Lymphatic System and Immunity Notes

Lymphatic System and Immunology

Overview of System Complexity

• The lymphatic system and immunology are the most physiologically complex topics.
• Other systems have complexities as well:
  • Endocrine and cardiac function.
  • Respiratory function.
  • Digestive function (enzymes and numerous organs).
• Urinary function is also complex but will be covered later.

Lymphatic System: Structure and Function

• The lymphatic system is primarily a drainage system.
• Its major function is related to immunology.
• All organ systems contribute to defense against microorganisms, but the lymphatic system plays the largest role.
• It acts as a circulatory system, facilitating movement throughout the body.

White Blood Cells: Primary Defense

• Movement of white blood cells provides a primary defense.
• Specialized white blood cell clusters are located at key areas.
• White blood cells are present in nearly every system, acting as surveillance or sentinels.
• Example: White blood cells beneath the skin's surface (dermis and epidermis).
• Concentration of white blood cells is highest in the lymphatic system, especially the spleen, lymph nodes, and tonsils.
• Lymphocytes are major specialists in these areas.

Additional Functions of the Lymphatic System

• Minor Function: Lipid transport from the intestines.
• If this process is impaired, it leads to problems with lipid processing and metabolism, potentially causing death.
• The lymphatic system transports lipids from the intestines mainly to the liver.
• It serves as a transport mechanism.

Lymphatic System as Circulatory System

• There are two circulatory systems: cardiovascular and lymphatic.
• Blood pressure (BP) is higher than osmotic pressure, leading to fluid movement.
• Approximately 20 liters of plasma are extracted daily.
• This fluid carries nutrients, vitamins, and hormones to cells.
• Most, but not all, fluid returns to the cardiovascular system as osmotic pressure increases.
• The returning volume is less than the volume that left, with about 3/5 not returned through this process.
• Without lymphatic return, an individual would perish in less than a day.
• Medical issues like pregnancy, obesity, diabetes, and hypertension can disrupt filtration and reabsorption, impacting the extra 15% that should return to the blood.

Lymph Flow

• Lymph fluid flows from tissues toward the heart.
• It is a one-way flow system, unlike the cyclic flow of blood.
• Smallest vessels (lymphatic capillaries) lead to larger vessels.
• Lymph empties into the blood at the subclavian bifurcation before reaching the heart.

Lymphatic Capillaries

• These are the only vessels where substances can naturally enter the lymphatic system.
• Their walls are thin to allow movement, similar to blood capillaries.
• Fluid can only naturally enter unless there is pathology that raise the pressure in the system.

Collecting Vessels

• Larger vessels similar to venules and small veins.
• Nothing can enter or exit through their walls.

Lymph Nodes

• Filters located along collecting vessels.
• They clean lymph by removing cellular debris, bacteria, and viruses.

Lymphatic Trunks

• Medium-sized vessels similar to veins.

Lymphatic Ducts

• Two large vessels (right and left).
• They connect at the junction of the internal jugular and subclavian veins.
• Lymph re-enters the bloodstream as plasma.
• The process involves capillary exchange leading to interstitial fluid formation, entry into the lymphatic system, and return to the blood.

Lymphatic Vessel Structure

• Lymphatic vessels are nearly identical to veins: thin walls, three tunics, and valves to prevent backflow.
• Capillaries are unique: blind-ended tubes similar to cul-de-sacs.
• Entrance occurs between cells.
• Endothelial cells overlap loosely forming mini-valves.
• These vessels are more permeable than blood capillaries (except sinusoidal capillaries).
• White blood cells can enter even without inflammation.
• Red blood cells usually do not enter.
• Fluid enters based on pressure differences.
• Hydrostatic pressure must be lower in the capillary than in the interstitial fluid.
• Pressure is generally zero in the lymphatic capillaries as fluid is continually pulled into the blood.
• Blood flow to the subclavian vein creates suction, aiding lymph movement.
• Movement of muscles squeezes lymphatic vessels, promoting drainage.

