Lymphatic System and Immunity

Part 1. Lymphatic System

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I. The lymph system Figure 1.

1.                       Consists of a group of vessels that carry tissue fluid, called lymphatic capillaries, which help in returning tissue fluid to bloodstream.

2.                       Primary function is the production of lymphocytes.

3.                       Additional and vital functions are circulation of nutrients, transport of hormones, maintenance of blood volume, elimination of wastes from tissues, transportation of lipids from digestive tract, defense against infection

4.                       Collecting vessels - lymphatics.

5.                       Two large lymph ducts connect with the venous circulation at jugular and subclavian veins.

6.                       Inter spaced are clusters of cells called lymph nodes. Act as filters and producers of lymphocytes.

7.                       Lymph is tissue fluid and resembles plasma.

II. Lymphatic capillaries Figure 2.

1.                       Capillaries are microscopic tubes with walls of thin, flat endothelial cells. Are more permeable that blood capillaries and have larger diameters. Large particles, such as free plasma proteins and other substances can pass into vessels.

2.                       Form branching network throughout body. Capillaries in villi of small intestine are called lacteals. Absorb fats from intestine and distribute into circulatory system. 

III. Lymphatic vessels (sometimes called veins).

1.                       Capillaries connect and drain into series of lymphatic veins.

2.                       Similar to blood veins: 3 tissue layers - 1. Internal coat of thin endothelial cells; 2. Middle coat of smooth muscle with elastic fibers; 3. External coat of connective tissue and smooth muscles.

3.                       Contain many one-way valves. 

IV. Lymph nodes Figure 3. Figure 4.

1.                       Produce antibodies, monitor contents of lymph, remove debris and pathogens from lymph, act as a "way" station for cancer cells, produce lymphocytes, and contain macrophages and plasma cells.

2.                       Situated on route of lymphatics.

3.                       Enclosed in capsule of fibrous connective tissue.

4.                       1 to 25 mm in length. Bean shaped. Slight depression on concave side called hilum. Efferent lymphatics leave node. Afferent lymphatics enter node along convex side and are more numerous.

5.                       Within node are compartments divided by framework of partitions called trabeculae.

6.                       Within nodes are supporting network of reticular fibers.

7.                       Spaces or channels inside node are called sinuses.

8.                       The outer portion if the node is called the cortex. In the cortex is the lymphatic nodule.  Lymphocytes are produced inside the germinal center, which is inside the lymphatic nodule.

9.                       The inner region is called the medulla. Within the medulla the lymphocytes are arranged in strands called medullary cords, which also contain macrophages and plasma cells.

10.              Lymph enters the afferent lymphatics, passes through the cortical sinuses, then through the medullary sinuses, and finally out through the efferent lymphatic vessels.

11.              One way valves prevent back flow.

12.              Lymph nodes are found throughout the body. They are more prevalent in cervical region, neck, armpit, inguinal (groin), iliac, lumbar, thoracic region, and mesentery of small intestine.


V. Lymphatic ducts - 2 large terminal ducts.

1.                       Right lymphatic duct enters into right subclavian vein. Drains lymph from right side of head, neck, upper extremities, right side of thorax, heart, right lung, and upper surface of liver.

2.                       Left lymphatic duct receives lymph from extensive area of body. Lower extremities, intestines, pelvic region, kidneys. Cisterna chyli collects lymph from lumbar region. Left lymphatic duct empties left subclavian vein.


VI. Organs of Lymph System
1. Tonsils

a. Masses of lymphoid tissue in mucous membrane.
b. Palatine tonsils are 2 masses on each side of palatine arches in back of mouth.
c. Pharyngeal tonsils (adenoids) are located on posterior wall of nasopharynx.
c. Surface of tonsils has pits called crypts.
d. Produce lymphocytes and antibodies. Strategically located.

2. Thymus.

a. Thymus gland is located in mediastinum behind sternum. Reaches maximum size at age 25, then decreases. It is replaced by fat and connective tissue as get older.
b. Helps produce T cells that destroy invading microbes directly or indirectly.

