Innate immunity

MODULE 9: LYMPHATIC SYSTEM & First line of defenses: Skin and mucous membranes
• Provide both physical and chemical barriers
IMMUNITY • Physical barriers
Wednesday, April 28, 2021 03:00 PM ○ Epidermis – closely packed, keratinized cells
Immunity or Resistance ▪ Periodic shedding (part of household dust)
• Ability to ward off damage or disease through our defenses ○ Mucous membranes
• 2 types of immunity ▪ Mucus traps microbes and foreign substances
○ Innate or nonspecific immunity –present at birth ○ Nose hairs trap and filter
▪ No specific recognition of invaders, no memory component ○ Cilia of upper respiratory tract propel trapped particles up and out (nose or mouth)
▪ 1st and 2nd line of defenses • Fluids
▪ e.g. Skin, mucous, tears ○ Lacrimal apparatus of eye (tearing)
○ Adaptive or specific immunity ▪ Washing action of tears
▪ Specific recognition of invaders with a memory component ▪ Lysozyme breaks down bacterial cell walls – also present in saliva, perspiration, nasal
▪ e.g. Memory T cells and vaccination secretions, and tissue fluids
○ Saliva washes mouth
Lymphatic system structure and function ○ Urine cleanses urinary system
• Consists of lymph, lymphatic vessels, structures and organs containing lymphatic tissue, red bone ○ Vaginal secretions (fighting off pathogens sensitive in pH), defecation and vomiting
marrow • Chemicals
Functions of the lymphatic system ○ Sebaceous (oil) glands secrete sebum – protective film, acid
1. Drain excess interstitial fluid ○ Perspiration, gastric juice, vaginal secretions – all acidic
2. Transport dietary lipid
▪ Dietary lipids and lipids soluble vitamins A, B, E, K which are transported by the system Second line of defenses: Internal defenses
3. Carry our immune responses • General reaction
▪ Highly specific Antimicrobial substances
1. Interferons
Components of the Lymphatic System ○ Produced by lymphocytes, macrophages, and fibroblasts infected by viruses
○ Prevents replication in neighboring uninfected cells
2. Complement
○ Proteins in blood plasma and plasma membranes
○ Acts to put holes in the cell walls of pathogens
▪ Likened to a bullet that would pierce through the body
○ “complement” or enhance certain immune reactions
○ Causes cytolysis of microbes, promotes phagocytosis, contributes to inflammation
3. Iron-binding proteins
○ Inhibit growth of bacteria by reducing available iron
4. Antimicrobial proteins (AMPs)
○ Short peptides that have a broad spectrum of antimicrobial activity
○ Can attract dendritic cells and mast cells that participate in immune responses

Phases of Phagocytosis
1. Chemotaxis
○ Process of inviting phagocytes to the site of infection
Areas drained by the terminal duct prior to drainage to the subclavian veins 2. Adherence
Lymphatic ducts ○ The microbe would be adhering to the phagocyte
• Exit passageways from the lymphatic system to the blood 3. Ingestion of the microbe
4. Digestion
○ Lysosomes that contain digestive chemicals which would insert its contents into the ingested
microbe
5. Killing
○ Microbe is killed inside the phagocyte
Residual body - indigestible materials

Inflammation
• Nonspecific, defensive response of body to tissue damage
• 4 signs and symptoms (5 cardinal signs of inflammation) – redness, pain, heat and swelling
○ Calor - heat
○ Dolor - pain
○ Rubor - redness
Note the arrows pointing towards the drainage areas – towards the ○ Tumuor - swelling
○ thoracic duct ○ functio laesa - loss of function
▪ Areas drained • Attempt to dispose of microbes, prevent spread, and prepare site for tissue repair
□ Rest of the body • 3 basic stages
□ Left side of the body ○ Vasodilation and increased blood vessel permeability
□ Left upper extremity ○ Emigration (diapedesis)
□ Rest of the thoracic area ▪ Moving out of WBCs from blood vessels going to the site of injury
□ Abdominal region ○ Tissue repair
□ Lower extremities
Adaptive immunity
○ right lymphatic duct
• Ability of the body to defend itself against specific invading agents
▪ Areas drained
• Antigens (Ags) – substances recognized as foreign and provoking an immune response
□ Part of the head (right side)
• Distinguished from innate immunity by
□ Part of the thoracic area
○ Specificity
□ Right upper extremities
○ Memory
Lymphatic vessels and lymph circulation

