Lymphatic system

What is Lymph

a fluid that is similar to plasma but has no plasma proteins

• helps maintain fluid balance

• fights infections

• absorbs fats

Where are Lymphocytes produce in?

Lymphoid tissues → tonsils

Lymphoid organs → spleen, thymus, lymph nodes

Red bone marrow

What are the Primary Lymphoid Tissues and Organs?

sites where the lymphocytes are formed and mature

• Red Bone Marrow → formed

• Thymus → T-cells mature

What are the Secondary Lymphoid Tissues and Organs?

sites where the lymphocytes are activated

• Tonsils → intercepts inhaled or ingested pathogens

• MALT (Mucosa Associated Lymphatic Tissue) → scattered around mucous membranes

• Lymph nodes → filter lymph fluid & activates immune cells

• Spleen → largest secondary organ

What is the function of Lymphatic system?

produce, maintain, distribute lymphocytes and other lymphoid cells

return excess fluid from tissues to bloodstream → help maintain normal BP

regulates composition of interstitial fluid → transports hormones, nutrients, wastes

What do Lymphatic Vessels (Lymphatics) do?

carry lymph from peripheral tissues to venous system

What are Meningeal lymphatics?

network of vessels → in the Dura mater

• drains CSF to Cervical lymph nodes

• removes wastes

• transports immune cells

What are Lymphatic capillaries?

smallest lymphatic vessels → present at almost every tissue of the body

What are Lymphatic lacteals?

lymphatic capillaries in the Small Intestine → transports lipids absorbed by digestive tract

What are the differences between Lymphatic and Blood capillaries?

L: originates as pockets

• has a larger diameter → for easier travel

• thinner walls → in order to have large diameter

• irregular shape in cross section

• has lymphatic valves → for unidirectional flow

Within Lymphatic capillaries, why do they have gaps present?

Allows entry of large molecules, excess fluid, immune cells that are too large to enter to re-enter blood capillaries

What do Small to Medium Lymphatic vessels contain?

3 layers in vessel wall → similar to veins

Valves → prevent backflow of Lymph

Shares same path with Blood vessels

What is Lymphedema

chronic condition which causes localized swelling (arms or legs) → due to obstruction of lymphatic vessels

• prevents lymph drainage

• can become permanent

• interferes w/ immune system function!

What is Superficial Lymphatics?

Vessels within the Subcutaneous layer, Areolar layer of Mucous membranes and Serous membranes

• collects interstitial fluid, antigens, and immune cells

What is Deep Lymphatics?

Network of larger vessels that accompany arteries and veins

• located deeper in the body

  • drains → muscles, bones, joints within limbs and torso

What does the Superficial and Deep lymphatics converge into?

forms large Lymphatic Trunks

• empties into 2 major collecting vessels→ Thoracic Duct & Right Lymphatic duct

What is the Thoracic Duct?

Collects lymph from all body regions which are inferior to diaphragm and the left side of the body superior to diaphragm

• collects ¾ of total lymph fluid (75%)

• empties into Left Subclavian Vein

What is the Cisterna chyli?

an expanded chamber at the base of the Thoracic duct

• receives lymph from the inferior parts of the abdomen, pelvis, lower limbs

  • sends them upwards into Thoracic Duct

What is the Right Lymphatic Duct?

Collects lymph from the Right side of the body, superior to the diaphragm

• collects ¼ of total lymph fluid (25%)

• empties into the Right Subclavian Vein

What area does the Thoracic Duct drain from?

Lower limbs, Pelvic cavity, Abdomen, Left side of Thorax, Left upper limb, and Left side of Head and Neck

What area does the Right Lymphatic Duct drain from?

Right side of the Head and Neck, Right upper limb, and Right side of the Thorax

Where does the Thoracic Duct enter the venous system and drains lymph?

Left Subclavian Vein → Superior Vena Cava → R. Atrium

Where does the Right Lymphatic Duct enter the venous system and drains lymph?

Right Subclavian Vein → Superior Vena Cava → R. Atrium

What is the percentage of Lymphocytes from WBC?

20-40%

What are T-cells?

