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What are the main functions of the lymphatic system. Why must it drain off interstitial fluid?
Is there more filtration or reabsorption in bulkflow?
- 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.
Do lymphatic vessels connect like capillaries do to venules?
What is a "blind ended" vessel?
Does pressure have anything to do with lymph flow?
What is "lymph"? What is "chyle"? What is "lacteal"?
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)
How do endothelial trap doors on a lymp vessle work?
What is the anchoring filament anchored to?
Is lymph flow one way? Which way? What is the purpose of the trap door? Why do some lymphatic vessles have valves?
- 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
Are lymphatic vessels found in all structures?
The lymphatic system is widespread but is not found in avascular tissue (cartilage, epidermis), The CNS, portions of the spleen, and red bone marrow.
Name the 2 lymphatic ducts and draw the areas of the body that drain into them.
- 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
Name the 5 lymphatic trunks
- 1. Lumbar
- 2. Intestinal
- 3. Mediastinal
- 4. Subclavian
- 5. Jugular
Whats another name for the thoracic duct?
What is the cicterna chyli?
Where does the thoracic duct empty into? The R lymphatic duct?
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.
Where is lymph made?
Does it contain anything? protein?
Lymph is the same as interstitial fluid - excess interstitial fluid causes pressure that pushes it into the lymphatic system.
Lymph does absorb proteins
What 2 pumps aid int he 1 way flow of lymph?
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.
How many different types of lymphocytes are there?
- 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
What is APC?
A dendritic cell?
- 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
Name the primary and secondary lymphatic organs.
Where is the thymus located and what does it do?
What is clonal deletion?
- 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
Is lymph flow through a lymph node one way? What is the purpose of the lymph node?
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
What does the word parenchyma mean?
Stroma? What is a capsule? hilus? trabeculae?
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
What are the 2 types of pulp in the spleen?
Name the 3 impressions
What 2 vessles enter at the hilus?
- 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
What tissue type is lymphoid tissue?
What is MALT?
Where are Peyer's patches found?
Discuss Tonsils and Tonsillectomy.
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.
What's the difference between nonspecific and specific immunity?
1st line defenses
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
What is the lacrimal apparatus?
How does saliva provide defense?
What is the pH of the stomach?
What is bacterial colonization?
What gland in the skin makes sebum?
- 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)
Table of 1st, 2nd, 3rd line of defense
What is interferon?
What cells secrete interferon?
- 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
Discuss complement, transferrin and natural killers role in the 2nd line of defense.
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
Beside APC - what are the 2 major phagocytes?
What does a monocyte turm into? What vessel can a WBC squeeze through? List where fixed macrophages can be found.
- 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
Name the 5 steps on phagocytosis
What is chemotaxis? Are complement factors and certain cytokines chemotactic?
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
What are the signs & symptoms of inflamation? Purpose?
Name the 3 stages of inflammation.
Name substances that increase capillary permeability in inflammation.
- 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
What is fever? Where in the CNS is your body temp set? What's a pyrogen? What is the purpose of fever? How does aspirin lower your fever?
- 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.
Name the 2 major categories of immune reactions
- 1. Cell mediated response (T cells)
- 2. Antibody mediated or humoral response - (B cells & plasma cells)
Why are T cells called T cells? B cells?
- T cells = thymus derived
- B cells = bursa derived (bursa of checken, not human)
Where are T & B cells produced? From what cell? Where does each mature?
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
What is a clone of cells?
A population of identical cells
Specific Immunity has 2 characteristics that non-specific immunity lacks:
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
The cell mediated and antibody mediated immune reactions often times coordinated and act at the same time? How?
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.
- Specific Ag/ T cell→ cytokines → direct T cell attack
- Ab mediated:
- Specific Ab/ B cells → plasma cells → Abs attack
Where is an epitope found? A hapten? What binds to them? What organic molecule are most Ags?
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
Where is an Ag receptor found?
Do you have many different ones?
- 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
What is HLA or MHC antigen?
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
Are dendritic cells APCs? Where to APCs present Ags?
Dendritic cells can function as APCs. They present the Ag to the T cells in the lymphatic tissue.
Describe endogenous & exogenous Ag processing
- 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
What are cytokines? What type of molecule? Function? Which cells make them?
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
Describe cell mediated immunity from Ag presentation to formation of cytotoxic and helper T cells and their respective memory cells
- 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
What is the purpose of memory cells?
- 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
How do cytotoxic T cells kill?
- 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)
What is immune surveillance?
Cytotoxic T cells (CD8 cells) are always scanning for transformed cells (tumor, cancer) to destroy them
Name all the subjects in Ab mediated immune response.
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
What similarity is there between the Ab receptor in the B cell and the Ab produced by the plasma cell from that B cell?
They are identical
What cell makes Ab?
Where is complement made?
- 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
Describe the primary and seconday antibody mediated responses.
This is the principle for immunization.
- 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
What is self recognition? Self Tolerance? What Ags are involved? Which clones have been deleted? Why?
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
Does immune function decline with age? With stress? Why is both cases?
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.