3. Spleen

a. Largest organ of lymphatic tissue.
b. In adult about 12 cm x 7 cm x 4 cm.
c. Lies below diaphragm and left of stomach.
d. Hilum - blood vessels, lymphatic vessels, and nerves enter.
e. Surface is covered with capsule - outer serous and internal fibroelastic coat.
d. Internal framework contains white pulp and red pulp.
g. White pulp is lymphatic tissue or nodules. Source of lymphocyte production.
h. Red pulp  consists of venous sinuses filled with blood.
i. Produces B-lymphocytes which produce anti-body producing plasma cells.
j. Spleen also phagocytizes bacteria and worn-out and damaged red blood cells and platelets.
k. Spleen stores blood in case of demand.

Part 2. Immunity and Resistance

I. Nonspecific Resistance
1. Body maintains homeostasis by counteracting action of disease-producing organisms called pathogens.
2. Ability to ward of disease is called resistance.
3. Vulnerability or lack of resistance is susceptibility.
4. 2 broad categories of defense: nonspecific and specific or immunity (involves antibodies).
5. Nonspecific resistance is inherited and provides general response.  


II. Skin and mucous membranes (physical barriers/mechanical factors)

1. Mechanical factors.
a. Intact skin has 2 portions: epidermis (outer epithelial tissue) and dermis (inner connective tissue).

Epidermis has layers (stratified squamous) and is keratinized (waxy), which provides barrier. Shedding of skin helps removes microbes. Bacteria rarely penetrates skin except for breaks, burns, cuts, etc. Infection is usually staphylococci which normally inhabits hair follicles and sweat glands (sudoriferous). Moist skin is vulnerable to fungus (athlete's foot).

b. Mucous membranes have epithelial layer and underlying connective tissue.

Mucous membranes line body cavities: gastrointestinal, respiratory, urinary, reproductive. Epithelial layer secretes mucous (goblet cells), which prevents drying and traps many microbes and foreign substances (viscous). Hairs in nose trap and filter air: dust and pollutants. Cilia (microscopic projections of epithelial cells) line upper respiratory tract and move mucous towards the throat (ciliary escalator) 1 to 3 cm per hour. Swallowing of mucous sends microbes into stomach, which is a pH of 2 – acidic. Coughing and sneezing speed escalator. Epiglottis covers and protects voice box. Some microbes live on moist mucous membranes and can penetrate membrane. Use toxic products or prior conditions of tissue. Mucous membranes are less effective than skin. Lacrimal apparatus (tears) wash and drain eyes (have antiobiotic substance). Saliva washes microbes from surfaces of teeth and mucous membranes of mouth. Flow of urine washes out urinary system.

2. Chemical factors – an overview

Sebaceous (oil) glands secrete sebum, which forms a protective film. Unsaturated fatty acids in sebum inhibit growth of bacteria and fungi. Fatty acids also produce a low pH ( 3- 5), which inhibits microbes. However, some bacteria actually metabolize sebum and cause inflammation associated with acne. Perspiration eliminates waste and flush microbes from skin. Lysozyme in perspiration breaks down cell walls of bacteria. Also found in tears, saliva, nasal secretions. Hyaluronic acid in loose connective tissue prevents spread of infections. Gastric juice in stomach has HCl, enzymes and mucous. pH of 1.2 to 3 destroys most microbes. Interferons are chemical messengers that coordinate and protect cells against viral infections. Damaged cells release them to surrounding cells to prevent viral replication in neighboring cells.
Complement is a system of circulating proteins (20) that assist in destruction of pathogens.

III. Antimicrobial Substances.
1. Complement is a group of 20 proteins in blood serum. (It "complements" immune reactions of antibodies).

a. Some complement causes cytolysis - forms holes in bacteria, causing contents to leak out.
b. Some enhances inflammation buy releasing histamine from mast cells, basophils, and platelets. Also attracts phagocytes (leukocytes) through chemotaxis.
c. Some complement bind to surface of microbe and interact with phagocytes. Called opsonization or immune adherence.

