Chapter 9

Immunity

OBJECTIVES

• At the end of this lesson, the SPN will be able to:– 1. Describe the functions of the lymphatic system– 2. Describe the components that make up the

lymphatic system– 3. Describe the lymphatic vessels and organs

within the immune system– 4.Describe non-specific and specific defense

mechanisms that humans use against all pathogens and foreign substances

OBJECTIVES CON’T.

– 5. Describe acquired immunity-• Active Natural Immunity• Active Artificial Immunity• Passive Natural Immunity• Passive Artificial Immunity

The Lymphatic System

• The lymphatic system is sometimes considered to be a part of the circulatory system because it transports fluid through vessels and empties it into venous blood

• The lymphatic system consists of organs that work together to perform certain functions

• The lymphatic system also has a major role in the body’s defense against disease

FUNCTIONS OF THE LYMPHATIC SYSTEM

• The lymphatic system has 3 primary functions.– 1. It returns excess interstitial fluid to the blood.– REVIEW-Capillary microcirculation-fluid leaves the

capillary at the arteriole end and returns at the venous end

– Of the fluid that leaves the capillary, about 90% is returned. The 10% that does not return becomes part of the interstitial fluid that surrounds the tissue cells

Functions Con’t.

– Small protein molecules may “leak” through the capillary wall and increase the osmotic pressure of the interstitial fluid

– This further inhibits the return of fluid onto the capillary, and fluid tends to accumulate in the tissue spaces-the result is Blood volume and Blood Pressure decreases while the volume in the tissue increases resulting in edema

– Lymph capillaries pick up the excess interstitial fluid and proteins and return them to the venous blood

Functions Con’t

• 2. The second function of the lymphatic system is the absorption of fats and fat-soluble vitamins from the digestive system and the subsequent transport of these substances to the venous circulation

• There are special lymph capillaries in the small intestine called lacteals which absorb the fats and fat-soluble vitamins

• The lymph in the lacteals has a milky appearance because of its high fat content and is called chyle.

Functions Con’t

• 3. The third function is defense against invading microorganisms and disease– Lymph nodes and other lymphatic organs filter the

lymph to remove microorganisms and other foreign particles

– Lymphatic organs contain lymphocytes that destroy invading organisms.

Components of the Lymphatic System

• The lymphatic system consists of a fluid(lymph), vessels that transport the lymph, and organs that contain lymphoid tissue.

• We will look at these in more detail

Lymph

• Lymph is a fluid similar in composition to blood plasma

• It is derived from blood plasma as fluids pass through capillary walls at the arterial end

• As the interstitial fluid begins to accumulate, it is picked up and removed from by tiny lymphatic vessels and returned to the blood

• As soon as the interstitial fluid enters the lymph capillaries, it is called lymph

Lymph Con’t.

• Returning the fluid to the blood prevents edema and helps to maintain normal blood volume and pressure

LYMPHATIC VESSELS

• Lymphatic vessels only carry fluid away from tissues

• The smallest lymphatic vessels are the lymph capillaries, which begin in the tissue spaces as blind-ended sacs

• Lymph capillaries are found in all regions of the body except the bone marrow, central nervous system, and tissues such as the epidermis, that lack blood vessels.

Lymphatic Vessels Con’t.

• The wall of the lymphatic capillary is composed of endothelium in which the simple squamous cells overlap to form a simple one-way valve

• This arrangement permits fluid to enter the capillary but prevents lymph from leaving the vessel

• The microscopic lymph capillaries merge to form lymphatic vessels

Lymphatic Vessels Con’t.

• The lymphatic vessels are similar to veins in structure, but they have thinner walls and more valves than veins.

• Small lymphatic vessels join to form larger tributaries, called lymphatic trunks, which drain large regions.

• Lymphatic trunks merge until the lymph enters the two lymphatic ducts

Lymphatic Ducts

• The RIGHT LYMPHATIC DUCT receives lymph from the vessels in the upper right quadrant of the body. This includes:

• The right side of the head and neck• The upper right extremity• The right side of the thorax

• The right lymphatic duct empties into the right subclavian vein

Lymphatic Ducts Con’t.

