Anatomy Ch 22

• 1. Absorb excess interstitial fluid and moving it back to venous circulation.
• 2. transport dietary lipids
• 3. Participate in immune response with T cells (cell mediated immunity) and B cells (antibody mediated immunity)

The lymphatic system must drain off extra interstitial fluid because there is more filtration than reabsorption in bulk flow (by about 3 L) and it has to be rerouted back to the venous circulation. Occurs due to interstitial pressure.

Lymphatic capillaries are blind ended - start form nothing, they dont connect to anything - but continue to unite and form larger lymphatic vessels (like capillaries join to venules)

Lymph flow is a one way flow from high pressure to low pressure

Lymph is interstitial fluid that enters lymphatic capillaries (via interstital fluid pressure)

Lacteals - lymph vessles in the small intestine that carry CHYLE - white milky liquid what contains dietary lipids (being carried to the blood)

• Lymphatic vessles have trap doors (endothelial cells that overlap slightly) that allow one way flow INTO the lymphatic vessel (fluid cannot move back out)
• Anchoring filaments contain elastic fibers and attach the lymphatic endotheial cells to surrounding tissue. When extra interstital fluid accumulates and causes tissue swelling the anchoring filaments are pulled and the trap doors open more to allow more fluid to flow into lymphatic capillaries

The lymphatic system is widespread but is not found in avascular tissue (cartilage, epidermis), The CNS, portions of the spleen, and red bone marrow.

• 1. Right lymphatic duct - covers upper right quadrant of body - drains R side above ribs
• - empties into right subclavian vein → RA

• 2. Thoracic duct - (left lymphatic duct) - 3/4 of body - drains eveything below ribs + left side above ribs
• - strats at cisternal chyli (lymphatic reservoir)
• - empties into left subclavian vein → RA

• 1. Lumbar
• 2. Intestinal
• 3. Mediastinal
• 4. Subclavian
• 5. Jugular

The thoracic duct is called the L lymphatic duct becuase it receved lymph from the left side of the body as well as the bottom.

The cicterna chyli is the beginning of the thoracic duct - it is a dilation that serves as a lymph reservoir.

The thoracic duct empties into the left subclavian vein which empteis into the RA

The R lymphatic duct empties into the right subclavian vein which empties into the RA.

Lymph is the same as interstitial fluid - excess interstitial fluid causes pressure that pushes it into the lymphatic system.

Lymph does absorb proteins

1. Skeletal muscle pump - compression "milking action"

• 2. Respiratory pump - Inhale - lymph flows from absominal (higher pressure) to thoracic (lower pressure)
• Exhale - valves prevent backflow of lymph

Lymph always flow from high pressure to low pressure.

• 1. T Cells - cell mediated immunity
• -a. Cytotoxic T cells - CD8 (co-receptor)
• -b. Helper T cells - CD4 (co-receptor)
• -c. Memory T cells - CD4 & CD8 (co-receptors)
• -d. Regulatory T cells - turn off specific immune response

2. B cells - humoral immunity - antibody (Ab) mediated immunity

3. NK cells - natural killer cells - non-specific lymphocytes

• APC - Antigen Presenting Cell
• 1. They eat (phagocytosis) invaders
• 2. Attach a peptide fragment to their plasma membrane via MHC (major histocompatibility complex)
• 3. Travel to lymphatic tissue to present the antigen to T cells

A dendritic cell is a type of APC -it is nonspecific

• Primary:
• 1. Red bone marrow - B cell maturation from lymphoid stem cells
• 2. Thymus - T cell maturation from lymphoid stem cells - makes thymosin which is involed in T cell maturaion

• Secondary: (most immune responses)
• 1. Lymph nodes
• 2. Nodules (no capsule - not an organ)
• 3. Spleen

The thymus is in the mediastinum between the sternum and aorta. It is large in a child and smaller in adults.

