THE

LYMPHATIC
SYSTEM AND
IMMUNITY

Submitted by: Submitted to:

Navarro, Micah Joyce T. Dr. Gallardo
Orjalo, Mark Angelo B.
BS PSY 3-1
 THE LYMPHATIC SYSTEM AND IMMUNITY

 The lymphatic system consists of lymph, lymphatic vessels, lymphatic tissues, and red
bone marrow.
 The lymphatic system assists in circulating body fluids and helps defend the body against
disease-causing agents.
 Lymphatic tissue is a specialized form of reticular connective tissue that contains large
numbers of lymphocytes.
 Two types of lymphocytes participate in adaptive immune responses: B cells and T cells.

Functions of the Lymphatic System

 The lymphatic system has three primary functions:

1. Drains excess interstitial fluid - Lymphatic vessels drain excess interstitial fluid from
tissue spaces and return it to the blood. Without this function, the maintenance of
circulating blood volume would not be possible.

2. Transports dietary lipids - Lymphatic vessels transport lipids and lipid-soluble vitamins
(A, D, E, and K) absorbed by the gastrointestinal tract.

3. Carries out immune responses - Lymphatic tissue initiates highly specific responses
directed against particular microbes or abnormal cells.

Lymphatic Vessels and Lymph Circulation

 Lymphatic vessels begin as lymphatic capillaries, which are located in the spaces
between cells, and are closed at one end.
 Lymphatic capillaries unite to form larger lymphatic vessels, which resemble small veins
in structure but have thinner walls and more valves.

 In the skin, lymphatic vessels lie in the subcutaneous tissue and generally follow the
same route as veins; lymphatic vessels of the viscera generally follow arteries, forming
plexuses (networks) around them.

 Tissues that lack lymphatic capillaries include avascular tissues, the central nervous
system, portions of the spleen, and red bone marrow.

Lymphatic Capillaries
 Lymphatic capillaries have greater permeability than blood capillaries and thus can
absorb large molecules such as proteins and lipids.

 Lymphatic capillaries are also slightly larger in diameter than blood capillaries and have
a unique one-way structure that permits interstitial fluid to flow into them but not out.

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  Attached to the lymphatic capillaries are anchoring filaments, which contain elastic
fibres.

 In the small intestine, specialized lymphatic capillaries called lacteals carry dietary lipids
into lymphatic vessels and ultimately into the blood. The lymph in small intestine is
called chyle because they appear creamy white

Lymph Trunks and Ducts

 As lymphatic vessels exit lymph nodes in a particular region of the body, they unite to
form lymph trunks.

 The principal trunks are the: lumbar, intestinal, bronchomediastinal, subclavian, and
jugular trunks.
 The lumbar trunks drain lymph from the lower limbs, the wall and viscera of the pelvis,
the kidneys, the adrenal glands, and the abdominal wall; The intestinal trunk drains
lymph from the stomach, intestines, pancreas, spleen, and part of the liver;
The bronchomediastinal trunks drain lymph from the thoracic wall, lung, and heart;
The subclavian trunks drain the upper limbs; The jugular trunks drain the head and
neck.

 Lymph passes from lymph trunks into two main channels, the thoracic duct and the right
lymphatic duct, and then drains into venous blood.

 The thoracic (left lymphatic) duct begins as a dilation called the cisterna chyli anterior to
the second lumbar vertebra.
 The thoracic duct is the main duct for the return of lymph to blood.

 The thoracic duct receives lymph from the left side of the head, neck, and chest, the left
upper limb, and the entire body inferior to the ribs.

 The right lymphatic duct receives lymph from the right jugular, right subclavian, and
right bronchomediastinal trunks. Thus, the right lymphatic duct receives lymph from
the upper right side of the body.

Formation and Flow of Lymph

 Most components of blood plasma, such as nutrients, gases, and hormones, filter freely
through the capillary walls to form interstitial fluid, but more fluid filters out of blood
capillaries than returns to them by reabsorption.

 The excess filtered fluid — about 3 litres per day — drains into lymphatic vessels and
becomes lymph.

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  The sequence of fluid flow is blood capillaries (blood) → interstitial spaces (interstitial
fluid) → lymphatic capillaries (lymph) → lymphatic vessels (lymph) → lymphatic
ducts (lymph) → junction of the internal jugular and subclavian veins (blood).

The same two ‘pumps’ that aid the return of venous blood to the heart maintain the flow of
lymph:

1. Skeletal muscle pump - The ‘milking action’ of skeletal muscle contractions

compresses lymphatic vessels (as well as veins) and forces lymph towards the junction
of the internal jugular and subclavian veins.

2. Respiratory pump - Lymph flow is also maintained by pressure changes that occur
during inhalation. Lymph flows from the abdominal region, where the pressure is
higher, towards the thoracic region, where it is lower. When the pressures reverse
during exhalation, the valves in lymphatic vessels prevent backflow of lymph.

