Lymphatic System & Immune Function Concepts

Question 1

Name and describe briefly, the 3 roles of the lymphatic system (keep the transport of lipids in the back of your mind for a couple of weeks, and focus heavily on the other 2 roles!!!)

Answer 1

• Collect and return excess interstitial fluid back to the circulatory system
• Transport dietary lipids from the GI tract to the blood
• Immune response by constant filtration of circulating lymph through organs and tissues

Question 2

Describe lymph as a filtrate of blood and compare it, conceptually to other blood filtrates (urine, aqueous humor, CSF…)

Answer 2

Lymph is a filtrate of blood - everything blood has without the “formed elements” and biggest proteins

Question 3

Review the dynamics of bulk flow from the capillaries and the ratio of fluid leaving the capillaries and fluid returning to the capillaries. Link bulk flow to the interstitial fluid to lymph!

Answer 3

• Overall, filtration is a bit higher than resorption, so more fluid is pushed into the interstitial fluid, on average, than is reabsorbed
• To keep tissues from swelling, excess interstitial fluid is drained via lymph

Question 4

Describe briefly the location, anatomy, and function of lymphatic capillaries, focusing on the “one-way” dynamics that allow excess interstitial fluid to enter (but not exit) lymphatic capillaries

Answer 4

• Lymphatic capillaries “begin” in the interstitial spaces and drain excess interstitial fluid into their lumen
• Lymph capillaries have endothelial cells that act like a door that swings in only one direction
• Endothelial cells lining lymph capillaries overlap

Question 5

Describe the simple relationship between lymph vessels and lymph nodes. Briefly review the 3 mechanisms of venous blood movement that are in play with lymphatic vessels, too.

Answer 5

At intervals along lymphatic vessels are about 600 bean-shaped lymph nodes that are full of leukocytes

3 mechanisms of venous blood movement:
- One-way valves
- Skeletal pump
- Respiratory pump

Question 6

Contrast, location-wise and size-wise, the right & left lymphatic ducts.

Answer 6

Right lymphatic ducts:
- About 1 cm long
- The area drained by the right lymphatic duct is on the right side of the upper body
Left lymphatic ducts (thoracic duct):
- 40 cm long
- The area drained by the left lymphatic duck is the entire left side of the body and the bottom of the right side

Question 7

Name and give the location & function of the 2 primary, and 2 secondary lymph organs, and 1 type of tissue that has an immune function but isn’t necessarily a lymph organ

Answer 7

2 primary:
Redbone marrow= makes mature B cells and “pre-T cells”
thymus= develops T cells and sends them out to populate secondary lymphatic organs

2 secondary:
Spleen= filters blood
Lymph nodes= filters lymph

1 tissue with immune function:
lymph “nodules” = similar to nodes, but not covered by C.T. capsule, so technically not “organ”

Question 8

Contrast the synthesis and maturation of B & T cells.

Answer 8

• Produce immunocompetent B cells and T cells from pluripotent stem cells
• Red bone marrow makes mature B cells and “pre-T cells”
  “pre-T cells” move to the thymus to mature and develop into immunocompetent cells
• Both mature B cells and T cells move to secondary (filtering) organs of the lymphatic system

Question 9

Describe the location, anatomy & function of the thymus.

Answer 9

• Sit within the mediastinum, just posterior to the sternum, superior to the heart, and medial to the lungs
• Immature (pre-t) cells migrate from red bone marrow to the thymus to mature
• Two lobes are separated by a connective tissue capsule that covers the thymus superficially and penetrates deep into the thymus as trabeculae that divide each lobe of the thymus into smaller lobules

Question 10

Discuss how and why the thymus changes ontogenetically – particularly after puberty

Answer 10

• The thymus is hugely active in infants, children, and adolescents, then starts significantly slowing down as you age
• After puberty, functional thymic tissue is slowly replaced by adipose and loose areolar C.T.