Clonal delection occurs in-utero and any T cells that could attack the own body are deleted

Lymph nodes - have a capsule - about 600 in body - < 1 inch long

The nodes clense & filter lymph - using loose reticular CT - one way flow through nodes

• Lymph enters via afferent vessels
• Lymph leaves via efferent vessles

Parenchyma is the functioning part of a lymph node - it is devided into a superficial cortex and a deep medulla

Stroma is the supporting CT of a lymph node - it consists of the capsule, trabeculae, and reticular fibers.

Capsule - dense CT - covers the lymph node

hilus - slight depression in the node where efferent lymphatic vessels emerge

Trabeculae - extensions of the capsule that divide the node into compartments, provide support, and route blood

• 1. Red pulp = platelet storage (platelet count drops when spleen is removed)
• - resident macrophages - destroy pathogens and eat worn out RBC & platelets
• * red pulp consists of blood-filled venous sinuses and cords of splenic tissue

• 2. White pulp = resident T and B lymphocytes carry out immune response
• *white pulp is arranged around the branches of the splenic artery

• Splenic impressions:
• 1. gastric impression - stomach
• 2. renal impression - left kidney
• 3. colic impression - colic fixture of large intestine

The splenic artery, splenic vein, and efferent vessels pass through the hilus

Lymphoid tissue is loose reticular CT (for filtration)

Mucosa-Associated-Lymphatic-Tissue - named such becuase they occur in the CT of mucus membranes that line the respiratory and digestive tracts.

Peyer's patches (lymphatic nodules) are found in the ileum of the small intestine.

• Tonsils - 5 total - 2 lingual (base of tongue), 2 palatine, and 1 pharangeal (adenoids)
• Tonsils participate in immune responses against inhaled or ingested foreign substances.
• In a tonsillectomy (T & A) the palatine tonsils and sometines the lingual tonsils are removed.

Tonsillectomy can be dangerous because the pateint may bleed and not know about it.

Nonspecific immunity = innate resistance that is present at birth

Specific immunity = immunity to specific pathogen- it is acquired over a lifetime

• 1st line of defence:
• 1. Skin - thick, tight (cell junctions)
• - keratin - tough
• - water repellent - sebum
• - acidic sebum - bacteria dont like acid

• 2. Mucous membranes - trap pathogens
• - often ciliated - trap & filter and propel mucus one way

• Lacrimal apparatus:
• Secretes tears into ducts
• - dillutes pathogens
• - tears contain lysozyme - antibacterial digestive enzyme -breaks down bacteria cell wall
• - contain IgA

Saliva - dillutes pathogens - contains lysozyme and amylase

Stomach - Gastric Juices contain HCL and have a pH of 2 (bacteria dont like acid)

Baterial colonization refers to growth - some flow of fluids stop colonization because bacteria can adhere - if blockage occurs it alows bacterial sepsis (contaimination)

Sebum is made by sebatious glands and is acidic (bacteria dont like acid)

• Interferon - antiviral protein - secreted by lymphocytes, macrophages, and virus-infected cells
• *interferon goes to neighboring cells and releases anti-viral proteins that prevent viral replication

Complement - groups of plasma proteins that supplement (enhance) certain immune responses (when triggered)

Transferrins - are iron transport proteins - if transferrins bind all the iron there is less available for bacterial growth

• Natural Killer Cells - non-specific - kills anything that is not self
• NK cells are WBCs that arise from lymphoid stem cells
• - Monitor for abnormal cells
• - invades bacterial or fungal cells
• - promotes lysis of virus-infected or cancerous cells - secrete graules containing perforin (bores a hole in cell membrane) and granzymes (digestive enzymes) that kill infected cell

• 1. Neutrophils (PMNs)
• 2. Macrophages

A monocyte matures into a macrophage in tissue (not in blood stream)

WBCs are able to squeeze thorugh sinusoid capillaries.

