Immunology Lecture Notes 2023 PDF

ASF 1106: Immunology Immunology Dr. Pabodha Weththasinghe Department of Animal Science Faculty of Agriculture University of Peradeniya Immunity Immunity  Pathogen Any organism with the potential to cause dise...

ASF 1106: Immunology Immunology Dr. Pabodha Weththasinghe Department of Animal Science Faculty of Agriculture University of Peradeniya Immunity Immunity  Pathogen Any organism with the potential to cause disease Opportunistic pathogens – – Colonize in the body without causing a disease – Cause disease if the body’s defenses are weakened or if the microbe gets into the ‘wrong’ place Four types – Bacteria, Viruses, Fungi and Parasites  Antigens Antigens: stimulate an immune response in the body Proteins, polysaccharides and lipids that are found on the surface of the pathogen Antigens are unique to a pathogen  Antigens Inhaled molecules (e.g., proteins on cat hairs that can trigger an attack of asthma in susceptible people) Ingested molecules (e.g., shellfish proteins that trigger an allergic response in susceptible people) Proteins encoded by the genes of viruses that have infected a cell Proteins encoded by mutant genes; such as mutated genes in cancer cells Immunity: according to the response…… Immunity Innate/Natural Adaptive/Acquired Immunity Immunity Second Line First Line Defenses Defenses Innate Immunity/Natural Immunity  Innate Immune System – First Line Defenses Innate immunity: the immediate response to infection Physical and chemical barriers of the body – Skin: physical barrier – Sweat: has chemicals to kill pathogens – Tears: has lysozyme – Saliva: has lysozyme – Epithelial tissue: provide effective physical and chemical barriers that prevent access to the internal tissues and organs Antimicrobial peptides (defensins) secreted at mucosal surfaces kill pathogens Mucus: can trap pathogens, which are then sneezed, coughed, washed away, or destroyed by chemicals – Stomach acid – destroys pathogens  Innate Immune System – First Line Defenses Physical barries colonized by commensal microorganisms protect against infection by pathogens – Skin – Mucosal epithelia that line the digestive, respiratory and urogenital tracts  Commensal microorganisms Enhance animal nutrition by processing digested food and making several vitamins Prevent colonization of dangerous, disease- causing microorganisms – Pathogen must compete successfully with the residant commensals for nutrients and space – Secrete antibacterial proteins Use of antibiotics – Kill normal bacteria along with the disease-casing bacteria  Innate immunity – Second line of defenses The macrophages resident in an infected tissue are responsible for inducing second line of defenses Macrophages have cell-surface, endosomal, and cytoplasmic receptors - recognize the distinctive chemical properties of the sugars, fats, proteins and nucleic acids of pathogens – Many different types receptors - recognize features shared by groups of pathogens and are not specific for a particular pathogen Once the pathogen is recognized, the second line of defense response is started Destructive effector mechanisms that kill and eliminate pathogen – E.g., Phagocytosis - Capture, engulfment, and killing of microorganisms  Inflammation Activation of resident macrophages induces a state of inflammation at sites of infection When infection has been detected in a tissue, the resident macrophages become activated to recruit other cells to the infected tissue by secreting several cytokines Cytokines are small soluble proteins used as a method of communication between cells – E.g., IL-1β, IL-6, IL-I2, CXCL8, tumor necrosis factor – α (TNF – α) Collectively, these cytokines are called inflammatory cytokines, or pro- inflammatory cytokines, because their combined efect is to create a state of inflammtion in the infected tissue Inflammation is associated with heat, pain, redness, and swelling  Inflammation Cytokines - induce the local dilation of blood capillaries - increasing the blood flow causes the skin to warm and redden Vascular dilation introduces gaps between the cells of the endothelium of blood vessels This makes the endothelium permeable and increase the leakage of blood plasma into the connective tissue This actively recruit neutrophils, monocytes, and natural killer (NK) cells into the infected tissue from blood circulation  Inflammation Cytokines also change the adhesive properties of the vascular endothelium, inviting white blood cells to attach to it and move from the blood into the inflamed tissue White blood cells present in inflamed tissues and release substances that contribute to the inflammation are called inflammatory cells Expansion of the local fluid volume and infiltrated cells cause swelling, putting pressure on nerve endings and causing pain  Pentraxins The inflammatory cytokines also changes the patterns of protein synthesis in the liver, the source of many plasma proteins The overall effect is to increase the production of proteins contributing to innate immunity at the expense of other proteins Plasma proteins of innate immunity - Pentraxins Bind microorganisms and target them to phagocytes One such protein whose concentration rises markedly is c-reactive protein Second line of defense - Complement system Complement is