Inflammation and Immunity PDF

Dr. Hiba Alzoubi, MD Inflammation  Inflammation is a protective response that is intended to eliminate the initial cause of cell injury, infectious agents, the necrotic cells, and to initiate the process of repair.  Components of Inflammation Inflammatory responses involve an inte...

Dr. Hiba Alzoubi, MD Inflammation  Inflammation is a protective response that is intended to eliminate the initial cause of cell injury, infectious agents, the necrotic cells, and to initiate the process of repair.  Components of Inflammation Inflammatory responses involve an interaction of: – Blood vessels – White blood cells and platelets Loading… – Plasma proteins and chemical mediators: Coagulation / fibrinolytic system, kinin system, complement system Extracellular matrix and stromal cells Structural fibrous proteins, adhesive glycoproteins, proteoglycans, basement membrane.  Inflammation Acute inflammation Chronic inflammation - Onset: Fast: minutes to – Onset: Slow: days hours – Duration: Long: days - Duration: Short, from to years minutes to days Loading… – Cellular infiltrate: – Cellular infiltrate: Mainly Monocytes/ neutrophils macrophages and lymphocytes – Tissue injury, fibrosis: - Tissue injury, fibrosis: usually mild and self Often severe and limited progressive 5  External manifestation of Acute Inflammation Heat. Redness. Swelling. Pain. Loss of function.  Systemic effects of inflammation Fever: Elevated body temperature Elevated plasma levels of acute phase proteins. Leukocytosis. Increased heart rate. High blood pressure. Decreased sweating. Rigors (shivering) Chills (perception of cold) Malaise Anorexia.  Stimuli for Acute Inflammation Infections (bacteria, fungal, viruses, and parasites). Trauma, various chemical and physical agents (heat, cold, burns, radiation). Chemicals (acids, alkali, bacterial toxins, metals). Tissue necrosis (from any cause) Foreign bodies Immunologic reactions  Components of acute inflammation Vascular changes: - Alterations in vessel caliber resulting in increased blood flow (vasodilation) - Structural changes that permit plasma proteins to leave the circulation (increased vascular permeability). Cellular events: - Emigration of the leukocytes from the microcirculation and accumulation in the focus Increased Vascular Permeability: - Leads to the movement of protein-rich fluid and even blood cells into the extravascular Loading… tissues. This in turn increases the osmotic pressure of the interstitial fluid, leading to more outflow of water from the blood into the tissues. - Fluid accumulation in extravascular spaces produces tissue edema.  Edema TRANSUDATE EXUDATE Mechanism: Hydrostatic Mechanism: Alteration in pressure imbalance across normal permeability of vascular endothelium small blood vessels in area of injury Fluid of low protein content Fluid of high protein (ultrafiltrate of blood content plasma) Typical in noninflammatory Typical in inflammation conditions  The steps of the inflammatory response can be remembered as the five Rs: (1) recognition of the injurious agent (2) recruitment of leukocytes (3) removal of the agent (4) regulation (control) of the response (5) resolution (repair).  MORPHOLOGIC PATTERNS OF ACUTE INFLAMMATION 1. Serous inflammation : - Exudation of cell- poor fluid into spaces created by injury to surface epithelia or into body cavities. - Example: skin blister resulting  from a burn or 2. Fibrinous inflammation - Occurs as a consequence of more severe injuries, resulting in greater vascular permeability that allows large molecules (such as fibrinogen) to pass the endothelial 3. Suppurative (purulent) inflammation and abscess formation: - Collection of large amounts of pus ( an exudate consisting of many neutrophils, debris of necrotic cells, and edema fluid) - Organisms (such as 4- Ulcer: - Local defect of the surface of an organ or tissue that is produced by sloughing (shedding) of inflamed necrotic tissue.  Outcomes of Acute Inflammation u Complete resolution u Healing by connective tissue replacement (scarring or fibrosis) u Progression to chronic inflammation  Chronic Inflammation Inflammation of prolonged duration (weeks to years). Characterized by: Infiltration with mononuclear cells, including macrophages, lymphocytes, and plasma cells Tissue destruction Repair  Macrophages and mononuclear phagocyte system Macrophages (Dominant cells of chronic inflammation) B and T lymphocytes (CD4 and CD8) 22  Eosinophils: Characteristic in: A. Inflammatory sites around Parasitic infections A. Allergic diseases such as asthma Mast cells: - Source of histamine early in allergic reactions Tissue Repair 25  Tissue repair Repair (Healing): Restoration of tissue architecture and function after an injury 1- Regeneration: – Replacement of damaged cells by similar parenchymal cells and return to a normal state – Typical response to injury in the rapidly dividing epithelia of the skin and intestines – Requires intact connective tissue 2- Scar formation - The injured tissues are incapable of regeneration, or the supporting structures of the tissue are severely damaged - Occurs by the laying down of connective (fibrous) tissue  Immunity The immune system is responsible for: - protecting the body against an array of microorganisms. - removing damaged cells and destroying cancer cells.  Innate and Adaptive Defenses: Innate immunity provides immediate protection and is nonspecific, meaning it provides protection against all invaders: skin Loading… and mucous membranes Adaptive or acquired immunity can take 7 to 10 days to provide protection, but it is specific to the antigen (cellular or humoral immunity) - T-cell function or cellular immunity: destroy the antigen. - B-cell function or humoral immunity: produce  Altered Immune Response Malfunction at any point in any of the numerous and highly complex immune responses can create a pathologic state. Malfunctions may include: - exaggeration (hypersensitivity) - misdirection (autoimmune) - diminution (immunodeficiency)  Hypersensitivity Inappropriate response to an antigen. Inflammation and destruction of healthy tissue. Four types of hypersensitivity reactions: - type I (IgE mediated) - type II (cytotoxic) - type III (immune complex mediated) - type IV (cell mediated)  Autoimmune Disorders The body’s normal defenses become self- destructive—that is, they perceive the self as foreign. Autoimmune disorders affect women more often than men. Examples: systemic lupus erythematosus, rheumatoid arthritis  Immunodeficiency A diminished or absent immune response that increases susceptibility to infections. Primary (a defect with the immune system, from genetic or congenital abnormalities (e.g., hypogammaglobulinemia) Secondary (an underlying disease or factor that is suppressing the immune system): infection, malnutrition, hepatic disease, drug therapy, or stress.  Immunodeficiency Immunodeficiency states predispose patients to opportunistic infections. Opportunistic infections are infections caused by pathogens that do not usually cause disease in healthy individuals (e.g., toxoplasmosis, Kaposi sarcoma, candidiasis infections). Opportunistic infections can be difficult to treat successfully and can become life threatening.  AIDS Acquired immunodeficiency syndrome (AIDS) deadly, sexually transmitted disease caused by the human immunodeficiency virus (HIV). HIV attacks and weakens the immune system. HIV is transmitted through direct contact with infected