Inflammation and Immune Response Jennifer Bowdish 3 Types/Levels of Response: Innate : Body produces chemicals (PH of skin, stomach
) or fluids (tears) to protect itself from environmental exposure to antigens Inflammation: Localized response to a pathogen with 5 hallmarks: Edema, Erythema, Pain, Heat and Loss of function Immune: Response of the immune system that is complex. Involves T-Cells (Thymus derived) and BCells to create an “immune response” to an antigen by identifying, producing, and creating antibodies or immunoglobulins. Also involves creating “memory” cells which remember antigens to mount a response if subsequent infection/inflammation occurs. Types of White Blood Cells This is taken directly from the books website and was reproduced for study purposes only... (Holes Anatomy and Physiology, Twelth Edition, Chapter 12) A. White blood cells: 1. Are leukocytes 2. Protect against disease 3. WBC hormones are interleukins and colony-stimulating factors which stimulate development 4. There are five types of WBCs in two categories: a. Granulocytes 1). Neutrophils 2). Eosinophils 3). Basophils b. Agranulocytes 1). Lymphocytes 2). Monocytes Neutrophils A. Light purple granules in acid-base stain B. Lobed nucleus C. Other names 1. Segs 2. Polymorphonuclear leukocyte 3. Bands (young neutrophils) D. First to arrive at infections E. Phagocytic F. 54% - 62% of leukocytes G. Elevated in bacterial infections Review Figure 14.10 Eosinophils A. Deep red granules in acid stain B. Bi-lobed nucleus C. Moderate allergic reactions D. Defend against parasitic worm infestations
These leukocytes can squeeze between the cells of a capillary wall and enter the tissue space outside the blood vessel (called diapedesis) Review Figure 14. Similar to eosinophils in size and shape of nuclei Review Figure 14. Slightly larger than RBC B. Low WBC count (below 5. Deep blue granules in basic stain B. and other debris Review Figure 14. measles. B cells produce antibodies E. 3% .16 White Blood Cell Counts A. mumps. A procedure used to count number of WBCs per cubic millimeter of blood 1. Less than 1% of leukocytes E. kidney-shaped. dead cells. Phagocytize bacteria. great loss of body fluids D. WBCs protect against infection B. Acute infections. 25% . Differential WBC count 1. Largest of all blood cells B. Elevated in parasitic worm infestations and allergic reactions Review Figure 14. oval or lobed nuclei C. Typically 5. Leukopenia: 1. flu.9% of leukocytes E. T cells and B cells 1.12 Monocytes A. Platelets are also known as thrombocytes B. May change in particular diseases Review Table 14. AIDS C.000) 2.13 Lymphocytes A.3% of leukocytes F. They lack a nucleus and are roughly half the size of a RBC
.000 per cubic millimeter of blood B.11 Basophils A.000 – 10.E. Large spherical nucleus surrounded by thin rim of cytoplasm C. Release histamine C. vigorous exercise. Both important in immunity D.15 Review Figure 14. High WBC count (above 10. Spherical. Leukocytosis: 1. They are cell fragments of megakaryocytes C. chicken pox. 1% .2 Clinical Application Blood Platelets A. Typhoid fever.000) 2. Lists percentages of types of leukocytes 2.14 Functions of White Blood Cells A. Release heparin D.33% of leukocytes Review Figure 14.4 14. Leave bloodstream to become macrophages D.
D. They help repair damaged blood vessels by sticking to broken surfaces
NOTE: the image below. This simply means the granulocytes have “granules” in their cytoplasm and agranulocytes do NOT. Thrombocytes are also known as platelets Lymphocytes differentiate into the 2 different types of lymph cells: B-cells which develop in bone
. a thrombocyte is equal to the terminology “platelet” cell
About this picture: The above diagram shows the differentiation of blood cells.000 – 360. for inflammation response.000 per cubic millimeter of blood E. There are approximately 130. we are mainly concerned with WBC's which come in two types: granulocytes and agranulocytes.
this atrophy begins in childhood/adolescence.