Thymus-dependent cells

• key fighters in adaptive immune system

What are Cytotoxic T-Cells?

aka killer T cells or CD8+ T Cells

• WBC → attack cells which are infected by Viruses

  • produce Cell-Mediated immunity

What is Cell-Mediated Immunity?

Adaptive Immune response → which protects the body w/o using antibodies

• relies on → T-cells, Macrophages, Natural Killer cells

  • which help destroy infected/abnormal cells

What are Helper T-cells?

aka CD4+ cells

• type of WBC that act as master coordinators of the adaptive immune system

Activated when their T-cell receptor binds to antigen fragments→ thanks to Antigen-presenting cells (ex. Dendritic cells, B cells, Macrophages)

• release Cytokines to stimulate & activate → T-cell and B-cells

What are Suppressor T cells?

help inhibit the activity of T cells and B cells

What are Memory T cells?

Long-lived type of WBC that persists in the body after an infection or vaccination

• remembers a specific pathogen and launches a faster & stronger immune response

What are B-cells?

Bone marrow-derived cells

• forms vital part of body’s adaptive immune system

  • Adaptive: slow start, takes days to activate & highly specific to pathogen

recognize foreign pathogens/invaders → produce antibodies to destroy or neutralize them

What do B-cells provide?

Antibody-mediated immunity

• contain B-cell receptors → spot and bind foreign pathogens

  • once activated can turn into: Plasma cells (antibody factories) or Memory cells

What is the lifespan of B cells?

4-20 years

How much do B cells make up in circulating lymphocytes?

10-15%

What are Natural Killer cells?

aka Large Granular Lymphocytes

• act as immunological surveillance

rapidly destroy virus infected, stressed, or malignant tumor cells w/o prior exposure or activation

• part of Innate immunity → acts immediately & non specific

How much do Natural Killer cells make up in circulating lymphocytes?

5-10%

What is the flowchart of Lymphocyte production from Red Bone Marrow?

Hemocytoblasts → Lymphoid stem cells → NK cells or B cells

What is the flowchart of Lymphocyte production in the Thymus?

Hemocytoblasts → Lymphoid stem cells →Thymosins→ Mature T-cells

Where are Lymphoid Tissues without fibrous capsules located in?

Lymphoid Nodules:

• Respiratory tract

• Digestive tract → Peyer’s Patches, Appendix (MALT)

• Urinary tract

Tonsils:

• Adenoid (Pharyngeal) → single

• Palatine → pair [R & L]

• Lingual → pair [R & L]

Where are Lymphoid Organs covered with capsule located?

Thymus, Spleen, Lymph nodes

What is Mucosa-Associated Lymphoid Tissue (MALT)?

Lymphoid tissues associated with the digestive, respiratory, urinary and reproductive tracts

WIth Tonsillitis, which tonsil is more commonly affected?

Palatine tonsil → inflammation of the tonsil pair

In a Lymph node, what is the Outer cortex primarily composed of?

packed with D-cells and B-cells

• stores B lymphocytes → quickly catch and respond to antigens flowing in the lymph

In a Lymph node, what is the Germinal center mainly composed of?

B cells

• dedicated region for B lymphocytes to multiply, mutuate, and refine their antibodies against specific pathogens

In a Lymph node, what is the Deep cortex composed of?

T cells

• sits right next to special blood vessels that bring in T cells from the bloodstream

• houses Dendritic cells that present pathogens to them

What is the Trabeculae in a Lymph node?

Bundles of collagen fibers that extend from the capsule into the interior of the node

What is the Hilum in a Lymph node?

Shallow indentation → blood vessels & nerves reach the node

What is the Afferent Lymphatics in a Lymph node?

Vessels that carry Lymph into the node from peripheral tissues

What are Efferent lymphatics in a Lymph node?

Vessels that carry Lymph away from the node

What is the purpose of D-cells (Dendritic cells)?

Help initiate an immune response

What is the functions of our Lymph nodes?

help filter Lymph before entering venous system

provide early warning system for immune responses → thanks to D-cells

produce antibodies → B cells & plasma cells

What is Lymphadenopathy?

