Lymphatic System: Overview Lymph – interstitial fluid once in lymphatic vessels Consists of 2...

Lymphatic System: Overview

• Lymph – interstitial fluid once in lymphatic vessels

• Consists of 2 semi-independent parts:– A network of lymphatic vessels– Lymphoid tissues and organs

scattered throughout body• Returns interstitial fluid and leaked

plasma proteins back to blood

• One-way system: lymph flows toward the heart

• Lymph vessels include:–Microscopic, permeable

lymphatic capillaries– Lymphatic collecting

vessels– Lymphatic trunks and

ducts

Lymphatic Capillaries

• Similar to blood capillaries, with modifications:– More permeable– Loosely joined minivalves– Withstand interstitial

pressure and remain open• Minivalves function as one-way gates that:– Allow interstitial fluid to enter, but not escape

lymph capillaries• During inflammation, lymph capillaries absorb cell

debris, pathogens, cancer cells• Lacteals – specialized lymph capillaries present in

intestinal mucosa - absorb digested fat and deliver chyle to the blood

Lymphatic Vessels & Transport• Have 3 tunics (as veins)• Have thinner walls, with more internal

valves• Collecting vessels in the skin travel

along superficial veins• Deep vessels travel along arteries• Nutrients are supplied from branching

vasa vasorum (network of small arterioles, capillaries, and venules that supply the outer tissue of large blood vessels)

The lymphatic system lacks a pumping organ

Vessels are low-pressure conduits

Uses the same methods as veins to propel lymph:

Pulsations of nearby arteries Contractions of smooth muscle in the

walls of lymphatics

Lymphatics & the Breast

Lymphatic Trunks• Lymphatic trunks are formed by

union of largest collecting ducts• Major trunks include:

– Paired lumbar, bronchomediastinal, subclavian, and jugular trunks

– A single intestinal trunk• Lymph is delivered into 1 of 2 large

trunks– Right lymphatic duct – drains

right upper arm and the right side of head and thorax

– Thoracic duct – arises from cisterna chyli and drains rest of body

Lymphoid Cells• Lymphocytes are THE main cells

involved in immune response • 2 main kinds: T cells and B cells,

they protect body against antigens• Antigen – anything the body

perceives as foreign: bacteria, viruses, mismatched RBCs or cancer cells

• T cells: manage immune response; attack foreign cells

• B cells: produce plasma cells, which secrete antibodies => Antibodies immobilize antigens

Other lymphoid cells:• Macrophages – phagocytize

foreign substances and activate T cells

• Dendritic cells – spiny-looking cells, functions similar to macrophages

• Reticular cells – supports other cell types in lymphoid organs

Lymph Nodes• Principal lymphoid organs of the body• Within connective tissue and along

lymphatic vessels• Aggregations of nodes occur near

body surface in inguinal, axillary, and cervical regions of the body

• 2 basic functions:– Filtration – macrophages destroy

microorganisms and debris– Immune system activation –

monitor and attack antigens

Scattered reticular tissue elements in every body organ

Lymphoid Tissue

Structure of a Lymph Node• Nodes are bean-shaped and surrounded by a capsule• Trabeculae extends inward from capsule and divide node into

compartments• Nodes have 2 histologically distinct regions: a cortex and a

medulla • Cortex contains follicles with dividing B cells• Cortex houses T cells

Lymph nodes

2 Regions:• Cortex– B cells – T cells

• Medulla– Lymph Sinuses &

macrophages

Lymph Nodes Animation

Lymphoid Organs

• Lymph Nodes• Spleen• Thymus• Tonsils• Peyer’s patches• MALT

Spleen• White pulp

– B and T cells carry out immune function.

• Red pulp– Removes aged and

defective RBCs– Stores breakdown

products of RBCs

• Erythrocyte production in fetus

• Stores blood platelets

• Has regenerative properties

Thymus• Secretes

thymopoietin, thmosins to make T-cells immunocompetent

• Bilobed organ• Trabeculae divide

lobe into lobules.• Thymic corpuscles

Tonsils & Adenoids

• Trap bacteria which work their way into the follicles where they are destroyed

• This helps develop memory

Appendix

• Possibly works with the Peyer's patches to help defend against invaders from the digestive system

