WRITTEN REPORT In NCM104

Submitted by: Rochelle Abdul Liberty P. Alvarez Aaron Paul Austria Grace Atienza Jayvilyn Barundia Joannamarie Baloaloa Fatima N. Castrillo Clarissa Mae A. Cule Mark Paulo Diaz

Submitted to: Mr. Alvin T. Doctora

CELLS AND TISSUES OF THE IMMUNE SYSTEM

CELLS WHITE BLOOD CELLS are the most important cellular components of immunity. White blood cells are produced in red bone marrow and lymphatic tissue and are released into the blood. Chemicals released from microorganisms are damaged tissues attract the WBC and they leave the blood and enter affected tissues. Important chemicals known to attract WBC include complement, leukotrienes, kinins and histamine.The movement of the WBC toward these chemicals is called Chemotaxis. 2. PHAGOCYTIC CELLS Phagocytosis is the ingestion and destruction of particles by cells called phagocytes. The particles can be microorganisms or their part, foreign substances or dead cells from the individuals body. The most important phagocytes are neutrophils and macrophages , although other WBC also have limited phagocytic ability.
1.

NEUTROPHILS are small phagocytic cells that are usually the first cells to enter infected tissues from the blood in large numbers, however neutrophils often die after phagocytizing a single microorganism. PUS is an accumulation of fluid, dead neutrophils, and other cells at a site of infection. MACROPHAGES are monocytes that leave the blood, enter tissues and enlarge about fivefold. Monocytes and macrophages form the mononuclear phagocytic system because they are phagocytes with a single, unlobed nucleus. Sometimes macrophages are given specific names such as dust cells in the lungs. Kupffer cells in the liver, and microglia in the central nervous system. Macrophages can ingest more and larger items than can neutrophils. Macrophages usually appear in infected tissues after neutrophils and are responsible for most of the phagocytic activity in the late stages of an infection, including the clean up of dead neutrophils and other cellular debris. In addition to leaving the blood in response to an infection, macrophages are also found in uninfected tissue, the macrophages may phagocytize the microorganism before they can replicate or cause damage. For example, macrophages are located at potential points of entry for microorganisms into the body, such as beneath the skin and mucous membrane, and around blood and lymphatic blood vessels. They also protect lymph in lymph nodes and blood in the spleen and liver. 3. CELLS OF INFLAMMATION
a. BASOPHILS are derived from red bone marrow, are motile WBC that can

leave the blood and enter infected tissues. b. MAST CELLS are derived from red bone marrow, are non motile cells in connective tissue, especially near capillaries. Like macrophages, mast cells are located at potential points of entry for microorganisms into the body such as the skin , lungs gastrointestinal tract, and urogenital tract. Basophils and mast cells can be activated through innate immunity (e.g. by compliment) or through adaptive immunity. When activated, they release chemicals such as histamine and leukotrienes that produce an inflammatory response or activate other mechanisms such as smooth muscle contraction in the lungs.

c. EUSINOPHILS are produced in red bone marrow, enter the blood and within

a few minutes enter tissues. Enzymes released by eosinophils breakdown chemicals released by basophils and mast cells. Thus at the same time that inflammation is initiated , mechanisms are activated that contain and reduce the inflammatory response. Inflammation is beneficial in the fight against microorganisms, but too much inflammation can be harmful, resulting in the unnecessary destruction of healthy tissues as well as the destruction of the microorganisms.
4. NATURAL KILLER (NK) CELLS are a type of lymphocyte produced in red bone

marrow, and they count for up to 15% of lymphocytes. NK cells recognize classes of cells , such as tumor cells or virus infected cells in general, rather than specific tumor cells or cells infected by a specific virus. For this reason , and because NK do not exhibit a memory response, NK cells use a variety of methods to kill their target cells, including the release of chemicals that damage cell membranes , causing cell to lyse.
Reported by: Grace Atienza