• The THORACIC DUCT collects the lymph from the remaining regions of the body.

• The thoracic duct begins in the upper abdomen and ascends through the thorax to empty into the left subclavian vein.

•

How does lymph travel???

• Like veins, the lymphatic tributaries have thin walls and have valves to prevent backflow of blood

• There is no pump in the lymphatic systemlike the heart in the cardiovascular system.

• The pressure gradients to move lymph through the vessels have to come from external sources-such as skeletal muscle contraction, respiratory movements, and from contraction of smooth muscle within the wall of the vessel.

Lymph Travel

• Because there is no rhythmic heart to pump it along, lymph transport is sporadic and much slower than the transport of blood in the veins.

Lymphatic Organs

• Lymphatic organs are characterized by clusters of lymphocytes and other cells , such as macrophages, enmeshed in a framework of short, branching connective tissue fibers

• REVIEW-Lymphocytes originate in the red bone marrow with other types of blood cells and are carried in the blood away from the bone marrow to the lymphatic organs

Lymphocytes Con’t

• When the body is exposed to microorganisms and other foreign substances, the lymphocytes proliferate within the lymphatic organs and are sent in the blood to the site of the invasion.

• This is part of the immune response that attempts to destroy the invading agent

• The lymph nodes, tonsils, spleen, and thymus are examples of lymphatic organs

• Let us look at each of these organs

LYMPH NODES

• Lymph nodes are small, bean-shaped structures that are usually less than 2.5 cm in length

• They are widely distributed throughout the body along the lymphatic pathways, where they filter the lymph before it is returned to the blood

• Lymph nodes are not present in the central nervous system

Lymph Nodes Con’t

• There are three superficial regions on each side of the body where lymph nodes tend to cluster.

• These areas are:• 1. the inguinal nodes in the groin• 2. the axillary nodes in the armpit• 3. the cervical nodes in the neck

Lymph Nodes Con’t.

• Lymph nodes are the only structures that filter the lymph, and this is their primary function!!!!!!

• As the lymph moves through the node, infectious agents, damaged cells, cancerous cells, and cellular debris become trapped in the fibrous mesh so that the lymph is cleansed before it enter the blood

• The lymphocytes react against the bacteria, viruses, and cancerous cells to destroy them

Lymph Nodes Con’t.

• Macrophages, also present in the node, engulf the destroyed pathogens, the damaged cells and the cellular debris.

TONSILS

• Tonsils are clusters of lymphatic tissue just under the mucous membranes that line the nose, mouth, and throat(pharynx)

• Lymphocytes and macrophages in the tonsils provide protection against harmful substances and pathogens that may enter the body through the nose and throat.

Spleen

• The spleen is located in the upper left abdominal cavity, just beneath the diaphragm , and posterior to the stomach

• It is similar to a lymph node in shape and structure but it is much larger

• The spleen is the largest lymphatic organ in the body

• Blood enters the spleen through the splenic artery, moves through the sinuses where it is filtered, and then leaves through the splenic vein

Spleen Con’t.

• The spleen filters blood in much the same way that the lymph nodes filter lymph

• Lymphocytes in the spleen react to pathogens in the blood and attempt to destroy them

• Macrophages then engulf the resulting debris, the damaged cells, and the other large particles

• The spleen along with the liver, removes old and damaged erythrocytes from the circulating blood

Spleen Con’t.

