Lymphatic System




Immune System

  • Immune System: Refers to the cells of the lymphatic systems that provide both defense against disease & permanent immunity against future infections

  • Innate Immunity: First line of defense that includes physical barriers and immune cells (Skin & Mucous; Fast)

    • Innate Cells:

      • Neutrophils & Macrophages - circulates blood to help w/ injury

      • Natural Killer Cells & Dendritic Cells - Release Perforin & Granzymes

      • Monocytes

      • Complement Cells

  • Adaptive Immunity: Immunity that involved memory cells (B & T) that target specific infections (T & B Cells; Slow) 

  • Inflammation: a complex biological response to tissue injury or infection 

    • Signals of Inflammation: Swelling, Redness, Pain, Heat, Joint Immobility

    • Permeability - The ability for the vessel to allow substance through its walls

      • Increase - More substances through its walls (More pores)

      • Decrease - Less substances through its walls (Less pores)

    • Cytokines - Proteins that signal an inflammatory response



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Lymphatic System: 

  • Collection of cells & biochemical cells that go through lymphatic vessels

  • Creates a network of tissues, organs, and vessels that circulate fluid

  • Associated with the cardiovascular system

  • Important part of the body's immune system 

Lymphatic Functions:

  1. Transports fluids away from interstitial spaces and returns it into the bloodstream

  2. Absorbs Lipids from digestive system towards bloodstream

  3. Defends the body from diseases and allows us to live in the world

Lymphatic Pathways:

  1. Lymphatic Capillaries

  2. Lymphatic Vessels

  3. Lymph Nodes

  4. Larger Lymphatic Vessels

  5. Lymphatic Trunks

  6. Lymphatic Collecting Ducts

  7. Subclavian Veins in Thorax

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Tissue Fluids & Lymph 

  • Lymph is tissue fluid that has entered a lymphatic capillary 

  • Lymph formation depends on tissue fluid formation 

Lymph Formation 

  1. Filtration from the plasma will exceed and result in a large amount of tissue fluid to form a network 

  2. This increase in hydrostatic pressure in the interstitial spaces will force the tissue fluid into the lymphatic capillaries; creating a lymph 

  3. This process prevents accumulation of excess tissue fluid to formulate (edema)

    1. Edema - Accumulation of excess fluid in the body’s tissue 

Lymph Flow 

  • Lymph normally has low hydrostatic pressure; meaning does not move efficiently

  • Good lymph flow requires several mechanisms to be functioning: 

    • Contraction of Skeletal Muscles:

      • Compresses lymphatic vessels -> increase lymph flow

    • Respiratory Process:

      • Sends lymph from abdomen to thorax -> increases lymph flow

    • Smooth Muscles: 

      • Contracts to aid in flow of lymph 

  • Valves in lymphatic vessels prevent backflow

  • Highest flow when conducting physical exercises 

Lymph Function

  1. Lymphatic Capillaries 

  • Absorbs & Delivers: excess fluid, foreign particles, & nutrients toward bloodstream and lymph nodes 

  • Easily transported because of Flap-Like valves between cells of lymphatic capillaries

  1. Lymphatic Tissues & Lymphatic Organs 

  • Lymphatic tissues contain several cell types including lymphocytes & macrophages 

  • Mucosa-Associated Lymphoid Tissue (MALT)

    • Helps with lymphatic system process

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Lymphatic Capillaries 

  • Network of blood capillaries throughout the body

  • Microscopic, close ended tubes 

  • Thin-Walled 

Next Steps:

  1. Tissue fluid will enter the lymphatic capillaries

  2. Fluids is now called Lymph

  3. Will eventually continue and merge into the lymphatic vessels



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Lymphatic Vessels:

  • Walls are similar to veins; but thinner

  • Is similar to the Capillary Veins

  • Composed of three layers 

  1. Inner Layer: Endothelial Lining

  2. Middle Layer: Smooth Muscle 

  3. Outer Layer: Connective Tissues 

  • Contain semilunar valves 

Next Steps:

  1. Large vessels lead it to the lymph nodes & then the larger lymphatic trunks 




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Lymph Nodes

  • Bean shaped; <2.5 cm long

  • Located on lymphatic vessels

  • Located everywhere except Central Nervous System 

  • Contain lymphocytes & macrophages

Function

  • Has two main functions:

    • Filtration: Filters potentially harmful particles from lymph 

    • Immune Surveillance: monitors fluid utilizing the lymphocytes and macrophages

Spleen 

  • Largest lymphatic organs 

  • Contains various tissue types

    • Allow for macrophages and lymphocytes to destroy

  • Lymph nodes conduct their functions here



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Larger Lymphatic Vessel 

  • Lymph will continue through its path in the larger lymphatic vessel until it eventually arrives at the lymphatic trunk 