Inflammatory Response: 1. infection is NOT always present with inflammation What happens:
. Sequential reaction to a cell's injury *Neutralizes/dilutes inflammatory agent *Removes necrotic materials *Environment suitable for repair *Inflammation and infection: not synonymous.marrow and T-cells which continue to develop in the thymus The thymus begins as a very large organ and slowly atrophies as we grow older.
swelling at site of injury Cellular Response to Inflammation Neutrophils and Monocytes move from circulation to injury ***Increased capillary permeability from vascular changes helps promote*** Chemotaxis (think chemical taxis): Migration of WBC to site of injury via chemical messengers.Vascular Response: Arterioles constrict : release of histamines and chemicals Arterioles and vessels dilate Increase blood flow Increased capillary permeability Fluid movement from capillary to tissues (diapedesis of white blood cells) Vasodilation contributes to: redness. Actual movement of WBC is called diapedesis
Neutrophils: First to arrive (6-12 hours) Phagocytic cells: eat bacteria Short life span (24 – 48 hours) = accumulation of cells = cell debris or “pus” Immature Neutrophils =Band cells (named because of appearance of nucleus in microscope) ***LEFT SHIFT*** = increased number of neutrophils = found in acute bacterial infections Monocytes: Phagocytic cells
enhances phagocytosis Lysis (destruction) occurs when final complement components create holes in cell membranes via different methods to destroy antigen cells and promote healing Prostaglandins and Leukotrines Prostaglandins: cells injury releases arachidonic acid and membrane produces prostaglandins Pro-inflammatory Vasodilators = increased blood flow and edema formation Sensitizing pain receptors = more painful stimulus Pyrogens = increase temperature regulation in the hypothalamus Thromboxane: Powerful vasoconstrictor and platelet aggregator Causes brief vasoconstriction Produces clot formation Short life. continued.Arrive 3-7 days after inflammation Transform into macrophages after leaving vascular circulation which “eat” debris *Macrophages the “display” the antigen/virus on their surface for identification via helper T-cells which attach and destroy the cells *Macrophage releases Interleukin-1 which calls T cells *T-cells release Interleukin-2 which causes reproduction of cytotoxic T-cells and B-cells to aid in defense against foreign viruses/bacteria Monocytes/Macrophages. gives way to prostaglandins and histamines Leukotrienes: Slow reacting substance of anaphylaxis Constricts smooth muscle of bronchi Narrowing of the airway Increases capillary permeability = airway edema
. attracts phagocytes. Clean before healing can begin Long lived = weeks Lymphocytes: Arrive later Humoral and cell mediated immunity Chemical Mediators Complement System: Enzymatic cascade of events Mediate inflammation Destroys pathogens Group of proteins in plasma and body fluids that interact in a cascade Classical pathway: complement protein binds to antibody attached to antigen Alternative pathway: Exposure to foreign antigens in the absence of antibodies Stimulates: inflammation.
LOCAL RESPONSE TO INFLAMMATION: REDNESS: Rubor HEAT: Calor PAIN: Dolor SWELLING: Tumor LOSS OF FUNCTION: Functio laesa
Physiology of inflammation: Release of cell mediators (arachidonic acid and prostaglandins) CD-40: releases cytokines Vasodilation Increased blood flow to the area Extravasation of fluids Cellular influx (chemotaxis and diapedesis) Elevated cellular metabolism
. blood flow to peripheral body *Adrenal epinepherine increases metabolic rate = net effect of fever Fever: *Kills microorganisms *Increases phagocytosis *Increases T-cells *Activates defense mechanisms Types of Inflammation: Acute: 2-3 weeks for healing. Corticosteroids. Ice. Acetaminophen. no residual damage.SYSTEMIC (Body-Wide) RESPONSES AND MANIFESTATIONS TO INFLAMMATION: Increased WBC Count or “Left Shift” of Immature Neutrophils/Band cells in bone marrow Malaise Nausea and anorexia Increased pulse and respiratory rate Fever Fever Triggered by the release of cytokines = cause metabolic changes in the hypothalamus *Synthesis of prostaglandins *Prostaglandins act to directly increase hypothalamus thermostat set point Hypothalamus triggers autonomic nervous system *Stimulates increased muscle tone *Shivering *Decreases perspiration. years *Repeated injury to tissues *Rheumatoid arthritis *Can result from altered immune response (autoimmune: body attacks itself) Nursing Interventions: Observations/Vitals Fever Management Drug therapy (NSAIDS.B. Compression. months. mucous membranes.C & D) RICE: Rest. bone marrow. mainly Neutrophils Subacute: features of acute with longer duration (weeks or months) Chronic: (Considered chronic when longer than 3 months) *Lasts weeks. Vitamins A. Elevation Cold and heat treatment Compression and Immobilization Elevation Healing: Regeneration: Depends on cells type Fast: Epithelium.