• Like other lymphatic tissue, it produces lymphocytes, especially in response to invading pathogens

• The sinuses in the spleen are a reservoir for blood• In emergencies the capsule of the spleen

contracts thus squeezing the blood out of the spleen into the general circulation

• If the spleen must be removed(splenectomy), its functions will be performed by other lymphatic tissue and the liver

THYMUS

• The thymus is a soft organ with two lobes that is located anterior to the ascending aorta and posterior to the sternum(pg. 158-text)

• The primary function of the thymus is the processing and maturation of special lymphocytes called T lymphocytes or T cells

• While in the thymus, the lymphocytes do not respond to pathogens and foreign agents

Thymus Con’t

• After the lymphocytes have matured, they enter the blood and go to other lymphatic organs where they help provide defense against disease

• The thymus also produces a hormone , thymosin, that stimulates the maturation of lymphocytes in other lymphatic organs

Resistance to Disease

• The human body is continually exposed to disease-producing organisms called pathogens and other harmful substances

• The body’s ability to counteract the effects of pathogens and other harmful agents is called resistance and is dependent on a variety of defense mechanisms (nonspecific and specific)

• Susceptibility is a lack of resistance

NONSPECIFIC DEFENSE MECHANISMS

• Nonspecific defense mechanisms are directed against all pathogens and foreign substances regardless of their nature

• They present the initial defense against invading agents

• Nonspecific defense mechanisms include:– 1. Barriers– 2. Chemical Action– 3. Phagocytosis– 4. Inflammation

BARRIERS

• A. SKIN-Intact, or unbroken, skin and mucous membranes form effective mechanical barriers against the entry of foreign substances

• B. MUCOUS MEMBRANES- that line the respiratory and digestive tracts are not as tough as skin, but the mucous produced by these membranes traps foreign particles before they gain entry

BARRIERS CON’T.• FLUIDS- such as tears flowing across the eyes,

saliva that is swallowed, and urine passing through the urethra, are examples of barriers mechanical barriers because they flush the pathogens out of the body before they have a chance to damage the tissues

• CHEMICAL BARRIERS-includes lysozymes found in tears, saliva, and nasal secretions. Sebaceous secretions and salt in perspiration, and hydrochloric acid in the stomach all have antimicrobial properties.

CHEMICAL ACTION

• Various body chemicals, including complement proteins, stimulate phagocytosis and inflammation

• Others, including interferon, are produced as a direct response to microbial invasion

• COMPLEMENT is a group of proteins normally found in the plasma in an inactive form

• Certain complement proteins become activated when they come in contact with a foreign substance

CHEMICAL ACTION CON’T

• Once the contact with the foreign substance occurs, a series of reactions, similar to the cascade reactions in the clotting process

• The reactions proceed in an orderly sequential manner

• The final activated complement enhances phagocytosis and inflammation. It also causes bacterial cells to rupture

CHEMICAL ACTION CON’T.

• INTERFERON-has particular significance because it offers protection against viruses

• When a cell becomes infected with a virus, the cell usually stops its normal functions

• The virus uses the cell’s metabolic machinery for one goal-viral replication

• When the cell is full of viruses, it ruptures and releases a myriad of viruses to infect new cells---the viral infection is established

Chemical Action Con’t.--Interferon

• When a virus infects a cell, that cell produces interferon, which diffuses into neighboring uninfected cells

• Interferon stimulates the uninfected cells to produce a protein that blocks viral replication

• Therefore, uninfected neighboring cells are protected from the virus!!!!

PHAGOCYTOSIS

• Phagocytosis is the ingestion and destruction of solid particles by certain cells

• The cells are called phagocytes• The solid particles may be microorganisms or

their parts, foreign particles, an individual’s own dead or damaged cells, or cell fragments

• The primary phagocytic cells are neutrophils and macrophages

Phagocytosis Con’t.

• Neutrophils-RECALL-are usually the first cells to leave the blood and migrate to the site of an infection, where they ingest and destroy the invading bacteria

• This is a “suicide mission” because the neutrophils die after engulfing only a few bacteria

• Pus is primarily an accumulation of dead neutrophils, cellular debris, and bacteria

• The number of neutrophils greatly increases in acute infections

Phagocytosis Con’t.

• Macrophages-usually appear at the scene of an infection after the neutrophils and are responsible for clearing away cellular debris and dead neutrophils during the latter stages of infection

• Macrophages are also present in uninfected tissues, where they may ingest the invading agents before there is tissue damage

INFLAMMATION

• Inflammation occurs in response to tissue damage from microorganisms or trauma

• Localized inflammation is contained in a specific region. It is evidenced by redness, warmth, swelling, and pain. Examples????

