Immunology & Inflammation Concepts PDF

IMMUNOLOGY & INFLAMMATION CONCEPTS INTRODUCTION - Production of Terms: o WBC,  “Immunity”...

IMMUNOLOGY & INFLAMMATION CONCEPTS INTRODUCTION - Production of Terms: o WBC,  “Immunity” o RBC, - Refers to the body’s specific protective o fats (glycerides) response to an invading foreign agent or o lymphocytes organism.  B (Bursa) Cells- mature in  Immunology bone marrow - the study of the immune system and is a  T Cells migrate from bone very important branch of the medical and marrow to-> Thymus where it biological sciences. The immune system matures. protects us from infection through various Two Types of Bone Marrow lines of defense. 1. Red Bone Marrow- produce platelets, RBCs and - the study of the protection of invading WBCs organism 2. Yellow Bone Marrow- produce adipose cells that  Immunopathology give rise to triglycerides and fats - the study of the different abnormalities B. Thymus Gland - bilobed organ (mediastinum- between sternum and  Viruses, Bacteria, Fungi and etc. are called Pathogens. aorta) (front of your chest and behind sternum)  Pathogens are directly - Hugging will increase your immune system, it will  However, these pathogens might not be enough to trigger stimulate the thymus and produce effects. - it stops growing after puberty. Thymic involutionn  Strain of Covid-19 during March was D-614 not until July Lobule they found a new strain called G-614. Thus they are  Outer cortex evolving o Large number of T cells  5 Dengue strains  Central Medulla Homeostasis o Widely scattered, more mature T cells Maintaining homeostasis in the body requires ways to Functions: continually combat harmful agents in our environment. Despite - Immature T cells migrates constant exposure to a variety of pathogens, most people remain - The epithelial cells secrete a hormone called healthy. thymosin (stimulates the maturation of the T  Immune function are affected by: age, risky lifestyle, cells) and heredity, environment, central nervous function, - The site of maturation of T cells emotional state, medications (pseudolupus Cells of the THYMUS are: erythematosus), stress of illness, trauma and  Thymic stromal cells: surgery. - Thymic cortical epithelial cells Review on Anatomy and Physiology of the Immune System - Thymic medullary epithelial cells  Immune System - Dendritic cells - comprises CELLS and MOLECULES  Cells of hematopoietic origin - functions as the body’s denfense - Developing T cells= thymocytes mechanism against invasion and infection. II. Secondary Lymphatic Organs  Lymphatic System A.Lymph Nodes - “major part of immune system” - containing large numbers of leukocytes - A system comprising ducts or tubes that are - Contain large number of leukocytes (WBC) called as lymphatic vessels filled with - mammary glands, axillae and groin lymph. - has borders  Lymph Functions: - recycled blood plasma because they drain - To filter lymph excess interstitial fluids as fluids pass - serve as a center for the production of through capillary walls at the arterial end. phagocytes - Circulatory processes your blood and - They act as filter and traps the foreign particles usually carries 20 L of blood plasma, B. Lymph Nodules “capillary filtration” where you remove - Tonsils plasma from the blood. 3 L left in the - Peyer’s Patches (in intestines) interstitial fluids. Lymphatic vessels are the o smaller and localized collection of accessory route to get those excess and lymphoid tissue and have no border or recycle it. not well defined borders. Primary functions of Lymphatic System (Part of the o found below the covering of the Circulatory System) and Immune System membranes 1.) Draining excess interstitial fluids C. Spleen 2.) Transporting dietary lipids - is located in the upper left portion of the 3.) Carrying out immune responses abdominal cavity (behind stomach) Function of LYMPH - We ask the patients if there is abdominal pain. It 1. protecting your body from illness causing invaders because of the possibility of bleeding 2. maintaining body fluid levels - temporary splenomegaly (abdominal pain, 3. absorbing digestive tract fats petechiae, hemostaxis) 4. removing cellular waste 2 types of tissue: 5. blockages, disease or infections can affect your lymphatic a. White pulp-contains lymphocytes and macrophages system’s function b. red pulp- site for old and injured RBC’s to be Organs of Immune System destroyed Based on the Functions: Functions: I. Primary Lymphatic Organs a. Removal and destruction of foreign particles and A. Bone Marrow- WBC (leukocytes) found in medullary worn blood cells from blood. cavities of LONG BONES and spaces of SPONGY Bone. b. Stores and releases blood during hemorrhage. PADS 1  IMMUNOLOGY & INFLAMMATION CONCEPTS c. Site of B cell proliferation into plasma cells to A. Antimicrobial proteins antibodies 1. Interferons d. Storage of platelets, 1/3 of body supply - Released by host cells in response to the e. Production of cells during fetal life. presence of pathogens (Viruses, bacteria, WBC Leukocytes parasite or tumor cell) - it defends our body from the foreign bodies (7L or 7,000 wbc  Function: per microliter of blood). They make up 1% of the total - Antiviral and antitumor properties blood volume of a healthy patient. It serves as an indicator - Modify immune response of infection or disease. - Facilitate cytolytic role of macrophages and NK Basic Types of Leukocytes cells A. Phagocytes - cells that “chew up” invading organism  Other function Types of Phagocytic cells - Activate immune cells 1.) Neutrophils - Increase recognition of infection or tumor cells 2.) Eosinophils - Increase the ability of uninfected host cells to 3.) Mast cells resist new infection by virus 4.) Macrophages 2. Complement a. Monocytes become macrophages - Refers to a group of least 20 plasma proteins 5.) Dendritic cells that normally circulate in the blood in an inactive B. Lymphocytes state - Cells that allow the body to remember and recognize - It activation unleashes chemical mediators that previous invaders and help the body destroy them. amplify virtually all aspects of the inflammatory - Remember the foreigners who invaded before. process (cascade effects) - 20-40% - It also causes cell lysis that killed certain - Involved in cellular and humoral immunity bacteria and other cell types - 3 Kinds of Lymphocytes - Function: 1.) B