Pathophysiology Week 3 PDF

Immunity p.1 Innate and Adap*ve Immunity Innate Immunity first line of defence (skin and mucous membranes) second line of defence (phagocytes, NK cells, inflamma*on, and an*microbial cells) Skin mechanical barrier to pathogens waterproof and has resistance to weak acids an...

Immunity p.1 Innate and Adap*ve Immunity Innate Immunity first line of defence (skin and mucous membranes) second line of defence (phagocytes, NK cells, inflamma*on, and an*microbial cells) Skin mechanical barrier to pathogens waterproof and has resistance to weak acids and bacteria due to kera*n Mucous Membrane Stronger together, protect body cavi*es from external environment Mucus traps microorganism Cilia moves mucus and the debris that is stuck to it out of the lower respiratory tract Tears cleans the eye and contains lysozyme Saliva cleans oral cavity and contains lysozyme Urine cleanses lower urinary tract, acidic pH and inhibits bacterial growth Phagocyte Finds and s*cks to the germs or debris Swallows it and forms a bubble (phagosome) Lysosomes join with the bubble to make phagolysosome Enzymes break down the germ inside the bubble Example of protec;ve chemicals Skin’s acidity (pH 3-5) stops bacteria from growing Oil from skin glands kills bacteria Stomach makes acid that destroys germs Saliva and tears have enzyme that kills bacteria Mucus in the diges*ve and breathing system traps germs Cilia in the nose and breathing tubes help trap and remove germs Inflamma;on Part of body’s 2nd line of defence Response to things like injury, infec*ons, allergies, or lack of blood flow Happens fast, process is always the same, no maVer the cause Acute Inflamma;on Helps protect body Meant to remove harmful things Can be warning sign Vasodila;on Makes blood vessels wider, causing redness and heat in the inflamed areas Increased Capillary permeability Let’s helpful substances like cloWng factors and an*bodies leave the blood and enter *ssues Leads to swelling (edema) because a protein called albumin leaks out and pulls more fluid from the blood, even though it's usual job is to keep fluid in Systemic Effects of Inflamma;on Causes *redness, feeling unwell, headaches, and loss of appe*te Fever (pyrexia) - higher than normal body temp - fights infec*ons by killing germs and speeding up cell ac*vity - part of general body defense - fever over 42*C (108*F) can be dangerous and may harm cells, can lead to cell …. death Fever Occurs when WBC detect harmful substances and release special chemicals called pyrogens (interleukin 1, interleukin 6, and tumours necrosis factor) These pyrogen travel in the blood to the brain’s hypothalamus, makes body temporarily increase temp Local Inflamma;on Causes less swelling and fluid than acute inflamma*on More immune cells like macrophages and lymphocytes Involves more fibroblasts and collagen (can help with *ssue repair) Systemic chronic Inflamma;on (SCI) Long-term, low-level inflamma*on throughout the body Can be weaken the immune system and affect how cells work Increase the risk of other diseases NK Cells Patrol blood and lymph to find and kill cancer or virus-infected cells before 3rd line of defense kicks in They look for missing “self” marks on cells These cells kill their targets by releasing a chemical called perforins An;microbial Proteins Proteins that fight germs directly or stop them from reproducing Includes interferon and complement proteins Interferon Group of proteins made by body cells, including alpha, beta, and gamma interferons Helps protect from viruses by stopping virus spread It also ac*vates macrophages and mobilizes NK cells to fight infec*ons Complement Group of over 20 proteins that circulate in the blood in an inac*ve form When ac*vated, complement helps destroy pathogens and boosts inflamma*on to fight infec*ons Adap;ve Immunity Target specific foreign invaders Takes longer to ac*vate but more effec*ve Involves immune and lymphoid *ssues Mains cells are T and B lymphocytes and an*bodies. Macrophages and dendri*c cells also play important roles Immunity Protects whole body, not just the site of infec*on Immune system can recognize different pathogens and dis*nguish them from normal cells Adap*ve, it can remember previous infec*ons, so it response faster and stronger if the pathogen is encountered again Can cause allergies and autoimmune diseases Normally defends against infec*ons, cancer cells, and organ transplant An;gens An*gens are foreign substances that can trigger an immune response, also called immunogens immune system recognizes an*gens using receptors on immune cells and an*bodies (proteins made to fight the an*gen) examples are bacteria, virus, fungi, pollen, poison ivy, insect venom, and transplanted organs An;genic Determinants immune cells