Immunity Lecture PDF

Immune System Dr. Nnamdi Okereke DVM, MSc, PhD Where opportunity creates success Learning outcomes ➢ Compare the main characteristics of the innate and adaptive immune response ➢ what are the differences between the innate and adaptibe immune system ➢ Describe the physical and chemical barriers...

Immune System Dr. Nnamdi Okereke DVM, MSc, PhD Where opportunity creates success Learning outcomes ➢ Compare the main characteristics of the innate and adaptive immune response ➢ what are the differences between the innate and adaptibe immune system ➢ Describe the physical and chemical barriers against infection. ➢ Differentiate between primary and secondary lympoid organs ➢ Cells of immune system ➢ Key Features of the Complement System ➢ What are Immune Complexes ➢ Epitopes vs Antigens What is Immunity Funtional component of the Immune system; innate vs adaptive! Where opportunity creates success • Immunity can broadly be defined as the total activity of the cellular system (what are these cellular system) concerned with mechanisms of preserving the integrity of the external and internal environment of the animal. • It is able to generate an enormous variety of cells and molecules, capable of specifically recognising and eliminating apparently limitless variety of foreign invaders. • The environment is full of a large variety of pathogens such as bacteria, fungi, parasites and viruses. The immune system of the healthy animal provides the check against these potentially harmful organisms (how does the system provide these checks). Innate Imunne System Defence that exists in the body • Physical/Anatomic barriers – Skin, eyelashes, cilia, mucous membranes (tight junctions) • Biochemical factors – Mucus, wax, gastric acid, lysozyme, lactic acid, pH, • Soluble (inflammatory) Factors • – complements, lactoferrin, transferrin – Inflammation, non-specific cellular responses (macrophages, neutrophils) Cellular (Phagocytic) Factors Key Features of Innate Immunity 1. Inherent from Birth: Present from birth and consistently active. 2. First Line of Defense: Initial barrier against potential pathogens. 3. Limited Longevity: Doesn't provide lasting or protective immunity. 4. Absence of Antigen Memory: No requirement for previous antigen exposure, lacking memory. Roles of Innate Immunity 1. Mobilization of Immune Cells: Summons immune cells to infection sites. 2. Complement Cascade Activation: Triggers the complement cascade to detect bacteria, activate cells, and facilitate the elimination of deceased cells or immune complexes. 3. Recognition and Clearance: Identifies and eradicates foreign agents within the bloodstream, lymph, organs, and tissues via specialized cell activities. 4. Initiation of Adaptive Immunity: Initiates the adaptive immune response by facilitating antigen presentation. Adaptive Immunity • Adaptive immunity is capable of recognising and selectively eliminating specific foreign microorganisms and molecules, unlike innate immunity • The adaptive immune system is made up of specialised cells that effectively eradicates pathogens and impedes their proliferation and disease-causing effects. • The adaptive immune system offers a tailored response to specific pathogens. • This system "learns" to recognize and remember pathogens it encounters, enabling a faster and more precise reaction upon subsequent exposures. Key Features of Adaptive Immunity 1. Recognition 2. Specificity 3. Memory 4. Amplification 5. Effector mechanism Cells of Immune System Where opportunity creates success Phagocytes; what are they and what do they do? • Phagocytes are any of the white blood cells that can: Ingest and destroy pathogens using enzymes • Signal for more phagocytes to come and help • These include neutrophils, monocytes, macrophages, mast cells, and dendritic cells Cells of Innate immunity Cells of Adaptive Immunity • Neutrophils • T-Cell • Eosinophils • B-cells ❖ macrophages (APC) ❖ Dendritic cells (APC) ❖ dendritic cells (APC) ❖ macrophages (APC) • Complement System • Basophils and Mast Cells *APC-Antigen Presenting Cell* Lymphoid organs contain lymphocytes at various stages of development and are grouped into: ❖Primary/central lymphoid organs ❖Secondary/peripheral lymphoid organs Neutrophils • Neutrophils are the most abundant type of white blood cells. • Represent over 90% of granulocytes. • They are rapid responders to sites of infection (notable bacteria infection) and inflammation. • Neutrophils engulf and destroy pathogens through a process called phagocytosis. Eosinophils • Functionally, eosinophils are poorly phagocytic but are triggered to degranulate promptly in the presence of appropriate stimuli such as chemotactic factors and the cross linking of a membrane bound IgG or IgE with an antigen • Eosinophils are involved in defense against parasitic infections. • They release toxic substances to destroy parasites. Basophils and Mast cells • Basophils constitute <1% of circulating PBLs. • These cells release histamine and other inflammatory molecules in response to allergens and pathogens. • They contribute to the immediate response to infections and allergic reactions. • They are characterised by deep violet blue granules. • Mast cells are often indistinguishable from basophils although the relationship between them is not completely clear. • Mast cells are associated with mucosal epithelial cells and also commonly occur in connective tissues. Macrophages and Monocytes • The predominant role in innate immunity is to remove (engulf) particulate (phagocytosis) or soluble (pinocytosis) antigens. • Phagocytic tissue macrophages form a network: reticuloendothelial system (RES), which occurs in many organs e.g. blood, liver, kidney, lungs, serosa, spleen, brain and lymph nodes. Lymphocytes • Circulate in the tissues, blood and lymph • Lymphocytes are the white blood cells involved in the specific immune response. • They recognise specific antigens on invading pathogens. • Antigens are molecules, often proteins, located on the surface of cells that trigger a specific immune response. Complement • Reports has shown that the ability of antibody to destroy foreign materials depended upon the collaboration of another factor – COMPLEMENT (are they cells?). • The complement system is a group of proteins that play a critical role in defending the body against infections, particularly by enhancing the effectiveness of the immune response. • It is an integral component of both the innate and adaptive immune systems. Key Features of Complement System ❖ Enhancing immune functions ❖ Opsonisation ❖ Cell Lysis ❖ Inflammation ❖ Clearance of Immune complexes ❖ Classical/Alternate Pathway Dendritic cells • Dendritic cells are specialized antigen-presenting cells. • They capture antigens at sites of infection and transport them to lymph nodes to activate adaptive immune responses. Natural Killer (NK) cells • NK cells are a type of lymphocyte that recognizes and destroys infected or cancerous cells. • They play a role in the early containment of viral infections and tumor growth. • NK cells release cytotoxic substances to induce apoptosis (programmed cell death) in target cells. T-cells • Helper T Cells (CD4+ T Cells): These cells play a central role in coordinating immune responses. They assist B cells in producing antibodies, activate macrophages, and stimulate cytotoxic T cells. • Cytotoxic T Cells (CD8+ T Cells): Cytotoxic T cells directly target and kill infected or cancerous cells by releasing cytotoxic substances. • Regulatory T cells are important for immune system regulation and preventing autoimmune responses. They help maintain immune tolerance by suppressing excessive immune reactions. Antigen Presenting cells (APC)-are there other cells that can function as an APC and what are they? • The role of APCs is to present antigens to specific antigen sensitive lymphocytes. • APCs are found primarily in the lymph nodes, spleen and thymus. • Examples include; Langerhans cell in the skin, interdigitating cell in the paracortex (T cell area) of lymph nodes and spleen particularly in the germinal centres, dendritic cell in the blood, interdigitating follicular • Cell in the medulla of thymus and some monocytes in the blood B-cells • B cells are responsible for producing antibodies also known as immunoglobulins (Ig). • Each B cell produces a unique antibody that can bind specifically to a particular antigen. • When activated, B cells differentiate into plasma cells, which secrete antibodies into the bloodstream to neutralize pathogens. • Progenitor B cells-Mature b cells- naive b cells (no antigen b cells)- activated b cellsplasma cells (secrets antibody)-memory b cell Immune Responses Where opportunity creates success Ways by which Immune cells recognise antigens: • The humoral branch of the immune system recognises an enormous variety of epitopes (what are epitopes); those displayed on the surfaces of bacteria or viral particles as well as those displayed on soluble proteins, glycoproteins, polysaccharides or lipopolysaccharides that are been released from invading pathogens. • The cell mediated branch recognises protein epitopes displayed together with MHC molecules on self cells including altered self cells such as virus infected self cells and cancerous cells. Major Histocompatible Complex (MHC) • The major histocompatibility complex is a large genetic complex with multiple loci which are encoded by two major classes of membrane bound glycoproteins called Class I and Class II MHC. • MHC molecules function as antigen recognition molecules, they do not posses the fine specificity for antigens and attribute characteristic of antibodies and T-cell receptor, rather each MHC molecule binds to a spectrum of antigenic peptides derived from the Intracelluar degradation of antigens. (MHC Class I and MHC Class II) • T-helper cells generally recognise antigens (peptide