Aggregates of Lymphoid Follicles

• Peyer’s patches – isolated clusters, similar to tonsils– In the wall of the distal portion

of the small intestine– Similar structures are found in

the appendix• Peyer’s patches and the

appendix:– Destroy bacteria– Generate “memory”

lymphocytes for long-term immunity

MALT• Mucosa-associated lymphatic tissue– Peyer’s patches, tonsils, and appendix

(digestive tract)– Lymphoid nodules in the walls of the

bronchi (respiratory tract)• MALT protects the digestive and respiratory

systems from foreign matter

Causes of Edema• Edema Accumulation of

interstitial fluid • Blockage of lymphatic system• Increased pressure in veins• Lack of albumin– Decreases fluid returning to

blood capillaries by osmosis

• Inflammation

Homeoimbalances of the Lymphatic System

– Autoimmune Lymphoproliferative Syndrome (ALPS)

– Lymphatic Filariasis– Mesenteric Lymphadenitis– Swollen Lymph Nodes– Castleman Disease– Adenoids– Splenomegaly– Hodgkin's disease – Kawasaki disease

Immunity: 2 Defense Systems• Innate (nonspecific) system

responds quickly and consists of:– First line of defense – skin and

mucosae prevent entry of microorganisms

– Second line of defense – antimicrobial proteins, phagocytes• Inhibit spread of invaders

throughout the body• Inflammation is its most

important mechanism • Adaptive (specific) defense

system– Third line of defense – mounts

attack against foreign substances• Has memory, antigen-specific,

and antigen-mediated immunity

• Works in conjunction with the innate system

• Recognizes specific foreign substances– Immobilizes, neutralizes,

or destroys foreign substances

First line of defense: Surface membrane barriers

• Skin and mucous membrane– Layered epidermis and shedding of

epithelial cells– Sebum inhibits growth of bacteria and fungi– Mucous traps microbes, dust and pollutants.

• Lacrimal apparatus• Saliva• Vaginal secretions• Flow of urine• Defecation and vomiting• Gastric juices destroy bacteria and

their toxins

First line of defense: Surface membrane barriers

• Skin and mucous membrane– Layered epidermis and shedding of

epithelial cells– Sebum inhibits growth of bacteria and fungi– Mucous traps microbes, dust and pollutants.

• Lacrimal apparatus• Saliva• Vaginal secretions• Flow of urine• Defecation and vomiting• Gastric juices destroy bacteria and

their toxins

Second line of defense: chemical and cellular defenses

• Antimicrobial proteins– Interferon– Complement– Transferrins

• Natural killer cells • Phagocytes– Neutrophils– Dendritic cells – Macrophages

• Wandering• Fixed

– Eosinophils

Interferons• Produced by

lymphocytes, macrophages and fibroblasts.

• Interfere with translation of viral proteins

• Degrade viral RNA

• Activate macrophages and NK cells

• Interferon Animation

Complement

Complement Cascade Animation

Figure 21.2a

Phagocytes• Macrophages are the chief phagocytic cells

– Free macrophages wander in search of cellular debris

• Kupffer cells (liver) and microglia (brain) are “fixed” macrophages

• Neutrophils become phagocytic when encountering infectious material

• Eosinophils are weakly phagocytic against parasitic worms• Mast cells bind and ingest a wide range of bacteria

Mechanism• Pseudopods engulf the antigen into a phagosome• Invaders are digested by proteolytic enzymes• Indigestible and residual material is

removed by exocytosis

Phagocytosis

Phagocyte Mobilization

Fever• Abnormally high body temperature in response to

invading microorganisms• Body’s thermostat is reset upwards in response to

pyrogens, chemicals secreted by leukocytes and macrophages exposed to bacteria and other foreign substances

• High fevers are dangerous because they can denature enzymes

• Moderate fever can be beneficial, as it causes:– Liver and spleen to sequester iron and zinc – Increases metabolic rate, which speeds up tissue

repair

Inflammatory responseStages Inflammation Animation• Release of Chemical Alarms• Vasodilatation & Permeability of BV• Emigration of phagocytes: Dispose cellular debris

& pathogens• Sets the stage for repair• Prevent spread of damaging chemicals &

pathogens

Signs of inflammation– Redness– Heat– Swelling– Pain– Impairment of function

Comparison of Immune Cells

Adaptive Resistance• Specificity—recognition of

particular antigens• Memory—remembers

previously encountered antigens

• Systemic—immunity is not restricted to the initial infection site

• Immune responses– Antibody-mediated or

humoral immune responses (late 1800s)

– Cell-mediated immune responses (mid 1900s)

Antigens and antigen receptors

• Antigens can be entire microbes, parts of microbes or chemical components of pollen, egg white, blood cells,…….

