Innate & Adaptive Immunity PDF

Innate & Adaptive Immunity Dr Sherko Ali Omer Dept. of Basic Medical Sciences Learning objectives By the end of this session, students should be able to: • Define innate immunity and adaptive immunity • Understand components involved in innate and adaptive immunity • Understand the active and pass...

Innate & Adaptive Immunity Dr Sherko Ali Omer Dept. of Basic Medical Sciences Learning objectives By the end of this session, students should be able to: • Define innate immunity and adaptive immunity • Understand components involved in innate and adaptive immunity • Understand the active and passive immunity and their difference • Find difference between primary and secondary immune response. 2 Immunity • The term 'immunity’ was derived Latin word ‘immunitas’, means exempt from public service. • Immunity is defined as the resistance offered by the host against microorganism(s) or any foreign substance(s). • Immunity can be broadly classified into two types: • Innate immunity: immunity present right from the birth • Adaptive : acquired during the course of the life. 3 Innate immunity • Innate (natural) immunity is the inborn resistance against infections that an individual has right from the birth, due to genetic makeup. • Features of innate immunity: • Acts in minutes • Prior microbial exposure is not required • Diversity is limited • Non-specific • No memory 4 Innate immunity • In addition to host defense, another important function of innate immunity is to heal damaged tissue and clear away dead cells and debris from various organs. • The innate arm of our host defenses performs two major functions: • killing invading microbes and, • activating adaptive immune processes. 5 Components of innate immunity • Many organs, tissue, cells and proteins play role using different mechanism to provide innate immunity: 1. 2. 3. 4. 5. Anatomical and physiological barriers Cells such as phagocytes, Natural killer (NK) cells and other Classes of lymphocytes, Mast cells, dendritic cells Acute phase reactant proteins (APRs), Complement protein, cytokine Inflammatory response Normal resident flora 6 Anatomical and physiological barriers Anatomical Barrier Skin Barrier Function • • • Mechanically prevents entry of microbes Produces sebum containing antimicrobial peptides and fatty acids Killing of microbes by intraepithelial lymphocytes Mucosal Barrier 1. Mucous membrane Prevents entry of microbes mechanically and by producing mucous which entraps microbes 2.Cilia Cilia present in the lower respiratory tract propel the microbes outside 3.Normal flora Intestinal, upper respiratory, genitourinary tract are lined by normal flora 7 Anatomical and physiological barriers Physiological Barrier 1. Temperature Function Normal body temperature inhibits the growth of some microbes 2. Low pH Gastric acidity inhibits most of the microbes 3.Secretory products of mucosa Saliva Tears Gastric juice Trypsin Bile salts Fatty acids Spermine Lactoferrin Enzymes in saliva damage the cell wall and cell membrane of bacteria Contains lysozyme, that destroys the peptidoglycan layer in bacterial cell wall HCl kills microbes by its low pH Hydrolyse bacterial protein Interfere with bacterial cell membrane Denature the bacterial proteins Present in semen, inhibits growth of Gram positive bacteria Binds to iron, thus interferes with acquisition of iron by bacteria 8 Phagocytes • Neutrophils, Macrophages are the main phagocytes component of innate immunity. • These cells are rapidly recruited to the infection sites. Phagocytosis involves three sequential steps: ▪ Engulfment of microbes and subsequent hosting in phagosome. ▪ Fusion of lysosome with phagosome to form phagolysosome ▪ Microbial killing by different mechanism 9 Natural killer (NK) cells and other classes of lymphocytes • Natural killer cell are a class of lymphocytes that kill virus infected cells and tumor cells. • γδ T cells (also called as intraepithelial lymphocytes)-present in epithelial lining of skin and mucosa • NK-T cells - present in epithelium and lymphoid organs • B-1 cells - found mostly in the peritoneal cavity and mucosal tissues • Marginal-zone B cells - present at the edges of lymphoid follicles of spleen 10 Dendritic cells • These cell respond to microbes by producing numerous cytokines that initiate inflammation. • They also serve as vehicle in transporting the antigen(s) from the skin and mucosal site to lymph nodes where they present the antigen(s) to T cells so server as a bridge between innate and adaptive immunity. Dendritic cells as a class of antigen present cells 11 Mast cells • They are present in the epithelial lining of the respiratory and other mucosa. • Activated by microbial products binding to toll like receptors or by IgE antibody dependent mechanism. • They release abundant cytoplasmic granules rich in histamine, prostaglandins & cytokines that initiate inflammation and proteolytic enzymes that can kill bacteria. 