and an*bodies recognize small parts of an an*gen called epitopes or an*genic determinants single an*gen can have several epitopes, each triggering an immune response  Hapten is a small substance that usually doesn’t cause an immune response on its own but can do so when aVached to a larger protein Immune Cells Main cells in the immune system are T and B lymphocytes, which are type of WBC Macrophages and dendri*c cells help process an*gens and ac*vate lymphocytes Immune cells can be regulatory or effector cells - Regulatory cells (T helper cells) help control and coordinate the immune response - Effector cells (T cytotoxic cells) help destroy and remove the an*gens Lymphocyte AJer training, T and B lymphocytes stay in the lymph nodes, spleen, and mucosal ;ssues, ready to fight specific an;gens Before they can work, they must become “educated” meaning they learn to recognize harmful invaders and avoid aSacking our own cell Lymphocytes are made in bone marrow from special stem cells called hemocytoblasts Lymphocyte ac;va;on Ac*vated when their surface receptors recognize specific an*gen B-cells have receptors made of an*bodies that aVach to a specific an*gen T-cells recognize an*gens that are shown with special “self” markers called MHC (major histocompa*bility complex) The MHC markers are found on special cells called an*gen-presen*ng cells (APCs), which helps T cells iden*fy the an*gen Lymphocyte ac;va;on process When an an*gen recognized, cytokines are released to ac*vate T and B cells. This led to the crea*on of effector cells (to fight the infec*on) and memory cells (to respond faster in the future) Mature T and B cells have special surface markers called CD (cluster of differen*a*on) that help iden*fy their func*on CD4 + helper cells (regulatory cells), release cytokines to help ac;vate B cells and other T cells CD8 + cytotoxic cells (effector cells), destroy virus-infected and cancer cells Memory Lymphocytes (T and B cells) Made during an immune response and stay in the body for a long *me Help body respond faster and stronger if the same an*gen appears again Quick response oien happens without us no*cing, except for mild signs like feeling *red Major Histocompa;bility Complex (MHC)  MHC are cell surface proteins that help the body recognize its own cells and detect foreign invaders Each person has unique set of MHC proteins Also called Human Leukocyte An*gens (HLA) because they were first found in WBC 2 types, Class 1 and Class 2 MHC Class 1 These proteins on cell surfaces that work with CD8 T cytotoxic cells Has grooves that holds a piece of an an*gen, signalling that a cell is infected or cancerous T cytotoxic cells are ac*vated when they aVach to the MHC Class 1 – an*gen complex MHC Class 2 Works with CD4 T helper cells Aier foreign substance is eaten by a cell, pieces of it aVach to MHC Class 2 T helper cells recognize this complex and become ac*ve Once ac*vated, they release cytokines to boost the immune response Macrophages From monocyte and move into different *ssues Some roam freely to find invaders, others stay in specific organs Digest foreign substance coated with an*bodies Releasing cytokines to ac*vate T and B cells Presen*ng an*gens to T helper cells using MHC Class 2 Destroying infected or cancerous cells when ac*vate by T cells Dendri;c Cells Star-shaped cells that act as an*gen-presen*ng cells (APCs) IN places where invaders might enter, like lymphoid *ssues and skin IN the skin, they are called, Langerhans’s cells, and in lymph nodes, they are follicular dendri*c cells They are very good at binding to MHC class 2 molecules Immunity p.2 Humoral Vs Cell mediated Immunity B cells control humoral immunity by producing an*bodies T cells control cell-mediated immunity by aVacking infected cells Both types work together for a strong immune defense B lymphocytes  Control humoral immunity by figh*ng bacteria, neutralizing toxins, and stopping viruses Targets an*gen that are easy to detect Their surface has: an*bodies(immunoglobulins), MHC class II, Complement receptors, CD4 molecules B lymphocyte Ac;va;on B cells ac*vate when they meet a matching an*gen and get signals from T helps cells Once ac*vated they mul*ply and turn into: Plasma cells (produce an*bodies), Memory cells (stay in body for future defense) This process of mul*plying is called clonal selec*on Memory cells last longer than plasma cells and are ready for future infec*ons B lymphocytes as APCs B cells act as an;gen-presen;ng cells by - engulfing the an;gen bound to their surface an;body - Breaking it into small pieces - presen;ng these pieces on an MHC II molecule T helper cell recognize the MHC II/an;gen complex and release signals (cytokines) to help B cells mul;ply An;bodies Travel in blood and lymph to find and bind