Lecture 1: An Overview of The Immune System PDF

Lecture 1: An Overview of The Immune System IMMC  Objectives To understand the dual nature of the immune system (innate and adaptive immunity) and how these components interact to protect the body from infection. To recognize th...

Lecture 1: An Overview of The Immune System IMMC  Objectives To understand the dual nature of the immune system (innate and adaptive immunity) and how these components interact to protect the body from infection. To recognize the significance of historical milestones in immunology that have paved the way for modern vaccines and treatments. To identify the various components of the immune system, including organs, cells, and molecules, and their roles in the immune response. To appreciate the complexity of the immune response, including the distinction between humoral and cell-mediated immunity, and the phases of adaptive immunity.  History of Immunology Ancient Observations: As early as 430 BC, Thucydides noted that survivors of the Athenian plague were immune to reinfection. Prophetic Era: He has emphasized the principle of infection. (‫ ﻓِ ﱠر ﻣن اﻟﻣﺟذوم ﻓرارك ﻣن اﻷﺳد‬:‫ وﻗﺎل‬،ٍ‫ﺻ ّﺢ‬ ِ ‫ض ﻋﻠﻰ ُﻣ‬ ٌ ‫ورد ُﻣ ْﻣ ِر‬ ِ ُ‫ ﻻ ﯾ‬:‫)ﻗﺎل ﷺ‬ Early Practices: By the 15th century, the Chinese and Turks used variolation, a form of early inoculation. Variolation in Europe: Lady Mary Wortley Montagu introduced variolation to Europe in 1718 after witnessing its use in Turkey.  History of Immunology Birth of Vaccination: In 1796, Edward Jenner developed the smallpox vaccine using material from cowpox pustules. Koch’s Discovery: Discovery of causative agents of tuberculosis (1882) and cholera (1883) by Robert Koch. Louis Pasteur's Advances: Pasteur improved vaccination by using weakened bacteria, demonstrating its effectiveness in chickens with cholera and coining the term "vaccine" from 'vacca' (Latin for cow). Human Vaccination: In 1885, Pasteur successfully vaccinated Joseph Meister against rabies, marking a milestone in human disease prevention. Edward Jenner Robert Koch Luis Pasture  Immunology and Immunity Immunity: is derived from the word immunis Latin for exemption. It means protection from disease especially infectious diseases. Immunology: is the study of the body’s defense mechanisms against foreign agents such as pathogens. forfeign A thatcancauseadisease body Immune system mediate Immunity by variable immune organs, cells and molecules.  Immune Components Organs White Blood Cells: Soluble and non-soluble Molecules  Anatomy of Immune System Organs: Primary: Bone marrow, thymus, Secondary: lymph nodes and spleen. White Blood Cells: Myeloid (macrophages, granulocytes, mast cells and dendritic cells) Lymphoid (T cells, B cells and NK cells) Molecules: 2m (Complement components, C Reactive Proteins (CRP), Defensins, Cytokines, and Chemokines)  Immune Response The central problem that the immune system deals with is invasion by microbial pathogens. The task of the immune system is to distinguish self from non-self. It must not attack self, but it has to eliminate microbial threats: 1. Extracellular organisms (bacteria, fungi, parasites, etc). 2. Intracellular pathogens (viruses). Immune responses are tailored to the type of organism involved. The immune system's complexity originate from its innate and adaptive components working together.  Innate Immunity Innate Immunity: is the body's immediate defense against pathogens, offering non-specific protection without requiring prior exposure. Components Physical Barriers: Skin and mucous membranes that prevent pathogen entry. Chemical Barriers: Substances like stomach acid, enzymes in saliva, and antimicrobial peptides that destroy pathogens. Cellular Defenses: White blood cells like macrophages, neutrophils, and dendritic cells that engulf and destroy invaders. Complement System: A group of proteins in the blood that, when activated, can lyse II invading cells, recruit immune cells, and enhance phagocytosis. Inflammatory Response: A process that recruits immune cells to the site of infection, increases blood flow, and facilitates repair of damaged tissue. Fever: A high body temperature which increases body metabolism, accelerates defenses and accelerates body defenses  Innate Immunity Recognition Systems: Pattern Recognition Receptors (PRRs) which molecules on or within the immune cells that recognize and bind to Specific structures on pathogens, known as pathogen- associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) from host cells. Pattern Recognition Receptors (PRRs) include: Toll-like Receptors (TLRs) NOD-like Receptors (NLRs) C-type Lectin Receptors (CLRs) Mechanisms of innate immunity: Inflammation, Phagocytosis, and complement system. Inflammation Important in inflamation They have innate immune rceptors Release cytokines Question Which of the functions, below, might be important mechanisms involved in innate immune defense? (select all that apply)  Physical and chemical barriers, such as the epithelial linings of the skin and gut.  