2.Interferon is a protein produced by infected cells, as well as lymphocytes, fibroblasts, and leukocytes.

a. It diffuses to uninfected neighboring cells and binds to surface receptors. Uninfected cells synthesis antiviral proteins which inhibits viral replication.
b. Body's first line of defense against viruses. It is being used as an anti-cancer agent.
c. There are 3 kinds of interferon - alpha, beta, and gamma. Alpha (a)interferon is used in a nose spray to prevent spread of colds.

3. Properdin is complex of 3 proteins which, with complement, fights against bacteria, enhances inflammation, and phagocytosis.


IV. Phagocytosis: ingestion and destruction of microbes.

See Unit 10 Leukocytes Figure: WBC


1. After penetration of skin, microbes are attacked and ingested by phagocytes.
2. 2 broad categories of WBC (Leukocytes) that show phagocytosis: microphages and macrophages. Granulocytes are microphages; Macrophages are Agranulocytes. Lymphocytes are also agranulocytes - see specific resistance. There are Also NK Cells.
3. Granulocytes: (a review of other functions)  Develop from red bone marrow.

High count in acute bacterial infections.

High count indicates allergic reaction or parasitic infection.

 

High count indicates allergy.

4. Agranulocytes: Develop from lymphoid tissue (lymph glands, nodes) and red bone marrow (myeloid tissue). No cytoplasmic granules.

High count indicates a chronic infection.

5. NK (Natural Killer cells) - Sometimes called large granular    lymphocytes.

Important in cancer prevention and spread of viruses.

5. Chemotaxis: Chemical attraction of phagocytes to microorganisms.  


V. Inflammation
1. Injury and illness is a form of stress which sets off inflammatory response.
2. Symptoms: redness, pain, heat, swelling, loss of function.
3. Neutralizes and destroys toxic agents and prevents spread.
4. Stages:

1. Vasodilatation and increased permeability of blood vessels. Substances normally in blood allowed into tissues: white blood cells, clot forming materials, chemicals.

a. Histamine: produced by mast cells, platelets, basophils. Causes redness and vasodilatation.
b. Nuetrophils produce chemicals releasing histamines.
c. kinins: chemical causes vasodilatation and permeability. Attracts neutrophils.
d. Prostaglandins: produced by injured tissue from fatty acids. Vasodilation and permeability. Works to intensify kinins and histamine.
e. Heat and redness from increased blood and metabolic reactions.
f. Pain caused by toxic chemicals, damage to nerves, pressure, prostaglandins or kinins. Prostaglandins increases and prolongs pain.

2. Phagocyte migration
3. Release of nutrients to support defensive cells.
4. Fibrin formation from fibrinogen. Blood Clotting.
5. Pus formation: thick fluid containing living and dead white blood cells and debris. 

VI. Fever
1. Fever is an abnormally high body temperature caused usually by bacterial and viral infections. The high body temperature inhibits microbial growth and speeds body reactions that aide repair.  


VII. Immunity (Specifiec resistance)
Note: Cellular immunity and Humoral immunity are the 2 components of specific resistance. They are both the products of lymphoid tissue.
A. General components of immune system.

1. Specific resistance to disease is called immunity.
2. Immunology is the branch of science dealing with response to angigens.
3. Antigen or imunogen is any chemical substance that , when introduced into the body, causes the body to produce specific antibodies and/or specific cells called T cells.
4. Most antigens are proteins or combination of proteins and nucleic acids, lipids, carbohydrates or large polysaccharides.
5. Antibodies or imunoglobulins are proteins produced b the body in response to the presence of an antigen and is capable of combining specifically with the antigen.
6. They are Y shaped when activated. (T shaped before). Behave like a switch. Have hinge area.

