Introduction to Immunology PDF

INTRODUCTION TO IMMUNOLOGY  LESSON OBJECTIVES Define immunology and immunity Explain concept and history of immunology Introduction Immunology The study of all aspects of host defense against infection & of adverse consequences of immune responses. Study of mechanism involved...

INTRODUCTION TO IMMUNOLOGY  LESSON OBJECTIVES Define immunology and immunity Explain concept and history of immunology Introduction Immunology The study of all aspects of host defense against infection & of adverse consequences of immune responses. Study of mechanism involved to neutralize, metabolize or eliminate foreign without injury to the host tissue. The study of the cellular, physiological mechanisms which enable the body to recognize materials as foreign Consider physical barriers , protective chemical substances, cells specialized abilities to recognize self/not self Study the tendency of the body to maintain stability while continually adjusting to conditions that are optimal for survival (Homeostasis) Cont. Immunity is body's ability to resist/eliminate potentially harmful foreign materials/abnormal cells from the body Consists of following activities: Defense against invading pathogens/noxious chemicals Removal of 'worn-out' cells (e.g., old RBCs) & tissue debris (e.g., from injury or disease) Identification & destruction of abnormal or mutant cells (primary defense against cancer) Rejection of 'foreign' cells (e.g., organ transplant) Maintain body’s homeostatic condition Inappropriate responses: Allergies - response to normally harmless substances Autoimmune diseases Immune system A system that involve different body structures to react and protect individuals from invading pathogens and cancer. It is able to generate an enormous variety of cells and molecules capable of specifically recognizing and eliminating an apparently limitless variety of foreign invaders A system that develop immune response, which is  Collective and coordinated reply to the introduction of foreign substances in an individual & mediated by the tissues, cells and molecules Cont.  What are the main principles of the immune responses?  Recognition: the ability to discriminate between 'self' and 'non-self'; and 'danger' vs 'non-danger'  Response: appropriate and specific for the pathogen and present progressively after the exposure; rapid  Memory: secondary infections are more rapid and give a stronger response  Regulation: the immune response must be down- regulated, when a pathogen is eliminated from the body (chronic inflammation, auto-immune disease) Cont.  What are the role of the immune system?  Protect from pathogens Intracellular(e.g. viruses and some bacteria and parasites) Extracellular (e.g. most bacteria, fungi and parasites)  Rejection of 'foreign' cells (e.g., organ transplant)  Identification and eliminate of modified or altered self cells: defense against the growth of tumor cells/kills the growth of tumor cells  Protect from environmental stimulant substances such as toxins, poison ivy, allergens  Keeping Homeostasis Destruction of abnormal, infected or dead cells (apoptosis) (e.g. white blood cells, antigen-antibody complex) Removal of 'worn-out' cells (e.g., old RBCs) & tissue debris (e.g., from injury or disease) Source of exposure The subject of immunology is associated with one of the branches of science ‘’Biomedicine’’. Immunology deals with the immune system and how get immuned from foreign attack. It deals with the structure and functioning of immune system. For many decades this discipline is alive and it's evolving continuously.  Immunology act as an independent subject: (In 1971, International Conference of Immunology, in USA ) Response to Infection Historical perspective Cont Plague  Black death disease  430 BC, Thucydides (plague of Athens)  Bacterial infection transmitted by vector flea, killed millions  Compassion the sick had recovered from the disease  Recovered ones (care givers) never attacked again Smallpox  Endemic in China in10th century  Caused by the Variola major virus  Spreads very easily from person to person and fatal  Survivors scarred for life but never came down with it a 2nd time Use of cowpox safer than variolation Vaccination -Induced Cont Observing recovered care givers/nurse sick ones from Athens plague (Thucydides) in 430BC Chinese(1500A.D) custom of inhaling crusts from smallpox lesions to prevent expansion of small pox in later life. Initiate experiential Immunology (the 17th century- the middle of 19th century) In 1670, Chinese medical practitioners: practice variolation (Exposing healthy people to material from the lesions of the disease or inserting powdered scabs from smallpox pustules into the nose) But has ethical issue Edward Jennar -An English physician in 1796 investigate cowpox vaccination that protected against smallpox Cont.  Vaccine  A preparation of microbial antigen, often combined with adjuvants, that is administered to individuals to induce protective immunity against microbial infections. Developed by using attenuated or weaken pathogen Vaccination: Immunization against infectious diseases. Originally derived from Vaccinia virus The announcement by the WHO in 1980 that smallpox was the first disease that had been eradicated worldwide by a program of vaccination Cont. Milestones in the history of immunology 1798 Edward Jenner initiates smallpox vaccination. 1877 Paul Erlich recognizes mast cells. 