lymphocytes  Defending the body against bacterial - Bone marrow - B cells infection 2.) T lymphocytes - Thymus Gland- T Cells  Bridging natural and acquired 3.) Natural Killer Cells/ NK C immunity SPECIFIC AND NON-SPECIFIC RESPONSE TO DISEASE  Disposing of immune complexes and TERMINOLOGY the byproducts associated w/  Resistance- is the ability to ward off damage or disease inflammation “ Ab-ag complexes” ( through our defenses antigen-antibody complexes) - Effects  Susceptibility- is lack of resistance or vulnerability cytolysis - lysis and destruction of cell Resitance and its type membrane of body cells or pathogens 1. Non specific resistance or innate Opsonization- complement proteins 2. Specific resistance or immunity attract to antigen particles NONSPECIFIC RESITANCE TO DISEASE chemotaxis - chemical attraction of  Type neutrophils and phagocytic cells to the o External defense/ 1st line of defense antigen o Internal defense/ 2nd line of defense Anaphylaxis- activation of mast cells and  Mechanism basophils o physical/mechanical barriers 3. Transferrins o Chemical barriers - Iron-binding CHON’s that inhibit the growth of  Surface membrane- 1st line of Defense ceratin bacteria by reducing the amount of 1. Epidermis/Skin available iron  Physical barrier to foreign materials B. Phagocytes  pH of the skin is acidic to inhibit bacterial growth  Specialize cells that perform phagocytosis o Sebum is toxic to bacteria  Types: o Vaginal secretions are very acidic  Granulocytes 2. Mucus membrane  Agranulocytes  Mucus- traps microbes in respiratory tract and Phagocytic Cells: gastrointestinal tracts Granulocytes  Nasal hairs- filter out microbes and dust in the I. I.Neutrophils nose - 62% average  Cillia- traps and remove microbes and dust from - primarily fights BACTERIA, small particles the upper respiratory tract - 1st to arrive at the site of invasion 3. Lacrimal - Polymorphonuclear (nuclei has multiple  Tears dilute and wash away irritating lobes substances and microbes - 6-10 hours to 5 days 4. Saliva - The activity of death is formation of the  Washes microbes from surface of teeth and pus. mucous membranes of mouth II. Eosinophils 5. Defecation and vomiting - 2.3% of yout total WBC (1-3%) 6. Urine - (Bilobe) 7. Lysozymes- enzyme found in saliva, lacrimal fluid - PARASITIC Worm and respiratory mucus - Involve also in hypersensitivity response 8. Gastric juices - Life span of 8-12 days - has hydrochloric acid - Circulates 4-5 hours in the body if there is - has protein-digesting enzymes infection  2nd line of Defense internal III. Basophils PADS 2  IMMUNOLOGY & INFLAMMATION CONCEPTS - 0.5%-5% - Do not need to recognize a specific antigen before being - Releases h activated. - Bioactive Mediators – releases histamine - Knows how to detect which is a normal cell and abnormal cell (increase the permeability of the - they do not require prior activation. They function in its own. capillaries), bradykinin (it causes to dilate - MHC in NK cells the blood vessels), serotonin, leukotrines in Mast Cells acute hypersensitivity reaction - contains many granules rich in histamine and heparin Agranulocytes - has a role in allergy and anaphylaxis IV. Monocytes/Macrophages - wound healing - 2-3% Dendritic cells - Kidney shape - together with macrophages present - Mature intro macrophages when in the body - Found in lymphoid tissues and other body areas where tissues antigen enters the body - It will present the pathogens to the T cells so - Messenger that if the pathogens will go back, the T cells Infection and Inflammatory Response will recognize it. Terminologies - Vacuum cleaner (neutrophils and monocytes  Host- any organism capable of supporting the nutritional have the same role) growth of the organism. - Leaves the bloodstream and becomes  Infection- the presence and multiplication of a living macrophages organism in the host - Macrophages (scavenger) mature forms of  Normal flora- organism living in another organism but blood monocytes not causing harm - General scavenger cells of the body (they  Commensalism- neither of the organisms cannot benefit remove the dead cell materials or necrotic from each other. The interaction with the host and the cellular debris)  Mutualism- infection in which the microorganism and the - Process and present antigen to specific host derive benefits from the interaction. lymphocytes  Infectious Disease- pathologic response in accordance Phases of Phagocytosis to the infection (process)  Virulence- the disease producing potential for the microorganisms. Severity of the harm  Pathogens- group of microorganism  Saprophytes- harmless free living organisms that live in decaying or dying material.  Opportunistic Pathogens- Secondary infections. Capable of producing an infectious disease. It usually enters to the scene if the immune system is so down. Infection- invasion of the body by pathogenic organism that multiplies and produce. 1. Infectious Agent 2. Reservoir 3. Portal of Exit- schistosomiasis coming from the snail o Respiratory tract = coughing, sneezing o Gastrointestinal tract = feces, saliva o Geneoturinary tract o skin o blood=biting arthorpods,needle/syringes 4. Mode of transmission- sex, kissing, coughing, air borne a. Indirect 1. Chemotaxis b. direct  Chemically stimulated movement of phagocytes 5. Portal Entry- respiratory tracts to a site of damage 6. Susceptible Host 2. Adherence/attachment a. age  Attachment to that phagocyte to the microbe or b. disease other foreign material c. nutritional status Opsonization d. compound immune status 3. Ingestion/ engulfment e. Trauma  Process of engulfing the microbes Classification  It forms a vesicle 1.) Extent of Involvement: 4. Digestion a. Local-limited to only one locality of the body. For ex. It is only limited to the toe.  