Association with Blood Capillaries

• Lymphatic capillaries intertwine with blood capillaries.
• This association is crucial since excess fluid accumulates around blood capillaries.
• Imbalance causes fluid accumulation in tissue spaces, leading to edema.
• Edema increases pressure outside blood vessels, impeding nutrient delivery and waste removal.
• Localized edema occurs when pressure rises outside the blood capillary.

Edema and Its Consequences

• Example: Edema after a radical mastectomy impacts lymphatic drainage.
• Affected arm requires elevation, and procedures like IVs or blood pressure measurements are avoided.
• Worm infestations in developing countries can clog lymphatic filters, causing edema.
• Increased pressure outside blood capillaries starves cells, leading to tissue necrosis.
• Edema indicates compromised cellular servicing.
• Pulmonary edema can lead to drowning.

Lymphoid Organs: Structure

• Lymphoid organs (tonsils, lymph nodes, spleen) have a framework of reticular fibers produced by reticular cells (specialized fibroblasts).
• Unlike blood clots, this meshwork allows docking points for white blood cells.
• Lymphoid tissues are packed with B and T lymphocytes and macrophages.
• Macrophages attack invaders and act as phagocytes.
• This arrangement allows white blood cells to circulate throughout the body and hang up for a while.

Lymph Nodes: Filters

• Small, numerous filters (hundreds) throughout the body.
• They have valves that control lymph flow.
• Collecting vessels filter multiple times before reaching subclavian circulation.
• Areas inside are packed with macrophages and lymphocytes.
• T cells reside in the center, B cells in the periphery, and macrophages in between.
• Macrophages engulf debris, and lymphocytes activate in response to problems.

Lymph Node Clusters

• Found at major body junctures (arms, legs, head meet the torso).
• Mesenteric lymph nodes are extra collections monitoring the gut.

Other Lymphoid Organs

• Tonsils: Located in the mouth and nasal cavity, they control entry points by sampling any air,food, or liquid and controlling the area of the body. Tonsils used to be removed with surgery but it is not as common now unless is a reoccurring or chronic problem.
• Thymus: Produces hormones for T cell development and maturation.
• Spleen: Filters blood, removes old red blood cells, and acts as a blood reservoir.
• Mucosa-Associated Lymphoid Tissue (MALT): Includes gut-associated (GALT) and skin-associated (SALT) tissues.
• These tissues are networks of white blood cells under barriers like mucous membranes, waiting for breaches.

Defending Against the External Environment

• All living things need nutrients, energy, and water.
• Living organisms have higher concentrations of these elements.
• Infection occurs when organisms seek nutrients and energy, not out of malice.
• These organisms must also avoid our immune system.

Evolution of Immune Systems

• Life has developed defense mechanisms early on.
• Bacteria have simple immune systems (e.g., CRISPR).
• Immune systems became more elaborate in animals and vertebrates, especially reptiles, birds, and mammals.

Categories of Immunity

• Genetic Immunity: Species-specific immunity (e.g., humans cannot get distemper).
• This is due to the microorganism's inability to attach to tissues.
• Organisms sometimes jump species if they are close enough. An example of this is HIV.

Defense Mechanisms

• The body has many defenses to counter microorganisms.
• Weapons are divided into two categories: innate and adaptive.

Innate Immunity

• Present from birth and responds immediately.
• Includes barriers and underlying defenses.
• Effective against most mild threats.

Adaptive Immunity

• Requires activation and takes time (up to two weeks).
• Involves white blood cells.
• Leads to immunological memory after winning a battle.

