primary lymphoid organs: Produce most immune system cells. These organs include the bone marrow and the thymus Secondary lymphoid organs: It is in these organs where the cells of the immune system mature and meet pathogen for the first time These organs include:  the lymph nodes (~600),  the spleen,  the tonsils and  specialized tissue mucous membrane layers in the body https://courses.lumenlearning.com/atd-herkimer-biologyofaging/chapter/anatomy-of-the-lymphatic-and-immune-systems/ Immune response to infection  The immune response consists of two parts:  Detection/recognition that a pathogen is present  Response to kill and eliminate the pathogen How are pathogens detected by the immune system? Pathogen entry into human body detected by immune system via two main mechanisms: 1) soluble proteins e.g. complement and 2) cell-surface receptor proteins (pattern recognition receptors) that bind to the pathogen and its products  PRRs recognize structural features that distinguish microbial carbohydrates, lipids, proteins, and PRR nucleic acids from their mammalian counterparts  PRRs and the cells that carry them distinguish between the healthy cells of the human body (‘self’) and ‘non-self,’ (all bacteria, fungi, viruses, and parasites, as well as unhealthy infected human cells) After detection, how are pathogens killed/eliminated? Response to invading pathogens involves special cells called effector cells that:  engulf bacteria,  kill virus-infected cells, or  attack protozoan parasites Some effector cells … Where do immune cells originate? https://www.cancer.gov/publications/dictionaries/cancer-terms/def/bone-marrow Origin of white blood cells  The cells of the immune system are principally the white blood cells or leukocytes Cellular building blocks hematopoiesis  Leukocytes are continually generated by the body in the developmental process known as hematopoiesis Hematopoietic stem cell differentiation  Hematopoiesis is active throughout life White blood cell (leukocyte)  Leukocytes derive from a common progenitor called the pluripotent hematopoietic stem cell Where does hematopoiesis occur?  The site for hematopoiesis changes with age  Early embryo - yolk sac and later in the fetal liver  Third to the seventh month of fetal life - the spleen  Fourth month of fetal growth till birth - bone marrow  Adults - the bone marrow of the skull, ribs, sternum, vertebral column, pelvis, and femurs Hematopoietic stem cell fate  Hematopoietic stem cells can divide to give further hematopoietic stem cells, a process called self renewal self renewal Hematopoietic stem cell Hematopoietic stem cell Lymphoid cell lineage Myeloid cell lineage Erythroid cell lineage  Alternatively, they become more mature stem cells that commit to one of three cell lineages:  Erythroid (mostly innate immunity)  Myeloid (innate immunity)  Lymphoid (mostly adaptive immunity) Erythroid cell lineage Erythroid lineage  The erythroid cell precursor gives rise to the erythroid lineage of blood cells— the oxygen-carrying erythrocytes and the platelet-producing megakaryocytes  Megakaryocytes (‘cell with giant nucleus’)) are giant cells that have nuclei containing multiple sets of chromosomes  Megakaryocytes are permanent residents of the bone marrow  Platelets:  are small packets of membrane-enclosed cytoplasm that break off from megakaryocytes  are small non-nucleated cell fragments of plate-like shape  maintain the integrity of blood vessels  initiate and participate in the blood clotting reactions Myeloid cell lineage Neutrophils  Most abundant of all white blood cells is the neutrophil  Neutrophils are: https://cellcartoons.net/wp-content/uploads/2017/02/Phagocytosis-nom-nom-01-1024x793.png  effector cells of innate immunity  rapidly mobilized to enter sites of infection and can work in the anaerobic conditions that often prevail in damaged tissue  specialized in phagocytosis (eat cell), the capture, engulfment and killing of microorganisms  short-lived and die (within hours-days) at the site of infection, forming pus https://journals.sagepub.com/doi/10.1177/0145561321989441?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed& Basophils, Eosinophils and Mast cells  Basophils, eosinophils and mast cells defend against helminth worms and other intestinal parasites  Contain numerous granules rich in histamine and heparin  The activation and degranulation of mast cells at sites of infection make major contributions to inflammation  Basophils, eosinophils and mast cells play important roles in the development of allergies https://answers.childrenshospital.org/food-allergies-tolerance/ Monocytes and macrophage  Monocytes are the mobile progenitors of sedentary tissue cells called macrophages (‘large phagocyte’ )  They travel in the blood to tissues, where they mature into macrophages and take up residence  Macrophages are the general scavenger cells of the body, phagocytosing and disposing of dead cells and cell debris as well as invading microorganisms  Macrophages are the long-lived cells provide warning to other cells orchestrate the local response to infection  Macrophages resident in the infected tissues are generally the first cell to sense an invading microorganism  As part of their response to the pathogen, macrophages secrete the cytokines that https://cellcartoons.net/phagocytosis/ recruit neutrophils and other leukocytes into the infected area Dendritic cells  Dendritic cells (DCs) are resident in the body’s tissues Dendritic cell and have a distinctive starshaped morphology  Dendritic cells act as cellular messengers that are sent to call up an adaptive immune response when it is needed T cell  Dendritic cells that reside in the infected tissue will leave the tissue with a cargo of intact and degraded pathogens and take it to one of several lymphoid organs that specialize in making adaptive immune responses Lymphoid cell lineage Natural killer cells  Natural killer cells (NK) cells are important in the defense against viral infections  They enter infected tissues, where they prevent the spread of infection by killing virus-infected cells and secreting cytokines that impede viral replication in infected cells 1. Virus infection of cells triggers 2. Interferon drives proliferation 3. Natural Killer Cells 4. Natural Killer Cells cause virus the release of interferons of Natural Killer Cells transform to killing mode infected cells to undergo self killing (apoptosis) Natural Killer Cell interferon virus virus infected cells B cells B cell B-cells produce antibodies that bind to pathogens and neutralize them Antibodies Neutralized pathogen cannot infect new cells Coronavirus Neutralized pathogen ‘eaten’ Antibodies attach to virus attachment sites (phagocytized) by innate immune cells Neutralized Coronavirus No attachment, no infection Human cell T cells Killing mediated by injecting cell damaging proteins into virus infected cells Natural Killer-Cell T Cell Production killing of killing of of interferon virus-infected cells virus-infected cells Perforin (pokes holes in cell membrane) T cell Infected cell Granzyme Virus number (causes cell death) 1 5 10 Time after viral infection (days) T cell killing activity initiated days after Natural Killer cell activity starts