Lymphatic System and Immunity
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Lymphatic System and Immunity
Chapter 16
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Functions of Lymphatic System
1. Draining interstitial fluid
2. Transporting dietary lipids
3. Protection
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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
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• Lymphatic vessels carry lymph into and out of lymph nodes
• and finally back to the vascular system.
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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:– Avascular tissues– Central nervous system– Splenic pulp– Bone marrow
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Lymphatic vessels join to form lymphatic trunks.
Lymphatic trunks join to form :
Thoracic duct (3/4 of body)
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.
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Formation of lymph:Fluid leaves capillaries by diffusion and filtrationEscaped 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 Primary organs
• Thymus gland
• Lymph nodes
• Lymph nodules Secondary organs
• Spleen
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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
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• 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 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
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Tonsils – lymphoid tissue under the mucous membranes of the throat
palatine tonsils
pharyngeal tonsil – adenoid
lingual tonsils
First line of defense
Tonsillectomy
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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
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White pulp:
little islands, mostly B cells
Red pulp:
Venous sinuses
Splenic cords – RBCs, macrophages, lymphocytes, plasma cells and granulocytes
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Functions of Spleen
• Blood formation –– All blood cells in fetus– Only lymphocytes and monocytes after birth
• Blood filtration– Removes bacteria, particles, worn out RBCs
and platelets (recycles iron)
• Blood storage – Can contain over one pint of blood
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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.
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Immunity
Immunity involves activation of specific lymphocytes to combat a specific foreign agent.
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Nonspecific Resistance
Species (Inborn) Resistance – certain species contract certain diseases, while other species do not.
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Mechanical Barriers
• Skin and mucous membranes :– First line of defense– Physical barrier– Shedding of dead cells– Mucus– Hairs– Cilia– Coughing and sneezing, production of tears, saliva,
urine, defecation and vomiting physically remove harmful substances
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Chemical ProtectionSebaceous 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
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Normal Microbiota – bacteria living on skin inhibit the growth of pathogens by producing antibiotics
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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 Complement 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
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Fever :
Causes liver and spleen to sequester iron
Increases phagocytosis
Inhibits growth of microbes
Speeds up body repair
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Inflammation:
Characterized by:
Heat, swelling, redness, and pain
(and sometimes loss of function)
calor, tumor, rubor and dolor
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Stages of inflammation
1. Vasodilation and increased permeability of blood vessels
2. Phagocyte migration1. Neutrophils come first
2. Followed by macrophages
3. Tissue Repair
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Phagocytosis
Three phases:
1. Chemotaxis
2. Adherence
3. Ingestion
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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
• 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:– Large– Complex– Recognized as foreign
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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.
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Two 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
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“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.
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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.
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Humoral or Antibody mediated 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.
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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.
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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)
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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.
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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.
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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
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Tc Cells are effective against bacteria which are intracellular parasites, viruses, fungi, cancer cells associated with viral infections, and transplanted cells.
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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
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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.See increase in rare diseases:
TB, Kaposi sarcoma, etc.
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Hypersensitivity
“The immune system gone bad.”
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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
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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.
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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)
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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