• Inflammation is aimed at localizing the damage and destroying its source

Inflammation Con’t.

• Systemic Inflammation is not contained in a localized region but is widespread throughout the body.

• Systemic inflammation-the symptoms of localized inflammation may be present at specific sites but there are three additional responses that are evident of systemic inflammation.

Inflammation Con’t.

• The 3 additional responses to systemic inflammation include:– 1. Bone marrow is stimulated to produce more white

blood cells, especially neurophils and monocytes– 2. Chemical mediators include pyrogens that influence

the hypothalmus and cause a fever. The fever speeds up the metabolic reactions in the body, including those directed at destroyingthe invading pathogens

– 3. Vasodilation and increased permeability causes a drastic and dangerous decrease in BP

SPECIFIC DEFENSE MECHANISMS

• Specific defense mechanisms are programmed to be selective. This characteristic is called specificity.

• Another characteristic of specific defense mechanisms is memory. Once the system has been exposed to a particular invading agent, components of the specific defense mechanisms “remember” that agent and launch a quicker attack if it enters the body again

SPECIFIC DEFENSE MECHANISMS

• Specific defense mechanisms provide the third line of defense against microbial invasion

• This third line of defense is specific resistance or immunity. The primary cells involved are lymphocytes and macrophages

• Nonspecific mechanisms and immune responses take place at the same time, and resistance to disease depends on the interaction of all the mechanisms

Specific Defense Mechanisms Con’t.-Self vs Nonself

• Recognition of Self vs. Nonself- For the immune system to function properly, lymphocytes have to distinguish between self and nonself

• During their development and maturation process, the lymphocytes learn to recognize the proteins and other large molecules that belong to the body. They interpret these as “SELF”

Self vs Nonself Con’t.

• Molecules that are not recognized as self are interpreted as “NONSELF”, and defense mechanisms are set in motion to destroy them

• A molecule that is interpreted as nonself and that triggers an immune response is called a foreign antigen

• Antigens are usually some form of protein or large polysaccharide molecules on the surface of cell membranes

Self vs Nonself Con’t.

• Normally, antigens that cause problems are foreign molecules that enter the body, but sometimes the body fails to recognize its own molecules and triggers an immune reaction against itself

• This damages normal body tissues and is the basis of autoimmune diseases such as rheumatoid arthritis

Specific Defense Mechanisms-Development of Lymphocytes

• RECALL-lymphocytes develop from stem cells in the bone marrow

• During fetal development, the bone marrow releases immature and undifferentiated (unspecialized) lymphocytes into the blood

• Some of these go to the thymus gland where they acquire the ability to distinguish between self and nonself molecules

• These lymphocytes differentiate to become T lymphocytes, or T cells. About 70% of circulating lymphocytes are T cells

Lymphocytes Con’t.

• Lymphocytes that do not go to the thymus travel in the blood to some other area, probably the fetal liver, where they differentiate into B lymphocytes or B cells.

• After they acquire the ability to distinguish between self and nonself and are prepared for their special roles in immune responses, B cells enter the blood

• B cells account for about 30% of the circulating lymphocytes

Lymphocytes Con’t

• In the differentiation and maturation process, thousands of different types of T cells and B cells are produced

• Each type of cell has receptor sites that fit with specific antigens. Thus, they provide specific resistance

• There has to be an exact match between the receptor site on the lymphocyte and the antigen of the invader before an immune reaction occurs.

Specific Defense Mechanisms-Cell-Mediated Immunity

• T cells are responsible for cell-mediated immunity, in which the t cells directly attack the invading antigen

• Cell-mediated immunity is most effective against virus-infected cells, cancer cells, foreign tissue cells (transplant rejection), fungi, and protozoan parasites

• When the antigen is introduced into the body, it is ingested by a macrophage, which then presents the antigen to the T cell population

Cell-Mediated Immunity Con’t.

