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Lymphatic System and ImmunityAnatomy & Physiology-HonorsTurner College & Career High School

Lymphatic System

• One way system: to the

heart.

• Return of collected

excess tissue fluid.

• Return of leaked protein.

• “Lymph” is this fluid.

• Edema results if system

blocked or surgically

removed.

Lymph Capillaries

• Have one way mini valves

allowing excess fluid to enter but not leave.

• Picks up bacteria and viruses as

well as proteins, electrolytes and fluid(lymph nodes destroy most pathogens).

Lymphatic System

• Lymph capillaries

o Absent from bone, bone marrow, teeth, CNS.

o Enter lymphatic collecting vessels.

• Lymphatic collecting vessels

o Similar to blood vessels (3 layers), but thin & delicate.

o Superficial ones in skin travel with superficial veins.

o Deep ones of trunk and digestive viscera travel with deep

arteries.

o Very low pressure.

o Distinctive appearance on lymphangiography.

o Drain into lymph nodes.

• Lymph nodes: bean shaped organs along

lymphatic collecting vessels.

• Up to 1 inch in size.

• Clusters of both deep and superficial LNs.

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Functions of Lymphatic System

1. Draining interstitial fluid.

2. Transporting dietary lipids.

3. Protection.

Lymphatic Vessels

• Begin as closed ended lymph capillaries in tissue

spaces between cells.

• NOT A CIRCULATING FLUID.

• Interstitial fluid drains into lymphatic capillaries, forming lymph.

• Lymph capillaries merge to form lymphatic vessels.

• Lymphatic vessels carry lymph into and out of

lymph nodes.

• And finally back to the vascular system.

Lymphatic Capillaries

• Made of a single layer of squamous

epithelial cells.

• Slightly larger than blood capillaries.

• Cells overlap and act as one-way valves.

• Opened by pressure of interstitial fluid.

• Anchoring filaments attach cells to

surrounding tissue.

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Lymphatic Vessels

• Resemble veins (same 3 layers).

• Found throughout body except:

oAvascular tissues.

oCentral nervous system.

o Splenic pulp.

o Bone marrow.

Lymphatic Vessels

• Lymphatic vessels join to form lymphatic

trunks.

• Lymphatic trunks join to form :

o Thoracic duct (3/4 of body).

o Right lymphatic duct (drains right arm, and right

side of head, neck and upper torso).

• These empty into subclavian veins at

junction with internal jugular vein.

Formation of Lymph

• Fluid leaves capillaries by diffusion and

filtration.

• Escaped proteins.

• If lymph flow blocked = tissue swelling or

edema.

• Specialized lymphatic capillaries in vili of

small intestine transport lipids - they are

called lacteals, and the fluid is called chyle.

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Lymphatic Organs

• Red bone marrow

• Thymus gland

• Lymph nodes

• Lymph nodules Secondary organs

• Spleen

Primary organs

Lymph Nodes

• Lymph is filtered through lymph nodes.

• Found in clusters.

• “Waste water treatment plants”.

• Vary in size.

• Principal groupings in cervical, axillary and

inguinal regions.

• Provide biological filtration.

• Site of cancer growth and metastasis.

• Vessels enter node on convex side.

• Lymph passes through irregular channels called sinuses.

• Leaves node through one or two efferent

vessels at the hilum or hilus.

• Capsule, cortex and medulla.

• Cortex contains lymph nodules.

• Follicular dendritic cells.

• Germinal centers – B cells proliferate.

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Lymph Nodules

• Lymph nodules are also found singly or in groups throughout the mucous membranes of

the respiratory, urinary, reproductive and digestive tracts.

• MALT – mucosa associated lymphoid tissue.

• Peyer’s patches in ileum.

• Tonsils.

• Some in appendix.

Development of Lymphocytes

• Originate in bone marrow from lymphoid stem cells

• B cells stay in bone marrow, hence “B” cells

• T cells mature in thymus, hence “T” cells

• These divide rapidly into families

• Each has surface receptors able to recognize one

unique type of antigen=immunocompetence

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Development of Lymphocytes

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Lymphocytes

• Naive immuno-competent lymphocytes “seed” secondary lymphoid organs (esp. lymph nodes).

