LECTURER: Lorraine Veraces-Pilapil, OTRP, OTR

Fluid balanceFat absorptionDefense

FLUID BALANCE30 L of fluid blood capillaries to interstitial

spaces each day27 L of fluid interstitial spaces into blood3 L of fluid enters the lymphatic capillaries

(lymph) and passes through the lymphatic vessels to return to the blood.

Lymph contains solutes derived from two sources:Substances in plasma, such as ions, nutrients,

gases, and some proteinsSubstances such as hormones, enzymes, and waste

products derived from cells within the tissues.

FAT ABSORPTIONFrom the digestive tractLacteals (special lymphatic vessels)

located in the lining of the small intestine fat enters lymphatic vessels venous circulationChyle is lymph that is milky in appearance

due to the fat content.

DEFENSE

Microorganisms and other foreign substances filtered from lymph by lymph nodes and from blood by the spleen.

Lymphatic system does not circulate blood to and from tissues.Carries fluid in one direction from tissues to the circulatory system.

LYMPHATIC CAPILLARIESTiny closed-ended vessels consisting of simple

squamous epithelium.More permeable than blood capillaries because they

lack a basement membrane, and fluid moves easily into the lymphatic capillaries

Overlapping squamous cells of the lymphatic capillary walls act as valves that prevent the back-flow of fluid.

Are located in most tissues of the body except the CNS, bone marrow, and tissues without blood vessels such as epidermis and cartilages

Superficial group drains the dermis and hypodermis

Deep group drains muscles, viscera, and other deep structures

LYMPHATIC VESSELSResemble small veinsBeaded appearance because of one way valvesThree factors that cause compression of the

lymphatic vessels:Contraction of surrounding skeletal muscle during

activityPeriodic contraction of smooth muscle in the lymphatic

vessel wallPressure changes in the thorax during respiration

Lymphatic vessels converge and eventually empty into:Right lymphatic duct upper right limb and the

right half of the head, neck, and chest and empties into the right subclavian vein.

Thoracic duct rest of the body and empties into the left subclavian vein.

Tonsils Lymph Nodes SpleenThymus Gland

LYMPHATIC TISSUESConsists of many lymphocytes and macrophagesFound within lymphatic organsOriginate from the red bone marrow and are

carried by the blood to lymphatic organsThey divide and increase in number when the

body is exposed to microorganisms or foreign substances

Has very fine reticular fibers that form an interlaced network that holds the lymphocytes and other cells in place as well as traps microorganisms and other items in the lymph.

TONSILSThey form a protective ring of lymphatic

tissue around the openings between the nasal and oral cavities and the pharynx.

Provide protection against pathogens and other potentially harmful material entering from the nose and mouth.

In adults, the tonsils decrease in size and may eventually disappear.

Three group of tonsils:Palatine tonsils (“the tonsils”) – located on

each side of the posterior opening of the oral cavity.

Pharyngeal tonsils – located near the internal opening of the nasal cavity and when enlarged is commonly referred as “adenoid”

Lingual tonsils – posterior surface of the tongue.

LYMPH NODESRounded structures that vary in size.Distributed along the various lymphatic vessels

and most lymph passes through at least one lymph node before entering the blood.

Three superficial aggregations:Inguinal nodesAxillary nodesCervical nodes

Capsule – dense connective tissue that surrounds each lymph node

Trabeculae – extensions of the capsule and subdivides lymph nodes into compartments containing lymphatic tissue and lymphatic sinuses.

LYMPH NODESLymphatic nodules – are dense

aggregations of lymphatic tissue containing lymphocytes and other cells

Lymphatic sinuses – spaces between lymphatic tissue which contain macrophages on a network of fibers.

Germinal centers – lymph nodules containing rapidly dividing lymphocytes

Lymph enters the lymph node through afferent vessels, passes through the lymphatic tissue and sinuses, and exits through efferent vessels.

2 functions:Activation of the immune systemRemoval of microorganisms and foreign substances

from the lymph by macrophages

SPLEENRoughly the size of a clenched fist located

in the left, superior corner of the abdominal cavity.

Outer capsule – dense connective tissue and a small amount of smooth muscle

Trabeculae – divide the spleen into small, interconnected compartments containing two specialized types of lymphatic tissue:White pulp – lymphatic tissue surrounding the

arteries within the spleenRed pulp – associated with veins and consists of

a fibrous network filled with macrophages and red blood cells, and enlarged capillaries that connect to the veins.

SPLEENSpleen filters blood instead of lymph.Cells within the spleen detect and respond to

foreign substances in the blood and destroy worn-out red blood cells.

Also function as a blood reservoir holding a small volume of blood.