Lymphatic Organs and Tissues

 Primary lymphatic organs are the sites where stem cells divide and
become immunocompetent, that is, capable of mounting an immune response.
 The primary lymphatic organs are the red bone marrow and the thymus.
 The secondary lymphatic organs and tissues are the sites where most immune responses
occur.
 It includes lymph nodes, the spleen, and lymphatic nodules (follicles).

Thymus
 The thymus is a bilobed organ located in the mediastinum between the sternum and the
aorta. An enveloping layer of connective tissue holds the two lobes closely together,
but a connective tissue capsule separates the two.

 Extensions of the capsule, called trabeculae, penetrate inward and divide each lobe into
lobules.

 Each thymic lobule consists of a deeply staining outer cortex and a lighter-staining
central medulla.

 The cortex is composed of large numbers of T cells and scattered dendritic cells,
epithelial cells, and macrophages.

 Immature T cells (pre-T cells) migrate from red bone marrow to the cortex of the thymus,
where they proliferate and begin to mature.
 Dendritic cells, which are derived from monocytes, assist the maturation process.

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  Each of the specialised epithelial cells in the cortex has several long processes that
surround and serve as a framework for as many as 50 T cells. Additionally, they
produce thymic hormones that are thought to aid in the maturation of T cells.

 Only about 2% of developing T cells survive in the cortex. The remaining cells die via
apoptosis.

 Thymic macrophages help clear out the debris of dead and dying cells. The surviving T
cells enter the medulla.

 The medulla consists of widely scattered, more mature T cells, epithelial cells, dendritic
cells, and macrophages.

 Some of the epithelial cells become arranged into concentric layers of flat cells that
degenerate and become filled with keratohyalin granules and keratin called thymic
corpuscles or Hassall’s corpuscles.

 Because of its high content of lymphoid tissue and a rich blood supply, the thymus has a
reddish appearance in a living body.

Lymph Nodes
 Located along lymphatic vessels are about 600 bean-shaped lymph nodes.

 They are scattered throughout the body, both superficially and deep, and usually occur in
groups.

 Large groups of lymph nodes are present near the mammary glands and in the axillae and
groin.
 Lymph nodes are 1–25 mm (0.04–1 in.) long and are covered by a capsule of dense
connective tissue that extends into the node.

 The capsular extensions, called trabeculae, divide the node into compartments, provide
support, and provide a route for blood vessels into the interior of a node.

 Internal
to the capsule is a supporting network of reticular fibres and fibroblasts. The
capsule, trabeculae, reticular fibres, and fibroblasts constitute the stroma a lymph node.

 The parenchyma (functioning part) of a lymph node is divided into a superficial cortex
and a deep medulla.
 The cortex consists of an outer cortex and an inner cortex.

 Within the outer cortex are egg-shaped aggregates of B cells called lymphatic nodules
(follicles). A lymphatic nodule consisting chiefly of B cells is called a primary
lymphatic nodule.

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  The inner cortex does not contain lymphatic nodules. It consists mainly of T cells and
dendritic cells that enter a lymph node from other tissues.

 The medulla of a lymph node contains B cells, antibody-producing plasma cells that have
migrated out of the cortex into the medulla, and macrophages. The various cells are
embedded in a network of reticular fibres and reticular cells.
 As you have already learned, lymph flows through a node in one direction only.
 Flow of Lymph through the Lymph node: Afferent Lymphatic Vessels — Subcapsular
Sinus — Trabecular Sinuses — Medullary Sinuses — Efferent Lymphatic Vessels
 Lymph nodes function as a type of filter.

Spleen
 The oval spleen is the largest single mass of lymphatic tissue in the body.
 It is located in the left hypochondriac region between the stomach and diaphragm.

 The superior surface of the spleen is smooth and convex and conforms to the concave
surface of the diaphragm.

 Like lymph nodes, the spleen has a hilum. Through it pass the splenic artery, splenic
vein, and efferent lymphatic vessels.
A capsule of dense connective tissue surrounds the spleen and is covered in turn by a
serous membrane, the visceral peritoneum.

 Trabeculae extend inward from the capsule. The capsule plus trabeculae, reticular fibres,
and fibroblasts constitute the stroma of the spleen

 The parenchyma of the spleen consists of two different kinds of tissue called white pulp
and red pulp.

 (1) White pulp is lymphatic tissue, consisting mostly of lymphocytes and macrophages
arranged around branches of the splenic artery called central arteries. (2) The red pulp
consists of blood-filled venous sinuses and cords of splenic tissue called splenic cords
or Billroth’s cords.

 Within the white pulp, B cells and T cells carry out immune functions. Spleen
macrophages destroy blood-borne pathogens by phagocytosis.

 Within the red pulp, the spleen performs three functions related to blood cells: (1)
removal by macrophages of ruptured, worn out, or defective blood cells and platelets;
(2) storage of platelets, up to one-third of the body’s supply; and (3) production of
blood cells (haemopoiesis) during foetal life.

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Lymphatic Nodules
 Lymphatic nodules (follicles) are egg-shaped masses of lymphatic tissue that are not
surrounded by a capsule.