Phagosome+Lysosome b. Focal- from local infection, it spreads to the  The microbe-containing vesicle fuses with a other part of the body lysosome c. Systemic – the infectious agent is spread 5. Killing throughout the system or distant parts of the  Releasing of lysozyme, other digestive body. enzymes, lethal oxidants 2.) Length of Infection Process: 6. Exocytosis a. Acute  Contents of secretory vesicle out of the cell o Rapid onset, short course membrane o Immediate immune response Natural Killer Cells/ NK Cells (part of the innate immune b. Chronic (6 months or more) system) o Gradual onset/longer - not identifiable as either T cells or B cells o Delayed immune response - non-specific effector cells that can kill tumor and virus infected o DM cells o Kidney diseases PADS 3  IMMUNOLOGY & INFLAMMATION CONCEPTS 3.) Etiology  H- Heat (calor) a. Primary Purpose of Vascular Changes o Develops after initial exposure to 1. Increase blood flow to the local area antigen (the root of infection) 2. Mobilize the transport cells to the area b. Secondary/Opportunistic 3. Initiate healing. o Develops when antigens take b. Cellular Response advantage of the weakened defense Key Players: Tissue or cells resulting from primary infection 1.) Leukocyte (WBC) (granulocyte-neutrophils- which is o AIDS- secondary immunodeficiency the first one to arrive at the site) disorder a. Emigration of Phagocytes- Squeezing c. Occult Infection through the blood vessels (Immigration) o Asymptomatic infection b. Margination- leukocyte exit the central o Hidden infection blood stream and initiate leukocyte and o This is where no presentation of endothelial cell interaction symptoms to be verifiable and c. Diapedesis- the passage of blood cells into detected. the intact walls of the capillaries o Cats and other pets 2.) Erythrocyte (RBC) o Seldom in humans a. Leak to tissue -> hemorrhage Stages of Infectious Process Key Players: Vessels 1.) Incubation Stage- the pathogen is present and starting 1.) Fibrinogen- protein or the clotting factor 1. to multiply (Infection is presence and multiplication) but Essential for blood clot formation there are no symptoms. (COVID- 14 days incubation) 2.) Fibronectin- general cell adhesion by anchoring 2.) Prodromal Stages- There are already initial symptoms cell (general) but may not be specific. 3.) Platelets- to prevent the bleeding 3.) Acute- there is already pronounced symptoms. (Clear 4.) RBC- “rouleau” they stack together. It coils or symptoms of the infection) This is caused by the toxic clamping. metabolic process by the organism. WBC Function in Cellular Response a. It causes different defining symptoms o Destroying infective organism 4.) Convalescent- diminished symptoms. o Remove damage cell (macrophages) 5.) Resolution- The pathogens are already diminished or o Releasing more inflammatory mediators eliminated. (basophils) Affecting infectious process o Control further inflammation 3 components: o Healing - host Chemical mediators assist this response by: - agent o Minimizing blood loss - environment o Walling off the invading organism Inflammatory process o Activating phagocytes Inflammation-non-specific body defense to cell/tissue o And promoting formation of fibrous scar injury. It is the mechanism of the elimination of the tissue and regeneration of injured tissue harmful substances. (process of reaction/mechanism) Other Effects of Inflammation -Helps restore tissue hemeostasis 1.) Production of acute phase proteins (Ex. Main Features of Inflammatory Response Complement- that amplifies the immune response) 1.) Vasodilation – widening of the blood vessels to increase 2.) Fever the blood flow to the area. (Histamine, cell mediators) - Abnormally high body temperature 2.) Increased Vascular Permeability- to allow the diffusal Hypothalmus heat regulation can be reset of the components to enter to the site of injury. by pyrogens (secreted by white blood cells) 3.) Cellular Infiltration- due to chemotaxis (attraction) The o High temperatures inhibit the movement of the inflammatory cell to the walls and to the release of iron and zinc from liver injury. The changes in the biosynthetic of the organs and spleen needed by bacteria (there will be changes in the enzymes) o Fever also increases the speed of 4.) Activation of the Cells of the Immune System – tissue repair Phagocytic Cells, Plasma Cell. 3.) Systemic immunity -> lymphocyte activation Stages of Inflammatory Response (peripheral lymphoid tissues) I. Acute Inflammation (short duration, minutes-several Local Manifestations of Inflammation days) o Serous exudates- watery fluids. Plasma proteins and a. Vascular Response (change) cell count. Fluid with high content of protein and cellular i. Momentary Constriction of small debris. It has been deposited to tissues caused by the vessels. Followed by Vasodilation. This inflammation. will result to hyperemic response (time o Result from Plasma entering the inflammatory wherein increased blood flow the sites. causes congestion or rubor or o Pus- dead neutrophils. Thick and redness of the site and the callor or the yellowish/white compared to exudates which are heat) watery. ii. Increase in capillary permeability o Hemorrhagic Exudates- severe tissue injury wherein the fluid excapes into tissues o damage to the blood vessels and results to tumor or swelling and the o leakage of red cells from capillaries dolor or the pain which will lead to o Fibrinous Exudates- contain fibrinogen immobility or the functiolaesa) o Form a blood clot o Common in abrasion 5 Cardinal Signs: Prish o Thick and sticky  P- Pain (dolor) o Membranous or pseudomembranous exudates  R- Rubor (redness) o Develop on the mucous membranes surfaces  I- Immobility (functiolaesa) o Composed of necrotic cells enmeshed in a  S- Swelling (tumor) fibropurulent exudate. o Purulent or suppurative exudate (center is pus) PADS 4  IMMUNOLOGY & INFLAMMATION CONCEPTS o Contains pus, which is composed of degraded - results from abnormality in healing mechanisms. white blood cells, proteins and tissue debris. a. Exuberant Granulations and Keloids o Abscesses- typically have a central necrotic core - proud flesh” containing purulent exudates surrounded by a layer of - Keloids- excessive, bulging, tumorous scars that neutrophils. extend beyond the confines of the original wound o Ulceration- refers to a site of inflammation where an and seldom regress. epithelial surface (e.g., skin or gastrointestinal epithelium) b. Excessive Contracture has become necrotic and eroded (erosion), often with - wound that continues to contract after closure and associated sub-epithelial inflammation. produces disfiguring scar or disability. c. Dehiscence- (wound separation) - a surface disruption that results in the bursting open of a previously closed wound. Evisceration- refers to internal organs moving through a dehiscence. 