12 Recognition and interaction to microorganism • The cells of innate immunity will recognize microorganism through receptor interaction • Following the exposure of microorganisms, several mediators of innate immunity are recruited to the site of infection. • The first step that takes place is attachment, which involves binding of the surface molecules of microorganisms to the receptors of cells of innate immunity. 13 Recognition and interaction to microorganism • The cell identify microbial surface molecules of the microorganisms. • Repeating patterns of conserved molecules which are common to most microbial surfaces; called as Microbesassociated molecular patterns (MAMPs). • Examples of MAMPs are peptidoglycan, teichoic acid, lipopolysaccharides (LPS), and lipoproteins present on bacterial surface. 14 Recognition and interaction to microorganism • On the recognizing cells there are Pattern recognition receptors (PRRs) which identify MAMPs. • These receptors have conserved regions, encoded by germ line genes. • A classical example of PRRs is Toll like receptors (TLRs), NOD-like receptors (NLRs), and others. • TLRs binds to MAMPs → signals are generated → activate transcription factors → stimulate expression of genes encoding cytokines & enzymes →antimicrobial activity 15 Toll like receptors • So named because they are similar to Toll receptors present in the fruit fly- Drosophila, where it is the main receptor for induction of innate immunity. • There are 13 types of Toll like receptors (TLR 1 to 13). Important ones areo TLR-2 binds to bacterial peptidoglycan o TLR-3 binds to dsRNA of viruses o TLR-4 binds to LPS of Gram negative bacteria o TLR-5 binds to flagella of bacteria o TLR-7 & 8 bind to ssRNA of viruses o TLR-9 binds to bacterial DNA 16 Complement pathways • Alternative and lectin pathways are the chief mediators of innate immunity. Alternative complement pathway is activated in response to bacterial endotoxin, while Lectin pathway is stimulated by mannose carbohydrate residues on bacterial surface. • The biological effect of complement activation include: • Lysis of the target microbes by forming pores on the microbial surfaces. • Stimulate inflammation by secreting inflammatory mediators • Opsonization. 17 Inflammatory response Inflammation is defined as the biological response of vascular tissues to harmful stimuli, such as microorganisms or other foreign substances As a result of inflammation, there will be: • Vasodilation due to release of vasoactive substances from the damaged tissue and leakage of plasma proteins through blood vessels 18 Inflammatory response • Recruitment of phagocytes (e.g. neutrophils) to the site of inflammation. • Phagocytes undergo the following steps ▪ Margination (adherence to the endothelium). ▪ Rolling on endothelium ▪ Extravasation (moves out of the blood vessels). ▪ Chemotactic migration to the inflammation site 19 Inflammatory response The final effect of inflammation will be Engulfment of microbes and dead material by the phagocytes and their destruction of the microbes Inflammation is not always protective in nature - hypersensitivity reactions (injurious consequences) 20 Normal resident flora • Normal resident flora are bacterial lining intestinal, respiratory and genital tract exert several antimicrobial activities. • They compete with the pathogens for nutrition and attachment sites. • They produce antibacterial substances. 21 Cytokines In response to the microbial antigens, dendritic cells, macrophages, and other cells secrete several cytokines that mediate many of the cellular reactions of innate immunity such as: ▪ Tumor necrosis factor-α (TNF-α) ▪ Interleukin-1 (IL-1), IL-6, IL-8, IL-12 & IL-16 ▪ Interferons (IFN-α, β), and ▪ Transforming growth factor (TGF-β) 22 Acute phase reactant proteins (APRs) • Proteins synthesized by liver at steady concentration, but their synthesis either increases or decreases exponentially during acute inflammatory conditions. • APRs can also be synthesized by various other cells such as endothelial cells, fibroblasts, monocytes and adipocytes. 