kidney. ulceration and infections Large amounts of exudate Irregular wound margins Tertiary: delayed primary intention IMMUNE RESPONSE 3rd Line of Defense: Normal (Homeostatic) Immune Response: “State of responsiveness to foreign substances such as microorganisms and tumor proteins.Stable: (only with injury) = liver. Serves 3 functions: Defense: against invasion from antigens Homeostasis: damaged cellular components removed. *Placenta from mother to fetus *Injection of gamma globulin (antibodies) = immediately effective (rabies vaccine) *TEMPORARY and short lived because no synthesis occurred and no memory T-cells created Antigen: Substance that creates immune response *Can be foreign invader (bacteria. heart and skeletal muscle (scar tissue) Repair: Primary: neatly approximated edges (surgical incision) Initial/Granulation/Maturation or Scar Contraction Secondary: trauma. cell types remain uniform and unchanged Surveillance: Mutations and antibodies come into the body and are recognized and destroyed Types of Immunity: Active acquired immunity: invasion of antigen into the body. virus. fungi) *Can be own cells where the body cannot distinguish in “self” from non self or autoimmune Lymph organs: Central Thymus = differentiation/maturation and storage of T-cells Bone Marrow = creation and storage of B-cells
. bone Permanent: NO/Little DIVISION = CNS neurons. pancreas. *Body develops memory B and T cells to fight subsequent infections from the same disease *Results from naturally acquiring the disease (eg: Chicken Pox) *Results from receiving less virulent form of antigen to cause immune response and memory as in immunizations Passive acquired immunity: Host receives antibodies or immunoglobulin to an antigen instead of synthesizing the antigen and antibodies.
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. skin-associated Lymphoid Tissues: Lymph nodes Spleen http://www.gif&w=340&h=600&ei=62oUT4HGOML50gH5wOWtAw&zoom=1&iact=hc&vpx=813& vpy=230&dur=1511&hovh=298&hovw=169&tx=94&ty=154&sig=105437193438523133954&page= 2&tbnh=140&tbnw=79&start=21&ndsp=23&ved=1t:429.web.Peripheral Tonsil.com/imgres? hl=en&sa=X&biw=1264&bih=658&tbm=isch&prmd=imvns&tbnid=lvmUrR4Jy2HWPM:&imgrefurl =http://m.eb. gut.r:5.britannica.
or cell mediated immunity OTHERS: Natural Killer Cells *NK cells *Cell mediated immune response = large lymphocytes with granular cytoplasm *NO PRIOR SENSITIZATION/Antigen exposure *Recognize/kill virus/tumor cells for destruction Dendritic Cells *Cell mediated immune response *Atypical shape / process forms and retracts *Skin. intestines: immature in the bloodstream *Capture antigens at sites of contact with environment *Transport antigen until encountering T-cells = help activate immune response
. PROCESS. created and differentiated in the BONE MARROW (B) *Differentiate into plasma cells (after encountering antigen) and become antibody producing factories *Some are differentiated into memory cells which then store the antigen information for subsequent attacks by the same antigen T-Lymphocytes: *Migrate from the bone marrow to the THYMUS GLAND *70-80% of circulating lymphocytes *Responsible for immunity to intracellular viruses. tumor cells. stomach. fungi *Life span: months to lifetime Cytotoxic: *”CD8”: cells involved in attacking antigens on membrane and release toxins to destroy *Antigen specificity = sensitize to specific antigen *Some remain as memory T-cells for future infections Helper: *”CD4” cells: regulated cell mediated immune response *Regulate humoral antibody response *Differentiate into subsets that produce cytokines (Interleukins) *Mediate ingestion and destruction of microbes. nose. AND PRESENT ANTIGEN TO THE LYMPHOCYTE CELLS*** *Responsible for the cell mediated or humoral immune response *Phagocytize antigen and display the antigen for identification on the outside of the cell *Identified by T-cells first and then B-cells for destruction and immune response Lymphocytes: Produced in the bone marrow = T and B cells B-lymphocytes: *Mainly stored.Mononuclear phagocytes: Monocytes in the bloodstream = macrophage when it leaves vasculature and into tissues ***CAPTURE.
Permission required for reproduction or display. Some of them have surface receptors that recognize a specific antigen. Malignancies Interferon: *Helps body's natural defenses attack tumors and viruses *3 main Types *Enhance natural killer cell production *Inhibit tumor cell growth *Forms 2nd protein: antiviral protein = alters cells protein synthesis. The antigen-presenting cell is usually a phagocytic white blood cell called a macrophage. cytotoxic (TC) and suppressor (T3) cells or CD8 cells due to the CD8 glycoprotein and memory T cells. inc.
. differentiation. secretion and activity *100 different cytokines w/ distinct categories *Can be pro or antiinflammatory *Can be harmful: autoimmune disease. chronic inflammation. T4 or CD4 cells due to the presence of the CD4 glycoprotein on the cell surface.
