Introduction to the Immune System PDF

IMMUNOLOGY Dr. HÜSNİYE IŞIN Immunology Resources Textbooks: Kuby immunology, Abbas and Lichtman, Basic Immunology The Immune System  Immunity; in a biologic contex has historically refered to resistance to pathogens; however, reactions to some noninfectious foreing s...

IMMUNOLOGY Dr. HÜSNİYE IŞIN Immunology Resources Textbooks: Kuby immunology, Abbas and Lichtman, Basic Immunology The Immune System  Immunity; in a biologic contex has historically refered to resistance to pathogens; however, reactions to some noninfectious foreing substances including harmless environmental molecules, tumors and even unaltered host components are also considered forms of immunity, allergy, tumor immunity and autoimmunity, respectivly.  The collection of cells, tissues and molecules that mediate these reactions is called the ‘immune system’ The coordinated response of these cells and molecules to pathogens and other substances comprises an ‘immune response’. The most important physiologic function of the immune system is to prevent or eradicate infections. *Abbas and Lichtman, Basic Immunology Immune System Purpose/ Function? First line of defense= Epithelial integrity= skin, mucosal surfaces Defense against pathogens, Inside cells= kill the infected cell( viruses) Systemic= kill- Bacteria, Fungi, Parasites Two phases of response, Handle the acute infections, keep it from spreading Prevent future infections First line of defense Skin – physical barrier Lining of mucus membranes – physical barrier Secretions – tears, mucus etc - antimicrobial Blood cells and vasculature – WBCs Bone marrow Liver – makes complement proteins Lymphatic system and lymphoid organs Most tissues – have resident immune cells  Defense against pathogens Defense against invading pathogens (viruses & bacteria) 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) Inappropriate responses: Allergies - response to normally harmless substances Autoimmune diseases Overview of the Immune System Immune System Innate Adaptive (Nonspecific) (Specific) 1o line of defense 2o line of defense Innate and Adaptive Immunity Host defenses are grouped under innate immunity, which provides immediate protection against microbial invasion, and adaptive immunity, which develops more slowly and provides more specialized defense against infections Innate and Adaptive Immunity Innate immunity, also called natural immunity or native immunity, is always present in healthy individuals prepared to block the entry of microbes and to rapidly eliminate microbes that do succeed in entering host tissues. Adaptive immunity, also called specific immunity or acquired immunity, requires expansion and differentiation of lymphocytes in response to microbes before it can provide effective defense; that is, it adapts to the presence of microbial invaders. Innate Immunity vs Adaptive Immunity Innate Immunity Adaptive Immunity (first line of defense) (second line of defense) No time lag A lag period Not antigen specific Antigen specific No memory Development of memory *Abbas and Lichtman, Basic Immunology The Innate Immune System Innate Immune System External Internal defenses defenses Innate Immune System External Defenses A typical immune response INNATE IMMUNITY ACQUIRED IMMUNITY Rapid responses to a Slower responses to broad range of microbes specific microbes External defenses Internal defenses Skin Phagocytic cells Humoral response Mucous membranes Antimicrobial proteins (antibodies) Secretions Inflammatory response Invading microbes Natural killer cells Cell-mediated response (pathogens) (cytotoxic lymphocytes) Anatomical Barriers - Mechanical Factors Skin Mucociliary escalator Flushing action of saliva, tears, urine Anatomical Barriers – Chemical factors Antimicrobial HCl in stomach Lysozyme in tears /saliva Peptides in sweat Anatomical Barriers – Biological factors Normal flora – microbes in many parts of the body Normal flora – > 1000 species of bacteria Normal flora – competes with pathogens for nutrients and space Innate Immune System Internal Defenses  INNATE IMMUNITY ACQUIRED IMMUNITY Rapid responses to a Slower responses to broad range of microbes specific microbes External defenses Internal defenses Skin Phagocytic cells Humoral response Mucous membranes Antimicrobial proteins (antibodies) Secretions Inflammatory response Invading microbes Natural killer cells Cell-mediated response (pathogens) (cytotoxic lymphocytes) Innate Immune System Internal Defenses To prevent expansion of penetration, Recognize carbohydrates not normally present on cells such as mannose May cause nonspecific activation of white cells Phagocytosis – by neutraphils, eosinophils, basophils, or macrophages, mast cells, and dendritic cells Clotting mechanism which entraps organisms in fibrin clots Complement System can lyse cells or enhance phagocytosis Physiologic Barriers Soluble factors contribute to innate immunity, they are collectively known as acute phase reactants. Normal serum components, non-specific responders to inflammation Increase because of infection, injury, trauma Produced mostly by liver in response to inflammation and cytokine stimulation Cytokines: IL-1, IL-6 and TNF alpha which are produced by macrophages and monocytes at inflammatory site are activators Phagocytosis Is a form of endocytosis. Important body defense mechanism is process in which specialized cells engulf and destroy foreign particles such as microorganisms or damaged cells. Macrophages and segmented Neutrophiils are the most important phagocytic cells.  