• Fixed Macrophages:
• 1. Kupffer cells in liver
• 2. histiocytes in CT
• 3. microglia in CNS
• 4. tissue macrophages in spleen

1. Chemotaxis - chemicals released from damaged cells, WBC, complement, microbe that attract phagocytes to the area of infection/ inflmation

2. Adherence - of microbe to phagocyte

3. Ingestion - of microbe

4. Digestion - by lysosomal enzyme - microbe death

5. Release of residual body (materials that cannot be degraded further) - in a vesicle

• 1. redness - erythema
• 2. increased blood flow - hyperemia
• 3. Pain - kinins, pgs
• 4. Warmth - increased blood flow
• 5. swelling - edema (increased interstitial fluid)

• The purpose of inflammation:
• 1. Prevents spread - triggering agent to nearby tissue
• 2. Removes dead pathogens/ debris - pus is dead PMNs, macrophages, bacteria
• 3. Starts repair

• 3 stages of inflammation:
• 1. vasodilatiuon - arterioles
• 2. increased capillary permeability - caused by PGs, leukotrienes, kinkins, histamine - released by WBCs and platelets
• 3. Entry of WBC - emigration
• -PMNs & macrophages

• Fever is an elevated body temperature (> 37.2 C)
• The normal body temperature is set by the hypothalamus

Pyrogens are substances (such as PGs, bacterial toxins, cytokines) that go to the hypothalamus and reset the internal thermostat

• The purpose of fever is to speed up the metabolic rate of cells - faster repair process
• fever also slows bacterial growth and enhances interferons (antiviral) effectiveness

Aspirin counteracts the effects of PG and leukotrienes.

• 1. Cell mediated response (T cells)
• 2. Antibody mediated or humoral response - (B cells & plasma cells)

• T cells = thymus derived
• B cells = bursa derived (bursa of checken, not human)

T & B cells arise from pluripotent cells that are produced in the red bone marrow.

• B cells mature in the red bone marrow
• T cells mature in the thymus

A population of identical cells

Specificity - B and T cells can distinguish between self and nonself Ags

Memory - on the 2nd encounter with the same Ag the immune response will be faster and stronger

Cell mediated and Ab mediated immunity are closely allied and work together to act at the same time. They are both triggered by Ags that are foreign to the host.

• Cell-Mediated:
• Specific Ag/ T cell→ cytokines → direct T cell attack

• Ab mediated:
• Specific Ab/ B cells → plasma cells → Abs attack

Epitope = the part of an Ag that binds to the Ab and starts the immune response

Hapten = an Ag that needs to be combined with a carrier protein to cause an immune response

Both an epitope and a hapten are sites on the Ag where the Ab binds

Most Ags are proteins

• Ag receptors are found on T or B cells - they are proteins on cell membrane that recognizes a specific Ag
• each clone has a unique Ab receptor

MHC = Major Histocompatibility Complex Ag - also called HLA = human leukocyte Ags

These are the self Ags on all cells (excent RBCs) that prevent immune responses against your own cells - each person MHCs are unique - Help T cells recognize that an Ab is foreign

After organ transplants the patient must take medication that inhibits immune response becuase the Ag on the new organ are foreign - the body will try to attack it. This is also a factor in autoimmune diseases where lymphocytes attack the bodys cells. However, it is not an issue in blood transfusion becuase the RBC do not carry MHC Ags - they only carry blood type Ags

MCH Ags are involved in endogenous and exogenous Ag processing becuase in both cases they are used to fix the foreign Ab to the cell membrane

Dendritic cells can function as APCs. They present the Ag to the T cells in the lymphatic tissue.