Question 11

Give a brief overview of the location, anatomy, and function of lymph nodes. Anatomically, focus on cortex vs. medulla, parenchyma vs. stroma, and the C.T. capsule and trabeculae

Answer 11

• 600 smallish, bean-shaped organs plumbed in line with the lymph vessels. Concentrated heavily in the axillae, groin, and around mammary glands
• An outer C.T. capsule surrounds a superficial cortex and a deeper medulla
• The C.T. capsule extends inward to become trabeculae which subdivide the lymph node into compartments
• The cortex and the medulla are the “parenchyma” of the lymph node
• The C.T. capsule, trabeculae, reticular fibers, and fibroblasts are the “stroma” of the lymph node

Question 12

Connect the outer cortex, inner cortex, and medulla to B and T cells

Answer 12

The outer cortex is full of B cells

The inner cortex is the home of T cells developed by the thymus

The medulla of the lymph node contains tons of more B cells and macrophages

Question 13

Give a brief overview of the location, anatomy, and function of the spleen. Anatomically, focus on the C.T. capsule and trabeculae, as well as the red and white pulp.

Answer 13

• Located lateral to the pancreas and stomach, superior to the kidney
• C.T. Capsule surrounds the spleen superficially and penetrates inward in the form of trabeculae
• White pulp is lymphatic tissue (tons of B & T cells & macrophages) surrounding the central arteries of the spleen
• Within the red pulp, macrophages remove and destroy worn-out or defective RBCs, WBCs, and platelets

Question 14

Connect the sinusoid capillaries of the red pulp to the function of the red pulp.

Answer 14

• Sinusoid capillaries allow for the contents of blood vessels to flood out of capillaries
• Red Pulp removes and destroys worn-out or defective RBCs, WBCs, and platelets, so sinusoid capillaries allow for easy removal

Question 15

Which type of liquid connective tissue is filtered by the spleen?

Answer 15

blood

Question 16

Describe the general anatomical features of lymphatic nodules (MALT). As well as the typical locations of MALT

Answer 16

TONSILS

• Similar to lymph nodes but not covered by a C.T. capsule
• Typically scattered through the C.T. (lamina propria) underlying the epithelial of mucous membranes
• Found in the GI, urinary, reproductive, and respiratory tracts

Question 17

Contrast innate and adaptive immunity based on the specificity of the response.

Answer 17

• Innate immunity is non-specific, it doesn’t care what type of infectious or invading pathogen, etc. that it’s combatting
• Adaptive immunity is specific

Question 18

Explain, briefly, how the 2 major “external” membranes of the body confer external innate immunity, focusing on the role of keratinized stratified squamous epithelia, mucous, cilia, MALT, perspiration, sebum, saliva, lacrimal fluid, vaginal secretions, and gastric secretions. As well as some more “high velocity” defenses – urine flow, defecation, tussis – and some “super high velocity” defenses – diarrhea, sneezing, vomiting

Answer 18

Keratinized stratified squamous epithelium of the epidermis is a huge barrier to infectious pathogens

Mucous traps tons of inhaled, injected, and excretable infectious microorganisms

Cilia sweep trapped pathogens away from critical areas (like the lungs)

MALT filters lymph

Lacrimal fluid flush and contain lysozyme, which is bacteriocidal

Sebum coats and protects skin, and can slow pathogen growth

Saliva contains lysozyme and wash away pathogens

Perspiration flushes microbes off the integument

Vaginal secretions are slightly acidic and slow bacterial growth

Gastric secretions drop PH and destroy a huge range of ingested infectious microorganisms

Question 19

Explain, briefly, how “high velocity” defenses of the body confer external innate immunity – urine flow, defecation, tussis – and some “super high velocity” defenses – diarrhea, sneezing, vomiting – confer external innate immunity

Answer 19

Urinary flow cleanses the urethra

Defecation expels microbes

Tussis (coughing) expels mucous-containing microbes

Diarrhea, sneezing, and vomiting will expel infectious microorganisms from the body at rapid speeds

Question 20

Name and briefly give the function of the 4 types of non-specific anti-microbial chemicals you throw at invaders as part of innate immunity.