4.) Adhesion - Exudates cause scar tissue to bind or adhere to adjacent surfaces Wound Healing - primary objective is to fill the gap created by tissue destruction and restore the structural continuity of the injured part. (regeneration of the cells and the tissues) A. Inflammatory response - Begins at the time of injury - Prepares wound environment for healing - Hemostatic processes are activated - Cells migrate in area are essential for healing - Phagocytosis and release of of growth factor that stimulate epithelial growth, angiogenesis and fibrogenesis - Initiated immediately during the inflammatory response or after the injury - Lasts 3-5 days Sign and Symptoms  Pain  Warmth  Swelling  Palpable Tenderness Focus of Care  Decrease pain and swelling  Prevent chronic inflammation  Maintain mobility and strength in adjacent areas while injured areas are rested  Manage the PRISH II. Chronic Inflammation B. Proliferative Phase A. Cellular Response (only) - Begins 2-3 days of injury and may last as long as 8 Key players: weeks 1.) Macrophages - Focus on building on new tissues to fill the wound space a. Microbial killing - Key cells: Fibrolast- connective tissue that synthe b. Clearing up cellular and tissue debris Signs and Symptoms c. Remodeling the tissue  Less warmth and swelling 2.) Lymphocytes  Palpable tenderness decreases a. Either b or t cells  Pain felt with tissue resistance or stretch of III. Fluid Exudation (Edema) Focus of Care - most active: 24 hours after injury or invasion.  Range of motion exercises - Fibrinogen is converted into thick network of fibrin  Joint mobilizations threads -> clot isolates the invading microbes and their  Scar mobilization to produce a mobile scar toxins.  Light loads to promote tissue remodel - Palpabale lymph nodes C. Remodelling Exudate Component: - Begins approximately 3 weeks after injury and can It involves the movement of: continue for 6 months or longer or even years 1.) Plasma fluid - Simultaneous synthesis of collagen by fibroblast result to 2.) Immunoglobulins into the inflamed tissue the architecture of the scar becomes reoriented to IV. Healing: Reconstruction and Maturation increase tensile strength of wound. 1.) Reconstruction- begins once inflamed area is cleaned Signs and Symptoms and debrided, producing new cells to fill in the space left  Improved range of motion and strength by the injury. (Resolution in the process of infection) Focus of Care builds something that is destroyed  Stretching a. Fibrinogen, new endothelial cells  Active contraction 2.) Maturation- last stage of the development of the  Resistive loads reconstruction. Scar tissue is remodeled capillaries contract, structure and function of damaged tissue is restored. Specific Resistance (Specific immunity) 3.) Aberrant to Healing TYPES OF IMMUNITY - may cause complications, deformity and decrease  NATURAL (INNATE) IMMUNITY function of the injured tissue PADS 5  IMMUNOLOGY & INFLAMMATION CONCEPTS o also called in born/inherent immunity - To engulf antigens and present fragments of them, like o physical barrier; skin, chemical barrier; signal flags, on their own surfaces where they can be substance produced by the body cellular barrier recognized by T cells. and B lymphocytes THE IMMUNE RESPONSE  ACQUIRED (ADAPTIVE) IMMUNITY I. HUMUROAL IMMUNITY (ANTIBODY MEDIATED o developed after exposure to the disease and IMMUNITY) immunization  dominated by B lymphocytes  works mainly against” o antigens dissolved in body fluids o extracellular pathogens (bcateria) Antibody - Also called “Ig” or Immuno globulins or gamma globulins - Proteins produced by plasma cells in response to foreign antigens - Originated from the bone marrow- plasma cells- b cells - A heavy chain and 2 binding sites - Heavy chains are called as monomer - Agammaimmunoglobulinemia- no immunoglobulins Antibody Classes 5 types of Immunoglobulin (GAMED) Acquisition of Development Duration Immunity  Alpha- IgA Active A.Natural- Development Long term,oftem  Gamma- IgG exposed to slowly;protecti lifetime  Delta- IgD antigen by ve levels  Epsilon- IgE having the reached in a  Mu- IgM disease few weeks Ex.chicken pox b. Artificial- Develops Several immunization slowly; years;extended with antigen protective protection with ex.Vaccines, levels reached “booster” doses toxoids in a few weeks Passive a.Natural- immediate Temporary,sever transplacement al months and colostrums transfer from mother to child b.Artificial- ready immediate Temporary,sever made antibodes al weeks e.x HTIG 3 Means of Defending the Body 1. Phagocytic Immune Response (Phagocytic cells) 2. Cellular Immune Response (Lymphocytes- T cells) – they turn into cytotoxic t cells 3. Humoral or Antibody Immune Response (B-lymphocytes) Antigen- Any substance capable of exciting the immune system and provoking an immune response Types of Antigen  Endogenous Antigen- Antigens inside the body. (they initially harmless) But once they are triggered, they will create a pathogenic activity. (MHC 1) o Cancer Cells  Exogenous Antigen- Antigens coming from the outside. IgG They are identified with the surface which is the Major - 80% (or 75%) histocompatibility complex. Introduced by the (MHC 2) - Present in tissues and serum  Auto-antigens- Normal proteins (DNA & RNA) but are - Major role in blood borne and tissue infections exaggerated - Found in the breastmilk Functional properties of antigen - Crosses the placenta responsible for protection of  Reactivity- This how they will attack the body and react/ the newborn activate the lymphocytes. - Anti-viral; anti-toxin; anti-bacterial  Immunogenicity- ability of the antigen to provoke the - Enhances phagocytosis immune response. Ability to proliferate. (Anti generator). - Four subtypes Self-Antigens IgA  Out immune cells do not attack our own proteins - 10-15% average of 30%  Our cells in another person’s body can trigger an immune - Sweat, tears, mucus, breastmilk, GI secretions response because they are foreign - Tends to decrease during stress o Restricts donors for transplants - Helps prevent attachment of antigen to epithelial cell Antigen Presenting Cells (APC) surface Functions: PADS 6  IMMUNOLOGY & INFLAMMATION CONCEPTS - Protects body surfaces that are exposed to outside o Interleukin 1/IL-1 – mediator of the inflammatory foreign substances response - 2 Subtypes o Interleukin 2/ IL-2 – necessary for the IgM proliferation and function of helper T, cytotoxic - 5-10% average of 6% II. CELL-MEDIATED