• T cells that have receptor sites for that specific antigen recognize it and become activated

• Both the macrophage and the activated T cells secrete chemical that stimulate division of the activated T cells

• This results in large numbers of cells that are all alike, a clone of activated T cells.

• There are 4 subgroups within the clone of activated T cells, and each group has a specific function

Subgroups of T cells

• 1. Killer T cells-directly destroy the cells with the offending antigen

• 2. Helper T cells-secrete substances that stimulate B cells and promote the immune response

• 3. Suppressor T cells- have the opposite effect; they inhibit B cells and the immune response. The helper and suppressor T cells are regulatory cells that control the immune response

Subgroups of T cells

• 4. Memory T cells-these cells “remember” the specific antigen and stimulate a faster and more intense response if the same antigen is introduced another time

Specific Defense Mechanisms- Anitibody-Mediated Immunity

• B cells are responsible for antibody-mediated immunity.

• Like T cells, each type of B cell can respond to only one specific type of antigen

• There must be a match between the receptor on the B cell and the antigen

• Unlike T cells, B cells do not directly assault the antigen. Instead, they are responsible for the production of antibodies that react with the antigen or substances produced by the antigen

Antibody-Mediated Immunity Con’t.

• Antibody-mediated immunity is most effective against bacteria, viruses that are outside body cells, and toxins. It is also involved in allergic reactions

• When an antigen enters the body, a macrophage ingests and processes it, and then presents it to B cells and helper T cells.

• The B cells and helper T cells that have receptors for that specific antigen are activated

Antibody-Mediated Immunity Con’t.

• The activated helper T cells secrete substances that stimulate the activated B cells to rapidly divide and to form a clone of cells consisting of plasma cells and memory B cells

• Plasma cells rapidly produce large quantities of protein molecules, called antibodies, that are transported in the blood and lymph to the site of infection where they inactivate the invading antigens. This initial action is the primary response.

Antibody-Mediated Immunity Con’t.

• When the antigens are destroyed, macrophages clean up the debris, and suppressor T cells decrease the immune response

• Memory B cells remain dormant in lymphatic tissue until the same antigen again enters the system.

• The memory cells recognize the antigen and launch a rapid and intense response against it. This is called a secondary response.

Anitbody-Mediated Immunity Con’t.

• The purpose of vaccinations is to provide an initial exposure so memory cells are available for a rapid and intense reaction against subsequent exposure to the antigen.

• All antibodies have a similar structure but one portion of the molecule differs so that each antibody is capable of reacting with only a specific antigen.

Anitobody-Mediated Immunity Con’t.

• They belong to the class of proteins called globulins, and because they are involved in immune reactions, they are called immunoglobulins abbreviated Ig

• There are several classes (5) of immunoglobulins. Each class has a specific role in immunity. The classes are: IgG, IgA, IgM, IgE, and IgD

IMMUNOGLOBULINS

• IgG-Located in blood plasma and its function is a major antibody in primary and secondary immune responses; inactivates antigen, neutralizes toxins, crosses placenta to provide immunity to the newborn, and responsible for Rh reactions

• IgA-Located in saliva, mucous, tears, and breast milk and its function is it protects mucous membranes on body surfaces; and provides immunity for the newborn

Immunoglobulins Con’t.

• IgM- Is attached to B cells; and is released into the plasma during an immune response. It causes antigens to clump together; responsible for transfusion reactions in ABO blood typing system

• IgD- Is attached to B cells and are the receptor sites for antigens on B cells; binding with antigen results in B cell activation

Immunoglobulins Con’t.

• IgE- Produced by plasma cells in mucous membranes and tonsils. It binds to mast cells and basophils, causing release of histamine; responsible for allergic reactions.

Acquired Immunity

• There are 4 ways to acquire specific resistance, or immunity

• The terms active and passive refer to whose immune system reacts to the antigen

• Active immunity occurs when the individual’s own body produces memory T cells and B cells in response to a harmful antigen

• Active immunity takes several days to develop and lasts for along time because memory cells are produced

Acquired Immunity Con’t.