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Lymphatic Trunks: 

  • Drains lymph from lymphatic vessels 

Next Steps:

  1. Will eventually drain into the lymphatic collecting ducts 



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Lymphatic Collecting Ducts: 

  • Drain lymph from trunks 

  • There are two types of collecting ducts in the lymphatic system

  1. Thoracic Duct 

  • Longer & Wider

  • Drains a majority of the body

  • Begins as a sac called cisterna chyli empties into L Subclavian Vein

    • Temporary reserve for lymph 

  1. Right Lymphatic Duct 

  • Much smaller than thoracic duct

  • Beings in the left thorax and empties into R Subclavian Vein

  • Drains upper left portion of the body 





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Subclavian Veins 

  • Will allow for the tissue fluid to re-enter the bloodstream



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Antibody/Immunoglobulins 

  • Antibody = Immunoglobulins 

  • Reshape itself to adapt to the antigen it is going against

  • There are 5 major types of immunoglobulins 

    • IgG: 80%; protect against bacteria, viruses, toxins (Crosses Placenta and is needed for plasma cells)

      • IgG -> Giant 

    • IgA: 13%; Prevent attachment of infections through mucous (Dimer Shape and doesn't cross the placenta)

      • IgA -> sAliva, teArs, sweAt

    • IgM: 6%; Massive role in early stages of development & does not cross placenta (Pentamer Shape)

      • IgM -> Made by Baby

    • IgD: <1%; Create antibodies and function is unknown 

      • IgD -> The 2 D’s Does not cross placenta and directs differentiation 

    • IgE: <1%; Immediate hypersensitive and leads to inflammation (Activates Hypersensitivity) 

      • IgE -> Environmental Exposure








Antibody Attacks

  1. Neutralization - Covers toxins on antigens; making them harmless

  2. Precipitation - Making antigens insoluble; making phagocytosis is easier

  3. Agglutination - Clumping of antigens; making phagocytosis is easier 

  4. Opsonization - Antigen-Antibody complex; making phagocytosis is easier 

  5. Chemotaxis - Attract white blood cells to injury 

  6. Lysis - Rupture pathogens cell membrane; the walls 



Shape of Antibodies




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Primary Organs & Secondary Organs 

  1. Primary - bone marrow and thymus

  2. Secondary - Spleen, Lymph nodes, and MALT



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Complement System 

  • Complement System - The ways that the immune system conducts inflammation and promotes phagocytosis 

  • There are three different pathways: Classic Pathway, Alternate Pathway, & Lectin Pathway 



Classic Pathway 






  • Bacteria enter and the antibody will attach to the antigen (IgG & IgM)







  • The antibody will then attach the C Proteins

  • Order: C1, C4, C2, C3b, C5b, C6, C7, C8, C9 

    • C3a & C5a will behind and will be talked about later 







  • C3b & C5b will detach from each other 

  • C5b, C6, C7, C8, & C9 will combine and create a Membrane Attack Complex (MAC)

  • This will attach onto the bacteria to allow H2O & Na+ to enter; killing bacteria 

  • The C3b left alone will now have a receptor that attract WBC, leading to phagocytosis from integrins 

Alternate Pathway 









  • No Antibody, the C3b will just immediately attach to the antigen. 

  • Order: C3b, C5b, C6, C7, C8, C9









  • The C3b will detach with C5b, causing the MAC to form and then Phagocytosis.



Lectin Pathway 










  • The C4 will attach to a mannose 

  • Order: C4, C2, C3b, C5b, C6, C7, C8, C9










  • The C3b will detach with C5b, causing the MAC to form and then Phagocytosis



C3a & C5a Binding 











  • The reason there are C3b & C5b is because C3a & C5a will detach 

  • This will cause for more inflammation by interacting with the MAST Cell

  • This will release chemokines: 

    • Histamine

    • Prostaglandin 

    • Leukotrienes




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Phagocytosis 

  • There are two cells that mainly do phagocytosis 

  • This allows for the creation of T & B Cell production 

    • Macrophages & Neutrophils 

Macrophages 






  • The Macrophage will detect the bacteria and conduct phagocytosis using its pseudopods 










  • The infection will be engulfed into the macrophage and get surrounded by a phagosome (Sac)

  • The macrophage also has a lysosome which uses enzymes to decompose infections 








  • The lysosome will then merge with the phagosome and conduct phagolysosome (eating bacteria) 







 



  • Once the bacteria has been merged by the lysosome, MHC I & MHC II will emerge

  • MHC 1 - is presented in all cells except red blood cells 

  • MHC 2 - found on antigen presenting cell (APC) only present in 

    • B cell 

    • Dendritic cells

    • Macrophage 



Neutrophils 







  • Phagocytosis will occur using the integrins 







  • The infection will be engulfed into the macrophage and get surrounded by a phagosome (Sac)

  • The neutrophil also has a lysosome which uses enzymes to decompose infections 

  • The lysosome will then merge with the phagosome and conduct phagolysosome (eating bacteria) 










  • The neutrophil will not release the antigens it has engulfed and send it to the lymph nodes.