IMMUNITY - Limited to vascular system o dominated by T lymphocytes - First immunoglobulin produces in response to o needs the signal of TCR and APC for immune bacterial and viral infection response to occur - For initial response o Particularly effective against: cells attacking - Agglutinating agent and activates complement cells IgE  intracellular pathogen (parasite, fungi, - 0-1% or trace viruses) - Present in Serum  some cancer cells - Involved in allergic and hypersensitivity reaction  foreign tissue transplant - Similar to eosinophils o other termed as delayed hypersensitivity - They activate mast cells, eosinophils, basophils T Lymphocytes – on exposure to antigen, proliferate and - During worm parasitic differentiate into: IgD  Helper T cells- activated upon recognition of antigen - Location: B lymphocytes and stimulates the rest of immune response - Receptors on B lymphocytes o Helper T1- activates cytotoxic t cell - B cell maturation o Helper T2- increase B cell antibody - Total 0.2% production Actions o Helper T4- initiates and augments 1. Neutralizing inflammatory response 2. Immobilizing bacteria o Helper T8- kills tumor cells because of the 3. Agglutinating and precipitating Ag cytotoxic effect 4. Activating complements system  Suppressor T cells- has the ability to decrease B 5. Enhancing phagocytosis cell production, thereby keeping immune response at Types of antigen-antibody reaction: the level compatible with health. If they are having a - Agglutination (clamping) problem, they cannot identify when to - Precipitation (soluble antigens become insoluble  Memory T cells- responsible for recognizing antigens) antigens from previous exposure and mounting an - Neutralization (they block/ slow down the effect of immune response the of the antigen o Are programmed to recognize the original - Lysis (disintegration or breakdown, cell rupture or invading antigen death)  Cytotoxic T cells/ T8 cells- attach the antigen - Opsonization (coating or engulfing) 9the start of the directly by alterin the cell membrane and causing cell phagocytic reaction) lysis (disintegration) Immune Response  Recognition Stage o Body accomplished recognition using lymph nodes and lymphocytes for surveillance o Continuously discharge small lymphocytes into the blood stream. o Macrophages, neutrophils and complement help  Proliferation Stage o The sensitized lymphocyte stimulates some of the resident dormant T and B lymphocytes to enlarge, divide, and proliferate o T lymphocytes differentiate into cytotoxic (or killer) T cells, whereas B lymphocytes produce and relase antibodies o Enlargement of the lymphnodes o The proliferation is inside lymph nodes  Response Stage o Actual humoral and cell-mediated immune response  Effector Stage o Total destruction of the invading microbes or the complete neutralization of the toxin The Immune Response  Interleukin 4- stimulation of activated b cells into plasma cells  Interleukin 6- center role in host defense due to wide range of immune function. Acute Response Cytokines (also known as Immunomodulating Agents)  Regulatory proteins that are produced during all phases of an immune response  Lymphokines (producing lymphocytes), interleukin (intercellular communicator, messenger), chemokines (chemotaxis between cells)  Molecules that form a communication link between immune cells and other tissues and organs of the body PADS 7 IMMUNOLOGY & INFLAMMATION CONCEPTS PADS 8  IMMUNOLOGY & INFLAMMATION CONCEPTS Alterations in the Immune Response - 1952 Classification of Disorders: Clinical Features I. IMMUNE DEFFIENCEY - Spleen, lymph nodes, tonsils, adenoids, peyer’s patches a. PRIMARY decrease in size or absent in individuals b. SECONDARY - IgG depleted II. AUTOIMMUNI DISEAS - Serious enteroviral infections (Coxacki Disease- agent a. SLE for the foot, hand and mouth disease; echoviruses- b. DLE meningitis, encephalitis, myocarditis; Polio viruses_ III. ALLERGIES AND SENSITIVITY - Chronic pulmonary diseases IV. GAMMOPATHY - Skin disease V. RHEUMATOID ARTHRITIS - Inflammatory bowel disease (UC- ulcerative colitis and VI. SAR/MERS chron’s disease) GI problems VII. BPH AND PID - CNS complications 4 Primary Immune Aberrations; - Note: T-lymphocytes elevated  Immune deficiency - 1 in every 100,000 children  Autoimmune disorder B. Hypogammaglobulienemia  Allergy and Hypersensitivity - Called as common variable immunodeficiency (CVID)  Gammopathy o Term that encompasses of defects (ranging I. Immunodeficiency from IgA def. to panhypoglobulinemia) general 2 classifications: lack not absence. 1.) Primary Immunodeficiency - 1 in every 180,000  Congenital or inherited (people with no t - 1956 lymphocytes or leukocytes) Clinical Features 2.) Secondary Immune Deficiency  Growth retardation  Later obtained in life  Abnormalities in lymphoid tissues and organs Primary Immunodeficiency  Skin and mucus membrane abnormalities 10 Warning Signs of PID  Ear nose 1. 8 or more ear infections within a year Other manifestations: 2. 2 or more sinus infections within a year Common sites are: 3. 2 or more antibiotics with little effects (needs higher 1.) Inner ear : Otitis media gens) 2.) Sinuses: Sinusitis,rhinitis 4. 2 or more pneumonias in a year 3.) lower respiratory tract: Pneumonia, bronchitis 5. Poor growth 4.) meninges: meningitis 6. Recurrent deep skin or organ abscesses 5.) Blood stream: Sepsis 7. Persistent thrush in mouth/skin in a year Diagnostic Tests 8. Need for intravenous antibiotics to clear infection NORMAL VALUES 9. 2 or more deep-seated infections (meningitis, IgA 80-350mg/dl cellulitis or sepsis) 10. A history of primary immune deficiency IgG 620-1400mg/dl Other Symptoms: IgM 45-250 mg/dl  Frequent or unusual infections IgD.3-3mg/dl  Prolonged diarrhea IgE.002-2mg/dl  Poor childhood growth PID Disorders - Low, IgG: 200 mg/dl Characteristics: - IgA, IgM, IgG and IgE: low or absent - White blood cells counts are normal  Rare disorders with genetic origins - B- lymphocytes- absent  Seen primarily in infants and young children - T-cell responses- normal  Symptoms usually develop early in life Treatment  Without treatments they seldom survive to adulthood - Goal: Maintain Ig G at 500mg/dl  May involve one or more components of the immune - There is no cure for X-linked agammaglobulinemia system - Gammaglobulin Replacement therapy: IV ig dose of Type of Inherited B-Cell Deficiencies 300 mg/kg every three weeks, or more monthly 1st Type: Aggammalobulinemia - We can also give antibiotics  Lack of differentiation of B-cell (precursors into Prognosis mature B cells) - Without gammaglobulin treatment, these patients  Plasma cell are lacking-leads to complete lack of may die from infections at an early age. antibody production C. Selective IgA Deficiency 2nd type:Hypogammalobulinemia - it is the total absence or severe deficiency of IgA  Results from a lack of differentiation of B cells into - blood serum levels for IgA deficient persons are usually plasma cells found to be 7mg/dl.  