ANPHYD1-LEC Page 1
 • Ability of the body to defend itself against specific invading agents
▪ Areas drained
• Antigens (Ags) – substances recognized as foreign and provoking an immune response
□ Part of the head (right side)
• Distinguished from innate immunity by
□ Part of the thoracic area
○ Specificity
□ Right upper extremities
○ Memory
Lymphatic vessels and lymph circulation
• Vessels begin as lymphatic capillaries Types of Adaptive Immunity
○ Cell-mediated
○ Closed at one end
▪ Cytotoxic T cells directly attack invading antigens
• Unite to form large lymphatic vessels
▪ Particularly effective against intracellular pathogens, some cancer cells and foreign tissue
○ Resemble veins in structure but thinner walls and more valves transplants
• Passes through lymph nodes ○ Antibody-mediated
○ Encapsulated organs with masses of B and T cells ▪ B cells transform into plasma cells making antibodies (Abs) or immunoglobulins
▪ Works against extracellular pathogens in fluids outside cells
Lymphatic capillaries ○ Helper T cells aid in both types
• Slightly large diameter than blood capillaries
• Unique one-way structure Maturation of T Cells and B Cells
• Permits interstitial fluid to flow in but not out • Lymphocytes are named from the site of their maturation
• Anchoring filaments pull openings wider when interstitial fluid accumulates Small intestine has ○ CD4 & CD8
lacteal for dietary lipid uptake ▪ Names of proteins found in these cells
○ Chyle is lymph with lipids • Both develop from pluripotent stem cells originating in red bone marrow
○ B cells complete their development in red bone marrow
○ T cells develop from pre-T cells that migrate from red bone marrow to the thymus
▪ Helper T cells (CD4 T cells) and cytotoxic T cells (CD8 T cells)
• Immunocompetence – ability to carry out adaptive immune response
○ Have antigen receptors to identify specific antigen

Escape of blood plasma from blood vessels to become interstitial fluid

Volume of interstitial fluid ∝ pressure
○ Creating an passage of cells from capillaries becoming lymphatic fluid
○ In applying the Frank Sterling Law, 85% that would be reabsorbed back into the blood
capillaries
▪ For every volume of fluid that would come out, there should be 100% that would be
reabsorbed
▪ In the 85% that is reabsorbed back, 15% that would be entering the lymphatic system
which would be returned back to the blood circulation when it comes to the point where
they would be emptied in the blood vessels, veins located near the heart (subclavian
veins)

Lymph trunks and ducts

• Vessels unite to form lymph trunks
Principal trunks
○ Lumbar
○ Intestinal
○ Bronchomediastinal
○ subclavian
○ jugular
• Passes from lymph trunks into 2 main channels (thoracic and right lymphatic ducts) before
draining into venous blood

Formation and flow of lymph

• More fluid filters out of blood capillaries than returns to them by reabsorption
• Excess filtered fluid – about 3L/day – drains into lymphatic vessels and become lymph
• Important function of lymphatic vessels to return lost plasma proteins to blood stream
• Contain valves
• Same “pumps” aiding venous return also used; should be no regurgitation
○ Skeletal muscle pump – milking action
○ Respiratory pump – pressure changes during breathing CELL-MEDIATED IMMUNITY ANTIBODY-MEDIATED IMMUNITY
• Directed against intracellular pathogens, some cancer • Directed against extracellular pathogens
Relationship of the Lymphatic System to the Cardiovascular System cells, and tissue transplants

Clonal Selection
• Process by which a lymphocyte proliferates and differentiates in response to a specific antigen
○ Clone – population of identical cells all recognizing the same antigen as original cell
• Lymphocyte undergoes clonal selection to produce
○ Effector cell – active helper T cell, active cytotoxic T cell, plasma cell, die after immune response
○ Memory cell – do not participate in initial immune response, respond to 2nd invasion by
proliferating and differentiating into more effector and memory cells, long life spans

Antigens and Antigen Receptors

Antigens have 2 characteristics
Epitopes
• induce the production of different antibodies or activate different T cells.
• act as the triggers for immune responses
• Immunogenicity – ability to provoke immune response
• Reactivity – ability of antigen to react specifically with
antibodies it provoked
• Entire microbes may act as antigen
• Typically, just certain small parts of large antigen
molecule triggers response (epitope or antigenic
determinant)