 Mucous membranes lining the gastrointestinal, urinary, and reproductive tracts and the
respiratory airways, lymphatic nodules in these areas are also referred to as mucosa-
associated lymphatic tissue (MALT).
 Although many lymphatic nodules are small and solitary, some occur in multiple large
aggregations in specific parts of the body. Among these are the tonsils in the
pharyngeal region and the aggregated lymphatic follicles (Peyer’s patches) in the ileum
of the small intestine.

DEVELOPMENT OF LYMPHATIC TISSUES

 Lymphatic tissues begin to develop by the end of the fifth week of embryonic life.

 Lymphatic vesselsdevelop from lymph sacs that arise from developing veins, which are
derived from mesoderm.

 The firstlymph sacs to appear are the paired jugular lymph sacs at the junction of the
internal jugular and subclavian veins.

 From the jugular lymph sacs, lymphatic capillary plexuses spread to the thorax, upper
limbs, neck, and head. Some of the plexuses enlarge and form lymphatic vessels in
their respective regions.

 The next lymph sac to appear is the unpaired retroperitoneal lymph sac at the root of the
mesentery of the intestine. It develops from the primitive vena cava and mesonephric
(primitive kidney) veins.

 At about the time the retroperitoneal lymph sac is developing, another lymph sac,
the cisterna chyli , develops inferior to the diaphragm on the posterior abdominal wall.

 The last
of the lymph sacs, the paired posterior lymph sacs, develop from the iliac veins.
The posterior lymph sacs produce capillary plexuses and lymphatic vessels of the
abdominal wall, pelvic region, and lower limbs.
 With the exception of the anterior part of the sac from which the cisterna chyli develops,
all lymph sacs become invaded by mesenchymal cells and are converted into groups of
lymph nodes.

INNATE IMMUNITY
 Innate(nonspecific) immunity includes the external physical and chemical barriers
provided by the skin and mucous membranes. It also includes various internal

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 defences, such as antimicrobial substances, natural killer cells, phagocytes,
inflammation, and fever.

First line of defence: Skin and Mucous membranes

 The skinand mucous membranes of the body are the first line of defence against
pathogens.

 These structuresprovide both physical and chemical barriers that discourage pathogens
and foreign substances from penetrating the body and causing disease.

 The epidermis provides a formidable physical barrier to the entrance of microbes. In

addition, periodic shedding of epidermal cells helps remove microbes at the skin
surface.
 The epithelial layer of mucous membranes, which line body cavities, secretes a fluid
called mucous that lubricates and moistens the cavity surface because mucous is
slightly viscous; it traps many microbes and foreign substances. (e.g. mucous
membrane of the nose and upper respiratory tract)

 Other fluids produced by various organs also help protect epithelial surfaces of the skin
and mucous membranes. (e.g. lacrimal apparatus of the eyes, saliva)
 The cleansing ofthe urethra by the flow of urine retards microbial colonisation of the
urinary system.

 Vaginal secretions likewise move microbes out of the body in females. Vaginal
secretions also are slightly acidic, which discourages bacterial growth
 Defecation and vomiting also expel microbes.

 Sebaceous (oil) glands of the skin secrete an oily substance called sebum that forms a
protective film over the surface of the skin.
 Perspiration helps flush microbes from the surface of the skin.

 Gastricjuice, produced by the glands of the stomach, destroys many bacteria and most
bacterial toxins.

Second line of defence: Internal defences

 When pathogens penetrate the physical and chemical barriers of the skin and mucous
membranes, they encounter a second line of defence: internal antimicrobial substances,
phagocytes, natural killer cells, inflammation, and fever.

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Antimicrobial Substances
There are four main types of antimicrobial substances that discourage microbial growth: (1)
interferons, (2) complement, (3) iron-binding proteins, and (4) antimicrobial proteins.

1. Lymphocytes, macrophages, and fibroblasts infected with viruses produce proteins

called interferons (IFNs). IFNs do not prevent viruses from attaching to and
penetrating host cells but they do stop replication.
2. The complement system causes cytolysis (bursting) of microbes, promotes
phagocytosis, and contributes to inflammation.

3. Iron-binding proteins inhibit the growth of certain bacteria by reducing the amount of
available iron.
4. Antimicrobial proteins (AMPs) are short peptides that have a broad spectrum of
antimicrobial activity and kill a wide range of microbes. AMPs can also attract
dendritic cells and mast cells, which participate in immune responses.

Natural killer cells and Phagocytes

 About 5–10% of lymphocytes in the blood are natural killer (NK) cells.

 NK cells lack the membrane molecules that identify B and T cells, but they have the
ability to kill a wide variety of infected body cells and certain tumour cells.

 NK cellsattack any body cells that display abnormal or unusual plasma membrane
proteins.

 The binding of NK cells to a target cell, such as an infected human cell, causes the
release of granules containing toxic substances from NK cells.
 Phagocytes are specialised cells that perform phagocytosis.

 The twomajor types of phagocytes are neutrophils and macrophages. When an infection
occurs, neutrophils and monocytes migrate to the infected area.