a system of plasma proteins that mark pathogens for destruction Complement coats the surface of bacteria and extracellular virus particles and make them more easily phagocytosed Without such a coating, many bacteria resist phagocytosis, especially those that are enclosed in thick polysaccharide capsules  Second line of defense – Complement system Bacterial cell surface induces cleavage and activation of complement Form a co-valent bond between a fragment of complement protein and the pathogen The attached piece of complement marks the pathogen as dangerous The soluble complement fragment summons a phagocytic white blood cell (effector cell) to the site of complement activation The effector cell has a surface receptor that binds to the complement fragment attached to the pathogen The receptor and its bound ligand are taken up into the cell by phagocytosis, which delivers the pathogen to an intracellular vesicle called a phogosome  Adaptive immune response When innate immune response is not sufficient to slow the spread of infection, – It calls white blood cells called lymphocytes – Their contribution to defense is the adaptive immune response The long-lasting adaptive immunity that develops against one pathogen provies a highly specialized defense that is of little use against infection by a different pathogen  Adaptive immune response Lymphocytes recognize pathogens by using cell-surface receptors During infection, only those lymphocytes bearing receptors that recognize the infecting pathogen are selected to participate in the adaptive response These then proliferate and differentiate to produce large numbers of effector cells specific for that pathogen Effector cells and molecules of the adaptive immuity work with innate immunity Recovery from an infection - clearance of infectious organisms from the body and repair of the damage caused by both infection and the immune response  Acquired/ protective immunity Some of the lymphocytes selected during an adaptive immune response persist in the body and provide long-term immunological memory of the pathogen These memory cells allow subsequent encounters with the same pathogen to elicit a stronger and faster adaptive immune response The adaptive immunity provided by immunological memory is called acquired immunity or protective immunity  The first time that an adaptive immune response is made to a given pathogen is called primary immune response The second and susequent times that an adaptive immune response is made, and when immunological memmory applies, it is called a secondary immune response The purpose of vaccination is to induce immunological memory to a pathogen so that susequent infection with the pathogen elicits a strong, fast-acting adaptive response  The Immune System Main organs: spleen, lymph nodes, thymus, and bone marrow Cells  Immune system cells with different functions – White blood cells 1. Phagocytes – Cells specialized in the capture, engulfment and killing of microorganisms – Neutrophils, Eosinophil, Basophil, Monocytes, Macrophages, Mast cells, Dendritic cells – Innate immune response 2. Lymphocytes – Natural Killer (NK) cells – Innate immune response – T lymphocytes, B lymphocytes - Adaptive immune response  Immune system cells with different functions Monocytes – White blood cells (Leukocytes) that circulate in the blood – Bigger and have a distinctive indented nucleus  Immune system cells with different functions Macrophages – Macrophages are the mature forms of circulating monocytes – Monocytes travel in the blood to tissues, where they mature into macrophages and take up the residence – Large, irregular shaped cells charaterized by an extensive cytoplasm with numerous vacuoles, often containing engulfed material  Immune system cells with different functions Macrophages – Equipped for phagocytosis – Scavenger cells - phagocytosing and disposing dead cells and cell debris as well as invading microorganisms – Long-lived – Macrophages resident in the infected tissue are generally the first cell to sense an invading microorganism – As part of the response to pathogen, macrophages secrete cytokines that recruit neutrophils and other leukocytes into the infected area – Initiate immune response – Participate in both innate and adaptive immunity  Immune system cells with different functions Neutrophils – Most abundant white blood cell (Leukocytes) – Specialized in the capture, engulfment, and killing of microorganisms - Phagocytosis – The most numerous and most lethal phagocyte – Effector cells of innate immunity that are rapidly mobilized to enter site of infection and can work in the anaeroic conditions that often prevail in damaged tissue – Inflammatory cytokines recruit neutrophils from the blood to the infected tissue – Short-lived and die at the site of infection, forming pus  Immune system cells with different functions Mast cell – Resident in connective tissues – Major contributions to inflammation at the site of infection  Immune system cells with different functions Dendritic cells – Resident in the bodys tissues and have a distinctive star shaped morphology – Many properties are in common with macrophages – Unique function - act as cellular messengers that are sent to call up an adaptive immune response when it is needed – At such times, 