• “Antigenic challenge” – full activation upon meeting and binding with specific antigen.o The B cell’s antigen receptor is an antibody (see

slide 20)

• Full activationo Gains ability to attack its antigen

o Proliferates rapidly producing mature lymphocytes

o Mature lymphocytes re-circulate seeking same pathogens

Tonsils

• Tonsils –lymphoid tissue under the mucous

membranes of the throat.

o Palatine tonsils

o Pharyngeal tonsil – adenoid

o Lingual tonsils

• First line of defense.

• Tonsillectomy.

Tonsils

Thymus Gland

• In mediastinum above the heart.

• Largest at age 10-12 then begins to atrophy.

• Pre-T cells come from bone marrow and

develop into T cells.

• T cells then go to other lymphatic tissues.

• Thymus produces hormone thymosin - aids

maturation of T cells elsewhere in body.

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Spleen

• Largest lymphoid organ.

• In upper left quadrant of abdomen.

• Has a hilum and a capsule.

• Sinuses contain blood instead of lymph.

Spleen

• White pulp:

o Little islands, mostly B cells.

• Red pulp:

o Venous sinuses.

o Splenic cords – RBCs, macrophages,

lymphocytes, plasma cells and granulocytes.

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Functions of Spleen

• Blood formation

o All blood cells in fetus.

o Only lymphocytes and monocytes after birth.

• Blood filtration

o Removes bacteria, particles, worn out RBCs and

platelets (recycles iron).

• Blood storage

o Can contain over one pint of blood.

Nonspecific Resistance

• The ability to ward off disease is called

resistance.

• Lack of resistance is susceptibility.

• Nonspecific resistance refers to a wide

variety of body responses against a wide

range of pathogens. A pathogen is any

microorganism that causes disease.

Nonspecific Resistance

• Species (Inborn) Resistance – certain

species contract certain diseases, while

other species do not.

Mechanical Barriers

• Skin and mucous membranes :

o First line of defense.

o Physical barrier.

o Shedding of dead cells.

o Mucus.

o Hairs.

o Cilia.

o Coughing and sneezing, production of tears,

saliva, urine, defecation and vomiting physically remove harmful substances.

Chemical Protection

• Sebaceous glands produce sebum – fatty acids inhibit growth of bacteria and fungi.

• Lactic acid further decreases skin pH.

• Accumulation of salt.

• Vaginal secretions are also slightly acidic.

• Gastric juice – acid, enzymes and mucus.

• Lysozyme in tears, perspiration, saliva and tissue fluids.

• Normal Microbiota – bacteria living on skin

inhibit the growth of pathogens by producing antibiotics

Antimicrobial Substances

• Transferrins are proteins that tie up the free

iron in the blood and interstitial fluid.

• Interferon: “Paul Revere Chemical” – a

glycoprotein produced by virus infected

cells that cause neighboring cells to

produce anti-viral proteins. These also

enhance phagocytosis and can suppress

growth of tumor cells.

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The Compliment System

• 10- 20 normally inactive proteins

• When activated, they “complement” or

enhance certain immune, allergic and

inflammatory reactions.

1. Activation of inflammation

2. Opsonization – enhances phagocytosis

3. Cytolysis – membrane attack complex

Fever

• Causes liver and spleen to sequester iron.

• Increases phagocytosis.

• Inhibits growth of microbes.

• Speeds up body repair.

Inflammation

• Characterized by:

o Heat, swelling, redness, and pain (and sometimes loss of function) calor, tumor, rubor and dolor.

Stages of Inflammation

1. Vasodilation and increased permeability

of blood vessels

2. Phagocyte migration

1. Neutrophils come first

2. Followed by macrophages

3. Tissue Repair

Phagocytosis

Three phases:

1. Chemotaxis

2. Adherence

3. Ingestion

Natural Killer Cells

• Next line of defense (with phagocytes)

• Lymphocytes – but do not respond to

specific antigens

• Can kill a variety of microbes plus tumor

cells.

• May release perforins, or attack directly

• Cell may not display correct MHC antigens

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Immunity

• Immunity involves activation of specificlymphocytes to combat a specific foreign

agent.

• Specific resistance to disease involving the

production of a specific lymphocyte or antibody against a specific antigen.

• An antigen is any substance that elicits an

immune response. Best antigens are:

o Large

o Complex

o Recognized as foreign

• Haptens are molecules that are small,

foreign and complex. To elicit an immune

response, they must piggy-back on a larger

molecule, often blood proteins.

• Epitopes: a foreign protein may result in

several different antibodies. Each antibody

recognizes a different portion of the protein.

These regions are called epitopes.