 During this
migration, the monocytes enlarge and develop into actively phagocytic
macrophages called wandering macrophages. Other macrophages, called fixed
macrophages, stand guard in specific tissues.
 Phagocytosis occurs in five phases:

1. Chemotaxis - Chemicals that attract phagocytes might come from invading microbes,
white blood cells, damaged tissue cells, or activated complement proteins.
2. Adherence - Attachment of the phagocyte to the microbe or other foreign material.

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 3. Ingestion - pseudopods engulf the microbe in a process called ingestion. Pseudopods
surrounds the microorganism with a sac called phagosome

4. Digestion - The phagosome enters the cytoplasm and merges with lysosomes to form a
single, larger structure called a phagolysosome. The lysosome contributes lysozyme,
which breaks down microbial cell walls, and other digestive enzymes that degrade
carbohydrates, proteins, lipids, and nucleic acids.

5. Killing. The chemical onslaught provided by lysozyme, digestive enzymes, and

oxidants within a phagolysosome quickly kills many types of microbes. Any materials
that cannot be degraded further remain in structures called residual bodies.

Inflammation
 Inflammation is a nonspecific, defensive response of the body to tissue damage.

 Among the conditions that may produce inflammation are pathogens, abrasions, chemical
irritations, distortion or disturbances of cells, and extreme temperatures.

 The four characteristic signs and symptoms of inflammation are redness, pain, heat, and
swelling.
 Inflammation can also cause a loss of function in the injured area.

 Inflammation is an attempt to dispose of microbes, toxins, or foreign material at the site

of injury, to prevent their spread to other tissues, and to prepare the site for tissue repair
in an attempt to restore tissue homeostasis.

 The inflammatory response has three basic stages: (1) vasodilation and increased
permeability of blood vessels, (2) emigration (movement) of phagocytes from the
blood into interstitial fluid, and, ultimately, (3) tissue repair.

VASODILATION AND INCREASED BLOOD VESSEL PERMEABILITY

 Two immediate changes occur in the blood vessels in a region of tissue injury:
vasodilation (increase in the diameter) of arterioles and increased permeability of
capillaries.

 Increased permeability means that substances normally retained in blood are permitted to
pass from the blood vessels.

 Vasodilation allows more blood to flow through the damaged area, and increased
permeability permits defensive proteins such as antibodies and clotting factors to enter
the injured area from the blood.

 Among the substances that contribute to vasodilation, increased permeability, and other
aspects of the inflammatory response are the following.

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 1. Histamine. Neutrophils and macrophages attracted to the site of injury also stimulate
the release of histamine, which causes vasodilation and increased permeability of blood
vessels.

2. Kinins. Polypeptides formed in blood from inactive precursors called kininogens,

(kinins), induce vasodilation and increased permeability and serve as chemotactic
agents for phagocytes.

3. Prostaglandins. Prostaglandins (PGs), especially those of the E series, are released by

damaged cells and intensify the effects of histamine and kinins. PGs also may stimulate
the emigration of phagocytes through capillary walls.

4. Leukotrienes. Produced by basophils and mast cells, leukotrienes (LTs) cause

increased permeability; they also function in adherence of phagocytes to pathogens and
as chemotactic agents that attract phagocytes.

5. Complement. Different components of the complement system stimulate histamine

release, attract neutrophils by chemotaxis, and promote phagocytosis; some
components can also destroy bacteria.

 Dilationof arterioles and increased permeability of capillaries produce three of the signs
and symptoms of inflammation: heat, redness (erythema), and swelling (oedema). Heat
and redness result from the large amount of blood that accumulates in the damaged
area. As the local temperature rises slightly, metabolic reactions proceed more rapidly
and release additional heat. Oedema results from increased permeability of blood
vessels, which permits more fluid to move from blood plasma into tissue spaces.

 Painis a prime symptom of inflammation. It results from injury to neurons and from
toxic chemicals released by microbes. Kinins affect some nerve endings, causing much
of the pain associated with inflammation. Prostaglandins intensify and prolong the pain
associated with inflammation. Pain may also be due to increased pressure from
oedema.

 The increased permeability of capillaries allows leakage of blood-clotting factors into

tissues. The clotting sequence is set into motion, and fibrinogen is ultimately converted
to an insoluble, thick mesh of fibrin threads that localizes and traps invading microbes
and blocks their spread.

EMIGRATION OF PHAGOCYTES
 An hour after the inflammatory process starts, phagocytes appear on the scene.

 Neutrophilsbegin to stick to the inner surface of the endothelium (lining) of blood

vessels then the neutrophils begin to squeeze through the wall of the blood vessel to
reach the damaged area. This process, calledEmigration.

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  Neutrophils attempt to destroy the invading microbes by phagocytosis.
 Although neutrophils predominate in the early stages of infection, they die off rapidly.

 As the inflammatory response continues, monocytes follow the neutrophils into the
infected area.

 Once inthe tissue, monocytes transform into wandering macrophages that add to the
phagocytic activity of the fixed macrophages already present.

 Eventually,
macrophages also die. Within a few days, a pocket of dead phagocytes and
damaged tissue forms; this collection of dead cells and fluid is called pus.