Diminished antibody production - usually asymptomatic I. Antibody/ B cells Immunodeficiency Diagnostic: a. X-agamma globulinemia (Bruton’s disease) - IgA: &mg/dl or less b. Hypogammaglobulinemia Treatment c. Selective IgA Deficiency - no cure A. X-linked Agammaglobulinemia (1st type) - IgA Replacement - First immunodeficiency to be indentified - Palliative: immunosuppressive therapy, Antibiotics - Aka Bruton Type Agammaglobulinemia Prognosis - X-linked infantile agammaglobulinemia (common in - Many persons with selective IgA deficiency liver their full males) or congenital agammaglobulinemia (inherited due life span without any problems. to the mutation of the x chromosome 21.3 to 22) critical II. T cell Immunodefiency for the maturation of the B cells. a. DiGeorge’s Syndrome- congenital failure of the - Detected when the patient is already 6 months. thymus gland PADS 9  IMMUNOLOGY & INFLAMMATION CONCEPTS Manifestation  Medical Management  C- cardiac abnormality o IV Ig administration  A-bnormal facies  Surgical Management  T- Thymic aplasia (affect your parathyroid- o Stem Cell Transplant hypocalcemia or the hypoparathyroidism) o Bone Marrow Transplant  C-left Palate o Thymus Gland Transplantation  H- Hypoparathyroidism/hypocalcemia IV. Phagocytic cell disorder Hodgkins disease- neoplasm of the lymphoid Characteristics: tissue, impaired T cell function o increase incidence of bacterial and fungal b. Chronic Mucocutaneous Candidiasis infection  Candidal Infection o recurrent furunculosis  Nails may be markedly thickened o Cutaneous abscesses fragmented, and discolored o Bronchitis,pneumonia  Tetany and hypocalcemia a. Hyperimmunoglobulinemia (formerly known  Skin and hyperkeratotic (thickening or as Job Syndrome exaggeration of the growth of the skin) o white blood cells cannot produce an inflammatory response to the skin infections  Addison’s Disease Clinical Feature: Diagnostic Findings o may be asymptomatics  Lymphocyte count- NV= 16-45% less than o severe neutrophenia 16% o accompanied by deep and painful mouth ulcers, Medical/Surgical Mngt: gingivitis, stomatitis and cellulitis  P. carinii prophylaxis b. Chronic granulomatous disease  Management of hypocalcemia o produces recurrent or persistent infections of the III. Combined B and T cell Immunodeficiency soft tissues, lungs and other organs a. Wiskott-Aldrich Syndrome (WAS) o there are resistant to aggressive treatment with  x-linked recessive disease antibiotics accompanied by thrombocytopenia and Characteristics: ecxema (1954)  excessive inflammation even when there is not b. Ataxia- telangiectasia an infection i. Louis-bar syndrome  diarrhea ii. Autosomal recessive disorder (both  bladder and kidney problems mother and father) Management: iii. B and T lymphocytes are defected TRUE  P-rophylatic antibiotic iv. With accompanying IgA, IgG, IgE  R-aw foods should be avoided deficiencies  O-PV/ live virus vaccine should be Avoded v. With cerebral ataxia, telangiectasis,  T-each frequent handwashing recurrent, infections of the lungs and  E-xercise sinuses and increases incidence of  C-ontagious disease should be avoided cancer (Neurologic, endocronic  T-heraoy=BM transplantation; IV-ig problem) Secondary Immunodefiency vi. Ataxia Telangic Mutated Gene- Common causes: defected ATM gene abnormal cell  malnutrition death in various parts of the body  chronic stress including the brain responsible for the  burns coordination  certain autoimmune disorders Hallmark Signs:  certain viruses  Ataxia- uncoordinated muscles movement  exposes to immunotoxic medications and chemicals  Telangiectasia- vascular lesions caused by  self-administration and recreational drugs and dilated blood vessels alcohol o Usually appears in the first 4 years AIDS- ACQUIRED IMMUNODEFIENCY SYNDROME of life Human Immunodeficiency Virus  On 2nd decade of life – mental retardation, - retrovirus that causes AIDS lung disease - only affects human Medical Management - reproduces by over taking the machinery cells of the  Antimicrobial therapy body. There will be changes in the genum of the host cell.  Postural Drainage and physical therapy for - HIV 1 the most infectious in Philippines lung conditions - HIV 2- endemic only in west Africa. Rare worldwide  Transplantation - Incubation period of 10 years c. Severe Combined Immunodeficiency (SCIDS) Transmission  Bubble boy disease or alymphocytosis or 3 Modes: glanzmann-riniker syndrome or severe - unprotected sex/ penetrative sex mixed immunodeficiency syndrome or - Injection drug use/blood products thymic alymphoplasia - vertical transmission  Severe combined immunodeficiency Sources:  B and t absence  Blood  David Felit  Semen  Equates to an almost absent immune  Breast milk system  Urine  Characteristic:  Saliva- you need gallons before having the virus o Lymphoid aplasia  It is not spread by tears or sweat; use of phone or clothes o Thymic dysplasia (abnormal of the infected person; or even changing of utensils and growth of the thymus) insect bites PADS 10  IMMUNOLOGY & INFLAMMATION CONCEPTS Mode - The point at which an infected person converts to from  Human bites being negative for the presence of HIV antibodies in the  Puncture blood to being positive  Needles Window Period Risk Factors - Time after infection and before seroconversion  Viral Load - Onset of HIV and appearance of detectable antibodies to  Sexual Behavior the virus  STIs- increases the risk of HIV. If the patient has genital - 3-4 weeks ulcerations will become a higher risk of HIV. Classification of HIV infection  Lack of circumcision  650-1200 cells/mm3: COMPETENT IMMUNE SYSTEM  Genetic background- HLA class 1 disorders may a risk to  500-200 cells/mm3: SUPPRESSED IMMUNE SYSTEM transmit the virus  500 cell/mm3 OR END-STAFE HIV - CAT B= 200-499 