• Passive immunity results when the immune agents develop in another person (or animal) and are transferred to an individual who was not previously immune.

• Passive immunity provides immediate protection but is effective for only a short time because no memory cells are produced in the individual

Acquired Immunity Con’t

• The terms natural and artificial refer to how the immunity is obtained

• Natural immunity occurs when the immunity is acquired through normal, everyday living, without any deliberate action

• Artificial immunity is the result of some type of deliberate action being taken to acquire the immunity such as receiving a vaccination.

Acquired Immunity Con’t

• Combining the terms gives the four types of acquired immunity. They are:– 1.ACTIVE NATURAL IMMUNITY– 2. ACTIVE ARTIFICIAL IMMUNITY– 3. PASSIVE NATURAL IMMUNITY– 4. PASSIVE ARTIFICIAL IMMUNITY

• Let us discuss what each one of these means.

Active Natural Immunity

• Active natural immunity results when a person is exposed to a harmful antigen, contracts the disease, and recovers.

• Exposure to the pathogen stimulates production of memory cells.

• An example of this is a child that gets chickenpox, recovers, and never contracts it again although exposed many times

Active Artificial Immunity

• Active artificial immunity develops when a specially prepared antigen is deliberately introduced into an individual’s system. This is called a vaccination. The prepared antigen, called a vaccine usually consists of a weakened, inactivated, or dead pathogens or their toxins.

• The antigens stimulate the immune system but are altered so they do not produce the symptoms of the disease. An example of this is the mumps vaccine.

Passive Natural ImmunityPassive natural immunity results when antibodies

are transferred from one person to another through natural means.

This occurs only in the prenatal and postnatal relationship between mother and child

Some antibodies (IgG) can cross the placenta or breast milk.

This provides protection for the child for a short time after birth, but eventually the antibodies deteriorate and the infant must rely on its own immune system

Passive Artificial ImmunityPassive artificial immunity results when

antibodies that developed in another person(or animal) are injected into an individual. Provides immediate but short- term protection

Antiserum is the general term used for the preparation that contains the antibodies.

Antiserum may contain antibodies that act against microorganisms (hepatitis/rabies), bacterial toxins (tetanus/botulism), or venoms (poisonous snakes, spiders)

Applications of Immunology• Monoclonal antibodies are antibodies made by

cells cloned from a single antibody- producing B cell; are used in research and medicine; they are generally produced using genetically altered bacteria or sometimes plants.– Monoclonal antibodies are being used commercially in

home pregnancy tests, screening for prostate cancer, and other uses.

Figure 10.17Figure 10.17

Applications of Immunology

Immunotherapy alters the body’s own immune mechanisms to enhance defense against infections and cancer. Cytokines can be used to activate B

and T cells to fight cancer. Monoclonal antibodies can be used

to bind to proteins on cancer cells to draw NK cells to the tumor.

Applications of Immunology• Other monoclonal antibodies are bound

to toxins to make immuno-toxins; these bind to cancer cells, enter them, and prevent growth.

• Gamma interferon, produced by T cells, stimulates NK cells and boosts activity of macrophages; currently being used to treat hepatitis C.

• Beta interferon is being used to treat multiple sclerosis.

Allergies• In allergies, harmless

substances provoke an immune attack.– An allergy is an

immune response to a normally harmless substance called an allergen.

Figure 10.18aFigure 10.18a

Allergies

– Exposure to an allergen triggers production of IgE antibodies, causing release of hista-mines and prostaglandins from mast cells.• Histamines and prostaglandins fuel

inflammation.– In a few individuals, explosive inflammatory

responses trigger life-threatening anaphylactic shock in which air passages constrict and fluid rushes out of the capillaries.

Disorders of the Immune System• Food allergies, such as peanut allergies, and

wasp and bee venom allergies, can trigger anaphylactic shock.

• Rapid injections of the hormone epinephrine can prevent shock and save lives.

– Antihistamines - relieve the short-term symptoms of allergies; desensitization can be used to “train” the body not to see allergens.