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Anatomy, Physiology, and Disease An Interactive Journey for Health Professionals

CHAPTER

Second Edition

The Lymphatic and Immune Systems: Your Defense Systems

14

Anatomy, Physiology, & Disease: An Interactive Journey for Health Professionals, 2e Bruce J. Colbert • Jeff J. Ankney • Karen Lee

Multimedia Directory

Slide 22 Lymph Nodes Animation

Slide 23 Lymphatic Massage Video

Slide 45 Skin Cancer Video

Slide 59 Hand Washing and Gloving Techniques Video

Slide 72 Leukemia Video

Slide 131 HIV Animation

Slide 132 AIDS Video

Slide 167 Allergic Rhinitis Video

Slide 168 EpiPen Video

Slide 226 Pharmacy Video

Slide 227 Nuclear Medicine Video


Introduction

• Immune and lymphatic systems work to protect body from pathogens that can produce disease

• Without these systems, you would not survive for long


Learning Objectives

• List and describe the major components of the lymphatic and immune system and their functions

• Explain the antigen–antibody relationship

• Name and describe the functions of the blood cells responsible for protecting the body from invasion


Learning Objectives

• Discuss how inflammatory responses and fevers relate to infection

• Compare innate immunity to adaptive immunity

• Describe the function of T and B lymphocytes in the immune response

• List and describe several common diseases of the immune system


Pronunciation Guide

antigen

cytokines

cytotoxic T cells

dendritic cells

histamine

interferon

interleukins

leukocytes

lymph

lymphatic

(AN tih jenn)

(SIGH tow kinez)

(SIGH tow TOX ick)

(den DRID ick)

(HISS tah meen)

(in ter FEAR on)

(IN ter LOO kinz)

(LOO koh sights)

(LIMF)

(lim FAT ick)


Pronunciation Guide

lymphatic fluid

lymphatic vessels

lymph capillaries

lymph nodes

macrophages

myelogenous

neutrophils

pathogen

plasma cells

T lymphocytes

(lim FAT ick FLOO id)

(lim FAT ick)

(LIMF KAP ih LAIR eez)

(LIMF nohdz)

(MACK roh fage ez)

(my eh LOH jen us)

(NOO troh filz)

(PATH oh jenn)

(PLAZ mah)

(T LIMF oh sights)


Pronunciation Guide

thoracic duct

thymus

tumor necrosis factor

(thoh RASS ick)

(THIGH mus)

(neh KROH sis)


The Defense Zone

• If a group of pathogens try to enter body, they must first get past barriers, such as intact skin and secretions of mucous membranes

• If pathogen does get into body, it is recognized as not belonging

• Weapons in the form of specialized cells are engaged by immune and lymphatic systems to fend off the pathogens


The Defense Zone

• Weapons include specialized cells and powerful chemicals of immune and lymphatic systems

• Chemicals stimulate inflammatory and clean up responses

• Again, this is accomplished by combined and integrated efforts of immune and lymphatic systems


The Lymphatic System

• Both transport system and barracks of immune system

• Works closely with cardiovascular system



• Has four functions:

–Recycling fluids lost from cardiovascular system

–Transporting pathogens to lymph nodes where they can be destroyed

–Storage and maturation of some types of white blood cells

–Absorption of glycerol and fatty acids from food



• Smallest pipes of lymphatic system called lymph capillaries; run parallel to blood capillaries

• Lymph capillaries form network between cells of connective tissues, but unlike blood capillaries, are open ended



• Proteins and fluids are lost from cardiovascular capillaries and enter interstitial space.



• Once this fluid enters lymph capillaries, it is known as lymphatic fluid (lymph)

• Lymph: straw-colored, clear fluid; primary component is water

• Lymph capillaries empty into lymphatic vessels, similar to veins including valves; body movement and contraction of smooth muscles propels lymph through system


Figure 14-1 The lymphatic system and the relationship between blood and lymph capillaries.