Tissues of the Immune System

The primary tissues of the immune system are the bone marrow and thymus and these are involved in the creation and maturation of immune cells. The secondary tissues of the immune system are the spleen, lymphatic system, lymph nodes and MALT. These tissues contain mature immune cells and are the active part of the immune system. The immune system consists of a complex network of organs and tissues, connected by blood and lymphatic vessels, that work together to prevent infection. Many of these systems are unleashed by activation of other parts of the immune system. The extensive interdependence of the players of the immune system can make it difficult for the beginning student to understand. As we go through the immune system, you will encounter unfamiliar terms, but be patient because they will be explained later in the chapter. To try to make it a bit easier, we will first describe the anatomy of the immune system, then examine the various cell types involved in immunity, and finish this section by describing how these parts work together in reacting to an invading pathogen. Many different organs and tissues in the body contribute to the function of the immune system. These include the circulatory system, bone marrow, thymus, spleen, lymphatic system and Mucosal Associated Lymphoid Tissue (MALT). Together these tissues are responsible for the creation, transport and successful operation of mammalian immunity. In this section we will look at the role of each tissue and introduce a number of cells and proteins involved in immunity. The tissues of the immune system fall into two groups based upon their role in host defense. Primary (or central) tissues look after immature immune cells, creating and

educating them during their differentiation into mature cells. The bone marrow and thymus gland are parts of the primary immune system. Secondary (peripheral) immune organs look after mature cells that are an active part of defense. The secondary system encompasses the rest of the immune tissues: the spleen, the lymphatic system, lymph nodes and MALT. Of course it is not this simple and the spleen and MALT also help in the maturation of immune cells.
Reported by: Aaron Paul D. Austira

Immunoglobulin

Antibodies that binds to and destroy specific antigens The basic unit of every immunoglobulin molecule is a symmetric arrangement of four polypeptide chains: two heavy chains and two light chains. These heavy and light chains are kept together as a symmetric four-chain molecule (H2L2). The chains are held together by disulfide bonds and remain viable across a wide range of conditions ( heat stability, for instance) Clonal selection theory proposes that each B lymphocyte contains all the genetic information necessary to produce all possible specific antibodies. Thus, the gene for specific antibody is activated by contact with the antigen, and large amounts of antibody are formed. The binding of antigen stimulates the available number of B cells that recognize it to proliferate, producing sufficient cells to mount an immune response. The clonal selection model assumes that large amounts of antigenic stimulation trigger the immunocompetent lymphocyte to clonally reproduce and for those new cells to make large amounts of specific antibody.

Five Major Classes of Immunoglobulins IgG, IgM, IgA, IgE, and IgD. Major Characteristics of Immunoglobulins o IgG ( 75% of total Immunoglobulin) Appears in serum and tissues (interstitial fluid) Assumes a major role in blood borne and tissue and tissue infections Activates the complement system Enhances phagocytosis Crosses placenta Normal value : 600-1800 mg/dL

o IgA (15% of total Immunoglobulin) Appears in body fluids (blood, saliva, tears, breast milk and pulmonary, gastro intestinal, prostatic, and vaginal secretions)

Protects against respiratory, gastrointestinal, and genitourinary infectious Prevents absorption of antigens from foo Passes to neonate in breast milk for protection Normal value: 80-400 mg/dL

o IgM ( 10% of total Immunoglobulin) Appears mostly in intravascular serum Appears as the first immunoglobulin produced in response to bacterial viral infections. Activates the complement system Normal value: 55-250 mg/Dl

o IgD ( 0.2% of total immunoglobulin) Appears in small amounts in serum Possibly influences B-lymphocytes differentiation, but role is unclear Normal value: 0.5-12.0 mg/dL

o IgE ( 0.004% of total immunoglobulin) Appears in serum Takes part in allergic and some hypersensitivity reactions Combats parasitic infections. Normal value: < 1.0 mg/ mL