 Pus formation occurs in most inflammatory responses and usually continues until the
infection subsides.

Fever
 Fever is an abnormally high body temperature that occurs because the hypothalamic
thermostat is reset.
 Commonly occurs during infection and inflammation.

 Elevatedbody temperature intensifies the effects of interferons, inhibits the growth of

some microbes, and speeds up body reactions that aid repair.

ADAPTIVE IMMUNITY
 The ability ofthe body to defend itself against specific invading agents such as bacteria,
toxins, viruses, and foreign tissues is called adaptive (specific) immunity.

 Substances that are recognized as foreign and provoke immune responses are called
antigens (Ags), meaning antibody generators.
 Two properties distinguish adaptive immunity from innate immunity: (1) specificity for
particular foreign molecules (antigens), which also involves distinguishing self from
nonself molecules, and (2) memory for most previously encountered antigens so that a
second encounter prompts an even more rapid and vigorous response.

 The branch of science that deals with the responses of the body when challenged by
antigens is called immunology. The immune system includes the cells and tissues that
carry out immune responses.

Maturation of T cells and B cells

 Adaptive immunity involves lymphocytes called B cells and T cells. Both develop in
primary lymphatic organs.

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  B cells complete their development in red bone marrow, a process that continues
throughout life.

T cells develop from pre-T cells that migrate from red bone marrow into the thymus,
where they mature.

 B cells and T cells are named based on where they mature. The letter B stands for bursa
equivalent, which is the red bone marrow. T cells are so named because they mature in
the thymus gland.

 Before T cells leave the thymus or B cells leave red bone marrow, they develop
immunocompetence, the ability to carry out adaptive immune responses.

 This means that B cells and T cells begin to make several distinctive proteins that are
inserted into their plasma membranes.

 There are two major types of mature T cells that exit the thymus: helper T cells and
cytotoxic T cells.

 Helper T cells are also known as CD4 T cells, which means that their plasma membranes
include a protein called CD4.

 Cytotoxic T cells are also referred to as CD8 T cells because their plasma membranes
contain a protein known as CD8.

Types of Adaptive Immunity

 There are two types of adaptive immunity: cell-mediated immunity and antibody-
mediated immunity.
 In cell-mediated immunity, cytotoxic T cells directly attack invading antigens.
In antibody-mediated immunity, B cells transform into plasma cells, which synthesize
and secrete specific proteins called antibodies or immunoglobulins

 Cell-mediated immunity is particularly effective against: intracellular pathogens, some

cancer cells and foreign tissue transplants.
 Cell-mediated immunity always involves cells attacking cells.

 Antibody-mediated immunity works mainly against extracellular pathogens, which

include any viruses, bacteria, or fungi that are in body fluids outside cells.
 Antibody-mediated immunity is also referred to as humoural immunity.

 In most cases, when a particular antigen initially enters the body, there is only a small
group of lymphocytes with the correct antigen receptors to respond to that

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 A given antigen can provoke both types of adaptive immune responses. This is due to the
fact that when a specific antigen invades the body, there are usually many copies of
that antigen spread throughout the body’s tissues and fluids.

 Cell-mediated and antibody-mediated immune responses often work together to eliminate

the large number of copies of a particular antigen from the body.

Clonal selection: The Principle

 Clonal selection is the process by which a lymphocyte proliferates (divides) and
differentiates (forms more highly specialized cells) in response to a specific antigen.

 The result of clonal selection is the formation of a population of identical cells, called a
clone that can recognize the same specific antigen as the original lymphocyte.
 Clonal selection of lymphocytes occurs in the secondary lymphatic organs and tissues.

A lymphocyte that undergoes clonal selection gives rise to two major types of cells in the
clone: (1) effector cells and (2) memory cells.

 The thousands of effector cells of a lymphocyte clone carry out immune responses that
ultimately result in the destruction or inactivation of the antigen.
 Effector cells include active helper T cells, active cytotoxic T cells, and plasma cells.
 Memory cells do not actively participate in the initial immune response to the antigen.

 If the same antigen enters the body again, the thousands of memory cells of a lymphocyte
clone are available to initiate a far swifter reaction than occurred during the first
invasion.

 The memory cells respond to the antigen by proliferating and differentiating into more
effector cells and more memory cells.

 Memory cells include memory helper T cells, memory cytotoxic T cells, and memory B
cells.
 Memory cells have long life spans often lasting for decades.

Antigens and Antigen receptors

 Antigens have two important characteristics: immunogenicity and reactivity.

 Immunogenicity is the ability to provoke an immune response by stimulating the

production of specific antibodies, the proliferation of specific T cells, or both.

 Reactivity is the ability of the antigen to react specifically with the antibodies or cells it
provoked.

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  Entire microbes or parts of microbes may act as antigens.

 Chemical components of bacterial structures such as flagella, capsules, and cell walls are
antigenic, as are bacterial toxins.

 Nonmicrobial examples of antigens include chemical components of pollen, egg white,

incompatible blood cells, and transplanted tissues and organs.

