THE LYMPHATIC and IMMUNE SYSTEM

IMMUNITY (RESISTANCE)
Innate Immunity (Nonspecific resistance/immune response)
 Present at birth
 Includes defense mechanisms that provide general protection against invasion by a wide range
of pathogens
Adaptive Immunity (Specific immune response)
 Involves activation of specific lymphocytes that combat a particular pathogen or other foreign
substance
 The body system that carries out immune responses is the Lymphatic System

COMPONENTS OF THE LYMPHTIC SYSTEM

 The lymphatic system consists of several structures and organs that contain lymphatic tissue,
bone marrow, and a fluid called lymph that flows within lymphatic vessel
 What is the composition of lymph?
 Lymph is similar in composition to blood plasma. The main chemical difference is that lymph
does not contain erythrocytes.
 It also contains much lower concentration of protein than plasma since most protein molecules
are too large to filter through the capillary wall.
 Lymph contains water, some plasma proteins, electrolytes, lipids, leukocytes, coagulation
factors, antibodies, enzymes, sugars, urea, amino acids
 How much lymph is in the body?
 The body contains 1 to 2 liters of lymph which accounts for 1-3% of the body weight
 The lymphatic system returns slightly more than 3 liters of fluid from the tissues to the
circulatory system on a daily basis

LYMPHATIC SYSTEM STRUCTURE

 The lymphatic system consists of the lymphatic vessels, lymph and lymphoid organs such as
spleen, thymus, lymph nodes, etc. Together these components form a network that collects
and drains most of the fluid that seeps from the bloodstream and accumulates in the space
between cells.
 What are the primary functions of the lymphatic system? The lymphatic system is responsible
for maintaining proper fluid balance in tissues and blood, in addition to its role in defending
the body against disease-causing agents.
 The primary functions of the lymphatic system are:
1. Drain interstitial fluid - To collect the interstitial fluid that consists of excess water and
proteins and return it to the blood; the lymphatic system returns slightly more than 3
liters of fluid from the tissues to the circulatory system on a daily basis.
2. Transport dietary fats - To transport lipids and other nutrispleents that are unable to enter
the bloodstream directly
3. Carry out immune responses - To protect the body from foreign cells and
microorganisms.

LYMPHATIC VESSELS AND LYMPH CIRCULATION

1. Lymphatic vessels begin as lymphatic capillaries, which are closed on one end
 Lymphatic capillaries are located between cells of many tissues

2. Lymphatic capillaries merge to form lymphatic vessels, which have thin walls and many valves
3. From the lymphatic vessels, lymph passes through lymph nodes and then into lymph trunks
 Lymph trunks include the lumbar, intestinal, bronchomediastinal, subclavian, and jugular
trunks
4. Lymph trunks then merge to form either the thoracic duct or the right lymphatic duct

LYMPHATIC CAPILLARIES
 The smallest lymph vessels are lymphatic capillaries, which originate in the peripheral tissues.
 They are larger in diameter than blood capillaries but have a thinner wall.
 The lymphatic capillaries have a unique structure that allows interstitial fluid to flow into
them, but not out.
 Lymphatic capillaries are found in almost every tissue and organ of the body.
 They are not found in avascular tissues (tissues that lack a blood supply), such as cartilage, the
epidermis and cornea of the eye, the CNS, portions of the spleen, and red bone marrow.

ROUTES OF DRAINAGE
 Lymphatic capillaries - lymphatic vessels - lymph nodes - lymphatic trunk - thoracic duct or
right lymphatic duct
 Lymph flows from the lymphatic capillaries into larger lymph vessels that lead toward the
lymphatic trunk of the body.
 The lymphatics continue to join together, finally forming two large ducts: the right lymphatic
duct and the thoracic duct

FORMATION AND FLOW OF LYMPH

How does lymph move around inside its vessels?
 Slowly, through peristalsis, the action of semilunar valves, and the squeezing of surrounding
skeletal muscles
Peristalsis - refers to the involuntary constriction and relaxation of the muscles of the intestine or
another canal, creating wave-like movements that push the contents of the canal forward.