Copyright © The McGraw-Hill Companies. The T cell divides and differentiates into several types of cells: Helper T cells also known as TH.CYTOKINES: Soluble polypeptide factors created by WBC's in the body *Messengers between cells *Instruct cells to alter their proliferation. WBC production. but the antigen must be presented by another cell. prevents new viruses HUMORAL AND CELL MEDIATED IMMUNITY
Cell Mediated Immunity
T cells do not release antibodies. sepsis *Stimulate hematopoiesis (RBC production).
stimulating cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses. activating macrophages and NK cells. Cell-mediated immunity is directed primarily microbes that survive in phagocytes and microbes that infect non-phagocytic cells. and the release of various cytokines (def) in response to an antigen (def). Cellular immunity protects the body by: 1. 2. Cell Mediated Immunity: An Overview
Cell-mediated immunity (CMI) is an immune response that does not involve antibodies but rather involves the activation of macrophages and NK-cells. cells with intracellular bacteria. activating antigen-specific cytotoxic T-lymphocytes (CTLs) that are able to destroy body cells displaying epitopes of foreign antigen on their surface. and 3.A. enabling them to destroy intracellular pathogens. It is most effective in removing virus-infected
. the production of antigen-specific cytotoxic T-lymphocytes (def). such as virus-infected cells. and cancer cells displaying tumor antigens.
the chromosome forms a loop allowing different genes from different regions along the chromosome to align. Therefore.
Humoral immunity is what Meredith referred to as Antibody Mediated Immunity. In the light chain. This is called junctional diversity. chromosomal looping enables any V-light gene to attach to any J-light gene. it has evolved a system that possesses the capability of responding to any conceivable antigen. As a result of combinatorial diversity and junctional diversity. positive skin tests like the PPD test for tuberculosis. Subsequently. D. the immune system of the body has no idea as to what antigens it may eventually encounter. cancers. It also plays a major role in transplant rejection. Technically this is known as humoral immunity. and D genes. specialized enzymes in the T-lymphocyte cause splicing inaccuracies wherein additional nucleotides are added or deleted at the various gene junctions. The immune system can do this because both Blymphocytes and T-lymphocytes have evolved a unique system of gene-splicing called gene translocation (def) . any one of the V-heavy genes is attached to this DJ segment. In a manner similar to B-lymphocytes. I would expect
. Delayed hypersensitivity (def) is generally used to refer to the harmful effects of cell-mediated immunity (tissue and transplant rejections. This change in the nucleotide base sequence generates even greater diversity in Fab shape. Through random gene translocation. In the heavy chain any J-heavy gene and any D-heavy gene align and bind together as the genes are cut from one location and pasted into another. and J genes along their chromosomes. As mentioned earlier. each T-lymphocyte is able to produce a unique shaped T-cell receptor (TCR) capable of reacting with complementaryshaped peptide bound to a MHC molecule. As a result.cells. but also participates in defending against fungi. though on our exam. any combination of the multiple forms of each gene can join together resulting in thousands of possible gene combinations. Gene translocation of the V(D)J genes is initiated when an enzyme called V(D)J recombinase recognizes recombination signal sequences located at the ' end of V genes. T-lymphocytes are able to cut out and splice together different combinations of V. and intracellular bacteria. granuloma formation during tuberculosis and deep mycoses. contact dermatitis. Cellular immunity is also the mechanism behind delayed hypersensitivity (discussed later in this unit). protozoans.This is known as combinatorial diversity. During gene translocation. J genes. a type of gene-shuffling process where various different genes along a chromosome move and join with other genes from the chromosome. and destruction of virus-infected cells).
“bind” to receptors. *Mediated by B-cells *Helper T-cells call B-cells to action after cellular response *B-cells produce ANTIBODIES to attack the ANTIGEN *B-cells differentiate into plasma cells which are factories that produce antibodies they also will differentiate into memory cells which the body stores for future infection to a specific antibody *B-cells are SPECIFIC TO THE ANTIGEN. The receptors “bind” to the antigen Phase 1: Macrophage ingests antigen.
.Meredith's terminology. differentiate to plasma cells which create antibodies. helper T-cell reads and “Calls” B-cells
Phase 2: B-cells called to antigen cells.
and viruses prior to these agents entering cells. These antibody molecules circulate in the blood and enter the tissue via inflammation. Antibodies or immunoglobulins (def) are specific glycoprotein configurations produced by Blymphocytes and plasma cells in response to a specific antigen and capable of reacting with that antigen.Humoral immunity (def): humoral immunity involves the production of antibody molecules in response to an antigen (def) and is mediated by B-lymphocytes. Humoral immunity is most effective against bacteria.
. Antibodies (Immunoglobulins): An Overview
Humoral Immunity refers to the production of antibody molecules in response to an antigen (def). bacterial toxins.