1879 Louis Pasteur develops an attenuated chicken cholera vaccine. 1883 Elie Metchnikoff develops cellular theory of vaccination. 1885 Louis Pasteur develops rabies vaccine. 1891 Robert Koch explored delayed type hypersensitivity 1900 Paul Erlich theorizes specific antibody formation. 1906 Clemens von Pirquet coined the word allergy.  Cont 1938 John Marrack formulates antigen-antibody binding hypothesis. 1942 Jules Freund and Katherine McDermott research adjuvants. 1949 Macfarlane Burnet & Frank Fenner formulate immunological tolerance hypothesis. 1959 Niels Jerne, David Talmage, Macfarlane Burnet develop clonal selection theory. 1957 Alick Isaacs & Jean Lindemann discover interferon (cytokine). 1962 Rodney Porter and team discovery the struct. of Abs. 1962 Jaques Miller and team discover thymus involvement in cellular immunity. Cont 1962 Noel Warner and team distinguish between cellular and humoral immune responses. 1968 Anthony Davis and team discover T cell and B cell cooperation in immune response. 1974 Rolf Zinkernagel and Peter Doherty explore major histocompatibility complex restriction. 1985 Susumu Tonegawa, Leroy Hood, and team identify immunoglobulin genes. 1985 Scientists begin the rapid identification of genes for immune cells that continues to the present. 1987 Leroy Hood and team identify genes for the T cell receptor.  Comparison of Innate and Adaptive Immunity Innate immunity Acquired / Adaptive immunity Resistance to infection that an individual Resistance to infection that an possesses since birth individual acquires during his lifetime Immune response occurs in minutes Immune response occurs in days Prior exposure to the antigen is not required Develops following the antigenic exposure Diversity is limited, acts through a restricted More varied and specialized set of reactions responses Once activated against a specific type of The span of developed immunity can antigen, the immunity remains throughout be lifelong or short. the life. Limited and Lower potency High potency  Cont Innate immunity Acquired / Adaptive immunity Immunological memory responses are absent Immunological memory responses are present Respond to microbial antigens that are not Respond to specific microbial specific to some microbe, rather shared by antigens many microbes (called as microbes- associated molecular patterns) Host cell receptors (pattern recognition Host cell receptors are specific- e.g. receptors) are non- specific – e.g. Toll-like T cell receptors and B cell receptor immunoglobulin receptors The innate immune system is composed of physical and chemical barriers, phagocytic Adaptive immune system is leukocytes, dendritic cells, natural killer cells, composed of B cells and T cells. and plasma proteins. Lymphoid system and immune cells LESSON OBJECTIVES  Define lymphoid organs and tissue Describe types lymphoid organs and tissue Describing cells of the immune system  Lymphoid system and immune cells A system coordinates the migration of antigens, exosomes, and lymphocytes from peripheral tissues to the collecting vessels of the lymph nodes. Consists  Primary lymphoid organs- The sites where WBC,RBC, platelets originate & mature (bone marrow & thymus) Bone marrow  Site of hematopoiesis occurs mainly in the flat bones, sternum, vertebra, iliac (hip) bones & ribs Location where stem cells destined to become leucocytes and lymphocytes  IL-3 produced in the bone marrow stimulates the formation of granulocytes & monocytes Interleukin-7 produced by marrow stromal cells stimulates the maturation of B cells from precursor cells.  In developing embryos, blood formation occurs in aggregates of blood cells in the yolk sac, called blood islands.  As development progresses, blood formation occurs in the spleen, liver and lym ph nodes.  When BM develops used to form blood cells.  In children, haematopoiesis occurs in the marrow of long bones femur & tibia.  In adults, mainly in the pelvis, cranium, vertebrae & sternum Thymus  A bilobed organ in the upper anterior thorax right above the heart.  Each lobule consists of an outer cortex that contains a dense collection of pre T lymphocytes & an inner medulla sparsely populated with lymphocytes  The thymus has a rich vascular supply and efferent lymphatic vessels that drain into mediastinal lymph nodes.  The thymus undergoes physiologic involution with aging, so that by old age it is difficult to locate. Secondary lymphoid organs  Used for trapping antigen, facilitating & presentation to lymphocytes  Spleen  Large, ovoid situated high in the left abdominal cavity.  Specializes in filtering blood and trapping blood-borne antigens;  Can respond to systemic infections.  Mount immune responses to antigens in the blood stream.  Is inserted in the blood circulation than the lymph circulation  Two compartments  The red pulp populated by MØs, RBCs and few lymphocytes A site where old and defective RBCs are destroyed and removed  White pulp, is primarily populated by T cells and B cells  The Lymph Nodes  The first organized lymphoid structure to encounter antigens that enter the tissue spaces (skin, cut.).  