PRIMARY LYMPHATIC ORGANS

 Primary lymphatic organs are organs where immune cells become immunocompetent -
wherein they have the ability to carry out adaptive immune response
 Those organs where lymphocytes are formed and mature
 Red bone marrow and thymus

THYMUS
 Located in the mid thorax just behind the breastbone and between the lungs in the upper chest
(the superior mediastinum, if you want to be technical)the thymus is an amorphous (that is,
without a clearly defined shape or form), bilobed organ that sits superior to the aortic arch and
extend upward toward the neck
 As with other lymphatic structures, the thymus is surrounded by a fibrous capsule (Note:
Connective tissue covers the entire organ, making the thymus an encapsulated lymphoid
organ) that dips inside to create chambers called lobules.
 Within each lobule is a cortex made of T cells held in place by reticular fibers and a central
medulla of unusually onion-like layered epithelial cells called thymic corpuscles or Hassal’s
corpuscles, as well as scattered lymphocytes
 The thymus is special in that, unlike most organs, it is at its largest in children when they
weigh around 40 grams.
 Once you reach puberty, the thymus starts to slowly shrink (through a process called
involution the gland atrophies) and become replaced by fat.
 The term involution is the inverse of evolution
 By age 75, the thymus is little more than fatty tissue of around 6 grams. Fortunately, the
thymus produces all of your T cells by the time you reach puberty.
 The thymus gland serves its most critical role - as a nursery for immature T lymphocytes or T
cells - during fetal development and the first few years of a human’s life
 Prior to birth, fetal bone marrow produces lymphoblasts (early stage lymphocytes) that
migrate to the thymus
 Shortly after birth and continuing until adolescence, the thymus secretes several hormones,
collectively called thymosin, that prompt the early cells to mature into full-grown T cells that
are immunocompetent, ready to go forth and conquer invading microorganisms
 That’s why the thymus serves both as a lymphoid organ and as an endocrine organ that
secretes several hormones related to immunity [thymosin, thymic humoral factor (THF),
thymic factor (TF) and thymopoeitin promote the maturation of T-cells]
 In essence, thymus consists of a large number of lymphocytes, many of which become
specialized T cells
 Once mature, lymphocytes migrate out into the body and accumulate in various locations,
such as in organs of the digestive and respiratory tract, as well as stand-alone lymphoid organs
 Here, they are able to quickly and effectively encounter pathogens and mount an immune
response
 For a very long time the role of thymus in the body was a complete medical mystery because
it seemed to be just full of dead immune cells - “the place where cells went to die”, as Daniel
Davis put it in his superlative book The Compatibility Gene.
 In 1961, Jacques Miller, a French-Australian research scientist working in London, unravelled
the mystery.
 What Miller established was that the thymus is a “nursery for T-cells”
 T-cells are a kind of elite corps in the immune system, and the dead cells found in the thymus
were lymphocytes that had failed to pass muster because they were either not very good at
identifying and attacking foreign invaders or because they were too eager to attack the body’s
own healthy cells
 They had, in short, failed to make the cut. It was an immensely significant discovery
 As the medical journal The Lancet observed, it made Miller “the last person to identify the
function of a human organ”

RED BONE MARROW

 While all lymphocytes begin their lives in the bone marrow, only the B lymphocytes (B-cells)
mature there
 As naive (immature) B cells, they are not able to recognize antigens with their receptors and
are incapable of mounting an immune response
 The bone marrow is compartmentalized in such a way that these immature cells are unable to
enter the systemic circulation until they pass inspection, at which time they are mature and are
released into circulation
SECONDARY LYMPHATIC ORGANS
 Those organs that serve as filters in the lymphatic system
 Secondary lymphatic organs and tissues include:
 Lymph nodes
 Spleen
 Lymphatic nodules
Tonsils
Peyer’s patches
MALT - mucosa-associated lymph tissue

LYMPH NODE
 These encapsulated, bean-shaped lymphoid organs interrupt the path of the larger lymphatic
vessels
 There are approximately 600 lymph nodes, ranging in diameter up to 1 inch (2.54 cm),
scattered along the lymphatic vessels.
 The greatest concentration of lymph nodes are found in the neck, armpit, thorax, abdomen,
and groin.
 What are “swollen glands”?
 The condition commonly referred to as “swollen glands” is really enlarged lymph nodes.
 Is it correct to refer to lymph nodes as lymph glands?
 The lymph nodes were originally referred to as lymph glands because they resembled acorns.
 Unlike true glands, the lymph node do not secrete fluids, so they are now called lymph nodes
(from the Latin word node, meaning knob)
 The term “swollen glands” has been retained to describe the condition of a slight enlargement
of the lymph nodes along the lymphatic vessels draining a specific region of the body.
 It generally indicates an inflammation or infection of peripheral structures.

SPLEEN
 The spleen is the largest lymphoid organ
 It is about 5 inches (12 cm) long and weighs about 160 grams

 What are the functions of the spleen?