Antibodies “immunoglobulins”• Four looping polypeptide

chains linked together through disulfide bonds.

• Heavy chains are identical and have a hinge

• Light chains are half as long.

• Variable region is the antigen binding site

• Constant region forms the stem of the antibody and determines its class

• Do not destroy antigen; inactivate and tag it for destruction

• form an antigen-antibody (immune) complex

Antibody Action• Defensive mechanisms used by antibodies:

– Complement fixation – antibodies bound to cells change shape and expose complement binding sites

– Complement activation – uses a positive feedback cycle to promote phagocytosis

– Neutralization – antibodies block binding sites on viruses– Precipitation – soluble molecules are cross-linked into

large insoluble complexes

Immunoglobulin classes

• IgD is attached to B-cell plasma membrane

• IgM is released during primary response. Indicates current infection.

• IgG is the most aboundant. Can cross placenta & blood vessel walls.

• IgA found in body secretions prevents attachment to body surfaces.

• IgE causes release of histamine (allergies) by attaching to mast cells & basophils.

Immunological memory

• Primary immune response

• Secondary immune response

Lymphocytes• Immature lymphocytes released from bone marrow are

essentially identical• Whether a lymphocyte matures into a B cell or a T cell

depends on where in the body it becomes immunocompetent– B cells mature in the bone marrow– T cells mature in the thymus

Figure 20.8

Red bonemarrow

Bone marrowThymus

Lymph nodes, spleen, and other lymphoid tissues

ImmaturelymphocytesCirculation

in blood

Immunocompetent,but still naive,lymphocyte migratesvia blood

ActivatedImmunocompetentB and T cells recirculate in blood and lymph

= Site of lymphocyte originKey:

= Site of antigen challenge, activation, and final diff erentiation of B and T cells

= Site of development of immunocompetence as B or T cells; primary lymphoid organs

Lymphocytes destined to become T cells migrate to the thymus and develop immunocompetencethere. B cells develop immunocompetence in red bone marrow.

After leaving the thymus or bone marrow as naïveimmunocompetent cells, lymphocytes “seed” thelymph nodes, spleen, and other lymphoid tissueswhere the antigen challenge occurs.

Antigen-activated immunocompetent lymphocytes circulate continuously in thebloodstream and lymph and throughout the lymphoid organs of the body.

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T Lymphocytes

• CD4 T cell - also known as a T Helper (Th) cell

• CD8 T cell - also known as a Cytotoxic T (Tc) cell

B Lymphocytes

Clonal Selection

•Production of clones initiated by antigen binding•Plasma cells secrete antibodies•Memory cells are long lived

Humoral & Cell-Mediated Immunity

• Humoral = antibody mediated immunity– Involves B cells– Antibodies circulate

through “humors” inactive and mark invaders for destruction

• Cell-mediated = cellular immunity– Involves T cells– Attack targets directly

or release chemical mediators to enhance inflammation/ activate other WBCs

Homeostatic imbalances : Immunodeficiencies

• Abnormally behaving immune cells

• Severe combined immunodeficiency (SCID) syndromes– Congenital conditions

• Acquired immune deficiency syndromes – Hodgkin’s Disease– HIV– AIDS

Homeostatic imbalances : Autoimmune disease

– Tend to be more prevalent in women• Type I diabetes—destroys pancreatic beta

cells• Multiple sclerosis—destroys myelin sheaths• Myasthenia gravis—impairs communication

between nerve and muscle• Lupus erythematosus—systemic disease of

skin, kidneys, heart, and lungs• Rheumatoid arthritis—destruction of joints

Organ transplants

• Autografts—grafts from the same person to another body site

• Isografts—grafts between genetically identical individuals

• Allografts—grafts among the same species

• Xenografts—grafts taken from another animal species

Hypersensitivities

Hypersensitivity Reactions in the Skin

Hypersensitivities Acute Subacute Subacute

Delayed Immediate cytotoxic Immune complex

Type I Hypersensitivity

Type I Hypersensitivity Animation

Type II Hypersensitivity

Type III Hypersensitivity

Type III Hypersensitivity

Animations• Flash animation of a NK cell interacting

with a normal body cell. • Flash animation of a NK cell interacting

with a virus-infected cell or tumor cell not expressing MHC-I molecules.

• Flash animation of apoptosis by NK cells. • HIV Replication