The abnormal enlargement of Lymph nodes

• sign of: infection, cancer, or endocrine disorder

What can Lymph Node act as for Cancer cells?

Way stations→ since these vessels offer little resistance to their passage

Where are the largest Lymph nodes located in?

Groin, Axillae, and base of the Neck

What is the Thymus?

located in the Mediastinum (above the Heart)

• weighs: 40 g (2 yr old) → 12g (50 yr old)

  • gradual shrinking due to tissue wasting away → sex hormones and wear/tear

• to mature (in the medulla) and train T-cells

What do Reticular Epithelial Cells in the cortex of the Thymus do?

surrounds immature lymphocytes

maintain blood-thymus barrier

secrete thymosins

What does Reticular Epithelial Cells in the medulla of the Thymus do?

forms concentric layers (aka Thymic Corpuscles or Hassall’s Corpuscles)

mature T-cells can enter or leave bloodstream

no blood thymus barrier

What is the function of Epithelial Reticular cells?

maintain the blood-thymus barrier in the Cortex → to separate developing T-cells from general circulation

Where is the Spleen located in the body?

Lateral border of the stomach (upper left quadrant of abdomen)

• connected by Gastro-splenic ligament

What is the function of the Red Pulp in the Spleen

Recycles RBCs

• filters the blood and destroys old/damaged/abnormal RBCs

  • contains → majority of Macrophages, RBCs, and some lymphocytes

What is the function of White Pulp in the Spleen?

acts as a key immune hub→ detects blood-borne pathogens

• makes antibodies to fight them

contains → majority of Lymphocytes, some Macrophages, and Dendritic cells

What is the blood pathway towards the Spleen?

Splenic Artery → Hilus → White pulp → Capillaries (Sinusoids) → Red pulp → Small veins → Hilus→ Splenic vein

What site is considered to have the largest collection site of Lymphoid tissues?

Spleen

• internal structure is heavily packed with White pulp

  • dedicated to filtering blood

  • macrophages & lymphocytes aggressively monitor bloodstream for pathogens

What are some functions of the Spleen?

Remove abnormal blood cells & fragments (Red pulp)

Store recycled iron from old RBCs (Red pulp)

initiate immune response by T & B cells (White pulp)

What is Innate (NONSPECIFIC) Defenses?

type of defense that is against pathogens

• born with it

• always works the same way

• against anytime of pathogen

• nonspecific

• kicks right away or within hours

What is Adaptive (SPECIFIC) Defenses?

specific type of defense against pathogens

• depend on activities of lymphocytes → T or B cells

• B cells: mature and differentiate into plasma cells → make antibodies

• T-cells: mature and act directly against infected/abnormal cells

creates specific resistance (immunity)→ after exposure to infections/vaccine

• retains as memory T cells

What are some Nonspecific defenses we have?

Physical barriers (skin), Phagocytes, Immunological surveillance (NK cells), Interferons, Complement, Inflammatory response, and Fever

What helps differentiate Lymphoid stem cells into B cells or NK cells?

Interleukin-7

What helps differentiate Lymphoid stem cells into mature T-cells?

Thymosins

• mature and travel within the bloodstream and tissues

Within Non-specific defenses, what type of Microphages does it contain?

Neutrophils and Eosinophils

In Non-specific defenses, what type of Macrophages does it contain?

Monocytes

• fixed or free

Within Phagocytes, what are the Fixed macrophages?

Histiocytes

• WBC that permanently reside in specific organs/tissues

  • Bone marrow

  • Microglia→ in CNS

  • Stellate Macrophages or Kupffer cells → in liver sinusoids

Within Phagocytes, what are the Free macrophages?

Wandering macrophages

• mobile WBC within the bloodstream, lymphatic system, etc → hunt down pathogens

  • Alveolar macrophages → Dust cells in the Lungs

How do Free Macrophages and Microphages (neutrophils) move around?