23 Positive APRs Proteins whose levels increase during acute inflammation. Examples include: o C-Reactive Protein (opsonin on microbes) o Ferritin (Binding iron, inhibiting microbe iron uptake) o Complement Factors: (opsonization, chemotaxis, lysis, clumping of target cells) o Coagulation Factors: fibrinogen, prothrombin, factor VIII, von Willebrand factor (trapping invading microbes in blood clots, some cause chemotaxis) o Mannan-binding lectin o Alpha 2-macroglobulin o Haptoglobin o Ceruloplasmin o Serum Amyloid A o Hepcidin o Plasminogen activator inhibitor-1 24 Negative APRs • Proteins whose levels are decreased during acute inflammation, thus creating a negative feedback that stimulates the liver to produce positive APRs. • Examples of negative APRs include: o Albumin o Transferrin o Antithrombin o Transthyretin o Retinol-binding protein o Transcortin 25 Adaptive Immunity The adaptive (acquired) immunity is defined as the resistance against the infecting foreign substances that an individual adapts or acquires during the course of life. Adaptive immunity is characterized by being: • Specific: immunity is highly specific; directed against specific antigens that are unique to the microbes. • Memory: A proportion of T and B cells become memory cells following primary contact of the microbe, which play an important role when the microbe is encountered subsequently. • Wide diversity: immunity is acquired against a wide range of repertoire of antigens. 26 Adaptive Immunity • Response occurs in days: It requires the activation of T and B cells against the microbial antigens. • Requires prior microbial exposure- Adaptive immunity develops only after the exposure to the microbes. • Mediators: Include T & B cells, the chief mediators; and • Classical complement pathway • Antigen presenting cells (APSs) • Cytokines (IL-2, IL-4, IL-5) 27 Adaptive Immunity • Host cell receptors: adaptive immunity are specific against particular microbial antigen using receptors such T cell receptors and B cell immunoglobulin receptors. These receptors are encoded by genes produced by somatic recombination of gene segments. • The adaptive immunity can be divided into: • Active and passive immunity • Artificial and natural immunity 28 Active Immunity • The host’s immune system is actively involved in response to the antigenic stimulus; leading to the production of immunologically active T cells, B cells and production of specific antibodies. • Active immunity may be induced naturally or artificially: ▪ Natural active immunity occurs following a natural exposure to a microbial infection (e.g. measles virus infection) ▪ Artificial active immunity develops following an exposure to an immunogen by vaccination (e.g. measles vaccine). 29 Active Immunity • Active immunity is long-lasting- usually lasts for longer periods but the duration varies depending on the type of pathogen; e.g. following certain viral infections such as chicken pox, measles, mumps and rubella a long-life immunity occur while following influenza infection a short immunity occur • Active immunity may not be protective at all- e.g. for Haemophilus ducreyi, the patient may develop genital lesions following reinfection even while the original infection is active. 30 Passive immunity • Passive immunity is defined as the resistance that is transferred passively to a host in a 'ready-made' form without active participation of the host’s immune system. • Passive immunity can also be induced naturally or artificially. ▪ Natural passive immunity involves the IgG antibody transfer from mother to fetus across the placenta. ▪ Artificial passive immunity develops following ready-made transfer of commercially prepared immunoglobulin (e.g. Rabies immunoglobulin) 31 Properties and uses of passive immunity • Passive immunity develops faster; there is no lag phase or negative phase. • There is no immunological memory as the memory cells are not involved. • Booster doses are not effective Passive immunization can be used immunodeficient individuals (as host’s immune apparatus is not effective) and in post-exposure prophylaxis; when an immediate effect is warranted. 32 active vs. passive immunity Active immunity Passive immunity Produced actively by host immune system Immunoglobulins received passively Induced by• Infection (natural) • Vaccination (artificial) Acquired by• Mother to fetus IgG transfer (natural) • Ready-made antibody transfer (artificial) Long-lasting Lasts for short time Lag period present No Lag period Memory present No Memory Booster doses-useful Subsequent doses-Less effective Negative phase may occur No Negative phase Not useful in immunodeficient individuals Useful in immunodeficient individuals 33 Immune response • Active immune are with different responses; the primary immune response occur following the microbial exposure for the first time while in subsequent exposure the response is called secondary immune response. 34 Primary immune response When the antigenic exposure occurs for the first time, the following events take place: • Latent or lag period: active immunity develops only after a latent period following the antigenic exposure, which corresponds to the time required for the host's immune apparatus to become active. • Effector cells: majority of activated T & B cells against the antigenic stimulus become effector T and B cells where effector T cells such as helper T cells and cytotoxic T cells forms while effector B cells include plasma cells 35 Primary immune response • Memory cells: a minor proportion of stimulated T and B cells become memory cells, which are the key cells for secondary immune response. • Antibody surge • Activated B cells produce antibodies (mainly IgM type). • Antibodies appear in the serum in slow & sluggish manner; reach peak, maintain the level for a while and then fall down. • Finally, a low titer of baseline antibodies may be maintained in the serum. 