Answer 20

interferons= signaling molecules that work in a paracrine manner to alert neighboring cells of viral infection and to give them tools to prevent infection

Lymphocytes, macrophages, and fibroblasts will secrete interferons when virally infected to protect their neighbors

Question 21

Name the non-specific (innate) phagocytotic cells. Describe their “killing” mechanisms with perforin or granzymes.

Answer 21

Natural Killer cells release granules

• The granules either contain perforin, a protein that inserts into the membrane of the target cell, creates perforations in the membrane, and causes cytolysis
• Or the granules contain granzymes that induce target cells to undergo apoptosis. This releases the microbes into the tissue to be phagocytosed

Question 22

Briefly contrast wandering and fixed macrophages.

Answer 22

Wandering macrophages develop from monocytes and enter infected tissue to start eating like maniacs

Fixed macrophages post up in tissues as the first line of phagocytotic defense

Question 23

Review diapedesis, and connect it back to increased capillary permeability.

Answer 23

diapedesis= the squeezing of leukocytes between the intercellular clefts of endothelial lining of blood vessels into interstitial space to travel to sites of injury

Increased permeability of capillaries allows for easier diapedesis of leukocytes (neutrophils and monocytes) and easier access from the blood to the tissue for defensive proteins and antibodies

Question 24

Give the 4 (and sometimes 5) symptoms of inflammation – be prepared to connect all back to some physiological aspect of the inflammation response.

Answer 24

Redness
Pain
Heat
Swelling
Loss of function (sometimes)

Question 25

Describe the 3 parts of inflammation response – what are the key features of each, and what are they trying to accomplish?

Answer 25

Vasodilation and increased permeability of capillaries to increase delivery of blood to infected area to help remove toxins and damaged cells Emigration of phagocytes from the blood into the ISF to the site of infection to allow phagocytosis to occur Tissue repair for deep wound repair

Question 26

Name the inflammatory cytokines

Answer 26

Basophils

Question 27

Describe phagocytosis in detail.

Answer 27

- Microbe moves towards a phagocyte through positive chemotaxis - The phagocyte’s pseudopods wrap around the microbe and put it into a vesicle called a phagosome, ingesting it - The phagosome encounters a lysosome and the contents fuse, and the lysosome kills the microbe

Question 28

Name the 2 “pyrogenic” cytokines that are released by macrophages. Explain where they go, and how they produce fever once they get there. Explain the defensive value of fever.

Answer 28

Prostaglandins (PGs) and Interleukin-1(IL-1) move to the hypothalamic nuclei where they reset body temperature for a short period of time they are abundant in the blood - Increased temperature increases leukocyte function kills a percentage of invading microbes - Increased temperature speeds the anabolic processes needed for tissue repair

Question 29

Contrast innate and adaptive immunity based on “memory”

Answer 29

Adaptive immunity is a series of immune responses targeting a specific antigen and remembers, whereas innate immunity is non-specific.

Question 30

Contrast haptens with complete antigens.

Answer 30

Haptens: - Reactive - Not immunogenetic by themselves. They need to couple with a body protein to become a complete antigen Complete antigens: - Reactive, they can be specially bound by antibodies or immune cells - immunogenetic, they can induce the production of specific antibodies and immune cells

Question 31

Name the 3 primary ways that antigens enter the lymphatic system once they penetrate your innate defenses.

Answer 31

If they enter the blood, they’ll be filtered from the bl;ood by the white pulp of the spleen If they enter a lymphatic vessel, they’ll get filtered in a lymph node If they penetrate mucous membranes, they’ll be filtered by MALT or be eaten by an APC

Question 32

Explain how gene shuffling can account for about 1 billion different leukocyte receptors.

