lymphatic system: overview lymph – interstitial fluid once in lymphatic vessels consists of 2...
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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