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

E. 1% - 3% of leukocytes F. Elevated in parasitic worm infestations and allergic reactions Review Figure 14.11 Basophils A. Deep blue granules in basic stain B. Release histamine C. Release heparin D. Less than 1% of leukocytes E. Similar to eosinophils in size and shape of nuclei Review Figure 14.12 Monocytes A. Largest of all blood cells B. Spherical, kidney-shaped, oval or lobed nuclei C. Leave bloodstream to become macrophages D. 3% - 9% of leukocytes E. Phagocytize bacteria, dead cells, and other debris Review Figure 14.13 Lymphocytes A. Slightly larger than RBC B. Large spherical nucleus surrounded by thin rim of cytoplasm C. T cells and B cells 1. Both important in immunity D. B cells produce antibodies E. 25% - 33% of leukocytes Review Figure 14.14 Functions of White Blood Cells A. WBCs protect against infection B. These leukocytes can squeeze between the cells of a capillary wall and enter the tissue space outside the blood vessel (called diapedesis) Review Figure 14.15 Review Figure 14.16 White Blood Cell Counts A. A procedure used to count number of WBCs per cubic millimeter of blood 1. Typically 5,000 10,000 per cubic millimeter of blood B. Leukopenia: 1. Low WBC count (below 5,000) 2. Typhoid fever, flu, measles, mumps, chicken pox, AIDS C. Leukocytosis: 1. High WBC count (above 10,000) 2. Acute infections, vigorous exercise, great loss of body fluids D. Differential WBC count 1. Lists percentages of types of leukocytes 2. May change in particular diseases Review Table 14.4 14.2 Clinical Application Blood Platelets A. Platelets are also known as thrombocytes B. They are cell fragments of megakaryocytes C. They lack a nucleus and are roughly half the size of a RBC

D. There are approximately 130,000 360,000 per cubic millimeter of blood E. They help repair damaged blood vessels by sticking to broken surfaces

NOTE: the image below, a thrombocyte is equal to the terminology platelet cell

About this picture: The above diagram shows the differentiation of blood cells, for inflammation response, we are mainly concerned with WBC's which come in two types: granulocytes and agranulocytes. 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

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, this atrophy begins in childhood/adolescence.

Inflammatory Response:

Inflammatory Response: 1. Sequential reaction to a cell's injury *Neutralizes/dilutes inflammatory agent *Removes necrotic materials *Environment suitable for repair *Inflammation and infection: not synonymous, infection is NOT always present with inflammation What happens:

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, heat, 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. 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

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, continued. 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, attracts phagocytes, 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, 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

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

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, 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, no residual damage, mainly Neutrophils Subacute: features of acute with longer duration (weeks or months) Chronic: (Considered chronic when longer than 3 months) *Lasts weeks, months, 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, Acetaminophen, Corticosteroids, Vitamins A,B,C & D) RICE: Rest, Ice, Compression, Elevation Cold and heat treatment Compression and Immobilization Elevation Healing: Regeneration: Depends on cells type Fast: Epithelium, bone marrow, mucous membranes, gastrointestinal

Stable: (only with injury) = liver, kidney, pancreas, bone Permanent: NO/Little DIVISION = CNS neurons, heart and skeletal muscle (scar tissue) Repair: Primary: neatly approximated edges (surgical incision) Initial/Granulation/Maturation or Scar Contraction Secondary: trauma, 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. Serves 3 functions: Defense: against invasion from antigens Homeostasis: damaged cellular components removed, 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. *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. *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, 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

Peripheral Tonsil, gut, genital, bronchial, skin-associated Lymphoid Tissues: Lymph nodes Spleen http://www.google.com/imgres? hl=en&sa=X&biw=1264&bih=658&tbm=isch&prmd=imvns&tbnid=lvmUrR4Jy2HWPM:&imgrefurl =http://m.eb.com/assembly/17656&docid=jek9x2KxONoeM&imgurl=http://media.web.britannica.com/eb-media/90/20890-0047A7058C9.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,r:5,s:21

Mononuclear phagocytes: Monocytes in the bloodstream = macrophage when it leaves vasculature and into tissues ***CAPTURE, PROCESS, 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, 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, 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, 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, nose, stomach, intestines: immature in the bloodstream *Capture antigens at sites of contact with environment *Transport antigen until encountering T-cells = help activate immune response