36 Secondary immune response When the same antigenic exposure occurs subsequently, the events which take place are as follows: o Latent period: either absent or of short duration. This is because memory cells become active soon after the antigenic exposure. o Negative phase: at the onset of secondary immune response, there may be a negative phase during which the antibody level may become lower than it was before the antigenic stimulus. o Antibody surge: secondary antibody response is prompt, powerful, long-lasting and mainly of IgG type. Hence, it is said that, the booster doses of vaccines are more effective than the first dose. 37 Primary vs. secondary immune response Primary immune response Immune response against primary antigenic challenge Slow, sluggish (appear late) and short lived Secondary immune response Immune response against subsequent antigenic challenge Prompt, powerful & prolonged (long-lasting) Lag period is longer (4-7 days) Lag period is absent or short (1-3 days) No negative phase Antibody produced in low titer & is of IgM type. Antibodies are more specific but less avid Antibody producing cells- Naive B cells Negative phase may occur Antibody produced in high titer & is of IgG type Antibodies are less specific but more avid Both T dependent and T independent antigens are processed Only T dependent antigens are processed Antibody producing cells- Memory B cells 38 Bridges between innate and adaptive immunity • Macrophages and dendritic cells: they belong to innate immune system but as antigen presenting cells, they present the antigenic peptides to T cells and also secrete cytokine like IL-1 T cell activation. • ADCC (antibody dependent cell mediated cytotoxicity): a type of cell mediated immune response (CMI), which involves both innate and adaptive components. Cells of innate immunity such as NK cell, eosinophils, and neutrophils destroy (by cytotxic effect) the target cells coated with specific antibodies. 39 Bridges between innate and adaptive immunity • Complements (classical pathway): part of both innate and adaptive immunity. It destroy the target cells which are coated with specific antibodies. • Cytokines: Secreted from cells of innate immunity can activate cells of adaptive immunity and vice versa. E.g. IL1 secreted from macrophage activates helper T cells and interferon-γ secreted by helper T cell can activate macrophage. 40 Bridges between innate and adaptive immunity • Rare classes of lymphocytes such as γδ T cells , NK-T cells, B-1 cells and Marginal-zone B cells. • These cells have many characteristics that place them in the border of innate & adaptive immunity. • Function in the early defense against microbes as part of innate immunity. • Although their receptors are encoded by somatic recombination of genes (similar to that of classical T and B cells), but these receptors have limited diversity. • They develop a memory phenotype in contrast to the property of innate immunity. 41 Mucosal Immunity • Local or mucosal immunity is immune response that is active at the mucosal surfaces such as intestinal or respiratory or genitourinary mucosa. • It is mediated by a type of IgA antibody called secretory IgA. • Local immunity can only be induced by natural infection or by live vaccination (but not by killed vaccines). 42 Herd immunity • Herd immunity is defined as the overall immunity of a community towards a pathogen. • Elements that contribute to create strong herd immunity are: ▪ Occurrence of clinical and subclinical cases in the herd ▪ On-going immunization programme. Following effective vaccination against some diseases like Diphtheria and Pertussis vaccine, Measles, Mumps and Rubella (MMR) vaccine, polio (oral polio vaccine), and Smallpox vaccine ▪ Herd structure i.e. type of population involved ▪ Type of pathogen- Herd immunity may not be strong in a community against all the pathogens. 43 Innate vs. adaptive immunity Innate immunity Adaptive immunity Specificity Time from exposure to effect Memory Non specific Rapid-acts within minutes No Specific Slow—requires several days before becoming effective Yes Development Present right after birth Natural killer cells, macrophages Complement Will develop during lifetime Examples of CellMediated Immunity Examples of Humoral Proteins Helper T cells, cytotoxic T cells Antibodies (produced by B cells) 44 Thank You