Reported by: Rochelle B. Abdul and Liberty P. Alvarez

Non Specific Inflammatory Response

INFLAMMATORY RESPONSE (Inflammation)

o Local reaction of the body to invasion or injury. o Defensive reaction intended to neutralize, control, or eliminate the offending agent and to prepare the site for repair. Cardinal Signs: calor (heat) tumor (swelling) rubor (redness) dolor (pain) loss of function CAUSES: burns chemical irritants TYPES: Acute Inflammation Is characterized by the local vascular and exudative changes and usually lasts less than 2 weeks. An acute inflammatory response is immediate and serves a protective function. After the injurious agent is removed, the inflammation subsides and healing takes place with the return of normal of near-normal structure and function. Chronic Inflammation Develops if the injurious agent persists and the acute response is perpetuated. Symptoms are present for many months or years. It may also begin insidiously and never have an acute phase. The chronic response does not serve a beneficial and protective function; on the contrary, it is delibitating and can produce long-lasting effects. As the inflammation becomes chronic, changes occur at the site of injury and the nature of the exudates becomes proliferative. A cycle of cellular infiltration, necrosis, and fibrosis begins, with repair and breakdown occurring simultaneously. Considerable scarring may occur, resulting in permanent tissue damage. frostbite toxins infection by pathogens physical injury, blunt or penetrating immune reactions due to hypersensitivity ionizing radiation foreign bodies, including splinters, dirt and debris trauma

VASCULAR RESPONSE: In response to injury, there may be a transient arteriolar vasoconstriction. This is evidenced on the skin by a transient blanching. This probably best demonstrated in thermal burns where the effect lasts several minutes. Youve probably noticed that a burn looks white for a while. Arteriolar constriction also occurs when the skin is abraded or lacerated. Vasoconstriction is probably mediated through autonomic nerves or as a direct result of injury to the smooth muscle wall of arterioles. Vasodilation follows vasoconstriction or may be the first observed response to injury. Stimulation of mast cells releases histamine. Histamine causes dilation of arterioles and contraction of andothelial cells in the venule. The result is increased blood flow and initial leakage of low protein content fluid from the vessel. Increased blood flow can be visualized

as redness (rubor) and felt as heat (calor). The histamine response is transient. More severe injuries which cause direct injury to endothelial cells cause a sustained response. Increased blood flow results in increased hydrostatic pressure in the capillaries and venules. According to Starlings hypothesis this drives fluid out of the vessel. Protein accumulates in the interstitium as a result of damaged vascular integrity or necrosis of cells. These accumulated proteins increase colloid pressure and more fluid flows from the vessel. The increased interstitial pressure contributes to partial collapse of lymphatics and discourages natural drainage. All these factors result in interstitial edema (tumor = swelling). The fourth cardinal sign of inflammation is pain (dolor). This is result of increased pressure in the interstitium due to edema. Pain fibers are stimulated through pressure receptors but also may be stimulated by the direct effects of bradykinin, a plasma protease end product of the kinin system.
Reported by: Joannamarie Baloaloa

PHAGOCYTOSIS
cell-eating Important means by which white blood cells take up and destroy harmful substances that entered the body. Process of ingestion and digestion by cells of substances such as other cells, bacteria, cell debris and foreign particles. Ingestion and destruction of particles are called phagocyte. Most important phagocytes are neutrophils, macrophages, although other wbc also have limited phagocytic ability. Neutrophils Small phagocytic cells that the first cells to enter infected tissues from the blood in large numbers; often die after phagocytizing a single microorganism
PUS accumulation of fluid, dead neutrophils and other cells at a site of infection.

Macrophages
Other terms (DUST CELLS-lungs, KUPFFER CELLS-liver, MICROGLIA- CNS)

Monocytes that leave the blood in large numbers, enter tissues and enlarge about fivefold.

 With monocytes form the mononuclear- phagocytic system because they are

phagocytes with a single, unlobed molecules. Usually appear in infected tissues after neeutrophils and responsible for most of the phagocytic activity in the late stages of an infection, including the clean- up of dead neutrophils and other cellular debris. If microorganisms enter, it may phagocytize the microorganisms before they can replicate or cause damage.
Reported by: Fatima N. Castrillo

COMPLEMENT SYSTEM
COMPLEMENT It consists of group of proteins that are normally present in the circulation as functionally inactive precursor. It is made in the liver and activated when an antibody connects with its antigen. It plays an important role in the defense against microbes. It is a primary mediator of both innate and adaptive immunity that enables the body to: a.) Produce an inflammatory response b.) Lyse foreign cells c.) Increase phagocytosis