Innate Defenses

• Innate defenses: barriers (keep out/contain) and internal defenses (deal with breaches).
• Barriers:
  • Skin serves other roles. It also prevents dehydration and produces vitamin D among other things.
  • Mucous also membrane have a protective barrier.
• Internal defenses:
  • Include phagocytes. Specialized version of dendritic cells and kupffer cells.
  • NK cells. Specialized in attacking virus infected cells.
  • Inflammation. Warning System.
  • Fever: Another Warning System
  • Chemicals. Includes Interferons which warn the neighbor of the presence of a virus.
  • Complement. Series of protein related to inflammation.
  • Iron binding of hiding all of the iron
  • Digestive Enzymes

Monitoring and Categorization

• Cells with a nucleus (excluding red blood cells) can monitor themselves and neighbors.
• They have receptors that identify and coordinate activity.
• White blood cells can move and squeeze through tissues, making them effective monitors.
• The body asks, "Are you me or not me?"
• Self: Genetically us = leave it alone.
• Nonself: Not us.
  • Do not automatically attack; must ask if it is harmful or not
  • Examples: Gut bacteria, food and unborn babies.
• If a threat, determine the best approach.
  • Distinction based on whether the threat is inside or outside cells.

Internal and External Receptors

• Every nucleated cell has external and internal receptors to detect foreign entities.
• Examples: lipopeptide and peptidoglycan on bacteria, viral genetic material.
• White blood cells have the greatest ability to use these receptors.
• They use cytokines and interferons to communicate and activate immunity.

Innate Immunity

• Structures are part of body design (e.g., skin).
• Functions immediately.
• Nonspecific defenses: work the same way against bacteria, viruses, and worms across the organism.
• Does not change significantly throughout life.

Matching Characteristics to Defenses:

• Innate: is this is going to be innate or adaptive. It is then broken into barrier, innate or adaptive.
• Level and type of barriers:
  Forms a continuous dry barrier is skin or moist version is mucous membranes that has better secretions. The dynamic movement is sneezing, coughing, committing, diarrhea.
• After going to the line of defense it goes to white blood cells

Characteristics of the White Blood Cells:

• Neutrophils:

• Macrophages: Specialized which engulf and digest.

• Different Types of White Blood Cells:

  • Based on the level of each population of white blood cells indicates clues about the disease.
  • Symptoms pain, nausea, lead to blood work.

Phagocytes: Eating Cells

• Phagocytes eat cellular debris and invaders.
• Neutrophils: foot soldiers; quickly engulf and destroy. They aggressively digest, causing self destruction after 20-30 bacteria.
• Macrophages: engulf and digest; process pieces and present them on their cell membrane.
  • This signals the adaptive response by showing lymphocytes what the invader looks like.
  • Does not use as much energy or vigorously of the neutrophil and can digest with slow method and meticulously.

Phagocytosis Process

• Invader is engulfed, ending up in a phagosome vesicle.
• Lysosomes (enzyme sacs) merge with the phagosome, now called a phagolysosome, forming the combination of the two.
• Digestive enzymes are dumped into the pouch, destroying the invader (cellular debris or pathogens).
• Neutrophils then dump remaining pieces out.
• Macrophages put the pieces into molecules and present them to the immune cells.
• Antigen processing cells: the police going door to door.

Complement

• Can cause bacteria to rupture.
• Influences in inflammation and can coat the bacteria for inflammatory purposes.

Inflammation

• Signaling process indicating a problem and increase of blood flow of the area.
  • Inflammation caused slowed pathogen the increase blood flow to area.
    This increase flow is to bring more immune system and help with removing the waste with the nutrients. At the same time is signaling the tissue to repair the damage.

Five Cardinal Signs of Inflammation

• Inflammation serves as a sign to indicate problems.
  Vasodilation of Arterioles. Opening up increase blood flow which gives heat and then red and two out of the five is temperature as well to indicate heat.
  Capillaries can then become more leaky leading to to local edema. At the time the protein is there they provide the anti-bacteria as well leading to inflammation. If happens there is no ability to repair and there are major issues.
  Pain in chemical signal and signal the favor of the wound and further damage.
  lost some function depends on what is broken and its a less known automatic sign of heat.