Phagocytosis Source: Kuby immunology 2007, 5th ed The Adaptive Immune System The Adaptive Immune System Immune System Innate Adaptive (Nonspecific) (Specific) 1o line of defense 2o line of defense The Adaptive Immunity Specific Second line of defense Repeated exposure - augmented – memory Faster response More vigorous response Longer lasting response Anamnestic Components Classic Immune System Cells (Cell mediated) =CMI Soluble Factors (Humoral immunity) = HI Types of Adaptive Immunity The two types of adaptive immunity, called humoral immunity and cell- mediated immunity, are mediated by different cells and molecules and provide defense against extracellular microbes and intracellular microbes Humoral immunity; is mediated by proteins called antibodies, which are produced by cells called B lymphocytes. Cellular Immunity; Defense against such intracellular microbes is called cell-mediated immunity because it is mediated by cells, which are called T lymphocytes. An effective immune response involves three major groups of cells: Cellular Immunity (T cells ), Humoral Immunity (B cells), Accessory cells (antigen-presenting cells). provide us with our specific adaptive immunity. Types of Adaptive Immunity In humoral immunity, B lymphocytes secrete antibodies that eliminate extracellular microbes. In cell-mediated immunity, different types of T lymphocytes recruit and activate phagocytes to destroy ingested microbes and kill infected cells. Types of Adaptive Immunity Immunity may be induced in an individual by infection or vaccination (active immunity) or conferred on an individual by transfer of antibodies or lymphocytes from an actively immunized individual (passive immunity). In active immunity, an individual exposed to the antigens of a microbe mounts an active response to eradicate the infection and develops resistance to later infection by that microbe. In passive immunity, a naive individual receives antibodies or cells (e.g., lymphocytes, feasible only in animal experiments) from another individual already immune to an infection. The Adaptive Immune Responses Capable of recognizing and selectively eliminating specific foreign microorganisms and molecules(i.e., foreign antigens). Unlike innate immune responses, adaptive immune responses are reactions to specific antigenic challenges Different populations of lymphocytes and their products are the major actors together with accessory cells – Antigen presenting cells (APCs) Cardinal features are : Specificity Diversity Memory, Cardinal Features Of Adaptive Immune Responses Specificity specific for distinct antigen, and for different structural components of a single complex protein, polysaccharide, or other macromolecules. Portions of such antigens recognized by individual lymphocytes are called determinants or epitopes. This fine specificity exists because individual lymphocyte express membrane receptors able to distinguish subtle (slight) differences in structure between distinct antigens. Diversity total number of antigenic specificities of the lymphocytes in an individual, called the lymphocyte repertoire, is extremely large. estimated mammalian immune system can discriminate 109 to 1011 distinct antigenic date ruminants. This property of the lymphocyte repertoire is called diversity. It is the result of variability in the structures of antigen- binding sites of lymphocyte receptors for antigens. Memory Exposure of the immune system to foreign antigen: enhances its ability to respond again to that antigen. Responses to second and subsequent exposure to the same antigen, called secondary immune responses, are usually more rapid and larger than the first or primary immune response. Specialization, the immune system responds in distinct and special ways to different microbes, maximizing the efficiency of antimicrobial defense mechanisms. Thus, humoral immunity and cell mediated immunity are elicited by different classes of microbes or by the same microbe at different stages of infection (extra cellular & intra cellular) Self –limitation, All normal immune responses returning the immune system to its resting or basal state with time after antigen stimulations, process called homeostasis.  Summary of innate and adaptive immunity Adaptive and Innate - Interactions Infectious Innate Immunity No Exposure holds Disease Innate Immunity Fails Adaptive Immunity Specific memory Disease Adaptive Second Infectious Recovery Exposure Immune system Same organism