 Epitopes or antigenic determinants are small parts of large antigen molecule that triggers
an immune response

 Antigens that get past the innate defences generally follow one of three routes into
lymphatic tissue. (1) Spleen, (2) Lymphatic vessels and Lymph nodes, and (3) MALT.

Chemical nature of Antigens

 Antigens are large, complex molecules. Most often, they are proteins.

 Nucleic acids, lipoproteins, glycoproteins, and certain large polysaccharides may also act
as antigens.
 Complete antigens usually have large molecular weights of 10 000 daltons or more, but
large molecules that have simple, repeating subunits (eg. cellulose and most plastics)
are not usually antigenic.
A smaller substance that has reactivity but lacks immunogenicity is called a hapten.

A hapten can stimulate an immune response only if it is attached to a larger carrier

molecule.
 As a rule, antigens are foreign substances; they are not usually part of body tissues.

Diversity of Antigen receptors

 Before a particular antigen ever enters the body, T cells and B cells that can recognise
and respond to that intruder are ready and waiting.

 The diversity of antigen receptors in both B cells and T cells is the result of shuffling and
rearranging a few hundred versions of several small gene segments in a process
called genetic recombination.

 The gene segments are put together in different combinations as the lymphocytes are
developing from stem cells in red bone marrow and the thymus.

 Because of genetic recombination, each B cell or T cell has a unique set of gene segments
that code for its unique antigen receptor.
 After transcription and translation, the receptor molecules are inserted into the plasma
membrane.

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Major Histocompatibility Complex Antigens
 Located in the plasma membrane of body cells are ‘self-antigens’, the major
histocompatibility complex (MHC) antigens.

 These transmembrane glycoproteins are also called human leukocyte antigens (HLA)
because they were first identified on white blood cells.

 MHC antigens help T cells recognize that an antigen is foreign, not self. Such recognition
is an important first step in any adaptive immune response.
 The two types of major histocompatibility complex antigens are class I and class II.

 ClassI MHC (MHC-I) molecules are built into the plasma membranes of all body cells
except red blood cells.
 Class II MHC (MHC-II) molecules appear on the surface of antigen-presenting cells.

Pathways of Antigen Processing

Antigen processing – antigenic proteins are broken down into peptide fragments that then
associate with MHC molecules.

Antigen presentation - insertion of the complex into the plasma membrane.

 Processing of Exogenous Antigens – foreign antigens present in fluids outside body

cells.
 Antigen presenting cells (APCs) – a special class of cells that process
and present exogenous antigen.
- Example: dendritic cells, macrophages, and B cells
- Location: epidermis and dermis of the skin, mucous
membranes that line the respiratory, GIT, urinary and
reproductive tracts, lymph nodes
 Steps in the processing and presenting of an exogenous antigen:
1. Ingestion of the antigen – by phagocytosis or
endocytosis.
2. Digestion of antigen into peptide fragments
3. Synthesis of MHC-II molecules
4. Packaging of MHC-II molecules
5. Fusion of vesicles
6. Binding of peptide fragments to MHC-
IImolecules
7. Insertion of antigen-MHC-II complexes into
the plasma membrane

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 Processing of Endogenous Antigen - foreign antigens present in fluids inside body
cells.
 Steps in the processing and presenting of an endogenous antigen:
1. Digestion of antigen into peptide fragments
2. Synthesis of MHC-I molecules
3. Binding of peptide fragments to MHC-I molecules
4. Packaging of antigen-MHC-I molecules
5. Insertion of antigen-MHC-I complexes into the plasma membrane

Fig. 1 Processing and presenting of exogenous antigen

Fig. 2 Processing and presenting of endogenous antigen

ing and presenting of endogenous antigen

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Cytokines

 Small protein hormones that stimulate or inhibit many cell functions, such as cell growth
and differentiation.
 Regulate activities of cells involved in innate defenses or adaptive immune responses.

Fig. 3 Summary of Cytokines participating in immune responses

Cell-Mediated Immunity

 Activation of T Cells
 T cell receptors (TCRs) – antigen receptors on the surface of T cells.
- Recognize and bind to specific foreign antigen fragments that
are presented in antigen-MHC complexes
 CD4 or CD8 proteins interact with the MHC antigens and help maintain
the TCR-MHC coupling; as such they are referred to as coreceptors.
 2 signals for T cell activation:
 First signal – antigen recognition by a TCR with CD4 or CD8
proteins
 Second signal – costimulation

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 Activation and Clonal Selection of Helper T
Cells

Process:

Inactive helper T cells recognize exogenous

antigen fragments associated with MHC-II
molecules at the surface of an APC

Antigen recognition would occur with the help

of CD4 proteins

Costimulationtakes place

The helper T cell is activated

Fig. 4 Activation and clonal selection Undergoes clonal selection

of helper T cells

 Active helper T cells – secretes a variety of cytokines such as interleukin-2 (IL-2).

 Memory helper T cells – not active cells. Proliferates and differentiates quickly.