Sites where immune responses are mounted to antigens in lymph. Cortex  Contains lymphocytes (mostly B cells), macro-phages, and follicular dendritic cells Paracortex  Populated largely by T lymphocytes  Contains interdigitating dendritic cells Medulla  Contain plasma cells actively secreting antibody molecules Tonsils Tonsils are collections of Lymphoid tissue facing into the aerodigestive tract. The Tonsils play a role in protecting the body against Respiratory and Gastrointestinal infections. Each tonsil consists of a network of crypts (pits) that store cells used to fight infection. The tonsils contain B & T- cells, that fights against infections. Tonsils also produce Antibodies against Polio, Streptococcal pneumonia, Influenza, and numerous infections. Tonsillitis occurs when bacterial or viral organisms cause inflammation of the Tonsillar tissue. This results in fever, difficulty swallowing, sore throat, ear pain, loss of voice and throat tenderness. MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT)  Covers large area 400m2 o Protected by mucus, antimicrobial peptides, enzymes, acids o Contains 75% of all lymphocyte and majority of antibodies o Possess several unique properties compared to systemic IR (lymph node & spleen)  Gut associated lymphoid tissues (GALT) lining intestinal tract  Bronchus-associated lymphoid tissue (BALT) respiratory tract  Urinogenital tract associated lymphoid tissues (UALT) lining the urinogenital tract.  Provide local immunity by way of sIgA and IgE production  Peyer’s patches, lymphoid tissue of appendix and isolated lymphoid follicles o Peyer’s patches: important to mount IR at gut o Distinctive appearance forming dome shaped aggregates of lymphocytes o 100-200 Peyer's patches found small intestine o They are richer in B cells o Follicle associated epithelium: contains enterocytes and M cells (specialized) o M cells not produce enzymes, mucus, lack glycocalyx, important for antigen removal o Exposed directly to the contents of intestine o Also contains lymphocytes and DCs o Isolated lymphoid follicle: are microscopic, distributed all over SI and LI, thousands in no o Composed of M cells overlying organized lymphoid tissue o Contain mainly B cells, develop only after birth in response to antigen stimulation Appendix Appendix - Blind - ended tube connected to the Cecum. The Appendix could perform a dual role. First, it is a concentrate of lymphoid tissue resembling Peyer's patches Is the site for immunoglobulin A production which is crucial to regulate the density and quality of the intestinal flora. A unique niche for commensal bacteria in the body. It is extremely rich in biofilms that continuously shed bacteria into the intestinal lumen. “rebooting” the digestive system after diarrheal illnesses. Appendicitis – Inflammation of Appendix. Cutaneous-Associated Lymphoid Tissue Epithelialcells the outer layer of the skin (keratinocytes) secrete cytokines to induce a local inflammatory reaction. Keratinocytes induced to express class II MHC molecules & function as APC. The Langerhans cells migrate from the epidermis to regional lymph nodes, differentiate to interdigitating DCs. Express high class II MHC molecules and activate naive TH cell  Tertiary lymphoid tissues TLOs- localized lymphoid tissues are Formed as a result of lymphoid neogenesis in the course of (chronic) inflammation Due to persistent microbial infection, autoimmune disease, or response to allograft. Involve APCs such as DCs and follicular DCs, stromal cells T and B cell compartmentalization  Cont Cells of the Immune System The process by which blood cells grow, divide & differentiate in the bone marrow is hematopoiesis. The cells of the immune system arise from pluripotent hematopoeitic stem cells (HSC) The sites where it occurs are known as hematopoietic tissues or organs (bone marrow, liver, spleen). After about week 6 in humans haematopoiesis occurs mainly in the liver and at birth shifts to the bone marrow (BM) Through two main lines of differentiation Myeloid lineage produces phagocytes and other cells Lymphoid lineage produces lymphocytes Pleuripotenthematopoeitic stem cells give rise to 2nd generation stem cells with restricted lineage potential= progenitors Schematic overview of hematopoiesis Cont Cell types Granulocytes Agranulocytes  Have large granules in their  Have granules in their cytoplasm that can be seen cytoplasm, but the granules under a light microscope are not visible under the after staining. light microscope after  Three types of cells on the staining. basis of how the granules  Three different types Stain:  Monocytes/macrophages  Neutrophils,  Dendritic cells  Basophils  Lymphocytes  Eosinophils. Cont  Neutrophils  Multilobed (1-6 lobes) therefore polymorpho nuclear leucocytes  One of the main effector cells in the innate immune system  50-70% of white blood cells  Released from bone marrow, live only a few days  Circulate 7-10 hrs, enter tissues  Numbers & recruitment increase during infections ‘’leukocytosis’’  Functions: 1. Phagocytosis: 2. Response to inflammation: release leukotrienes, prostaglandins, thromboxanes 3. Febrile response: contain fever producing substance, endogenous pyrogen Cont Eosinophils  Nucleus bi-lobed  Constitute 1%-3% of circulating leucocytes  Have Fc receptors for IgE and therefore are important in Killing of antibody coated parasites by piece meal degranulation  Function 1. Mild Phagocytosis: less motile than neutrophils 2. Anti-parasitic infestation: Major Basic Protein- Larvicidal Eosinophil cationic protein major destroyer of helminths & bactericidal Eosinophil peroxidase – destruction of helminths, bacteria & tumor cells 3. Anti-allergic reaction response: Detoxifying inflammation inducing components Inhibit mast cell degranulation Cont  Basophil 