CYTOKINES: Soluble polypeptide factors created by WBC's in the body *Messengers between cells *Instruct cells to alter their proliferation, differentiation, secretion and activity *100 different cytokines w/ distinct categories *Can be pro or antiinflammatory *Can be harmful: autoimmune disease, chronic inflammation, sepsis *Stimulate hematopoiesis (RBC production), WBC production, 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, prevents new viruses HUMORAL AND CELL MEDIATED IMMUNITY

Cell Mediated Immunity

T cells do not release antibodies. Some of them have surface receptors that recognize a specific antigen, but the antigen must be presented by another cell. The antigen-presenting cell is usually a phagocytic white blood cell called a macrophage. The T cell divides and differentiates into several types of cells: Helper T cells also known as TH, T4 or CD4 cells due to the presence of the CD4 glycoprotein on the cell surface; cytotoxic (TC) and suppressor (T3) cells or CD8 cells due to the CD8 glycoprotein and memory T cells.

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A. 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, the production of antigen-specific cytotoxic T-lymphocytes (def), and the release of various cytokines (def) in response to an antigen (def). Cellular immunity protects the body by: 1. activating antigen-specific cytotoxic T-lymphocytes (CTLs) that are able to destroy body cells displaying epitopes of foreign antigen on their surface, such as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens; 2. activating macrophages and NK cells, enabling them to destroy intracellular pathogens; and 3. stimulating cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses. Cell-mediated immunity is directed primarily microbes that survive in phagocytes and microbes that infect non-phagocytic cells. It is most effective in removing virus-infected

cells, but also participates in defending against fungi, protozoans, cancers, and intracellular bacteria. It also plays a major role in transplant rejection. As mentioned earlier, the immune system of the body has no idea as to what antigens it may eventually encounter. Therefore, it has evolved a system that possesses the capability of responding to any conceivable antigen. The immune system can do this because both Blymphocytes and T-lymphocytes have evolved a unique system of gene-splicing called gene translocation (def) , a type of gene-shuffling process where various different genes along a chromosome move and join with other genes from the chromosome. In a manner similar to B-lymphocytes, T-lymphocytes are able to cut out and splice together different combinations of V, D, and J genes along their chromosomes. Through random gene translocation, any combination of the multiple forms of each gene can join together resulting in thousands of possible gene combinations.This is known as combinatorial diversity. 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, J genes, and D genes. As a result, the chromosome forms a loop allowing different genes from different regions along the chromosome to align. 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. Subsequently, any one of the V-heavy genes is attached to this DJ segment. In the light chain, chromosomal looping enables any V-light gene to attach to any J-light gene. During gene translocation, specialized enzymes in the T-lymphocyte cause splicing inaccuracies wherein additional nucleotides are added or deleted at the various gene junctions. This change in the nucleotide base sequence generates even greater diversity in Fab shape. This is called junctional diversity. As a result of combinatorial diversity and junctional diversity, 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. Cellular immunity is also the mechanism behind delayed hypersensitivity (discussed later in this unit). Delayed hypersensitivity (def) is generally used to refer to the harmful effects of cell-mediated immunity (tissue and transplant rejections, contact dermatitis, positive skin tests like the PPD test for tuberculosis, granuloma formation during tuberculosis and deep mycoses, and destruction of virus-infected cells).

Humoral immunity is what Meredith referred to as Antibody Mediated Immunity. Technically this is known as humoral immunity, though on our exam, I would expect

Meredith's terminology. *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, helper T-cell reads and Calls B-cells

Phase 2: B-cells called to antigen cells, bind to receptors, differentiate to plasma cells which create antibodies.

Humoral immunity (def): humoral immunity involves the production of antibody molecules in response to an antigen (def) and is mediated by B-lymphocytes. Antibodies (Immunoglobulins): An Overview
Humoral Immunity refers to the production of antibody molecules in response to an antigen (def). These antibody molecules circulate in the blood and enter the tissue via inflammation. Humoral immunity is most effective against bacteria, bacterial toxins, and viruses prior to these agents entering cells. 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.