fragments) combined with Class II MHC molecules, whereas T-cytotoxic cells recognise antigens combined with Class I MHC molecules. Immune Dysfunction (role of immune tolerance) • Sometimes, the immune system fails to protect the host adequately or misdirect its activities to cause discomfort, debilitating diseases or even death. • There are several common manifestations of immune dysfunctions, namely: 1. allergy and asthma 2. graft rejection and graft-versus-host disease 3. autoimmune diz 4. immunodeficiency Antigen • Any molecule recognised by receptors of the immune system and can thus induce antibody production is an antigen. • Must be structurally complex and have a molecular weight of not less than 8,000 Da to be antigenic. • Antigens are typically found on the surfaces of pathogens (bacteria, viruses, fungi, and parasites), as well as on the surface of cells from other individuals (in the case of organ transplants) or on cancer cells. Sources of Antigen Antigens may arise in the body as a result of the following: • Invasion by infectious organisms • Development of mutant cells which are thus recognised as foreign. • Experimental procedures during which the antigens are introduced. • Autoantigens i.e. normally hidden molecules change and become antigenic. Classification of Antigen Antigens can also be classified as exogenous or endogenous. • Foreign Antigens (Exogenous Antigens): These are antigens that originate from outside the body, often from pathogens. They are taken up by antigen-presenting cells (APCs) like dendritic cells, which then display fragments of the foreign antigens on their surface to activate T cells and B cells. • Self Antigens (Endogenous Antigens): These are antigens that are derived from the body's own cells. They play a role in distinguishing between self and non-self. Self antigens are important for maintaining immune tolerance and preventing the immune system from attacking healthy cells. Antibody • Antibodies or immunoglobulins are a group of glycoprotein molecules present in the serum and tissue fluids of animals and are produced by plasma cells in response to an immunogen or antigen. • They can also be defined as recognition proteins found in the serum and other body fluids of vertebrates that react specifically with the antigens that induced their formation. Antibody https://s3-us-west2.amazonaws.com/courses-images Immunoglobulin G • Secreted by plasma cells in the blood. • Able to cross the placenta into the fetus • Only antibody to cross placenta therefore protecting infants from infections. • Infants have high levels of maternal IgG from birth. • Exposure to environmental immunogens stimulates native IgG production. Immunoglobulin A • IgA represents 15-20% of serum Ig. • Major Ig of external secretions (Found in plasma, extravascular fluid and secretions) e.g. saliva, tears, colostrum and mucus; • Being particularly evident during secondary response to antigens which gain access via mucosal surfaces. • Exists in different forms depending where found. • Sectretory IgA protects mucosal surfaces from infection. Immunoglobulin M • First antibody produced in immune response. • High levels of IgM indicate recent infection • Distribution is mostly intravascular and it is Pentamer • Very good at activating complement – potent immune response • Antibodies to ABO blood groups always IgM. • Because they are large they don’t cross placenta therefore of no danger to foetus. • Is the key antibody of primary immune response and is frequently directed against infectious agents that are antigenically complex. • It fades with progressive exposure to specific antigen in favour of other isotypes e.g. IgG and IgA. Immunoglobulin E • IgE is the least plentiful of all serum Igs. • However, its response can be dramatically felt by its ability to bind to receptors on mast cells and basophils. • It plays a role in active immunity to parasites but is more commonly associated with allergic diseases such as asthma and hay fever. • Causes symptoms of allergy eg hay fever, asthma and food allergies. Functions of Antibody • Each immunoglobulin is bifunctional: One end (paratope) binds to antigen. The other end anchors the antibody to host tissues, including various cells of the immune system, some phagocytic cells, and other complement system. Antibodies contribute to immunity in three ways: • They prevent pathogens from entering or damaging cells by binding to them; • They stimulate removal of pathogens by macrophages and other cells by coating (opsonising) the pathogen; and, • They trigger destruction of pathogens by stimulating other immune responses such as the complement pathway. Antibody Response • When an individual first encounters an antigen, the cells of the immune system recognise it and either produce immune reaction to it or become tolerant depending on the circumstances. • The immune reaction can be cell mediated or antibody (humoral) mediated. • Whether a