 While the spleen does have lymphoid characteristics, it also functions in the cleaning,
destruction and removal of dead RBCs
 Therefore, the primary function of the spleen is the filtering of blood and removal of abnormal
or dead RBCs by phagocytosis
 The spleen also stores iron from worn-out blood cells, which is then returned to the circulation
and used by the bone marrow to produce new blood cells
 The immune reaction begins in the spleen with the activation of immune response by B cells
and T cells in response to antigens in the blood
 Can a person function without a spleen?
 Individuals without a spleen are able to function without difficulty because the bone marrow
and liver can perform many of the functions of the spleen.
 However, these individuals are at a greater risk for bacterial infections

LYMPHATIC NODULE
 Often confused with lymph nodes, lymphatic nodules are simply aggregates of lymphocytes
 Lymphatic nodules are masses of lymphatic tissue that are not surrounded by a fibrous
capsule
 Lymphoid nodules are found in the connective tissues or the lamina propria of mucous
membranes lining the gastrointestinal, urinary, reproductive, and respiratory tracts.
 They are small, oval-shaped, and approximately a millimeter in diameter.
 Largely composed of B lymphocytes, nodules also consist of antigen-presenting cells and
reticular cells for structure and anchorage
 T lymphocytes also reside in the nodules but to a lesser degree

 The collection of lymphoid tissues lining the digestive system is referred to as mucosa-
associated lymphatic tissue (MALT) because they are found in the mucous membranes lining
the digestive tract
 Clusters of lymphoid tissue found in the intestine and appendix are called aggregated lymph
nodules, or Peyer’s patches
 Tonsils are a group of lymphoid tissues found at the junction of the oral cavity, nasal cavity,
and throat.
 There are three sets of tonsils in the back of the mouth, all of which contribute to the lymph
system’s cleaning function. The three sets are:
- the adenoid or pharyngeal tonsil
- the lingual tonsils
- the palatine tonsils
 Palatine tonsils - filled with lymphatic nodules and positioned at the back of the mouth
between the oral and pharyngeal cavities, these organs are in the perfect location to detect any
pathogens trying to gain entry into the body through the oral cavity
 Palatine tonsils - can become inflamed because of tonsillitis
 These tonsils are often surgically removed during a tonsillectomy
 Lingual tonsils - also protect the oral cavity, but to a lesser degree
 Located at the base of the tongue
 Much smaller in mass than that of the palatine tonsils
 Also filled with lymphatic nodules
 Pharyngeal tonsil - better known as the adenoid
 It is positioned higher in the pharynx, in the posterior wall of the upper part of the throat
 Provide protection from any pathogen seeking to gain entrance to the body

INNATE IMMUNITY: FIRST LINE OF DEFENSE - Skin and Mucous

 Innate immunity refers to a wide variety of body responses that serve to protect us against
invasion of a wide variety of pathogens and their toxins
 We are born with this kind of immunity
 The first line of defense against invaders are non-specific defenses, meaning
 Two lines of defense:
1. Skin and mucous membranes - mechanical defenses
2. Internal defenses
 Mechanical defenses
- Skin, mucous membranes, tears, saliva, mucus, cilia, epiglottis, urine flow,
defecating, vomiting

INNATE IMMUNITY: FIRST LINE OF DEFENSE - Fluids

 Mechanical defenses
- Skin, mucous membranes, tears, saliva, mucus, cilia, epiglottis, urine flow,
defecating, vomiting

INNATE IMMUNITY: FIRST LINE OF DEFENSE - Chemicals

 Chemical defenses
- Sebum, lysozyme, gastric juice

SECOND LINE OF DEFENSE - Interferons

 Also known as our Internal Defenses

SECOND LINE OF DEFENSE - NK Cells & Fever

 The primary cells of the lymphatic system are lymphocytes.
 Lymphocytes are actually white blood cells just like monocytes, neutrophils, eosinophils and
basophils , all of which play an active role in the immune system.
 Let’s go back to lymphocytes.
 There are three types of lymphocytes: T cells, B cells and NK cells
 T cells
- Account for approximately 80% of the circulating lymphocytes
- They are thymus-dependent
- They are primary cells that provide cellular immunity
 B cells
- Derived from the bone marrow;
- Account for 10-15% of the circulating lymphocytes
- They are responsible for antibody-mediated immunity
 NK (natural killer) cells
- Account for the remaining 5-10% of the circulating lymphocytes
- They attack foreign cells, normal cell infected with viruses, and cancer
cells that appear in normal tissues
 What is the role of fever in infection?
 Normal body temperature is 98.6 degrees Fahrenheit (37.2 degrees Celsius)
 Fever is defined as a higher-than-normal body temperature
 Certain pathogens and bacterial toxins may stimulate the release of pyrogens (a group of
cytokine proteins that regulate body temperature) such as interleukin-1
 The increased temperature helps fight an infection
 How? Increases in body temperature increase the metabolic rate and may speed up body
reactions that aid to resolve infections
 That is, increased temperature also increases the division,migration and metabolism of the
immune system cells and gives them an attack advantage over many pathogens
 Higher body temperatures destroy some pathogens directly
 Fever may also inhibit the growth of certain microbes
 Fever also appears to stimulate the liver to hoard substances that bacteria require, helping to
decrease bacterial growth
 When is fever dangerous?
 Only when the body temperature reaches or exceeds 105 degrees Fahrenheit (40.5 degrees
Celsius) will your cells be destroyed
 Any fever lasting for more than a few days and in excess of 38.5 degrees should lead one to
seek critical treatment from a doctor
SECOND LINE OF DEFENSE - Inflammation
 Mast cells is one of the cells aside from lymphocytes and other WBCs that play a role in the
immune system
 Mast cells are specialized cells of connective tissue
 What is the role of mast cells in inflammation?
 They release heparin, histamine, leukotrienes, and prostaglandins to stimulate the
inflammatory response