Antibody

7. Lymphocytes are agranualr leukocytes which detect presence of antigens.  They are produced in the bone marrow from lymphoblasts. About half migrate to thymus gland where they are developed into cells which can recognize specific antigens and react. Named T cells (thymus). They migrate to lymphoid tissue.
8. The other half bypass the thymus and develop in unknown areas of the body. They become B cells. (named after the "bursa of Fabricus" in birds where they are processed).
9. Macrophages also act in specific immune response. Phagocytosis and chemicals.
10. Spleen: breaks down old erythrocytes  and invaders.
11. Lymph nodes: sites of leukocyte action.
 

B. Cellular Immunity or Cell mediated Immunity.

1. Effective against fungi, parasites, intracellular viral infections, cancer cells, and tissue transplants.
2. T-cells are responsible for cellular immunity, while B-cells are responsible for humoral immunity.
3. Both T and B cells are derived from stem cells in bone marrow.
4. About 1/2 migrate to and develop in thymus gland where they are processed.- T cells.They differentiate into the different T-cells and migrate and become inbedded in body's lymphoid tissue.
5. Other 1/2 are processed in unkown area of body. They become B-cells and also migrate to lymphoid tissue, but occupy different regions.
6. Response of T and B cells depends on ability to recognize antigens. Macrophages help present antigens to both cells after macrophage has phagocytised them.
7. During presentation of antigens, macrophages secrete interleukin 1, a protein which induces proliferation of T and B cells.
8. There are 1000's of T-cells, each recognizes type of antigen. Usually innactive
9. When a specific T-cell is activated (sensitizes) it can respond to specific antigen.
10. Sensitized cell increases in size, devides and produces a clone - population of of identical cells.

Killer T-cells (cytoxic T cells): leave lymphoid tissue and migrate to site of infection. Secrete lymphotoxins which directly destroy antigens, and lyse invading cells. Also produce lymphokines - powerfl proteins which attract and intensify killer T cells and macrophages. Helper T-cells: cooperate with B-cells to amplify antibody production. Actually first interact with antigens before descendants of B-cells produce antibodies. Also produce interleukin 2. Lymphokine stimulates killer T-cells. IL-2 is stimulated by IL-1, released from macrophages. Suppressor T-cells: Serve to slow and stop immune response after several weeks. Inhibity killer T-cells and antibody production by plasma cells. Delayed hypersensitivity T-cells: Produce lymphokines that stimulate macrophages and cause hypersensitivity (allergy) . Amplifier T-cells: Stimulate helpler T-cells, suppressor T-cells, and B cells. Memory T-cells: Remain in lymphoid tissue to recognize invading antigens.

C. Antigen-antibody response  (humoral immunity)

Illustration

1. B cells have antibodies on surface of cell membrane.  Different B cells have different antibodies. They are proteins with amino acids is specific order and configuration to match antigen
2. Each antibody matches specific antigen.
3. When an antigen is recognized, a specific B cell becomes activated and enlarges.
4. It divides to form a cluster of cells called plasma cells. These are identical and called clones. These produce antibodies identical to B-cell. Also forms memory cells for aggressive response in future - immunity.
5. B cells stay in lymph tissue and each cell can produce 2,000 antibodies per cell per second until it dies (4 - 5 days).
6. Thousands of antibodies are produced.
7. Free antibodies are released into blood stream and bind with antigens. This forms antigen-antibody complex.
8. Binding results in agglutination.
9. Once agglutinated, bacteria are destroyed in several ways.

a. Macrophages engulf bacteria by phagocytosis. This often occurs in lymph nodes which become swollen and tender.
b. K (killer) lymphocytes (T-cells) bind to bacteria and kill them. Use lymphotoxins. Leave lymphoid tissue to attract at site of infection.
c. complement system through series of reactions bores into cell wall and destroys bacteria (lysis).