Lymph Nodes

• Large vessels empty into lymph nodes, ranging in size from pinhead to an olive

• Lymph nodes: filters placed all along pathways or vessels of lymphatic system


Lymph Nodes

• Small, encapsulated bodies divided into sections

• Consist of sections of lymphatic tissue containing WBCs known as lymphocytes


Lymph Nodes

• Lymphatic tissue surrounded by lymphatic sinuses filled with lymph fluid

• Filter and destroy pathogens using WBCs


Lymph Nodes

• Concentrated in cervical, axillary, inguinal, pelvic, abdominal, thoracic, and supratrochlear areas

• Adenoids and tonsils also part of lymph system


Figure 14-2 The lymph node structure.


Lymph Nodes Animation

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Lymphatic Massage Video

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Lymphatic Trunks

• Lymphatic vessels exiting lymph nodes empty into one of several lymphatic trunks

• Trunks, named for location, include lumbar, intestinal, intercostal, bronchomediastinal, subclavian, and jugular


Collecting Ducts

• Lymphatic trunks empty into one of two collecting ducts

– Lumbar, intestinal, and intercostal trunks empty into thoracic duct the largest lymph vessel; more than two-thirds of lymphatic system drains into this duct


Collecting Ducts

• Lymphatic trunks empty into one of two collecting ducts

–Bronchomediastinal, subclavian, and jugular trunks empty into right lymphatic duct; smaller duct within right thorax that empties into right subclavian vein


Circulation of Lymphatic Fluid

• Lymphatic fluid flows in only one direction: from body tissues and organs to heart

–Blood to tissue

–Tissue to lymphatic capillaries

– Lymphatic capillaries to lymphatic vessels


Circulation of Lymphatic Fluid

• Lymphatic fluid flows in only one direction: from body tissues and organs to heart

– Lymphatic vessels to lymph nodes

– Lymph nodes to lymphatic vessels

– Lymphatic vessels to lymphatic trunks

– Lymphatic trunks to collecting ducts

–Collecting ducts to subclavian veins and then back to the blood


Pathology Connection: Tonsillitis

• Inflammation of tonsils, usually caused by bacterial or viral infection

–Symptoms

Sore throat

Difficulty swallowing

Swollen tonsils

Fever



• Inflammation of tonsils, usually caused by bacterial or viral infection

–Symptoms

Upper respiratory symptoms

Swollen lymph nodes

Visible coating or spots on tonsils

Upset stomach



• Diagnosis

–Physical examination noting inflamed tonsils

–Bacterial tonsillitis can be diagnosed, or ruled out, by throat culture that tests for presence of strep throat

–Viral tonsillitis, like all viral infections, does not respond to antibiotics and will usually go away by itself



• Treatment

– In both types, symptoms managed with rest, fluids, and analgesic like Tylenol™

–Tonsillectomy: used regularly as treatment in past; today only used if tonsillitis becomes chronic or if tonsils become enlarged to point of obstructing airway


Lymph Organs

• Spleen

–Spongy saclike mass of lymphatic tissue in upper left quadrant of abdomen

–Structurally similar to lymph nodes but instead of lymphatic sinuses has blood sinuses

–Surrounding blood sinuses are islands of white pulp containing lymphocytes and islands of red pulp containing both RBCs and WBCs


Lymph Organs

• Spleen

–Functions to remove and destroy old, damaged, or fragile RBCs

–Also filters pathogens from bloodstream and destroys them like lymph node

–Not vital organ; can be surgically removed; removal in children can severely compromise immunity, but has lesser effect on adults


Figure 14-3 Spleen, thymus, tonsils, and lymphatic vessels.


