Immunity In Class Part 1 W25 (1) PDF

Immunity Defense mechanisms Lymphocytes Cytokines MHCs Humoral vs cell-mediated The immune system Immunity Remembe r the hematocri t?  Leukocytes are critical to our defenses against disease Unlike erythrocytes, leukocytes can move out of capillaries into tissue (a process called di...

Immunity Defense mechanisms Lymphocytes Cytokines MHCs Humoral vs cell-mediated The immune system Immunity Remembe r the hematocri t?  Leukocytes are critical to our defenses against disease Unlike erythrocytes, leukocytes can move out of capillaries into tissue (a process called diapedesis) “Plasma proteins” Immunity body is bombarded with insults daily that could harm cells, tissues and organs two intrinsic defense systems are in place that help combat these insults that may arise externally (e.g. microorganisms) or internally (e.g. development of cancerous cells) Innate and Adaptive Immunity the two systems work independently as well as cooperatively to protect the body from developing disease (immunity)  Surface barriers Skin Mucous membranes Innate Internal defenses defenses Phagocytes NK cells Inflammation Antimicrobial proteins Fever Humoral immunity B cells Adaptive defenses Cellular immunity T cells Immunity INNATE IMMUNITY first line of defense: the intact skin and mucous membranes protective chemicals of the skin and mucous membranes second line of defense: phagocytes, antimicrobial proteins, natural killer cells, and inflammation  Skin An intact epidermis acts as a mechanical barrier to pathogens keratin is a protein made by our keratinocytes, that provides waterproofing and is resistance to some weak Physical acids and bases as well as bacteria Mucous membranes Barriers Together with their secretions these line our “inner” epithelial linings When intact, these membranes help to protect the body cavities from the external environment. 1st line of Mucus: to trap microorganisms and other particles in the respiratory and digestive tracts defense Cilia: to move mucus and the debris stuck in the mucus out of the lower respiratory tract Tears: these lacrimal secretions constantly clean the eye and contain lysozyme Saliva: cleans the oral cavity and contain lysozyme Urine: cleanses the lower urinary tract, acidic pH inhibits bacterial growth  Physical Barriers 2nd line of defense Pathogens Four steps: that get 1. A phagocyte THROUGH the recognizes and first line of defence will adheres to a be attacked by pathogen or debris phagocytes 2. Phagocyte engulfs These immune the particle and cells are creates a capable of phagosome engulfing 3. Lysosomes fuse many different with the microorganism phagosome to s via forms a phagocytosis phagolysosome Phagocyte s Examples of protective chemicals acidity of skin (pH 3 to 5) inhibits bacterial growth bactericidal action of oil from sebaceous glands hydrochloric acid secreted by stomach saliva and tears contain lysozyme – an antibacterial enzyme mucus produced in digestive and respiratory tracts traps microorganisms; Ciliated mucous membranes in the respiratory tract move trapped microorganisms to be swallowed and digested by stomach acid and the mucus‐coated nose hairs help to trap particles Inflammation Acute inflammation Part of the body’s 2nd line is: Protective of defenses Normal Intended to Is a NON-SPECIFIC localize/remove an response, often due to injurious agent May act as a warning physical damage sign (abraisons, sprains, burns Cardinal signs: heat, etc.), chemical damage, redness, swelling, pain ischemia, allergic and loss of use” reactions, infections etc) Is USUALLY a rapid response Regardless of the cause  emb Rem r? e Innate defenses Internal defenses Tissue injury Vasodilation: causes redness Release of chemical mediators Release of leukocytosis- (histamine, complement, inducing factor and heat to local kinins, prostaglandins, etc.) inflammed areas Leukocytosis (increased numbers of white blood cells in bloodstream) Increased capillary Vasodilation Increased capillary Attract neutrophils, permeability: of arterioles permeability monocytes, and lymphocytes to Leukocytes migrate to allows clotting injured area area (chemotaxis) factors, antibodies Local hyperemia (increased blood Capillaries leak fluid Margination to move out of the Initial stimulus flow to area) (exudate formation) (leukocytes cling to capillary walls) blood and into the Physiological response tissues, but causes Signs of inflammation Leaked protein-rich Leaked clotting Diapedesis Edema… albumin Result (leukocytes pass through fluid in tissue spaces proteins form interstitial clots that wall off area capillary walls) leaks from the to prevent injury to blood to the surrounding tissue Phagocytosis of pathogens Heat Redness Pain Swelling and dead tissue cells interstitium and (by neutrophils, short-term; by macrophages, long-term) causes a pull via Locally increased Possible temporary Temporary fibrin osmotic pressure temperature increases limitation of patch forms metabolic rate of cells joint movement scaffolding for repair Area cleared of debris to leak MORE fluid from the blood when it’s usual job Healing is to keep fluid IN the blood! What do we do with inflammation?? https://www.lifemark.ca/document/users/diego.garcia%40lifemark.ca/ peaceandlove_infographic_fn.pdf Systemic effects of inflammation May include: Malaise Fatigue Headache Loss of appetite Pyrexia  The medical term for fever Abnormally high body temperature Is a systemic response to often help kill off invading organisms or increase the metabolic rate of your cells Is a non-specific line of defense Over 42oC or 108oF are considered dangerous and may be life threatening as they disturb mitochondria function and cellular proteins, possibly triggering apoptosis Fever Occurs when a WBC encounters a foreign substance and releases pyrogens (interleukin 1, interleukin 6, tumour necrosis factor) These pyrogens circulate through the blood and arrive at the hypothalamus where it triggers us to temporarily raise our normal body temperature  Acute vs Chronic Inflammati on Acute vs Chronic Inflammation Local chronic inflammation Less exudate and edema than acute More macrophages and lymphocytes More fibroblasts More collagen Systemic chronic inflammation (SCI) Low grade, persistent, systemic inflammation My lead to breakdown of the normal immune function and cell physiology May lead to an increased risk of other diseases! From Furman et. al, 2019 in BS  any openings to skin and mucous membranes (e.g. cuts) can lead to invasion by microorganisms and activation of the second line of defense Immunit y The second line of defense includes mechanisms that help clear the body of foreign matter that has breached the first line of defense phagocytic white blood cells: antimicrobial neutrophils, eosinophils, natural killer cells macrophages; proteins inflammation and fever Immunit patrol the blood and lymph y and have the ability to kill cancer cells, virus‐infected cells before the third line of Natural defence is activated Killer (NK) they attack their targets Cells non‐specifically by identifying the lack of “self” cell surface receptors and recognizing cell surface carbohydrates on target cells killing is accomplished by release of cytolytic chemicals called perforins  Immunity Antimicrobial Proteins: work by attacking microorganisms directly or by inhibiting their reproduction includes interferon and complement proteins interferon complement group of related proteins that consists of a group of more than 20 are produced by different cells plasma proteins that normally of the body circulate in an inactive form – C1,  alpha interferon, beta interferon, gamma C2, ….C9, factors B, D and P as interferon etc. well as some regulatory proteins interferon helps protect cells from once activated, complement being infected by viruses; they are helps destroy pathogens in the released by viral‐infected cells body as well as enhance all interferon also activates aspects of the inflammatory macrophages and mobilizes NK response cells  Innate defenses Internal defenses Virus Virus Viral nucleic acid enters cell. Antiviral proteins block viral reproduction. Interfero Interferon genes switch on. n Interferon Cell produces binding interferon stimulates cell to molecules. turn on genes for antiviral proteins. Host cell 2 Host cell 1 Binds interferon Infected by virus; from cell 1; interferon makes interferon; induces synthesis of is killed by virus protective proteins  Immunity ADAPTIVE IMMUNITY this defense mechanism helps clear specific foreign matter takes longer to mount than innate mechanisms but is more effective includes the immune system, central and peripheral lymphoid tissues major players are lymphocytes: T and B lymphocytes & antibodies; also important are macrophages and dendritic cells  Immunity Normally the immune system protects against most invading microorganisms, cancer cells and transplanted organs/grafts Immunity is not restricted to the initial site of infection (i.e. Systemic protection) this system is adaptive: immune system works by meaning it is able to recognizing one pathogen produce a memory undesirable effects of the from another (specificity) response, that allows a immune system include as well as foreign substances quicker and heightened allergies and autoimmune from normal cells and response when encountering diseases proteins a pathogen for a second or subsequent time Immunity Antigens describes substances that are foreign to the host that can induce an immune response also known as an immunogen antigens are recognized by receptors