THREE MAJOR PHYSIOLOGIC FUNCTIONS OF COMLEMENT SYSTEM: Defending the body against the bacterial infection Bridging natural and acquired immunity Disposing of immune complexes and the byproducts associated with inflammation. Three Phases of Complement System Reaction INITIAL ACTIVATION PHASE There are 3 parallel independent mechanisms for recognizing microorganisms that result in the activation of the complement system. Alternative Pathways - initiated by interaction with certain polysaccaride molecules characteristics of bacterial surfaces. 2. Classic Pathways initiated by antibody bound to antigens on the surface of microbes or through soluble immune complexes. 3. Lectin Pathways initiated after the binding of a mannosebinding lectin to mannose-containing molecules commonly present on the surface of bacteria and yeast.
1.

EARLY STEP INFLAMMATORY RESPONSE

The central component of complement for all three pathways is the activation of the complement protein C3 and its enzymatic cleavage into a large C3b fragment and a smaller C3a fragment. The smaller C3a fragment stimulate inflammation by acting as a chemoattractant for neutrophills The larger C3b fragment becomes attached to the microbe and act as an opsonin for phagocytosis The larger C3b fragment also act as an enzyme to cleave C5 into two components: a C5a fragment, which produces vasodilation and increase vascular permeability; and a C5b fragment, which leads to late step membrane attack response

LATE STEP MEMBRANE ATTACK The C5b fragment, which remains attached to the microbe, initiates formation of complexes of complement proteins C6, C7, C8, and C9 into membrane attack protein or pore, that allows fluid and ions to enter and cause cell lysis.

Reported by: Clarissa Mae A. Cule

HEALING
Healing is the restoration of damaged living tissue, organs and biological system to normal function. It is the process by which the cells in the body regenerate and repair to reduce the size of a damaged or necrotic area. Healing incorporates both the removal of necrotic tissue and the replacement of this tissue. The replacement can happen in two ways:

by regeneration: the necrotic cells are replaced by the same tissue as was originally there. by repair: injured tissue is replaced with scar tissue.

REGENERATION In order for an injury to be healed by regeneration, the cell type that was destroyed must be able to replicate. Cells also need a collagen framework along which to grow. Alongside most cells there is either a basement membrane or a collagenous network made by fibroblasts that will guide the cells' growth. Since ischemia and most toxins do not destroy collagen, it will continue to exist even when the cells around it are dead. REPAIR Healing must happen by repair in the case of injury to cells that are unable to regenerate (e.g. cardiac muscle or neurons). Also, damage to the collagen network (e.g. by enzymes or physical destruction), or its total collapse (as can happen in an infarct) cause healing to take place by repair. In response to an incision or wound, a wound healing cascade is unleashed. This cascade takes place in four phases: clot formation, inflammation, proliferative, and maturation.

Clotting phase Healing of a wound begins with clot formation to stop bleeding and to reduce infection by bacteria, viruses and fungi. Clotting is followed by neutrophil invasion three to 24 hours after the wound has been incurred, with mitoses beginning in epithelial cells after 24 to 48 hours. Inflammation phase In the inflammatory phase, macrophages and other phagocytic cells kill bacteria, debride damaged tissue and release chemical factors such as growth hormones that encourage fibroblasts, epithelial cells and endothelial cells which make new capillaries to migrate to the area and divide. Proliferative phase In the proliferative phase, immature granulation tissue containing plump active fibroblasts forms. Fibroblasts quickly produce abundant type III collagen, which fills the defect left by an open wound. Granulation tissue moves, as a wave, from the border of the injury towards the center. As granulation tissue matures, the fibroblasts produce less collagen and become more spindly in appearance. They begin to produce the much stronger type I collagen. Some of the fibroblasts mature into myofibroblasts which contain the same type of actin found in smooth muscle, which enables them to contract and reduce the size of the wound. Maturation phase During the maturation phase of wound healing, unnecessary vessels formed in granulation tissue are removed by apoptosis, and type III collagen is largely replaced by type I. Collagen which was originally disorganized is cross-linked and aligned along tension lines. This phase can last a year or longer. Ultimately a scar made of collagen, containing a small number of fibroblasts is left.
Reported by: Mark Paulo Diaz