Release of plasma fluids from blood capillaries → lymphatic capillaries → passing structures (lymph Antibodies and their structures
nodes) → heart→ systemic blood capillaries → systemic lymphatic capillaries → lymph nodes • Can combine specifically with epitope of the antigen that triggered its production
(immunoreactions) → lymphatic fluid → valves →lymphatic vessels → blood vessels → drained in the • Belong to group of glycoproteins called globulins
right atrium ○ Ab are immunoglobulins (Igs)
• 4 polypeptide chains – 2 heavy (H) chains, 2 light (L) chains

ANPHYD1-LEC Page 2
Release of plasma fluids from blood capillaries → lymphatic capillaries → passing structures (lymph Antibodies and their structures
nodes) → heart→ systemic blood capillaries → systemic lymphatic capillaries → lymph nodes • Can combine specifically with epitope of the antigen that triggered its production
(immunoreactions) → lymphatic fluid → valves →lymphatic vessels → blood vessels → drained in the • Belong to group of glycoproteins called globulins
right atrium ○ Ab are immunoglobulins (Igs)
• 4 polypeptide chains – 2 heavy (H) chains, 2 light (L) chains
Lymphatic tissues and organs • Hinge region – antibody can be T shape or Y shape
2 groups based on function • Variable (V) region at tips of each H and L chain
Differentiation - when stem cells become cells primary for immuno action ○ 2 antigen-binding sites - bivalent
1. Primary lymphatic organs • Constant (C) region – remainder of H and L chain
○ Sites where stem cells divide and become immunocompetent
○ Red bone marrow and thymus Antibody actions
2. Secondary lymphatic organs • Neutralizing antigen
○ Sites where most immune response occurs • Immobilizing bacteria
○ Lymph nodes, spleen, lymphatic nodules • Agglutinating and precipitating antigen
• Enhancing phagocytosis
Thymus and Medulla
• Activating complement
Thymus
○ Defensive system of over 30 proteins
• Outer cortex composed of large number of T cells
○ Destroy microbes by causing phagocytosis, cytolysis, and inflammation
○ Immature T cells migrate here from red bone marrow where they proliferate and begin to
mature ○ Acts in a cascade – one reaction triggers another
○ Dendritic cells derived from monocytes assist in T cell maturation
○ Specialized epithelial cells help educate T cells through positive selection Self-Recognition and Self-Tolerance
▪ only about 25% survive • Your T cells must have
○ Macrophages clear out dead and dying cells ○ Self-recognition – be able to recognize your own MHC
• shrinks with age from 70g in infants to 3g in old age ○ Self-tolerance – lack reactivity to peptide fragments from your own proteins
• Pre-T cells in thymus develop self-recognition via positive selection – cells that can’t recognize your
Location of the thymus relative to the thoracic cage: own MHC undergo apoptosis
○ Superiorly located to the heart • Self-tolerance occurs through negative selection in which T and B cells that recognize self peptide
○ Intermediate to the left and right lung fragments are eliminated
○ Deletion – undergo apoptosis
Medulla
• More mature T cells migrate here from cortex ○ Anergy – remain alive but are unresponsive
• More epithelial cells, dendritic cells and macrophages
ADDITIONAL NOTES FROM THE VIDEO
Functions of the Lymphatic System Control of lymph flow
• Fluid Balance • Skeletal Muscles
• Fat Absorption (large intestines) • Smooth muscles in the larger vessels
• Immunological Defense • Thoracic pressure
• One way valves

90% of interstitial fluid will go back to the blood vessel while 10% becomes lymph

Edema
• fluid buildup in the tissues
• (mild)Can occur during pregnancy when the weight of the baby slow the ability of the vessels to move
the lymph up the body
• (serious) Elephantitis
○ Occurs when a parasite blocks the vessels and the edema that is produced looks like the legs of
an elephant

Lymph nodes
• encapsulated masses of lymph tissue found along lymph vessels
Functions
○ testing stations
○ create lymphocytes
○ filtering stations