Emigration→ moving through capillary walls

Chemotaxis→ attracted or repelled by chemicals in surrounding fluids

Adhesion → phagocytosis attaching to target, forming vesicle to internalize it

What are Interferons?

chemical messengers that coordinate the defenses against viral infections

• released by activated lymphocytes, macrophages, or virus infected cells

considered a Body alarm (SOS signal)!

How do Natural Killer cells activate?

• Recognition & Adhesion→ identify abnormal membrane components & adheres to them

• Realignment of Golgi apparatus→ moves the face of the cell & produce Perforins

• Secretion of Perforins→ via exocytosis (moving material from inside to outside the cell)

• Lysis of cell→ Perforins help kill the cell

What are Interferons?

small proteins released by activated lymphocytes & macrophages + tissue cells infected w/ viruses

• are considered Cytokines→ chemical messengers released by cells

What are the types of Interferons?

Alpha, Beta and Gamma

What is Interferon Alpha (α)?

protein produced by cells infected w/ viruses

- signals neighboring cells to put up antiviral defenses

• interferes w/ viral replication

• stimulates NK cells

What is Interferon Beta (β)?

protein secreted by Fibroblasts

• slows inflammation in the damaged area

What is Interferon Gamma (γ)?

secreted by T-cells and NK cells

• help stimulate Macrophage activity

• helps coordinate a strong defense

What are Complement (C) proteins?

proteins in the blood

• against bacteria

• stimulates inflammation; Histamine released by Mast cells

• attracts phagocytes & enhance phagocytosis

Produced → by Liver

What is the Complement System and how many routes of activation?

group of 30 special proteins in Plasma

• assists/boosts the work of Antibodies-→ in the destruction of pathogens

Classical, Lectin, and Alternative

What is the Classical Pathway of Complement System?

Most rapid & effective mode of activation

• begins → binding of complement protein C1 to 2 Antibodies attached to an antigen

  • protein→ acts as enzyme and catalyzes a chain reaction in prod. of C3b

What is the Lectin Pathway of Complement System?

Mannose-binding lectin→ binds to Carbs on pathogen surfaces

• acts as an enzyme to prod. C3b

  • fast acting system→ fights off pathogens by recognizing carbs on surfaces of pathogens

What is Alternative Pathway of Complement System?

Properdin (factor P), Factor B and D → interact in plasma to produce C3b

• fast acting → spots and destroys pathogens without needing Antibodies

What causes Inflammation (Inflammatory response)?

thanks to Mast cells (mobile connective tissue cells) → release Histamine & Heparin

• causes swelling, redness, heat and pain→ within localized tissues

What are considered unwanted effects of Inflammation?

Necrosis → local tissue destruction or death in area of injury

Pus → mix of dead tissue cells, debris, fluid

Abscess → accumulation of Pus in an enclosed space

With a Fever, what causes the increase of temperature?

Macrophages → release Pyrogen and Interleukin-1

• help inhibit growth of bacteria/virus

• increases body metabolism

• increases tissue repair

• increase WBC movement

What are the 2 ways of Acquired Immunity someone has?

Active and Passive Immunity

What is Active Immunity in Acquired Immunity?

Develops after exposure to antigen

• Induced → vaccination

• Natural acquired

What is Passive Immunity in Acquired Immunity?

Produced by transfer of antibodies from another source

• Induced p.i → injecting antibodies

• Natural acquired→ via mother’s milk

What is Inactivated vaccines?

type of vaccine that contains a killed pathogen

What is Live-attenuated vaccines?

type of vaccine that uses a live weakened form of the pathogen

What is Messenger RNA vaccines?

type of vaccine that stimulates the synthesis of viral proteins→ triggers an immune response

What is Subunit, Recombinant, Polysaccharide and Conjugate vaccines?

type of vaccine that uses pieces of a pathogen

What is Toxoid vaccines?

type of vaccine that uses altered or weakened forms of bacterial toxins

What is Viral Vector vaccines?

type of vaccine that uses modified versions of a different virus to deliver protection

What are the properties of Adaptive Immunity?

Specificity, Versatility, Memory, and Tolerance

What is Specificity as one of the Properties of Adaptive Immunity?

T-cells or B-cells responding only to a specific antigen and ignores all others