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  Immune system cells with different functions Lymphocytes Two populations of blood lymphocytes are distinguished morphologically – Large lymphocytes with a granular cytoplasm – Small lymphocytes with almost no cytoplasm 1. Large granular lymphocytes are effector cells of innate immunity called natural killer cells (NK cells) 2. Small lymphocytes are the cells responsible for the adaptive immune response – B and T cells  Immune system cells with different functions Natural Killer (NK) cells – Large granuler lymphocytes – Circulating cytotoxic lymphocytes that contribute to the innate immune response – NK cells are important in the defense against viral infections Killing virus-infected cells Secreting cytokines that inhibit viral replication in infected cells – NK cells and macrophages activate each other at the sites of infection  Adaptive immune system cells B lymphocytes (B cells) and T lymphocytes (T cells) Small because they circulate in a quiescent and immature form that is functionally inactive Recognition of a pathogen by small lymphocytes lymphocyte selection, growth and differentiation produce a powerful response after 1-2 weeks against the invading organism The unique property of mature B and T cells, which distinguished them from other blood cells, is that they move through the body in both blood and lymph  Lymphoid tissues Vast majority of lymphocytes are to be found in specialized tissues known as lymphoid tissues or lymphoid organs The major lymphoid organs are bone marrow, thymus, spleen, adenoids, tonsils, appendix, lymph nodes and peyer’s patches Less organized lymphoid tissue - lining the extensive mucosal surfaces of the respiratory, gastrointestinal and urogenital tracts  Lymphoid tissues The lymphoid tissues are functionally divided into two types 1. Primary or central lymphoid tisuues – Lymphocytes develop and mature to stages at which they are able to respond to a pathogen – Bone marrow and thymus B and T cells both originate in the bone marow B cells complete their maturation in the bone marrow before entering the circulation T cells leave the bone marrow at an immature stage and migrate in the blood to the thymus where they mature 2. Secondary or peripheral lymphoid tisuues – All the lymphoid tissues except the bone marrow and thymus – Sites where mature lymphocytes become stimulated to respond invading pathogens  Lymphoid tissues Secondary lymphoid tissue is associated with, – Gut associated lymphoid tissue (GALT) – Bronchial-associated lymphoid tissue (BALT) – Mucosa-associated lymphoid tissue (MALT) Adaptive immunity is initiated in secondary lymphoid tissues In the lymph nodes, the small fraction of B and T cells bearing receptors that bind to the pathogen or its products will be stimulated to divide and differentiate into effector cells Antigen receptors of lymphocytes Cell surface receptors for pathogens – B cells – Immunoglobulins – T cells – T-cell receptors (TCR) Recognize and bind with antigens Immunoglobulins and T cell receptors are structurally similar molecules Differences in the amino acid sequences of the variable regions of immunoglobulins and T cell receptors create a vast variety of binding sites that are specific for different antigens thus for different pathogens A consequence of this specificity is that the adaptive immune response made against one pathogen provides no immunity to another  After binding with specific antigen, B cells and T cells differentiate into effector cells – B cells differentiate into Effector B cells, called plasma cells, secrete soluble forms of the immunoglobulins, which are known as antibodies – Antigen-activated effector T cells undertake a variety of functions within the immune response – T cell receptors are only expressed as cell-surface receptors, never as soluble proteins  B -Lymphocytes B- Lymphocytes Memory Plasma Cells Cells  B -Lymphocytes Some activated B cells → PLASMA CELLS these produce lots of antibodies The principal function of B lymphocytes is to produce antibodies The antibodies travel to the blood, lymph, and then to the infected tissue The number of plasma cells goes down after few weeks Antibodies stay in the blood longer but eventually their numbers go down  B -Lymphocytes Some activated B cells → MEMORY CELLS Memory cells do not react right away but are held in reserve for later infections Memory cells divide rapidly as soon as the antigen is reintroduced When the pathogen/infection infects again it is destroyed before any symptoms show – Produce large number of antibodies – Fast response Memory cell Chicken Pox Virus  T lymphocytes Effector T cells are subdivided into two main kinds – Cytotoxic T cells – Helper T cells – Regulatory T cells Cytotoxic T cells kills cells that are infected with viruses or with bacteria NK cells (during innate immune response) and cytotoxic T cells (during adaptive immune response) have similar effector functions Helper T cells secrete cytokines that help other cells of the immune system become fully activated effector cells Regulatory T cells - control the activities of the cytotoxic and other types of T cells and prevent unnecessary tissue damage and stop the immune response once the pathogen has been defeated Memory T cells Thank you