Forms of Immunity

• Humoral or antibody mediated immunity.

• B cells (mature in bone) make antibodies:

specific proteins that bind to specific

antigens.

OR

• Cell-mediated immunity.

• Tcytoxic lymphocytes attack virus infected

or tumor cells directly.

“The Story”

• Macrophage destroys a bacterium

• Takes bacterial antigen and fuses it with

MHC II complex

• MHC II complex and antigen are placed on

cell membrane.

• Displays antigen (like a proud cat) – so it is

called an antigen presenting cell.

• It shows antigen to helper T cells, until it finds

one that has a receptor that matches the

antigen complex.

• The helper T cell binds to the antigen

complex, and the macrophage is stimulated

to produce the cytokine Interleukin -1

• A cytokine is a protein hormone which

regulates normal cell functions, like growth

and differentiation.

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• Every step needs 2 signals to proceed.

• IL-1 binds to receptors on the helper T cell,

causing helper T-cell to clone itself and

produce IL-2.

• IL-2 causes lymphocytes to multiply.

• These steps are common to both humoral

and cell-mediated immunity.

Humoral or AntibodyMediated Immunity

• In order for B cells to become activated

and make antibodies against an antigen,

two things must happen:

1. B cell must encounter the antigen.

2. IL-2 produced by helper T cell must be

present.

• When both signals are present (the antigen

and IL-2). The B cell becomes activated and

forms two types of cells: plasma cells and

memory cells.

• Plasma cells produce large quantities of

their specific antibody into the blood.

• Memory cells lie in wait for the next

infection.

Humoral or AntibodyMediated Immunity Antibody Mediated Immunity

• B cells and Antibody-Mediated Immunity.

• Characteristics of B Cells

o Antibody-mediated immunity against pathogens.

o Produced and mature in bone marrow.

o Reside in lymph nodes and spleen, circulate in blood and lymph.

o Directly recognize antigen and then undergo clonal selection.

o Clonal expansion produces antibody-secreting plasma cells as well as memory B-cells.

Clonal Selection Model: B-Cells

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Antibodies

• “Y” shaped proteins – gamma globulins.

• Have a variable region that matches a

specific antigen (Fab region).

• Have a constant region – activates

complement (Fc region).

Structure of an Antibody

• Antibodies are also called immunoglobulins

(Ig’s).

• Y-shapedo Constant regions

o Variable regions

Antibodies

• The first antibodies produced are IgM.

Pentamers – with ten combining sites – very

effective in opsonization and activating

complement.

• Several days later, IgG is produced – single

unit antibodies, abundant in serum, cross the

placenta, and have the longest half-life.

Antibodies Cell Mediated Immunity

• A virus is a core of nucleic acid wrapped in

a protein.

• To reproduce, it must make use of a host cell

to replicate the viral nucleic acids and

proteins and assemble new viruses.

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• Infected cells put viral proteins on their

membranes.

• This antigen is processed by macrophages.

• Antibodies can’t get at viruses inside a cell,

so we need something different : a

Tcytotoxic or Tc Cell.

• The Tc encounters the viral antigen with the

MHC -1 complex on the infected cell.

Cell Mediated Immunity Cell Mediated Immunity

T cells

• A macrophage presents a portion of an

antigen to T cells.

• Types of T-cells:

o Helper T-cells

o Cytotoxic T-cells

Characteristics of T-Cells

• Cell-mediated immunity against virus infected cells and cancer cells.

• Produced in bone marrow, mature in thymus.

• Antigen must be presented in groove of an

MHC molecule.

• Cytotoxic T cells destroy non-self protein-

bearing cells.

• Helper T cells secrete cytokines that control the immune response.

Clonal Selection Model: T-Cells

• Now needs the second stimulus – IL-2 from the helper T cell.

• Tc cell clones itself, and makes activated Tc

cells and memory cells.

• Tc Cells bind to antigens on infected cells and release:

• Perforins – punch holes in cell membrane.

• Lymphotoxins – activate the cell’s own self-destruct mechanism.

Cell Mediated Immunity

• Tc Cells are effective against bacteria which

are intracellular parasites, viruses, fungi,

cancer cells associated with viral infections,

and transplanted cells.

Cell Mediated Immunity

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Immune Response

• The first time you encounter an antigen, you

have few B cells or Tc cells against that

antigen = primary response.

• The next time, you have many memory cells,

so response is much quicker, so you don’t

come down with the disease = secondary

response.