an*gens Does not destroy an*gens directly When they bind to an*gens (forming and immune complex), they help by - neutraliza*on – blocking harmful effects - agglu*na*on – clumping an*gens together - precipita*on – making an*gens easier to remove - complement fixa*on – triggering other immune response to destroy the an*gen Humoral Immunity Primary Response: occurs when the body first encounters an an*gen. Takes *me for B cells to mature into plasma cells and produce an*bodies Secondary Response: Happens when the body encounters the same an*gen again. It’s faster and stronger due to memory cells that were formed during the first response Humoral Immunity p2 Primary Response: Delay of about 1 week before an*bodies appear in the blood. This delay is because T helper cells need to release signals to help B cells turn into plasma cells that male an*bodies. Some B cells also become memory cells during this *me Secondary Response: The rise in an*bodies is faster and stronger because memory cells from the first exposure recognize the an*gen and quickly produce an*bodies Ac;ve and Passive Immunity  Ac*ve immunity happens when the body is exposed to a pathogen naturally (geWng sick) or ar*ficially (vaccina*on) Passive Immunity occurs when an*bodies are transferred naturally from a mother to her baby (through placenta or breast milk) or ar*ficially through an injec*on of an*bodies from another source T lymphocytes Different types of T cells that play different roles in the immune response T cell mature in the thymus them travel to other parts of the body to look for an*gens T cell receptors (TCR) are made up of 2 protein chains that form a groove to interact with an*gens presented by MHC complexes T Helper Cells Have CD4 marker on their surface Gets ac*vated when they bind to an an*gen presented by an MHC Class II molecule Once ac*vated, they release cytokines to help ac*vate other immune cells like B cells, T cytotoxic cells (CD8), NK cells, and macrophages Cytotoxic Cells Have CD8 marker on their surface Ac*vated when they bond to an an*gen on an MHC class I molecule of an infected or cancerous cell and receive cytokines from T helper cells Targets infected or cancerous cells, while normal cells with self-pep*des are not harmed T regulatory Cells Help turn off the immune response aier the threat is gone by releasing cytokines Supress ac*vity of B cells and other T cells Also called T suppressor cells T memory cells Responsible for secondary response Cytokines Proteins that help regulate immune response, made mostly by T-helper cells and macrophages Some cause inflamma*on by inducing fever or aVrac*ng immune cells Most interleukins help T cells, B cells, and macrophages communicate Example of Cytokines Interleukin 1(IL-1), made by macrophages, helps ac*vate T helper cells  Interleukin 1(IL-2), made by T helper cells, helps T cells, B cells, and NK cells grow and func*on Interleukin 6(IL-6), helps B cells turn into plasma cells Tumor Necrosis factor-alpha(TNF-a), made by macrophages, helps ac*vate T cells and phagocytes Cell Mediated Immunity T cells, with help from APCs, provide this type of immunity T helper cells are ac*vated when they bond to an*gen/MHC class II complexes on APCs, leading to their growth and release of cytokines T cytotoxic cells ac*vated when they bond to an*gen/MHC class I complexes, helping them grow and specialize T helper cells, release cytokines that boost the ac*vity of T cytotoxic cells and macrophages T cytotoxic cells destroy infected cells by releasing enzymes, toxic cytokines, and perforins or by causing apoptosis This process is crucial for killing virus-infected cells, which an*bodies cannot do An#bodies (immunoglobulins) An*bodies also known as immunoglobulins 5 types are: IgG, IgA, IgM, IgD, IgE All an*bodies have a Y shape, made of 4 protein chains, and have 2 iden*cal sites to bind an*gens An;body structure Y-shaped an*body has 2 forked ends called Fab region, which binds to specific an*gen Tail of the Y is called Fc region, which interact with cells and complement system Fc region is different for each an*body class and determines its func*on Each B cell makes an*bodies with unique Fab region that binds to specific an*gen Classes of An;bodies IgM – First an*body made, strong clumping an*gen, ac*vates complement IgA – found in mucus and secre*ons, help block pathogens IgD – found in B cells, works as B cell receptor IgM – most common an*body in blood, appears in later responses, can cross the placenta IgE- involved in allergies and parasite defense, triggers histamine release Inflamma/on Async Histamine Stored in platelets, basophils, and mast cells Triggers blood vessel widening and makes capillaries more permeable Plats a key role in star*ng inflamma*on Prostaglandins