• Endogenous Ab processing - for foreign antibodies that are INSIDE a cell
• 1. HLA 1 bind to Ag inside cell
• 2. HLA 1/ Ag complex inserted into cell membrane
• 3. Abnormal cell carried to lymphatic tissue and destroyed

• Exogenous Ag processing - foreign cells
• 1. APC eats foreign cell
• 2. Digests Ag into fragments
• 3. Uses HLA II to bind fragments to cell membrane
• 4. APC travels to lymphatic tissue and presents Ag to T cells

Cytokines are immune mediators - they coordinate the immune response. They are a protein that are made and released by cytotoxic T cells. Some examples are interlukins, interferon, granzymes, and perforin

• CD4 T cells: -Exogenous Processing (MCH II/ Ag)
• 1. APC presents Ag to CD4 lymphocyte - Ag binds at TCR (T cell receptor) and CD4 is the coreceptor
• 2. Costimulant (such as IL-2) causes cell to become activated
• 3. CD4 T cells make active helper T cells - they secrete cytokins (IL-2) and memory T cells - not active until next contact with Ag

• CD8 T cell - Endogenous processing (MCH I/ Ag)
• 1. APC presents Ag - Binds at TCR and CD8 is the coreceptor
• 2. Costimulator (possibly IL-2 secreted by activated CD4 cells) causes cell to be activated
• 3. Cell makes clones of active cytotoxic T cells - attack invaders and memory cytotoxic T cells - can quickly activate and make active and memory cytotoxic T cells at next meeting of Ab

• Memory cells do not attack invaders - they remain in the system as clones (thousands) after a specific immune response - they speed up immune response is same Ag is encountered again in the future
• - Memory T cells are long lived - decades
• There are both cytotoxic and helper memory T cells

• Cytotoxic T cells leave lymphatic tissue and travel to infection - bind to cells with specific microbial Ags
• kills cell by one of several options:
• 1. can release
• granzymes - protein -digesting enzyme that trigger apoptosis (progranned cell death)

2. can release Perforin and granulysin - perforn makes hole in cell membrane (cell lysis) and granulysin enters cell through hole and kills microbe by creating holes in it cell membrane.

3. can release lymphotixin - activates enzymes in the target cell that cause the cells DNA to fragment (cell dies)

Cytotoxic T cells (CD8 cells) are always scanning for transformed cells (tumor, cancer) to destroy them

Ab mediated immune response occurs in the lymphoid tissue.

• 1. B cell eats Ag and is broken down into peptide fragments (combined with MHC-II) and moved to B cell plasma membrane
• 2. Helper T cell binds to B cell and costimulates - B cell divides into: Plasma cells & Memory B cells
• 1. Specific B cell receptor (BCR) binds with an Ag
• 2. The cell is now actived and undergoes clonal selection - plasma cells that secrete Ab and memory B cells for next encounter
• 3. Plasma cells release thousands of Abs that travel in the lymph to site of infections

They are identical

Plasma cells

• Complement - 30 plasma proteins that complement the immune response
• - made in the liver
• - functions:
• 1. Enhance phagocytosis - opsonization - coats bacteria so adheres to phagocyte
• 2. Cytolsis - destroy cell membrane - osmotic death
• 3. Enhances inflammation - causes mast cells (WBC) to release histamine that increses blood vessel permeability
• 4. Chemotactic - attracts phagocytes

• Primary (takes 2 weeks):
• -Ag exposure causes limited immune response - B cells differentiate into plasma cells and memory B cells

• Secondary (quick response)
• - Ag reexposure causes immediate differentiation into plasma cells and memory B cells - faster - large quantities of Ab

Two properties of T cells:

1. Self recognition - ability to recognize self Ags - MHC Ags

2. Self tolerance - T cells dont react to self Ags - during clonal deletion in-utero (in thymus) the body eliminated T cells that could attack itself

Autoimmune diseases are a result of a loss of self- tolerance- T cells begin to attck body cells - lupus, rheumatoid arthritis

Immune function declines with stress becuase high stress levels cause the adrenal cortex to release cortisol which inhibits immune response.

• Immune function declines with age because the immune system exhibits lowered levels of function - results in increased susceptibility to all pathogens
• -less immune cells made, more autoantibidies, less Abs, and the thymus atrophies with age.