cell-mediated or antibody-mediated immune response is elicited will depend on the way the antigen is presented to the lymphocytes. • However, many immune reactions display both kinds of responses. • On second and subsequent encounters with the same antigen, the type of response is determined by the outcome of the first antigenic challenge, but the quality and quantity, of the responses are different Primary Antibody Response • When an individual first encounters an antigen, the cells of the immune system recognise it and either produce immune reaction to it or become tolerant depending on the circumstances. • The immune reaction can be cell mediated or antibody (humoral) mediated. • Whether a cell-mediated or antibody-mediated immune response is elicited will depend on the way the antigen is presented to the lymphocytes. • However, many immune reactions display both kinds of responses. • On second and subsequent encounters with the same antigen, the type of response is determined by the outcome of the first antigenic challenge, but the quality and quantity, of the responses are different Secondary Antibody Response Following a secondary antigenic challenge with the same antigen, the secondary responses differ from the primary responses in four major respects. 1. Time course: The secondary response appears more rapidly (shorter Lag phase and steeper Log phase), and has an extended plateau and decline phase. 2. Antibody titre: the antibody titre in the secondary plateau phase is typically ten-fold or more than plateau levels in primary response. 3. Antibody class: IgM antibodies form the first and major proportion of the primary response, whereas the secondary response consists almost entirely of IgG. 4. Antibody affinity: the affinity of the antibodies in the secondary response is usually much greater. This is referred as “affinity maturation”. Hypersensitivity Reactions • When an adaptive immune response occurs in an exaggerated or inappropriate manner, thereby causing tissue damage, the term hypersensitivity reaction is used to describe the response. • Hypersensitivity is characteristic of individual and is manifested on second contact with a particular antigen. • There are four types of hypersensitivity reactions, but in practice, these types do not necessarily occur in isolation from each other. • The first three types are antibody mediated, and the fourth is mediated primarily by T cells and macrophages Type I Hypersensitivity (immediate hypersensitivity) • This is mediated by IgE and mast cells. • When an IgE response is directed against innocuous antigens (allergens) such as pollen, the IgE sensitises mast cells by binding to it via the Fc receptor. • If the host encounters the antigen again and the antigen subsequently reaches the sensitised mast cell, the IgE cross links with the mast cell. • The mast cell then degranulates, and releases mediators which produce immediate and acute inflammatory reaction with symptoms such as asthma, Hay fever (rhinitis), eczema and urticarial. Type II Hpersensitivity (antibody-dependent cytotoxic hypersensitivity) • This happens when antibodies are directed against antigens on an individual’s own cells. • Binding of the cells by such antibodies leads to cytotoxic actions of phagocytes and killer cells or complement mediated lysis. • Examples include haemolytic disease of the new born and auto-immune haemolytic anaemias. Type III Hypersensitivity (immune complex mediated hypersensitivity) • Immune complexes are found every time antibody meets antigen and generally they are removed effectively by cells of the reticulo-endothelial system. • Occasionally, their formation can lead to a hypersensitivity reaction. • When the complexes are formed in large quantities such that they cannot adequately be cleared by the RES, they are deposited in the tissue. • This activates complement and polymorphs are attracted to the site of deposition, causing local damage, e.g. RA, SLE. Serum sickness, • Trypanosomosis, acute bacterial glomerulonephritis. Type IV or Delayed type Hypersensitivity (DTH) or cell mediated hypersensitivity • DTH is manifested when antigen-sensitized T cells to release lymphokines following a secondary contact with the same antigen. • Lymphokines induce inflammatory reaction and activate and attract macrophages to the site where they (macrophages) release mediators which amplify the local response. Types of delayed type hypersensitivity reaction • The Jones-Mote reaction which is maximal at 24hours after challenge. • Contact hypersensitivity which peaks at 24-48 hours after antigen challenge. • Tuberculin-type hypersensitivity peaking at 48-72hours after antigen challenge. • Granulomatous reaction that develops over a period of weeks not less than 2 weeks. Disease manifesting DTH include; Tuberculosis, Leprosy, Leishmaniasis, Deep fungal infection (e.g blastomycosis), Listeriosis, Helminth infection (e.g. schistosomosis). In Summary