Answer 32

Recombination of various smaller gene fragments to make complex combinations “Shuffle” the proteins together in different combinations to make a billion different receptors

Question 33

Explain the value of antigen presentation (by APCs) in maximizing the efficiency of B and T cell activation as part of adaptive immunity.

Answer 33

To become “active” and proliferate, an inactive B or T cell has to be presented with a specific antigen by an Antigen Presenting Cell (APC) Triggers the immune system

Question 34

Give a quick overview of the critical importance of clonal selection in adaptive immunity.

Answer 34

Clonal Selection of that perfect B or T cell lets you fight explosive, exponential microbial growth via mitosis with explosive, exponential leukocyte growth via mitosis

Question 35

Name the types of cells cloned, and contrast the effector and memory lines of cells.

Answer 35

Cytotoxic T cells, Helper T cells, and B cells are cloned - Cytotoxic T cells are the primary “effector” of cell-mediated immunity - B cells are the primary “effector” of antibody-mediated immunity - Helper T cells are essential for both

Question 36

Contrast processing and presentation of endogenous and exogenous antigens by APCs, identifying the MHCs responsible for both.

Answer 36

Endogenous: - If the antigen is contained within an infected cell, most body cells will digest the antigen internally, and bond it with an MHC-I molecule for presentation at the cell surface - This will signal that the cell is infected and in trouble, and the correct Cytotoxic T cell, with the perfect TCR for that antigen on the cell surface, will go to work via cell-mediated adaptive immunity and work to remove that antigen from the body Exogenous: - If the antigen is free within the interstitial fluid, an APC will ingest it via receptor-mediated endocytosis, digest the antigen into protein pieces, and then use MHC-II to deliver the antigen peptide fragments to the cell surface to be “presented” to other immune cells - APCS will wander the tissue looking to bind and present antigens. Once they do, they’ll migrate to the lymphatic system to present the antigens to T cells in secondary lymphatic organs

Question 37

Describe the bindings involved in the 2 positive and 1 negative selection of immature T cells in the thymus, including the fate of immature T cells that “fail” the selection tests.

Answer 37

T Cells in the Thymus are fitted out with TCRs (T-cell receptors) and CD4 and CD8 molecules They are “tested” by the epithelial cells of the Thymus: Can CD4 recognize MHC-II molecules? Can CD8 recognize MHC-I molecules? Will TCRs NOT bind to self-antigens presented on MHC-I and MHC-II? Failure of either the positive or the negative selection means apoptosis for the pre-T cells (death)

Question 38

Describe the relationship between a pathogen, an antigen, an epitope, and a hapten.

Answer 38

Pathogens are microbes that can infect the body and cause illness. Antigens are parts of the pathogen that alert the body to an infection. An epitope is part of an antigen where an antibody or lymphocyte receptor binds A hapten is essentially an incomplete antigen, and needs a protein to become a complete antigen

Question 39

Describe cell-mediated immunity in detail, focusing on the cells involved, how they’re activated, the specific MHC – CD bindings involved at each step, and what type of antigens they’re best against.

Answer 39

Cell-mediated immunity mostly deals with antigens within body cells, so works best with endogenous antigens. This mostly means cytotoxic T cells battling body cells infected with bacteria or viruses or cancer cells. In cell-mediated immunity, Helper T cells and Cytotoxic T cells must be activated and they are activated by a 2-step process. The first step is to have an APC express an antigen on the outside of a cell and present it to an inactive Helper T cell. This process has 4 moving pieces: MHC-II and the presented antigen molecule on the APC, and CD4 and TCR on the inactive helper T cell. MHC-II and the CD4 always bind together to lock the two cells together. TCRs of inactive helper t-cells match presented antigens on APCs. The second step is co-stimulation, where interleukin-2 molecules are released in a way to activate the inactive helper T cell. The activated helper T cell facilitates the production of massive amounts of clonally selected cytotoxic T cells. In this process of activating inactive Cytotoxic T-cells, an MHC-I on an infected body cell binds with CD8 of an inactive cytotoxic T-cell. Costimulation also occurs. These billions of clonally selected Cytotoxic T cells will leave secondary lymphatic organs to head to tissues to bind to all the rest of the infected body cells that have presented the infecting antigen on their cell surfaces. Memory helper t cells and cytotoxic t cells sit in secondary lymphatic organs waiting to initiate a response with the next infection.