Specialized receptors on cells that can recognize common microbial patterns.  Anti-microbial proteins at epithelial surfaces and in the blood.  Immune cells that can phagocytose (ingest) and kill microbes.  Immune cells that can recognize infected cells and kill them.  Proteins that promote inflammation. 12  Adaptive Immunity Adaptive Immunity: is the immune system's ability to identify, and specifically target and respond to pathogens, offering long-term protection (memory). iComponents : Humoral: Immunity that is mediated by B cells producing antibodies Cell mediate : Immunity that is mediated by antigen specific T cells. Lymphocytes: Specific immune cells that recognize antigens. B Cells: Recognize circulating antigens and produce specific antibodies. T Cells: Recognize processed antigens presented by other cells.  Cell mediated Immunity Innate Immunity Antigen Presentation T Cell Activation T Cell Activation Adaptive Immunity  Adoptive Immunity  Recognition Systems:  Highly Specific Receptors:  B Cell Receptor (BCR): Allows B cells to bind to specific antigens.  T Cell Receptor (TCR): Enables T cells to recognize antigens presented by MHC molecules.  Specificity: Lymphocytes, the cells of the adaptive immune system, have antigen-specific receptors: a subtle recognition system!  Lymphocytes can somatically create 109 to 1016 different antigen receptors (Antibodies or T cell receptors).  Adoptive Immunity  Defense Mechanisms:  Antigen-specific recognition: Through receptors on B cells (BCR) and T cells (TCR).  Clonal expansion: the specific B or T cells clone themselves to produce many cells targeting the same antigen.  Antibody production: Activated B cells differentiate into plasma cells that produce antibodies specific to the recognized antigen.  Cell-mediated immunity: Cytotoxic T cells (CD8+ T cells) directly kill infected cells presenting antigens with MHC Class I molecules, while Helper T cells (CD4+ T cells) assist in activating other immune cells by releasing cytokines.  Memory cells formation: Both B and T cells form memory cells after an initial encounter with an antigen.  Regulation of immune response: Regulatory T cells help modulate the immune response, preventing autoimmunity and overreaction.  Immunological Memory Immunological memory is the hallmark of adaptive immunity. A primary response is initiated upon first exposure to an antigen. Memory cells (lymphocytes) are left behind after antigen is cleared. A secondary response is initiated upon second exposure to the same antigen that stimulates memory lymphocytes. Stimulation yields a faster, more significant, and better response. Memory is not present in innate immunity. Fig. 1-8 © Macmillan Learning Memory Immunity  Innate vs Adaptive Immunity Kuby Immunology (8th ed., p. 264) 20  Immune Dysfunction There are broad categories of immune dysfunction (we will talk about them later in the course). Overly active or misdirected immune responses: hypersensitivity (e.g., allergies and asthma) autoimmune disease (e.g., multiple sclerosis, Crohn’s disease) Fig. 1-9 Immune deficiency (immunodeficiency) Primary (genetic) loss of immune function I Secondary (acquired) loss of immune function c 8Opportunistic infections (e.g., oral thrush) can occur in people with impaired immune responses. Immune imbalance (uncontrolled inflammation) © Macmillan Learning Fig. 1-10  Clinical Relevance  Vaccination  Leveraging immune memory to prevent diseases like smallpox, polio, and measles. Critical for global health and eradication of infectious diseases.  Autoimmune Disorders  Immune dysregulation causes conditions like rheumatoid arthritis and type 1 diabetes. Treatments focus on immune modulation to alleviate symptoms.  Allergies  Overreaction of the immune system to harmless substances. Treatments aim to prevent or reduce the immune response to allergens.  Immunotherapy  Utilizes monoclonal antibodies, checkpoint inhibitors, and CAR-T cell therapy for targeted cancer treatment, offering new hope in oncology.  Transplantation  Immunological principles are key to successful organ transplantation, managing rejection through immunosuppressive therapies. 22 Thank you 23