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Thymus 

  • It is a soft, bilobed gland

  • Located between your lungs (chest) 

  • Large at infancy & early childhood, but shrinks at puberty and adulthood. 

  • It allows for the activation of most inactive cells; called Thymocytes:

    • T Lymphocytes - Activated by Thymosins 



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T Cell & B Cell Creation 



T-Cells Maturation

  • The following steps below showcase how a T-Cell matures (NOT ACTIVATION)












  1. The immature T-Cells will enter the thymus and interact with the thymic cell 

  2. The thymic cell will interact with the chemokine found on the T-Cells, leading to interaction in the nucleus, which will creat RAG 1 & RAG 2

  3. These RAGs will created three things: 

    1. CD8+, CD4+, & TCR (T-Cell Receptor)

  4. Now the type of T-Cell that is created depends on the interactions between thymic cells and the three things just made.

    1. First Possibility 

      1. MHC 1 <-> CD8+

      2. MHC 2 <-> CD4+ 

        1. Creates: Strong Binding 

    2. Second Possibility 

      1. MHC 1 <-> CD8+

        1. Creates: Cytotoxic T Cell 

    3. Third Possibility 

      1. MHC 2 <-> CD4+ 

        1. Creates: T Helper Cell 

    4. Fourth Possibility 

      1. MHC 1 or 2 <-> TCR

        1. Creates: FAS (DEATH)

    5. Fifth Possibility 

      1. No binding; Interleukin 2 will go

        1. Creates: Regulatory T-Cells



T Helper Cell Activation 

  • Following steps show how the T Cell become activated (NOT MATURATION)











  • T-Cells need three signals to fully activate: 

  1. MHC 2 & TCR will interact, when they interact, CD3 will activate and then it will enter the DNA

    1. First step complete

  2. Macrophage will release B7, it will go to the T-Cell to interact with CD28 and enter the DNA

    1. This step is called costimulation

  3.  Macrophage will release IL - 1 and send it to another receptor and enter the DNA

    1. Once this step is complete, the T-Cell will release IL - 2, which will go back and interact with the DNA, 

      1. This process is called autocrine 


  • When autocrine occurs, the DNA will release interleukins to interact with each other  

    • IL-4, IL-5, IL-6, & IL-12 

  • These interleukins will give rise to two different types of T Helper cells

    • IL-4 <-> IL-5 

      • T Helper 2

        • Releases more IL-4, IL-5, & IL-2

    • IL-12 & T Cells

      • T Helper 1 

        • Releases INF, TNF, & Gamma



Cytotoxic T - Cell Role


  • This main thing that needs to be understood is the Cytotoxic T Cells & Natural Killer Cells release Perforin & Granzymes 

  • These proteins will ultimately lead to Apoptosis 



B-Cells 






  • Antigen released by the neutrophil will be sent to the B-Cell (Located in the Lymph Nodes Cortex) 

  • The antigens will increact with a receptor found on the B-Cell 









  • The antigen/nucleus combination will enter the B-Cell

  • The nucleus will not interact with the antigen/nucleus and cause DNA Recombination; used to remember the antigen 








  • Then after recombination, MHC 1, MHC 2, and BCR (B-Cell Receptor) will emerge. 

  • IL - 4 will enter the BCR and cause colonial expansion








  • Large amount of B-Cells will be produced and will interact with Interleukins 

  • If IL - 5 interacts, then it will create memory cells 

  • If IL - 5 & IL - 6 interact, it will create plasma cells, which creates IgG

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Types of Immunity 

Immunity 



Passive

Active

Immunity acquired without the body actively producing antibodies or immune cells.

Immunity developed through the body's own immune response after exposure to a pathogen or vaccination.



Naturally 

Acquired

Artificially
Acquired

Naturally 

Acquired

Artificially 

Acquired

IgG

IgA

Pre-Made Antibodies 

Infected by pathogen

Vaccine 

Booster Shots



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Hypersensitivity Reactions 

  • Exaggerated reactions to non-harmful antigens 

  • Only affect people with exaggerated immune response 

  1. Type I 

    1. Allergies that can lead to eczema, asthma, or anaphylactic shock

  2. Type II 

    1. Antigen binds to cells, causing phagocytosis 

  3. Type III

    1. Antigen-Antibody complex (Opsonization) 

  4. Type IV

    1. Affects almost anyone 

    2. Exposure of skin to allergen which activates T Cells and causes inflammation