 Inflammation is essentially the heat of the battle as the body defends itself from damage.
Blood vessels in the vicinity of an injury or wound dilate, allowing more blood to flow to the
site, bringing with it white blood cells to fight off invaders.
 That causes the site to swell, increasing the pressure on surrounding nerves, resulting in
tenderness.

CYTOKINES
 Unlike RBCs, white blood cells can leave the circulatory system to pass through surrounding
tissues, like an army patrol searching through jungle.
 When they encounter an invader, they fire off attack chemicals called CYTOKINES, which is
what makes you feel feverish and ill when your body is battling infection.
 It’s not the infection that makes you feel dreadful, but your body defending itself.
 The PUS that seeps from a wound is simply dead white cells that have given their lives in
defense of you
 Inflammation is a tricky thing. Too much and it destroys neighboring tissues and ca result in
unnecessary pain, but too little and it fails to stop infection.
 Faulty inflammation has been linked to all kinds of maladies, from diabetes and Alzheimer’s
disease to heart attacks and stroke.
 Sometimes the immune system gets so ramped up that it brings out all its defenses and fires
all its missiles in what is known as a CYTOKINE STORM.
 That’s what kills you. Cytokine storm shows up again and again in many pandemic diseases
such as COVID-19, but also in things like extreme allergic reactions to bee stings or seafoods
or antibiotics.

PHAGOCYTOSIS
 Phagocytosis refers to the ingestion of foreign invaders such as microbes by specialized white
blood cells
 Why is phagocytosis so important to the human body?
 XXXX

PHAGOCYTES
 Examples of specialized WBCs that ingest foreign invaders are monocytes and phagocytes

ADAPTIVE IMMUNITY: CELL-MEDIATED

 Adaptive immunity is the ability of the body to defend itself against specific invading agents
 Adaptive immunity has both specificity and memory and is divided into 2 types
1. Cell-mediated
2. Antibody-mediated
 Adaptive immunity is SPECIFIC in the sense that it involves the production of specific type
of cells (e.g., in the case of cell-mediated immune response) or specific antibodies (e.g.,
antibody-mediated immune response) to destroy a particular antigen
 An antigen is a substance recognized as foreign by the body that provokes or triggers the
immune response, causing the body to form and produce specific antibodies
 An antibody is a protein produced by B cells in response to an antigen.
 Antibodies are able to neutralize the antigens that provoke their production
 At the heart of the immune system are five types of WBCs: lymphocytes, monocytes,
neutrophils, eosinophils and basophils
 They are all important, but LYMPHOCYTES are the ones that excite immunologists the most
 Lymphocytes are “just about the cleverest or the smartest little cells in the whole body”
because of their ability to recognize almost any kind of unwanted invader and mobilize a swift
and targeted response
 As I’ve mentioned before, lymphocytes are actually white blood cells just like monocytes,
neutrophils, eosinophils and basophils , all of which play an active role in the immune system
 There are three types of lymphocytes: T cells, B cells and NK cells
 But the two principal types which are important in adaptive immunity are the B-cells and T-
cells
 B cells
- The B in B-cells comes, a little oddly, from “bursa of Fabricius”, an
appendix-like organ in birds where B-cells where first seen
- Humans and mammals don’t have a bursa of Fabricius
- Our B-cells are derived from the bone marrow, but it is entirely coincidental that
that starts with a B, too!
- Account for 10-15% of the circulating lymphocytes
- They are responsible for antibody-mediated immunity
 T cells
- T-cells are more faithful to their source
- Though created in the red bone marrow, they emerge from the thymus, a small organ in
the chest just above the heart and between the lungs
- Account for approximately 80% of the circulating lymphocytes
- They are primary cells that provide cellular immunity
- T cells are a special type of cell that can be trained to directly attack infected or
cancerous cells and prompt phagocytes to eat pathogens.
- Some T cells also stimulate B cells to produce antibodies
- Here’s a trivia: Only 2% of T cells pass their training - The rest are rejected as they might
attack us!