Lymph Organs

• Thymus

–Soft organ located between aortic arch and sternum

–Very large in children because it must fend off new infections

–Gets smaller; continues to have some activity in adults as immune system fully matures in its ability to fight infection


Lymph Organs

• Thymus

–Produces lymphocytes that mature into type of WBC called a T lymphocyte

–Secretes hormone that stimulates maturation of T lymphocyte in lymph nodes


Pathology Connection: Lymphatic Disorders

• Lymphadenitis

– Lymph nodes swell

–May be localized or generalized

–Result of bacterial infection, but viruses, parasites, and fungi can also be causes

–Symptoms: swelling of lymph nodes, fever, chills, excessive sweating, rapid pulse, and weakness

–Treatment: infection-specific medication



• Mononucleosis

–Viral infection; affects children, young adults

–Caused by Epstein-Barr virus

–Virus can be transmitted through oral contact



• Mononucleosis

–Symptoms: fatigue, sore throat, fever, lymphadenitis, increased number of lymphocytes

–Treatment: no specific



• Hodgkin's disease (Hodgkin's lymphoma)

–Rare cancer that affects lymphatic system

–Early symptoms: swollen lymph nodes, unexplained fevers, night sweats, fatigue, weight loss, and itchy skin



• Hodgkin's disease (Hodgkin's lymphoma)

–Cause unknown

–Treatment: chemotherapy, radiation, or combination of both


Pathology Connection: Cancer Stages and the Lymphatic System

• Cancer cells can spread around body via lymphatic system

–Degree of spreading can be used to predict patient's prognosis

Cancers that have already spread at time of diagnosis are much more likely to be fatal

Earlier patient with cancer is diagnosed, better chances are of beating disease


Pathology Connection: Cancer Stages and the Lymphatic System

• Stages of cancer (based on degree of spread)

–Stage 1: no spread from origin

–Stage 2: spread to nearby tissues

–Stage 3: spread to nearby lymph nodes

–Stage 4: spread to distant organs and tissues; often terminal


Skin Cancer Video

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The Immune System

• Provides weapons, and troops, to protect body from invasion

• Comprised of cells, chemicals, and barriers that protect body from invasion by pathogens

• Some processes active, some passive, some inborn, and others change with experience


Antigens

• Molecules on outer surface of cell membrane that identify them as friend or foe

• Each living thing has unique cell surface antigens, allowing immune system to distinguish between cells that are naturally yours and cells that are not


Antigens

• Ability called self-recognition and non-self-recognition; is heart of how immune system functions

• Well-functioning immune system ignores self antigens and attacks non-self antigens


Antibodies

• Proteins body makes that bind to antigens, eventually destroying them

• One of most potent weapons of immune system

• Called into action when foreign antigen invades the body


Innate Versus Adaptive Immunity

• Innate (natural) immunity

–First line of defense against invasion

–Body's inborn ability to fight infection; not affected by environment; permanent




–Prevents invasion, or if pathogens do get inside, takes steps to stop spread of infection from spreading

–Can only recognize that something is not native; can't actually identify invader




–Cannot improve with experience

–Because it does not recognize specific pathogens, it cannot "remember" an infection that body has encountered before




–Collection of relatively crude mechanisms for defending body from infection

–Other parts of innate immunity are like weapons of mass destruction, indiscriminately killing pathogens and healthy tissue alike



• Adaptive (acquired) immunity

–Backs up innate immunity, specifically targeting invaders and sparing healthy tissue as much as possible

–Remembers invaders from previous encounters and prepares for future invasion, improving response with experience by learning and changing



• Innate and adaptive immunity are not two separate entities, but work together

• Innate immunity prepares way for adaptive immunity, weakening some pathogens and stimulating components of adaptive immunity



• Adaptive immunity, in turn, stimulates innate immunity attacking pathogen on two fronts


Barriers

• Anything that prevents invaders from getting inside your body prevents infection

• Physical barriers act as first line of defense; located in areas most likely to be invaded

–Skin and mucous membranes of eyes, digestive, respiratory, reproductive systems act as barriers


Barriers

• Not only are these surfaces difficult to penetrate, but are packed with WBCs and lymph capillaries to trap invaders

• Fluids associated with physical barriers, including tears, saliva, urine, mucous secretions, and sweat; all contain chemicals that act as barriers


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Cells

• White blood cells (WBC or leukocytes) are cells responsible for defending body against invaders

• Red blood cells responsible for carrying oxygen throughout body

• Platelets responsible for blood's ability to clot


Cells

• Leukocytes

–Form in bone marrow; move to other parts of body to grow and mature

–Not released into bloodstream unless infection present

–Various types of white blood cells required to protect body in varying circumstances


Figure 14-4 A. Major leukocytes. B. Enhanced color photograph from a scanning electron microscope of a macrophage ingesting rod-shaped bacteria. (Source: Sebastian Kaulitzki/Shutterstock.com.)