Activation and Clonal Selection of Cytotoxic T Cells

Process:

Cytotoxic T cells recognize foreign antigens combined

with MHC-I on the surface of:
(1) body cells infected by microbes
(2) some tumor cells
(3) cells of a tissue transplant

Antigen recognition occurs with the help of TCR and

CD8 protein

Costimulation with the help of interleukin-2 or any

other cytokines

The cytotoxic T cell is activated

Undergoes clonal selection Fig. 5 Activation and clonal selection of

cytotoxic T cells

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  Active cytotoxic T cells – attack other body cells that have been infected with the
antigen.
 Memory cytotoxi T cells – does not attack infected body cells. Proliferates and
differentiates quickly.

Elimination of Invaders
 Cytotoxic T cell recognizes and attaches to target cells and kills it.
 It has receptors specific for a particular microbe and thus kill only target body cells
infected with one particular type of microbe.
 2 principal mechanisms for killing infected target cells:
1. Cytotoxic T cells bind to infected target cells then releases
granzymes, protein-digesting enzymes that trigger apoptosis.
Released microbes are destroyed by phagocytes.
2. Cytotoxic T cells bind to infected target cells and release 2
proteins:
 Perforin – inserts into the plasma membrane of the
target cell and creates channels in the membrane.
 Granulysin – enters through the channels and
destroys the microbes by creating holes in their
plasma membrane.
 Other methods used by Cytotoxic cells:
 Lymphotoxin – a toxic molecule which activates enzymes in the target cell
causing its DNA to fragment, killing it.

Immunological Surveillance

 If the immune system recognizes an antigen as nonself, it can destroy it before it spreads.
- Carried out by cytotoxic T cells, macrophages, and natural
killer cells.

Antibody-Mediated Immunity

 Activation and Clonal Selection of B cells

 During activation of a B cell, an antigen binds to B-cell receptors.
 Antigen processing in a B cell occurs in the following way:

Antigen is taken into the B cell broken to fragments and combined with MHC-II self-
antigens helper T cells recognize the antigen-MHC-II complex costimulation by
interleukins and cytokines B cell activates undergoes clonal selection

 Plasma cells – secrete antibodies

 Memory B cells – don’t secrete antibodies. Proliferates and differentiates quickly.

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 Antibodies

 Immunoglobulins (Igs)
 Antibody structure: 4 polypeptide chains
 Two heavy (H) chains
 Two light (L) chains
 Disulfide bond (S-S)
 Hinge region
 Stem region
 Variable (V) region – antigen-binding
site
 Constant (C) region

Fig. 6 Activation and clonal selection

of B cells

Fig. 7 Chemical structure of the IgG class of antibody

 5 different classes of immunoglobulins and its chemical structure and role:

 IgG – most abundant
 Location: blood, lymph, and intestines
 Function: protects against bacteria and viruses by enhancing phagocytosis
Neutralizing toxins and triggering complement system
 IgA
 Location: sweat, tears, saliva, mucus, breast milk, and GIT secretions
 Function: levels decrease during stress, lowering resistance to infection
Provides localized protection of mucous membranes against
Bacteria and virus
 IgM – first antibody to be secreted by plasma cells after initial exposure to antigen
 Location: blood and lymph
 Function: activates complement and causes agglutination and lysis of
microbes
 IgD
 Location: surfaces of B cells as antigen receptors
 Function: involved in activation of B cells

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  IgE
 Location: blood, mast cells, and basophils
 Function: involved in allergic and hypersensitivity reactions
Protection against parasitic worms
 Antibody Actions
1. Neutralizing antigen
2. Immobilizing bacteria
3. Agglutinating and precipitating antigen
4. Activating complement
5. Enhancing phagocytosis

 Role of the Complement System

 A defensive system that destroy microbes by causing phagocytosis, cytolysis, and
inflammation; also prevents excessive damage to body tissues.
 Process:
Inactivated C3 splits into activated C3a and C3b C3b binds to the surface of
a microbe and enhances phagocytosis by opsonization (promotes attachment of a
phagocyte to a microbe) formation of membrane attack complex
cytolysis mast cells release histamine that aids in inflammation
 C3 can be activated in three ways:
 Classical pathway – involves antibodies
 Alternative pathway – initiates interaction bet. lipid-carbohydrate
complexes and complement protein factors (B, D, P)
 Lectin pathway – proteins called lectins bind to the carbohydrates on the
surface of microbes

Immunological Memory
 Refers to the ability of the immune system to respond more rapidly and effectively to a
pathogen that has been encountered previously.
 happens due to the long-lasting antibodies and lymphocytes that arise from B and T cells
 Antibody titer (AT) – measures immunological memory
 Two responses: occur during microbial infection
 Primary response – AT slowly rises IgM and IgG gradual
decline in AT
 Secondary response – AT rises greatly

Self-Recognition and Self-Tolerance

 T cells must have two traits:

o Self-recognition – recognize own MHC proteins
o Self-tolerance – lack reactivity to peptide fragments from own proteins

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  Positive selection
 Negative selection – weeding out process
 Deletion – self-reactive T cells undergo apoptosis and die
 Anergy – inactive; unresponsive to antigenic stimulation

Fig.8 Development of self-recognition and self-tolerance

Stress and Immunity

 Psychoneuroimmunology (PNI) – deals with communication pathways that link the

nervous, endocrine, and immune systems.
 When stress piles up, health habits can change
o For example, people under stress are less likely to eat well or exercise regularly
 Ways to increase stress resistance:
o Cultivate an optimistic outlook
o Get involved in your work
o Build good relationship with others
 Important habits for a healthy immune system:
o Adequate sleep
o Relaxation
o Regular exercise
 After a long and hard day, don’t forget to unwind and relax!