- T-cells subdivide into four further categories: helper T-cells, killer T-cells, regulators and
memory T-cells
- Killer T-cells, as the name suggests, kill cells that have been invaded by pathogens
- Helper T-cells help other immune cells act, including helping B-cells produce antibodies
- Regulators calm the immune system and are critical in recognizing friendly microbes
- Memory T-cells remember the details of earlier invaders, and are therefore able to
coordinate a swift response if the same pathogen shows up again - what is known as
adaptive immunity
 - Memory T-cells are extraordinarily vigilant!
- I don’t get chickenpox because somewhere inside me are memory T-cells that have been
protecting me from a second attack for more than 50 years.
- When they identify an invader, they instruct B-cells to produce proteins known as
antibodies, and these attack the invading organisms.
- Antibodies are clever things because they recognize and fight off previous invaders
quickly if they dare come back.
- That’s why so many diseases only make you sick once.
 In cell-mediated immunity:
 - An antigen is recognized and bound
 - A small number of T cells proliferate and differentiate into a clone of effector
cells
 - The antigen is eliminated

ADAPTIVE IMMUNITY: ANTIBODY-MEDIATED

 In antibody-mediated immunity:
 - An antigen is recognized and bound
 - Helper T cells costimulate the B cell so the B cell can proliferate and differentiate into
a clone of effector cells that produce antibodies
 - The antigen is eliminated
 How many infectious diseases can the immune system respond to?
- It is thought that B cells alone can produce enough different antibodies to deal
with 1 billion different types of pathogens
 If the front-line response hasn’t contained the infection within 12 hours, the adaptive immune
response swings into action. The adaptive immune system remembers previous exposures to
the pathogen to launch a specific, targeted response.
 The B cells are a special type of cell that can be trained to produce antibodies in response to
the presence of a particular pathogen. They can multiply rapidly to increase the response.

 Looking For Trouble (How The Body Works)

 The B cells clone itself. Some of these clones become MEMORY CELLS, but most become
PLASMA CELLS, which produce antibodies that are specific to the invader’s antigens
 Plasma Cells - large, antibody-producing cells that are derived from B cells
 Each plasma cell that is derived from a single B cell manufactures millions of identical
antibodies
 These antibodies are then released into the blood to fight the antigen (virus, microbe, or other
foreign tissue /substances
 Antibodies are Y-shaped proteins produced by B cells.
 They stick to the surface of invaders and mark them out for destruction by phagocytes.
 In other words, if the body needs more help fighting the infection, B cells travel to the site of
infection and start producing antibodies that bind to the pathogens, marking them for
destruction
 Trivia: A single B cell may have up to 100,000 antibodies on its outer surface
 Question: Do all B cells produce the same antibodies?
 No, each B cell is programmed to produce one specific antibody.
 For example, one B cell produces the antibody that blocks a virus that is responsible for the
common cold, while a different B cell produces the antibody that attacks the bacterium that
causes pneumonia
ADAPTIVE IMMUNITY: CLONAL SELECTION

ANTIGEN
 An antigen is a substance recognized as foreign by the body that provokes or triggers the
immune response, causing the body to form and produce specific antibodies
 An antibody is a protein produced by B cells in response to an antigen.
 Antibodies are able to neutralize the antigens that provoke their production

 Immunogenicity
 Reactivity
 Entire microbes or just parts of microbes may act as antigens
 - Typically, just certain small parts of a large antigen molecule act as the triggers for
immune responses. These small parts are called epitopes.
 Pathways of Antigen Processing
- For an immune response to occur, B cells and T cells must recognize that a foreign
antigen is present.
- B cells can recognize and bind to antigens in lymph, interstitial fluid, or blood
plasma
- T cells only recognize fragments of antigenic proteins that are processed and presented
in a certain way

ANTIGEN RECEPTORS

Pathways of Antigen Processing

 - In antigen processing, antigenic proteins are broken down into peptide fragments that
associate with MHC molecules
 - The antigen–MHC complex is then inserted into the plasma membrane of a body cell.
 This process is called antigen presentation

ANTIBODIES (IMMUNOGLOBULINS)

 There are five classes of antibodies, known as immunoglobulins (Igs). The following lists the
known classes:

ACQUIRED ADAPTIVE IMMUNITY