dse. WITHIN 2-3 YRS - CAT C= 15YERS AND  HEADACHE HAVE STABLE CD4  LYMPHADENOPATHY COUNTS  PHARYNGITIS NO HIV RELATED  ARTHRALGIA DISEASES  MYGALIAS AIDS  NIGHT SWAETS  Is an infectious disease of the immune system caused by  GI PROBLEMS: DIARRHEA the retrovirus HIV-1  ASEPTIC TECHNIQUE  HIV/AIDS  ORAL AND GENITAL ULCERS  Is a secondary immunodeficiency disorder that results 2.) Category B from HIV infection, which is transmitted by blood, semen - Persons with symptoms of immune deficiency or vaginal fluids not serious enough to be AIDS defining Median Course of Infection time is 10 years 1.) Primary Infection Phase (Early acute phase) – manifest - CD4 count falls gradually from the normal range fever, fatigue sore throat, GI problem, night sweats, 3.) Category C lymph adephonities - Opportunistic infection may come in a. Initial response to HIV invasion: - Includes AIDS defining illnesses b. Destruction of Helper T cell/ CD4 cells and i. Pneumocystis carinii pneumonia increase in viral load ii. Candidiasis (oral thrush) c. appears 2-4 weeks after exposure to infection iii. Cytomegalovirus (bring about the and lasts 2 days to 2 weeks herpes simplex virus) d. 3 weeks to 3 months after the test iv. Mycobacterium avium complex 2.) Latency Phase (Chronic Asymptomatic Phase)- v. Recurrent pneumonia a. Over the next 2 to 10 years, virus slowly vi. Histoplasmosis destroys T helper cells in lymphatic tissues Opportunistic Infections throughout the body. 1.) Pneumocystis Carinii Pneumonia (PCP) b. 500 mg/dl (already suppressed or the marker) - The alveoli becomes filled with foamy, protein 600 and above CD4 count (normal) rich fluid that impairs gas exchange c. Lymph adenopathy at 3 months - s/s: mild cough, fever, sob, weight loss 3.) Overt Phase (Symptomatic Phase) 2.) Mycobacterium tuberculosis a. CD4 count is less than 200 mg/dl 3.) AIDS dementia complex b. AIDS defining illnesses - Detrioriation of intellectual faculties (memory, c. As the immune response weakens patient concentration, judgement) develop “indicator disease” with s/s of - Is a syndrome of cognitive and motor Opportunistic infection dysfunction d. 4F- flu like symptoms, fine, falling CD4 counts, - Emotional problems and mental problems final crisis - pseudopsychosis Seroconversion PADS 11  IMMUNOLOGY & INFLAMMATION CONCEPTS - S/s: impairment in attention, concentration and - With high risk for HIV-AIDS- counsel about significant of slowing of mental speed, agility apathetic testing and necessity for follow-up behavior (Initial: Unsteady gait) - Educational and Counseling strategies with AIDS 4.) Kaposi’s sarcoma Guidelines for care of the person with HIV/AIDS: - Is a malignancy of the endothelial cells that line - Prevent infection small blood vessels - Wash hands frequently - Lesions are nodules or blotches that may be - Use gentle soap; avoid bar soap that may irritate skin red, purple, brown or black and are usually - Provide for daily showering/basin bath; avoid tub bath if popular rashes are present - Can usually be seen in the hairlines at first (like - Use separate washcloth for lesions pimple) - Use soft toothbrush, nonabrasive toothpaste - No pus - Prevent skin breakdown - Signal the final stage of HIV infection, AIDS - Elevate and support areas of edema (pneumocytosis) - Observe surgical site and IV insertion sites daily for signs 5.) HIV wasting syndrome of infection - Caused by anorexia, metabolic, abnormalities, - Change dressings (if any) daily. endocrine dysfunction, malabsorption and - Avoid eating fresh fruits/ cytokine dysregulation Pregnancy and AIDS - Diagnostic criteria: involuntary weight loss  Patients who are pregnant exceeding 10% of the baseline body rate  Zidovudine (AZT)- recommended for prevention of - They might have chronic diarrhea for 30 days maternal fetal HIV transmission and administer after 14 - Manifest chronic weakness documented weeks AOG with PO Medicine; IVTT during labor and to persistent fever the neonate post birth for 6 weeks (3 times) 6.) Gynecologic  Nevirapine- reverse transcriptase inhibitor - Recurrent vaginal candidiasis Postpartum period - Genital ulcer disease  Monitor for signs of infection - Venereal warts  Restrict breastfeeding (vertical transmission) DIAGNOSIS:  Place mother in isolation if mother is immunosuppressed. 1.) Elisa (enzyme Linked Immunosorbent Assay)  Infant/neonate is seen by physician at birth, 1 week, 2 2.) Western Blot Assay- confirmatory test weeks, 1 month, 2 month, and 4 months of life. 3.) Orasure- saliva Child with AIDS 4.) CD4 cells count  PCP prophylaxis 1-12 months 5.) Polymerase chain reaction (PCR)- It can detect the  Need for additional prophylaxis is determined by CD4 presence of the virus instead of the antibodies. Generic counts diagnostic exam because it can detect other viruses. 5 means of HIV prevention  Immunizations A- Abstain from sex o Ensure administration of pneumococcal and influenza B- Be faithful vaccines: prevents streptococcal infection C- Correct and consistent use of condom o Avoid varicella vaccine D- Do not use illegal drugs/share needles Health teachings (children) E- Educate yourself  Discard unused refrigerated formula and food for 24 hrs Health Teachings:  Change diapers frequently clean up spills with bleach 1.) Promote good nutrition solution (10:1) ratio. a. High calorie  Provide high CHON, high calorie diet, monitor weight b. High protein daily c. High potassium  Avoid exposing the child to other illnesses. d. Low residue diet Medications (antiretroviral) e. Easy to swallow food- patient may have Goal: dysphagia 1.) To suppress infection, prolonging life f. Promote oral care 2.) To treat opportunistic infection g. Encourage out of bed and eat meals 3.) Effectiveness: monitors by viral load count, CD4 cell h. Not to eat raw foods- proned to infections; counts ( increasing 500 or more) t siveche or kinilaw might contain bacteria  Nucleoside reverse transcriptase inhibitors (NRTI)/ 2.) Promote self-care nucleoside analogs a. Plan and supervise patients to their ADLs o Blocking the elongation of the DNA b. Encourage to be as active and independent as o E.g Zidovudine (AZT, retrovir), Didanosine (DDI, possible Videx), Zalcitabine (DDC, HIVID) c. Assist in ROM exercises to prevent contractures  Protease inhibitors (protease- is a viral enzyme) bind to especially in hospital the protease enzyme and inhibit its