Lipids-based molecules made from arachidonic acid, which comes from cell membranes and certain foods like meat, fish, and eggs Help cause blood vessel widening, capillary permeability, pain, and fever Aspirin reduces inflamma*on by blocking prostaglandin produc*on Glucocor*coids lower arachidonic acid availability Plasma Protein Include kinins, complement proteins, and cloWng factors Bradykinin helps widen blood vessels, increase capillary permeability, and cause pain Complement protein (C1,C2,C3) are involved in inflamma*on and can directly kill microorganism Clo]ng system Creates a mesh at the inflamed site to trap fluids, microorganisms, and foreign bodies Helps prevent infec*on from spreading to nearby *ssues Keeps microorganisms near phagocytes for removal Forms clot to stop bleeding and aids in healing and repair Leukotrienes Made from arachidonic acid in WBC and mast cells Help white blood cells move to the site of infec*ons or injury Some cause blood vessels to widen Platelet-ac;va;ng factor Helps platelets s*ck together during cloWng Ac*vates and sends signals to eosinophils to move to the infec*on site Cytokines Produced by cells like lymphocytes and macrophages Includes interleukins (can cause fever), Interferons (help stop viruses from infec*ng nearby cells), other related proteins Acute inflamma;on Starts quickly, minimal damage, resolves fast  Serous exudate, watery, low protein, seen in mild inflamma*on Hemorrhagic exudate, caused by severe *ssue and blood vessel damage, leaking RBC Fibrinous exudate, contains fibrogen, crea*ng a thick, s*cky mesh Purulent exudate, contains pus (dead WBC, proteins, and *ssue debris) oien from infec*on Chronic Inflamma;on Can last weeks, months, or years May follow repeated or ongoing acute inflamma*on or result from low-grade response that don’t trigger a strong reac*on Involves macrophages and lymphocytes (instead of neutrophils moving ot the affected area Fibroblast grow, leading to scarring and possible deformi*es Caused by substance like talc, asbestos, silica, surgical material, or certain viruses, bacteria, and fungi Non-specific Chronic Inflamma;on Characterized by widespread buildup of macrophages and lymphocytes at the injury site Fibroblast grow, leading to scar *ssue, replacing the normal connec*ve *ssue or other *ssues Granulomatous lesion in chronic inflamma;on A granuloma is small lesion (1-2mm) where macrophages are surrounded by lymphocytes It forms due to contact with foreign material like splinters, sutures, or substance like silica, asbestos, and bacteria These substances are hard to break down, so macrophages gather around them, and a connec*ve *ssue membrane forms around the lesion to isolate it A tubercle is a type of granuloma caused by mycobacterium tuberculosis infec*on Cell Death Async Apoptosis controlled, natural, process of cell death, where cells die when they are no longer needed, are damaged, or have issues like excess produc*on or improper development it helps remove old, damaged, or excess cells, as well as those with DNA damage Examples include: Physiologic apoptosis: During development (like separa*ng webbed fingers) or removing WBC aier inflamma*on/Pathologic apoptosis: like liver cells loss during a hepa**s C infec*on  During apoptosis, enzymes break down the cell’s DNA and proteins, The cell’s membrane becomes leaky, allowing the body to remove the dead cell through phagocytosis Necrosis Unnatural, pathological form of cell death cause by injury It involves cell swelling, rupture of the cell membrane, and inflamma*on Necrosis involves unregulated breakdown of the cell’s components Includes: Coagula*ve, Liquefac*ve, Caseous, Fat, and gangrenous Coagula;ve Necrosis Most common type, usually by lack of oxygen (hypoxia) Proteins s*ck together, forming a solid mass Common in kidney, heart, and adrenal glands Liquefac;ve necrosis Caused by interrupted blood flow (ischemia) to brain cells or by bacterial infec*ons Cells break down into liquid crea*ng pus Caseous necrosis Oien seen in lungs during tuberculosis Mix of coagula*ve and liquefac*ve necrosis Dead cells breakdown but not fully, leaving a cheese-like appearance Fat Necrosis Happens when fat cell die, usually in breast, pancreas, or abdomen aier injury Fat breaks down into faVy acids that combine with calcium, crea*ng opaque, chalky lumps Gangrenous Necrosis Large *ssue area dies from lack of oxygen, oien due to blocked arteries Bacterial invasions worsen the condi*on Types include: Dry gangrene (coagula*ve narcosis, skin dries and turns black), Wet gangrene (liquefac*ve necrosis, *ssue is swollen, moist, and smells foul due to bacteria), Gas gangrene ( caused by bacteria like clostridium that release gas in the *ssue, oien from injuries with dirt, and can be fatal