Tonsils Spleen
Lymph nodes • get smaller as you mature and they can even • does not filter lymph, but blood
• Located along lymphatic vessels disappear altogether • Dispose of worn out erythrocytes
• Scattered throughout body • When inflamed due to infection, a condition • Cleanses the blood of foreign invaders
• Stroma – supporting connective tissue called tonsillitis occurs • Reservoir of oxygen-rich blood
○ Anchor the thymus to the thoracic cage
• Roughly the size of a clenched fist
○ Capsule, trabeculae, reticular fibers and fibroblasts Peyer's patches
• Parenchyma – functional part • Very similar to tonsils
○ Outer cortex – aggregates of B cells called lymphatic nodules (follicles) – site of plasma cell • groups of lymphocytes in lymph nodules in the
and memory B cell formation small intestine (last third)
○ Inner cortex – mainly T cells and dendritic cells
○ Medulla – B cells, antibody producing plasma cells from cortex, and macrophages

Pathogens
• Organisms that make us sick
► Bacteria ► Cancers
○ Not all are pathogenic ○ Our own cells that have been damaged
► Fungi ○ Cannot control their functions anymore
○ Most are yeast ▪ Instead of dying like they are supposed to
► Parasites ▪ When they get worn out, they undergo
○ Tapeworms, pinworms uncontrolled mitosis where they make
► Viruses more copies which leads to a tumor until
○ A bit of DNA/RNA that is wrapped in surrounding tissues get damaged

ANPHYD1-LEC Page 3
 ► Fungi ○ Cannot control their functions anymore
○ Most are yeast ▪ Instead of dying like they are supposed to
► Parasites ▪ When they get worn out, they undergo
○ Tapeworms, pinworms uncontrolled mitosis where they make
► Viruses more copies which leads to a tumor until
○ A bit of DNA/RNA that is wrapped in surrounding tissues get damaged
its own protein coat ○ Can break from the main tumor and spread to
○ Doesn’t have its own cell machinery; other places in the body
invades other cells and hijacks the ► Toxins
cell's machinery to make proteins
and copies of itself
○ When the cell gets full of copies, it
ruptures and the copies go on to
infect new cells
First line of Defense - majority of pathogens are stopped here
Route of lymph flow through a lymph node: • Skin • Stomach acids
• Afferent lymphatic vessel (where lymph fluid will be entering) ○ Waterproof due to keratin ○ Kills most pathogens before they can do any damage
↓ ○ Sweat, pH, sebaceous oil • Tears
• Subcapsular sinus glands ○ Contain an enzyme called lysozyme which break down
↓ • Mucus the cell walls of many bacteria
• Trabecular sinus ○ Traps microorganisms ○ Most common eye infection - pink eye
↓ ○ Gets rid of pathogens by use of • Symbiotic organisms
• Medullary sinus cilia ○ Live throughout the body
↓ ○ Specific (contains antibodies) ○ Flourish in the intestine and squeeze out populations of
• Efferent lymphatic vessel (where lymph fluid will be exiting going towards the nodes) and non-specific pathogenic bacteria and fungi
• Urine ○ In the skin: produce lactic acid which fights off
Spleen ○ Washes the tract that leads to pathogenic bacteria and fungi
• Largest single mass of lymphatic tissue in the body the outside
• Stroma – capsule, trabeculae, reticular fibers, and fibroblasts
• Parenchyma Second line of defense - (innate and adaptive immunity)
○ White pulp – lymphatic tissue (lymphocytes and macrophages) • Interferon
▪ B cells and T cells carry out immune function ○ Proteins produced by a cell infected by virus which will not save the cell but affect neighbor cells
○ Red pulp – blood-filled venous sinuses and splenic (Bilroth’s) cords – red blood cells, as it signals to strengthen themselves against viral attack
macrophages, lymphocytes, plasma cells, and granulocytes • Complement system
○ Macrophages remove ruptured, worn out or defective blood cells ○ Fights foreign cells - anti bacterial
• Storage of up to 1/3 of body’s platelet supply ○ Made up of 20 plasma proteins that will activate by antibodies bound to antigens or the mere
• Production of blood cells during fetal life presence of invaders (e.g. blood coagulation factors)
○ Liver makes them
Structure of the Spleen Innate immunity Disposal Adaptive immunity
lyse cell wall of chemotaxls - Attract macrophages and Complements are not part of the
bacteria neutrophils adaptive immune system, but the
adaptive immune system can recruit
complements.
• Inflammation and WBCs
○ WBCs (nonspecific)
▪ 12-hour life span
▪ Phagocytes - eat invaders an cell debris
► Neutrophils (54%- 62% of white blood cells in the body)
 First to respond
 consumes 20 bacteria (also fungi and some viruses)
 reside in liver, spleen. Lungs until needed
► Monocyte:(3%- 9% of white blood cells in the body)
 Second to respond
 largest of the white blood cells (macrophage) or big eaters
 consumes 100 bacteria and large pathogens
 reside in tissues, vessels walls, lymphatic vessel until needed
► Basophils (1% of white blood cells in the body)
▪ chemicals released from injured cells attract them
▪ Release
□ Leukotrienes
□ Prostaglandins
□ Heparin
 Inhibits blood clotting, allowing the wound to wash out any foreign matter
□ Histamine
 Triggers inflammation or vasodilation which brings in additional blood flow
 diapedesis: easier passage of white blood cells through vessel wall.
◊ Local inflammation - infection stays contained to the one location
◊ Systemic inflammation - Infection escapes into the blood stream and
spreads throughout the body
► Eosinophils (1% - 3% of the white blood cells in the body)
Neighboring organs make indentations in the visceral surface of the spleen
▪ Reduces inflammation
• gastric impression (stomach),
• Fever
• renal impression (left kidney)
○ Pyrogen - "fire maker" [interleukin-1 (IL-1)]
• colic impression (left colic flexure of large intestine).
▪ Chemicals which promote fever by acting on the hypothalamus (controls body temperature)
▪ Sometimes produced by WBCs