action d. Hand washing o Ritonavir (Norvir), Indinavir (Crixivan) 3.) Provide counseling (usually taken for granted)  Non-nucleoside reverse transcriptase inhibirots )NNRTI) a. Assess and support patient in coping o Nevirapine (Viramune), Delavirdine (rescriptor) mechanisms and the promotion of the readying  Others: Interferons: Alpha interferons, gamma-interferons b. Explore with patient and significant others  Receive pneumococcal, influenza, hepatitis B, vaccines c. Assist in the acknowledgement of anticipated  To prevent PCP/ the CD4 (decreased 200 = losses trimethoprim=sulfamethoxazole (Pentamidine) d. Provide information necessary Philippine Setting e. Religious appropriate support 1.) Lamivudine- nausea, vomiting and diarrhea f. Support groups 2.) Tenofovir- renal toxicity, rash, hepatoxicity Other management with AIDS: 3.) Efavirenz: Intense dreams, insomnia - Identification of person at risk a. Best given in the morning due to side effect of - Obtaining a complete accurate sexual history is important insomnia - Identify if IV drug user NEWER DRUGS FOR HIV - Check for other risk factors  Trogarzo PADS 12  IMMUNOLOGY & INFLAMMATION CONCEPTS  PEP-post exposure prophylaxis ( RAL TE GRAVIR TEN OF OUR , EM TR 111 TAB IN E) , PREP- Pre exposure prophylaxis - FDA approved HIV prevention regimen which include taking daily TRUVADA- a medication normally used to treat those living with HIV - Prevents the virus in replicating in the body after exposure - Prevents the HIV establishing the HIV - It has 92% proven efficacy compared to the use of condom in which theefficacy is only 80% Not yet available in the Philippines Taking PrEP to prvent HIV - people who use PrEP must commit to taking it every day and seeing their health care provider every 3 months for follow up and laboratory work up. PADS 13  IMMUNOLOGY & INFLAMMATION CONCEPTS II. AUTOIMMUNE DISORDERS 4. Systemic Lupus Erythematosus Autoimmunity  An autoimmune disorder, non-contagious, chronic, - Production of antibodies against the tissues of your own progressive inflammatory disease of the connective body. tissue that can cause body organ and sytem failure - The body cannot identify the self-antigen between the  The cause is unknown antigens.  Characterized by spontaneous remission (absence of - It produces auto immune diseases of hypersensitivity the disease or manifestations) and exacerbation (flare - The causes is still unknown. However, drugs can up) contribute to the changes in the immune system  Most common in young women (as young as 14 to 50? EFFECTS/CAUSES: years old)  Failure to display self-antigens  The increase in auto antibody production is due to  Presence of genetic abnormalities (idiopathic) abnormal suppressor T cell function, wherein they cannot  Self -reactive clones of T-cells & B-cells identify when to stop the production. It leads to immune Lupus Erythematosus complex deposition. The deposits of immune complexes  Collection of autoimmune disease (umbrella) in which the will be in the tissues, thus causing damages. human immune system becomes hyperactive and attacks Inflammation will be triggered due to the antibody and the normal healthy tissues process will always repeat.  Systemic or purely cutaneous (localized) form  SLE has a ratio of 100 in every 100,000  Lupus- “wolf” (wolf bite)  Affects 1 in 295 black American women  Erythematous- reddened  No treatment for SLE  Attributed to the thirteenth century physician Regorius  Available drugs only to control the manifestations who used to describe erosive facial lesions that were especially exacerbations reminiscent of of wolf bite Risk Factors Classification:  Genetic Abnormality- it may only have a genetic link.  Discoid Lupus Erythematosus Multiple genes can only be affected when triggered by  Drug-induced Lupus Erythematosus factors  Neonatal Lupus Erythematosys  Viral infection- it may have a connection with certain  Systemic Lupus Erythematosus (SLE) infectious agent like viruses and bacteria. No specific antigen can be consistently linked to the disorder 1. Discoid Lupus Erythematosus (DLE)  Medication- reversible condition. It generally disappears when the medication is stopped. o 38 medication Signs and Symptoms  Arthritis- (initial manifestation) to arthralgia (joint)  Weakness, fever, fatigue, weight loss  Photosensitivity from the sun  Butterfly rash/malar rash (bridge of the nose and to the cheeks)  Skin lesions Characteristics of Skin Lesions  Margins are bright red  Chronic skin condition of sores with inflammation (skin  May extend beyond the hairline scarring)  May occur in the exposed part of the neck  Usually seed in face, ears, scalp and other body areas.  May spread to the mucous membranes and other tissues  Lesions developed as red, inflamed, crusty (patchy) of the body  Center area may appear lighter in color (ring) and darker  Do not ulcerate but cause degeneration and atrophy of at the outside ring tissues involved  3 Divisions: o Localized – skin lesions localized above the nec, Favors areas :scalp, bridge of the nose, cheeks lower lips and ears o Generalized- less common; it can affect the thorax and the upper extremities with the addition of above the neck o Childhood discoid lupus ertyhematosus- has a low frequency of photosensitivity and higher progression of SLE; the presentation is similar to the adults with SLE 2. Drug- Induced Lupus Erythematosus  Medications that may trigger lupus erythematosus o Hydralazine (apresoline)- anti-hypersentive drug. o Procanamide- anti-arythmic o Isoniazid- anti-TB drugs o Clopromazine- anti-psychotic o Penicillin- antibiotic 3. Neonatal Lupus Erythematosus  The infants have no skin lessions at birth but only develop at 1st weeks of life  Usually benign and self-limited (it will heal on its own) PADS 14  IMMUNOLOGY & INFLAMMATION CONCEPTS Systemic Involvement of other organs – brought about the  antinuclear antibody (diagnostic exam for SLE) serositis (this refers to inflammation of the serous tissue of the  immunologic disorder body which are the tissues lining the lungs (pleura), heart  N- neurologic disorder (pericardium), inner lining of the abdomen (peritoneum)  M- malar rash  Lupus nephritis  D- discoid rash  Pleuritis Diagnostic Exams:  Pericarditis  Medical History  Peritonitis  Complete Physical Exam  Neuritis (general term of the inflammation of the nerve)  Laboratory Tests:  Anemia