Question 40

Describe some of the cytotoxic killing mechanisms

Answer 40

Once the MHC-I and CD8 connect (activation of cytotoxic T cells), there are 2 ways that cytotoxic t cells kill infected body cells: Granzymes are released by the cytotoxic t cells to enter the infected body cell and induce apoptosis Perforin is released to incorporate into the membrane of the infected cell to cause cytolysis

Question 41

Describe antibody-mediated immunity in detail, focusing on the cells involved, how they’re activated, the specific MHC – CD bindings involved at each step, what type of antigens they’re best against, and how antibodies are involved.

Answer 41

Antibody-immunity deals with antigens outside of cell bodies, so works best with exogenous antigens. Antibody-mediated immunity is focused on helper T cells and B cells. The first step is to have an APC express an antigen on the outside of a cell and present it to an inactive Helper T cell. This process has 4 moving pieces: MHC-II and the presented antigen molecule on the APC, and CD4 and TCR on the inactive helper T cell. MHC-II and the CD4 always bind together to lock the two cells together. TCRs of inactive helper t-cells match presented antigens on APCs. Co-stimulation occurs. Helper T cells become activated and undergo clonal selection in secondary lymphatic organs. B cells endocytose microbial antigens and present them to activated helper t cells, using MHC-II to CD4 binding connections. Activated B cells use their BCRs to bind to microbial or pathogenic antigens and costimulation also occurs. Effector B cells are activated and undergo clonal selection in secondary lymphatic organs and release loads of antibodies that circulate through the body to infected tissues to bind to antigens on invading pathogens. Memory helper t cells and cytotoxic t cells sit in secondary lymphatic organs waiting to initiate a response with the next infection.

Question 42

Describe the general structure of an antibody, including all 4 “regions”.

Answer 42

4 polypeptide chains bound together by disulfate bridges 2 heavy chains make up the center of the antibody and are covalently bonded together by disulfate bridges 2 light chains to the outside of the antibody bonded to the heavy chains by disulfide bridges Constant (bottom) and variable (top) regions

Question 43

Name and describe the 5 ways that antibodies defend against antigens and pathogens.

Answer 43

Neutralizing= “muzzle” the antigen by binding to it Immobilizing = slow spread Agglutinizing = clump antigens Activating complement = works innately to damage microbes Enhancing phagocytosis = “opsonization”

Question 44

Contrast the primary and secondary responses to infection, focusing on which antibodies are involved in each response and the difference between effector and memory cells.

Answer 44

The primary response upon first exposure is representative of war without the memory cells The second response shows how memory B cells can bomb IgG antibodies into tissues within hours to crush an invading pathogen the second time it tries to invade

Question 45

Contrast natural vs. artificial, and active vs. passive immunity, making a 2x2 matrix and giving a brief example of each

Answer 45

Active immunity, Naturally acquired: Following exposure to a microbe, antigen recognition by b cells and t cells and costimulation lead to the formation of antibody-secreting plasmocytes, cytotoxic t cells, and b and t memory cells Active immunity, Artificially acquired: Antigens introduced during vaccination stimulate cell-mediated and antibody-mediated immune responses, leading to the production of memory cells. Antigens are pretreated to be immunogenetic but not pathogenic (they will trigger an immune response but not cause significant illness) Passive immunity, Naturally acquired IgG antibodies are transferred from mother to fetus across the placenta, or IgA antibodies are transferred from mother to baby in milk during breast-feeding Passive immunity, Artificially acquired Intravenous injection of immunoglobulins (antibodies)