Third line of defenses - antibodies

• Humoral immunity: immunity which comes from antibodies in blood plasma
1. Bind directly to the Antigen (IgD)
2. Bind the antigens together (IgA)
3. Activate a complement (lgM, IgG)
4. Stimulate phagocytosis (IgG)
5. Stimulate inflammation (lgE)
• Antibodies - proteins (produced by B cells)
• variable region (antigen binding sites) - who it will fight
• constant region on heavy chain - How it will fight
• constant region on light chain - How it will fight
• Major Histocompatibility Complex
• It is virtually impossible for two people to have identical MHC's unless they
are identical twins. (MHC)
• Fingerprint for your cells
• Acquired immunity
• B cells proliferate and produce
○ Plasma B cells
▪ releases their antibodies into the plasma so the antibodies can attack the antigens to
which they can bind
▪ die
○ Memory B cells
▪ Long live B cells
▪ Do not release their antibodies and circulate the body, waiting for the next attack of
the antigens

ANPHYD1-LEC Page 4
 the antigens
▪ Means by which vaccinations provide immunity

Types of acquired immunity

a. Active natural
▪ Comes from being exposed to a pathogen
b. Active artificial
▪ Immunity received from vaccines
c. Passive natural
▪ Occurs between the mother and the baby
▪ Immunoglobin G - antibody that can travel across the placenta, providing the baby
with the same immunity that the mother has; found in breastmilk
d. Passive artificial
▪ A different individual (human, horse) is exposed to pathogens and thus creates
antibodies which are then removed from the individual and transferred to someone
else
▪ e.g. rabies, tetanus
• Vaccines
• Types
○ Weakened form of the pathogen
○ Synthetic - mimics real pathogen
• Periodic booster vaccinations
• T-cells (cell-mediated immunity)
• Antigen receptors do not contain antibodies; allow cell to recognize molecules on the plasma
membrane of other cells
• Types
○ Cytotoxic/cytotic T cell (effector T cells)
▪ Puncture any cell in the body infected with viruses/cancerous
○ Helper T cells (effector T cells)
▪ Connect macrophages via a MHC
▪ Greatly increase the rate of cell division of all lymphocytes
○ Memory T cells
▪ Stores chemical composition of the pathogens and the attacks against them
○ Suppressor T cells
▪ Shut down the immune system in case the attack is against the body itself - an
autoimmune response
○ Delayed hypersensitivity T cell
▪ respond to antigens by releasing chemicals which promote inflammation
▪ Promote phagocytosis by attracting macrophages thru chemotaxis
▪ Active in allergic reactions
• Auto-immunity
• Not good
• When the body cannot differentiate MHC of its own cells and that of others; attacks own cells
• Examples of autoimmune diseases
○ Multiple Sclerosis
○ Rheumatoid
○ Arthritis
○ Celiac Disease.
○ Lupus

ANPHYD1-LEC Page 5