THYMUSBilobed gland roughly triangular in shapeLocated in the superior mediastinumThe thymus increase in size until the first

year of life, after which it remains approximately the same size even though the size of the individual increases

After 60 years of age, it decreases in sizeBy 40 years of age much of the thymus has

been replaced with adipose tissue.Capsule – thin connective tissue that

surrounds each lobe of the thymusTrabeculae – divide each lobe into lobules

THYMUSCortex – an area near the capsule and trabeculae

where lymphocytes are numerous and form a dark-staining area

Medulla – lighter staining central portion of the lobule and has fewer lymphocytes

Thymus functions as a site for production and maturation of lymphocytes

Large numbers of lymphocytes are produced in the thymus, but for unknown reasons, most degenerate.

While in the thymus, lymphocytes do not respond to foreign substances

Matured lymphocytes enter the blood and travel to other lymphatic tissues help protect against microorganisms and other foreign substances

IMMUNITYIs the ability to resist damage from foreign substances,

such as microorganisms, and harmful chemicals, such as toxins released by microorganisms

Innate immunity – body recognizes and destroys certain foreign substances, but the response to them is the same each time the body is exposed to them

Adaptive immunity – body recognizes and destroys foreign substances, but the response to them improves each time the foreign substance is encountered.Specificity and memory are characteristics of adaptive immunity

which results in a faster, stronger and longer response.Specificity – the ability of adaptive immunity to recognize a

particular substanceMemory – the ability of adaptive immunity to “remember”

previous encounters with a particular substance

Mechanical mechanism Chemical mediators Cells Inflammatory response

MECHANICAL MECHANISMSPrevent the entry of microorganisms and

chemicals in 2 ways:Skin and mucous membranes form barriers

that prevent their entryTears, saliva, and urine act to wash them from

the surfaces of the body

CHEMICAL MEDIATORSMolecules responsible for many aspects of

innate immunity.Lysozyme in tears and saliva are surface

chemicals that kill microorganisms or prevent their entry.

Histamine, complement, prostaglandins, leukotrines, promote inflammation by causing vasodilation, increasing vascular permeability, and stimulating phagocytosis

Interferons protect cells against viral infections.

A. ComplementA group of approximately 20 proteins found

in plasmaNormally circulate in blood in an inactive

form activated by combining with foreign substances or by combining with antibodies each complement protein activates the next promote inflammation and phagocytosis and directly lyse bacterial cells

B. InterferonsProteins that protect the body against viral

infectionsViruses stimulate infected cells to produce

interferons bind to the surface of neighboring cells and stimulate them to produce antiviral proteins inhibit viral reproduction by preventing the production of new viral nucleic acids and proteins.

Some play a role in the activation of immune cells such as macrophages and natural killer cells

CELLSWhite blood cells are the most important

cellular components of immunityWBC are produces in the bone marrow and

lymphatic tissue.Chemotaxis – is the movement of WBC

toward chemicals (complement, leukotrines, kinins, and histamine).

A. Phagocytic CellsPhagocytes – most important are neutrophils,

and macrophagesPhagocytosis – is the ingestion and

destruction of particles by phagocytesNeutrophils

Small phagocytic cells that are usually the first to enter infected tissues

Often die after phagocytizing a single microorganism

Pus – is an accumulation of fluid, dead neutrophils, and other cells at site of infection.

A. Phagocytic CellsMacrophages

Monocytes that enlarge fivefold after entering the tissues.

Form the mononuclear phagocytic system because they are phagocytes with a single, unlobed nucleus.

Kupffer cells – liverMicroglia – CNSIngest more and larger items than neutrophils

and they appear in the later stages of infectionFound in uninfected tissues

B. Cells of InflammationBasophils – derived from red bone marrow are

motile WBC that can leave the blood and enter infected tissues.

Mast cells Derived from red bone marrow are nonmotile cells in

connective tissues near capillariesLocated at potential points of entry for microorganisms

such as the skin, lungs, GI tract, urogenital tract.

Basophils and mast cells can be activated in innate and adaptive immunity. They release chemicals such as histamine and leukotrines that produce an inflammatory response or activate other mechanisms such as smooth muscle contraction in the lungs.

B. Cells of InflammationEosinophils

Produces in red bone marrowEnzymes break down chemicals released by

basophils and mast cells that contain and reduce the inflammatory response

Too much inflammation is harmful, resulting in unnecessary destruction of healthy tissues as well as the destruction of the microorganisms.

C. Natural Killer CellsType of lymphocyte produced in the red bone

marrow15% of lymphocytesRecognize classes of cells such as tumor cells

or virus-infected cells in general do not exhibit memory response

Release chemicals that damage cell membranes, causing the cell to lyse.

Most are very similar, although some details can vary depending on the intensity of the response and the type of injury. Fibrinogen is converted to fibrin which isolates the infection by walling off the infected area.

A. Local InflammationConfined to a specific area of the bodySymptoms – redness, heat, swelling, pain,

and loss of function.Redness, heat, swelling – result of increased

blood flow and increased vascular permeability

Pain – caused by swelling and by chemical mediators acting on pain receptors

Loss of function – tissue destruction, swelling, and pain.