Activation Process

• Local cells release inflammatory molecules in order to attract more white blood cells and make neutrophils more sticky.

• Cells like mast cells releases histamine and other inflammatory molecules that vasodilate arterioles increasing blood flow to the area causing redness and heat.

• Protein rich fluid includes antimicrobial molecules.

• Inflammatory molecules trigger pain, causing favoring of the injured area.

• Chemical signals then make white blood cells aware of their specific ability to carry out the task to make a better recovery by using their power.

  Neutrophils only in the blood stream is the signal is sent out.

  Macrophages which activate is the signal out
  Chemotaxis- attraction by chemical signal on neutrophils
  nwhite blood cells is getting close area they adhere themselves in the sticky environment or margination. The squising through out of blood vessels and surrounding the areas is known as Diepedisis on to the machine.

  Effects of the Chemical Signal

• Tells bone marrow to increase white blood cell production.
  Epithelial cells undergo mitosis.
  Fibroblasts produce collagen and elastic fibers.
  Will signal local cells to repair.Epithelial cells to go through mitosis and fibroblasts for collagen.
  Can go through regeneration or fibrosis.

Interferon: Virus Warning

• A chemical signal that tells surrounding cells to protect themselves from a virus.
• Does not save current infected cells but slows progress to the next group.

Fever: Reset Thermostat

• Inflammatory molecules tell the hypothalamus to increase temperature.
• Creates a negative feedback loop in most viruses and bacteria.
• Bacteria group and chemical called Phrogin increases thermostat way and turns up to 5 or 6 degrees. Which causes damage by activation of enzyme.

Adaptive Response

• Develops after exposure but may take several exposure
  • 66 years old but have never being exposed I have never being face with HIV or Ebola.
  • The adaptive response, will be activated through the process of slow activation
    Identify specific invaders
• The adaptive response distinguish to the disease caused viruses, bacteria or worms or the other infections.
  Memory: It has better aspects After being exposed to survival
• Adaptive responses have slow activation by the specific nature of the time exposure and better during the first time

Antigen

• Can trigger an immune reaction.
  Triggered. After blood, you want to increase ability of the infection with long with them. MS and Type one, Diabetes and the single of bacteria which makes an antibody and is good for long protection.

Antigen Presentation and Lymphocyte Activation

• The cell then uses molecules of all invaders through processes to activate all of the cells and the fire is done with, will take care of the process to eliminate those issues.

  Types of Cell activation

  The molecules of the intracellular and extracellular.
  If the pieces are the molecules it wake the body and it's only skin cells and cancer and it take over the body and by waking the cell it destroy the virus that has hidden in the cell.
  The source is from outside of the molecules is going to the cell and that also gives the to the macrophage in and cell by the way that is done the type of cell is is given the is giving to the T cell for helping to what to do exactly and that specific. The memory gives a lot of additional benefit.

  Cytotoxic or Helper Cells activation

  Will activate B and will not activate because all the chemicals will stay inside that is is designed to to not happen in MHC is because the cytotoxic of the T cell but, The T cells for the is an outside source the B type.

• Intracellular=mhc1 which activates cytotoxic Tcell(kills infected cell) the Tcells
  *Extracelluar=mhc2 which activates Helper t cells to ramp up the anti-body response because it hits and kill it with antibody.

T Cell activation

Recognizing after antigen recognizing is and after by increasing its number after T cell activation The CD-mhc molecules determine whether
T cell from bone marrow will jump an head off to the thymus an they can shuffled and combine their DNA to identify any self easily. They also, recognize those that is no recognized. In the powerpoint there are many combination that it has come to take note that they may even take you to your grave due to circumstances.
Eventually, as the immune systems develop millions of combination can arise.

Eventually, the invaders start showing up and show the cell will recognize by the helper because it was activate and will do by being a membrane to and that gives the cell by. With high production there is not activated can activate them.

### Cell Immunity and Types of Lymphocytes for infections:

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