10. Helper T cells have membrane receptors similar to antibodies on B cells.
11. Release chemicals which stimulate B cells to divide.
12. Chemicals also activate macrophages.
13. Suppressor T cells counteract effect of helper T cells. Chemicals that inhibit B cells are macrophages are released.
14. Number of suppressor cells increases as infection comes under control.
15. Helper T cells stimulate cytotoxic T cells by releasing interleukin-2. These attack antigens on the host's cells. These include cancer cells; cells infected with viruses, and transplanted cells. Death results from lysis. Interleukin 2 also stimulates cytotoxc T cells.
16. Perforin released and perforates cells.
17. Interleukin 1: Produced by antigen-stimulated macrophages and stimulates T cells and B cell growth. Stimulates secretion of interleukin-2 by helper T-cells
18. Interleukin-2: Produced by helper T cells to stimulate proliferation of cytotoxic T cells and natural killer cells.
16. Memory T cells remain after infection.  These cells have membranes with antibodies.

VIII. Active Immunity: Vaccines

1. Vacca is the Latin word for cow. 1st vaccine was produced by using cowpox to infect people in order to develop antibodies against smallpox.
2. Inactive form of antigen is presented to body. T and B lymphocyte memory cells remain to actively produce clones and antibodies in the event of exposure to actual disease.

IX. Passive Immunity: Antiserum.

1. Person is given antibodies for disease. Usually from animal like cow or mice. Body is passive. Antibodies are given to person.

X. Aids and retrovirus - Acquired immune deficiency syndrome. The virus is called HIV - human immunodeficiency virus.

1. Many viruses are DNA viruses. They inject their DNA into a host cell. They take over the cell's DNA and nucleic acids replicating the viral DNA. Upon lysis, the replicated virus is released to infect other cells.
2. Retroviruses inject RNA into host cell. They make a DNA copy of the RNA strand. This DNA copy is attached to the RNA and later a complimentary strand of DNA. Process is called reverse transcription because DNA is formed from RNA, hence retrovirus. Some retroviruses reproduce inside cell. Others form proviruses. They become attached to DNA of host cell and remain dormant for years. Later they transcribe viral RNA and protein. Aids retroviruses also kill host cells.
3. Aids attacks and destroys helper T cells, which help trigger production of antibodies by B cells. Activities of macrophages, cytoxic T cells, and suppressor T cells are affected. Antibodies are not produced fast enough and immune system becomes overwhelmed.
4. Ideally a vaccine could be produced; however, HIV structure varies greatly. Many strains of HIV, each with different RNA and proteins. Virus also mutates frequently.
5. AZT blocks reverse transcription.

White Blood Cells and Their Functions:

Phagocytes:

Neutrophil: Participates in early stages of defense against microorganisms.
Monocyte: Arrives at site after neturophils, transforms into macrophages; Engulfs foreign materials, presents antigens to lymphocytes
Eosinophil: Responds to allergies and parasitic infections. Counteracts effect of histamine. Phagocytizes antigen-antibody complex. Destroys parasitic worms.
Basophils: Liberate heparin, histamine, and serotonin in allergic reactions that intensify the overall inflammatory response.

Lymphocytes (3 types)

1. T- Cells (Cellular Immunity)

2. B-cell: (Humoral immunity) when activated produces plasma, memory cells, and antibodies

Natural Killer cell: (Immune Surveillance) - Directly destroys virus infected cells and cancerous cells. Detects and destroys abnormal tissue cells.

Differential Count

An increase in the number or wbc indicates a state of inflammation or infection. A differential count is the number of each kind of WBC in 100 wbc.

Normal Differential count:

Neutrophils

60-70%

Eosinophils

3-4%

Basophils

.5-1%

Lymphocytes

20-25%

Monocytes

3-8%

Total

100%

1. High neutrophil count may indicate bacterial infection.
2. High monocyte count indicates a chronic infection.
3. High eosinophyl and basophils indicates allergic reaction.
4. High lymphocyte count indicates antigen-antibody reactions.