Hypersensitivity

• “The immune system gone bad.”

Delayed Hypersensitivity

• A type of cell mediated immunity.

• Td cell – requires usual two signals.

• Second time antigen is encountered, Td cell

produces several cytokines that attract and

activate macrophages, resulting in an

inflammatory reaction.

• Examples: poison ivy (urushiol), TB skin test.

Immediate Type Hypersensitivity

• Exposure to certain antigens (allergens)

results in the formation of IgE antibodies.

• IgE antibodies bind to mast cells by the Fc

end.

• When the antigen is encountered again,

binding with the antibody causes mast cell

to release histamine granules.

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• May be able to desensitize individual by

giving allergen to stimulate IgG antibodies.

These tie up antigen before they can bind

with IgE.

Acquired Immunity

• Active = person makes own antibodies

• Passive = person receives antibodies from

someone else

• Natural = “just happens”

• Artificial = caused by man (often using a

needle)

Acquired Immunity

• Natural active acquired immunity: person

comes down with measles.

• Artificial active acquired immunity: person is

immunized with a vaccine.

• Artificial passive acquired immunity: person

receives serum with antibodies.

• Natural passive acquired immunity: baby

receives antibodies with mother’s milk –

colostrum.

Active Immunity

• Develops naturally after a person is infected

with an antigen.

• A person produces an immune response

against an antigen.

• Can be induced by use of vaccines.

• Is dependent upon the presence of Memory

B Cells and Memory T Cells in the body.

Acquired Immunity

• Vaccines are pathogens or their products that have

been treated so they are no longer able to cause disease.

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Passive Immunity

• An individual is

given prepared

antibodies to

combat disease.

• Is temporary

because there

are no memory

cells.

Immunity Therapy

• Cytokines and Immunity

o Signaling molecules produced by T lymphocytes and macrophages.

o Interleukins

• Cytokines that enhance ability of T cells to fight cancer.

• Have many potential uses in medicine.

Monoclonal Antibodies• Group of plasma cells

from the same B cell

all produce same antibody.

• Use of monoclonal

antibodieso Diagnostic tests

• Ex: pregnancy tests

o Vehicles for drug delivery

o Identification of infections

Allergies

• Hypersensitivities to Substances

• Immediate Allergic Response

o Can occur within seconds of exposure to an antigen.

o IgE antibodies attach to mast cells.

o Allergen attaches to IgE, causing mast cells to release

histamine.

o Histamine is responsible for allergy symptoms.

• Anaphylactic Shock

o Immediate allergic response where allergen enters the blood

stream.

o Histamine causes a sudden, life-threatening drop in blood

pressure.

o Epinephrine can counteract this reaction.

Blood-Type Reactions

• In the ABO system, the presence or absence of type

A and type B antigens on red blood cells determines a persons blood type.

• If antibodies are present against a type of blood,

agglutination occurs.

• Transfusions

o Must consider recipient’s antibodies and donor’s antigens

to prevent agglutination and transfusion reaction.

o Type O is universal donor.

• Neither anti-A nor anti-B antibodies.

o Type AB is universal recipient.

• Neither A nor B antigens.

Blood-Type Reactions

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Blood Transfusions Rh System

• Rh+ Rh antigen is present on red blood cells.

• Rh- Rh antigen is absent on red blood cells.

• Significant in Pregnancy

o If a Rh- mother is pregnant with Rh+ baby.

o If baby’s cells leak into mother’s bloodstream, she forms

anti-Rh antibodies.

• Attack baby’s RBC’s- hemolytic disease of newborn

(HDN).

• This can be prevented by giving the Rh- mother anti-Rh

immunoglobulins in an injection.

• The injection must be given before the mother

becomes sensitized to produce her own antibodies.

Hemolytic Disease of the Newborn Disorders of the Immune System

• Autoimmune Disease

o Cytotoxic T-cells or antibodies attack a person’s

own cells.

• Myasthenia gravis - muscle weakness.

• Multiple sclerosis - neuromuscular disorder.

• Immune Deficiencies

o Immune system is unable to protect the body from disease.

• Acquired immune deficiency syndrome.

• Severe combined immunodeficiency syndrome

(inherited).

HIV/AIDS

• Human immunodeficiency virus.

• Attacks helper T cells.

• Without production of IL-2, there is no

second signal, and humoral and cell

mediated immunity are shut off … increase

in rare diseases:

o TB, Kaposi sarcoma, etc.