Aging and the Immune System

 People become more susceptible to all types of infection and malignancies as they grow
old.
 They tend to produce more autoantibodies (antibodies against their own body molecule)

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  Antibody levels do not increase as rapidly in response to a challenge by an antigen

Disorders: Homeostatic Imbalances

AIDS: Acquired Immunodeficiency Syndrome

 A condition in which a person experiences a telltale assortment of infections due
to the progressive destruction of immune system cells by the human
immunodeficiency virus (HIV).
 HIV Transmission
 Most effectively transmitted by actions or practices that involve the
exchange of blood or body fluids bet. people.
 Example: semen or vaginal fluid during unprotected sex, direct
blood-to-blood contact
 People cannot be infected by casual physical contact
 HIV is a very fragile virus and cannot survive outside the human body for
long.
o It can be eliminated from personal care items and medical
equipment by exposing them to heat (135°F for 10 minutes) and by
using common disinfectants.
 Signs, Symptoms, and Diagnosis of HIV infection
 Soon after being infected, most people experience a brief flulike illness.
 Common signs and symptoms are: fever, fatigue, rash, headache, joint
pain, sore throat, and swollen lymph nodes
 As early as 3-4 weeks after HIV infection, plasma cells begin secreting
antibodies against it. These became the basis for screening tests for HIV.
 Progression to AIDS
 After a period of 2-10 years, people infected by the virus experience the ff:
o Immunodeficiency
o Enlarged lymph nodes and persistent fatigue
o Involuntary weight loss and various lesions of the mouth and gums
o Affects the person’s memory producing visual disturbances
 Opportunistic infections – diseases caused by microorganisms that are
normally held in check but now proliferate because of the defective
immune system.
 Treatment of HIV Infection
 3 classes of drugs that extend the life of many HIV-infected people:
o Reverse transcriptase inhibitors – interfere with the action of
reverse transcriptase, the enzyme that the virus uses to convert its
RNA to DNA.
o Integrase inhibitors – block the enzyme integrase, which inserts
the HIV DNA copy into a host cell DNA.

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 o Protease inhibitors – interfere with the action of protease, a viral
enzyme that cuts proteins into pieces to assemble the protein coat
of newly produced HIV particles.
Lymphomas
 Cancers of the lymphatic organs, especially the lymph nodes.
 2 main types:
 Hodgkin disease (HD): Symptoms
o Primarily affects individuals between ages 15-35 and those over 60
o More common in males
o Painless swelling of lymph nodes in your neck, armpits or groin
o Persistent fatigue
o Fever and chills
o Night sweats
o Unexplained weight loss — as much as 10 percent or more of your
body weight
o Loss of appetite
o Itching
o Increased sensitivity to the effects of alcohol or pain in your lymph
nodes after drinking alcohol
 Non-Hodgkin lymphoma (NHL): Symptoms
o More common than HD and occurs in all age groups, the incidence
increasing with age to a maximum bet. ages 45-70
o Symptoms are mostly same with HD
o Enlarged spleen
o Anemia
o General malaise
 Treatment: for both include radiation therapy, chemotherapy, and bone
marrow transplantation.

Example of Hodgkin
disease (HD)

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Systemic Lupus Erythematosus
 A chronic autoimmune, inflammatory disease that affects multiple body systems.
 Characterized by periods of active disease and remission.
 Most often develop bet. ages 15-44 and is 10-15 times more common in females
than males
 Genetic predisposition to the disease and environmental factors (infections,
antibiotics, UV light, stress, and hormones) may trigger it.
 Signs and Symptoms:
o Joint and muscle pains
o Headache
o Kidney dysfunction
o Pale or purple fingers or toes
o Low blood cell count
o Nerve or brain dysfunction
o Slight fever and fatigue
o Oral ulcers
o Weight loss
o Swelling in the legs or
around the eyes
o Enlarged lymph nodes or
spleen
o Photosensitivity
o Rapid loss of large amounts
of hair
o Butterfly rash

 There is no cure for lupus, but drug therapy can minimize symptoms, reduce
inflammation, and forestall flare-ups.
 Most commonly used lupus medications are: pain relievers (aspirin and
ibuprofen), antimalarial drugs (hydroxychloroquine), and corticosteroids
(prednisone and hypocortisone).

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 REFERENCES

Tortora G. &Derrickson B. (2016). Anatomy and Physiology 1st Asia-Pacific Edition

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