on immune cells as well as by antibodies (or immunoglobulins), proteins that are produced in response to the antigen examples of antigens – bacteria, virus, fungus, pollen, poison ivy plant resin, insect venom and transplanted organs Antigenic determinents immune cells and antibodies recognize small pieces of the antigen called antigenic determinants or epitopes a single antigen may have several epitopes that can each elicit an immune response a hapten is a small substance that usually does not elicit an immune response but can stimulate the immune system when bound to a larger carrier protein  Immunity Immune Cells other cells are the major players macrophages and are T‐ and B‐ the immune cells dendritic cells which lymphocytes, part of act as regulatory help process the agranular white or effector cells antigen and activate blood cells the lymphocytes regulatory cells help effector cells help to to coordinate and destroy and clear control the immune the antigen (e.g. T response (e.g. T cytotoxic helper lymphocytes) lymphocyte)  Immunity Lymphocytes lymphocytes are produced in the bone marrow from stem cells called hemocytoblasts after production, the lymphocytes must become “educated” ‐ i.e. immunocompetent – able to recognize foreign cells and be self tolerant; able to recognize cells of the host after education, T‐ and B‐lymphocytes can be found in lymph nodes, spleen and mucosal tissues where they await a challenge by a specific antigen  activation of lymphocytes starts when an antigen is recognized by specific cell‐surface receptors receptor for B‐cells consists of membrane‐bound immunoglobulins (often Immunity also called antibodies!)that bind to a specific antigen receptor for T‐cells recognizes antigen associated with a marker that indicates a cell as “self”; these markers are MHC’s, major histocompatibility complex , & are located on antigen presenting cells (APCs) that process and present antigenic determinants to T‐lymphocytes  once the antigen is recognized, there is a release of cytokines that help to activate T & B‐lymphocytes into cloning of effector cells and memory cells mature T and B cells possess surface recognition molecules clusters of differentiation (CD) that distinguish between functionally different cells involved with the immune response CD4+ T‐helper cells (regulatory CD8+ T‐cytotoxic cells (an cell) – effector cell) release cytokines and help to activate kill tumor cells and virus‐infected cells B‐cells and other T‐cells Memory lymphocytes memory T and B cells, produced during an immune response reside in the body for a long period of time and provide a quicker and heightened response to a subsequent exposure to the same antigen, so that we are unaware of the response (we may only perceive the invader by a feeling of fatigue) Immunity Cell surface molecule Major Histocompatibility that helps distinguish Complex normal “self” cells/ molecules and foreign invaders each individual has a unique set of MHC proteins also known as Human Leukocyte Antigens (HLA) because they were first discovered in white blood cells two classes of cells: Class I and Class II Immunity Class I cell surface glycoproteins that interact with antigen receptors and the CD8 molecule on T cytotoxic cells contain a groove to bind a peptide fragment of antigen; binding of peptide fragment to the Class I molecule will alert the immune system that a cell has been infected by a virus or has become cancerous T‐cytotoxic cells will be activated only after it binds to the MHC Class I molecule/antigen complex Immunity Class II interact with CD4 T‐helper cells after phagocytosis, digested fragments are bound to Class II MHC T‐helper cells recognize the Class II/antigen complex and become activated activated T‐helper cells release cytokines to enhance the response by other lymphocytes Immunity Macrophages develop from monocytes as they migrate to various tissues can be free and wander throughout tissue looking for foreign invaders or fixed and permanent residents of a particular organ (e.g Kupffer cells in the liver, microglia in the brain) function as part of the second line of defense or can help with the immune response by: helping digest foreign substances when coated with antibody secrete cytokines to activate T and B‐cells act as antigen-presenting cells (by presenting a digested antigen with an MHC Class II molecule attached to T‐ helper cells) can destroy virus‐infected cells or tumor cells when appropriately stimulated by T‐cell cytokines Immunity Dendritic Cells star‐shaped cells that act as APCs located in lymphoid tissue and other areas where foreign invaders might enter the body dendritic cells found in the skin are called Langerhans’ cells; in lymph nodes they are called follicular dendritic cells Big MHC-II binders!