B. Systemic InflammationDistributed throughout the bodyThree features

Red bone marrow produces and releases large numbers of neutrophils

Pyrogens released by microorganisms, neutrophils, and other cells stimulate fever production Affect the temperature-regulating mechanisms in the

hypothalamus of the brain Fever promotes the activities of the immune system,

such as phagocytosis, and inhibits the growth of some microorganisms

In sever cases, vascular permeability can increase can cause shock and death

ADAPTIVE IMMUNITYExhibits specificity and memoryAntigens are substances that stimulate

adaptive response. Two groups of antigens:

Foreign antigenSelf-antigens

FOREIGN ANTIGENSIntroduced from outside the bodyBacteria and viruses, components of

microorganisms are examples of antigensPollen, animal hairs, foods, and drugs –

allergic reactionsTransplanted tissues and organs contain

foreign antigens

SELF-ANTIGENSMolecules produced by the person’s body

that stimulate an immune system response.Beneficial – recognition of tumor antigens

can result in destruction of the tumor.Harmful – autoimmune diseases

Divisions of Adaptive Immunity

Humoral immunity or antibody-mediated immunity

Cell-mediated immunity

LYMPHOCYTES2 TYPES:

B cellsGive rise to cells that produce proteins called

antibodies which are found in the plasma.Responsible for antibody-mediated immunity.

T cells Responsible for cell-mediated immunitySubpopulations

Cytotoxic T cells produce the effects of cell-mediated immunity

Helper T cells can promote or inhibit the activities of both antibody-mediated immunity and cell-mediated immunity.

ORIGIN AND DEVELOPMENT OF LYMPHOCYTESThere are about 5 T cells for every B cell

in the blood.Clones

Are small groups of identical B or T cells formed during embryonic development.

Each clone is derived from a single, unique B or T cell

Each can respond only to a particular antigen.

Antigen Recognition Lymphocyte proliferation

A NTIGEN RECOGNITIONLymphocytes have antigen receptors in their surface

(B-cell receptors, T-cell receptors)Each receptor binds with only a specific antigenB and T cells typically recognize antigens after large

molecules have been processed or broken down into smaller fragments

Major histocompatibility complex (MHC) moleculesGlycoproteins that have binding sites for antigensSpecific “serving trays” that hold and present a processed antigen

on the outer surface of the cell membrane.

ANTIGEN RECOGNITIONCostimulation is a second signal required

to produce a response from a B or T cell.Achieved by cytokins (ex. Interleukin I) which

are proteins or peptides secreted by one cell as a regulator of neighboring cells.

CD4 of helper T cells and CD8 of cytotoxic T cells helps connect the T cells to the macrophage by binding to MHC molecules.

LYMPHOCYTE PROLIFERATION

Helper T cells produce interleukin 2 receptors and interleukin 2.

Interleukin 2 binds to the receptors and stimulates the helper T cell to divide

Are proteins produced in response to an antigen

Y-shaped molecules consisting of four polypeptide chains: two identical heavy chains and two identical light chains.

Variable Region End of each arm of the antibodyPart of the antibody that combines with the antigenCan only join a particular antigen

Constant regionRest of the antibodySeveral functions: activate complement, or attach

the antibody to cells such as macrophages, basophils, and mast cells.

ANTIBODIES

ANTIBODIESAntibodies make up a large portion of the

proteins in plasmaMost plasma proteins can b separated into

albumin and alpha, beta, and gamma globulin portions.

Called gamma globulins because they are found mostly in the gamma globulin part of plasma

Called immunoglobulins (Ig) because they are globulin proteins involved in immunity.

Five general classes of immunoglobulins : IgG, IgM, IgA, IgE, and IgD

EFFECTS OF ANTIBODIES

Directly or indirectly

ANTIBODY PRODUCTIONPrimary response results from the first

exposure of a B cell to an antigenB cells divide and form memory cells and plasma

cells.Plasma cells – produce antibodiesNormally takes 3-14 days to produce enough

antibodies to be effective against the antigen

Secondary or memory responseMemory B cellsOccurs when the immune system is exposed to an

antigen against which it has already produced a primary response.

When exposed to the antigen, the B memory cells quickly divide to form plasma cells.

ANTIBODY PRODUCTIONSecondary or memory response

Provides better protection than primary response for two reasons:The time required to produce antibodies is lessMore plasma cells and antibodies are

producedAlso includes the formation of new memory

cells, which provides protection against additional exposures to a specific antigen

Plasma cells die after the destruction of antigen

Memory cells persists for many years

CELL-MEDIATED IMMUNITYFunction of cytotoxic cellsMost effective against microorganisms that

live inside the cells of the bodyInvolved with some allergic reactions, control

of tumors, and graft rejections.Essential for fighting viral infections.