Table 14-1 White Blood Cells Involved in Immune Response


Pathology Connection: Leukemia

• Cancer of bone marrow and blood

• Characterized by overproduction of white blood cells; in some forms these cells are immature or nonfunctional

• Types of leukemia

–Acute myelogenous

–Chronic myelogenous

–Acute lymphocytic

–Chronic lymphocytic



• Types of Leukemia

–Myelogenous leukemia: blood stem cells divide out of control

– Lymphocytic leukemia: cells that divide out of control are lymphocytes



• Types of Leukemia

–Acute leukemias: rapid onset of symptoms; overproduced WBCs are immature, nonfunctional cells

–Chronic leukemias: symptoms develop slowly; overproduced WBCs are mature, functional cells



• Epidemiology

–Causes of leukemia not known

–Some types of leukemia more common in children; others more common in adults



• Epidemiology

–Chronic myelogenous leukemia associated with Philadelphia chromosome (chromosomal abnormality)

–Down syndrome patients are higher risk for acute myelogenous leukemia



• Symptoms caused by

–Decreased function of immature WBCs (if cells are immature)

–Decreased numbers of red blood cells and platelets (crowded out by excessive numbers of WBCs)



• Symptoms

–Anemia; shortness of breath; fatigue; repeated infections; enlarged lymph nodes; weight loss; muscle aches; excessive bruising; and bleeding



• Diagnosis: CBC; bone marrow; genetic testing

• Treatments: chemotherapy; antibody treatments; stem cell or bone marrow transplants

–Chronic lymphocytic leukemia: no cure; disease and symptoms managed

–Acute lymphocytic leukemia: common childhood leukemia; very high rate of successful treatment


Leukemia Video

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Chemicals

• Found in body; assist in destroying and neutralizing invaders

• Cytokines:

– Involved in both innate and adaptive immunity


Chemicals

• Cytokines:

–Proteins produced by damaged tissues and WBCs that stimulate immune response in variety of ways, including increasing inflammation, stimulating lymphocytes, and enhancing phagocytosis


Chemicals

• Interferons

–Cytokine produced by cells that have been infected by virus

–Binds to neighboring, uninfected cells and stimulates them to produce chemicals that may protect these cells from viruses

–Has also had some success as anticancer drug, but still experimental


Chemicals

• Many cytokines are types of molecules called interleukins

–At least ten different interleukins; involved in nearly every aspect of innate and adaptive immunity

–Used with moderate success to treat some forms of cancer

–Tumor necrosis factor (TNF): another cytokine; stimulates macrophages; causes cell death in cancer cells


Chemicals

• Complement cascade

–Complex series of reactions that activate series of plasma proteins that are usually inactive in blood unless activated by pathogen invasion


Chemicals

• Complement cascade

–When activated, proteins have variety of effects including: lysis of bacterial cell membranes, stimulating phagocytosis, attraction of WBCs to site of infection, clumping of cells with foreign antigens

–Part of both innate and adaptive immunity


Inflammation

• Also called inflammatory response

• Typical symptoms: pain, swelling, heat, and redness

• Deliberate action of body in response to tissue damage, whether mechanical or pathological injury

• Response helps to wall off infected area to prevent further spread and allow battle to focus at site (margination)


Inflammation

• When tissue is damaged, cells send out chemicals such as histamine, an inflammation modulator

• These chemicals attract WBCs to site, increase permeability of capillaries, and cause local vasodilation; extra fluid causes swelling

• More blood comes to site, causing heat


Inflammation

• WBCs destroy pathogens and clean away dead cells

• Increase in fluid and cells coming to area increases pressure and creates pain

• Innate immune mechanism, but plays important part in adaptive immunity


Figure 14-5 Causes and consequences of the inflammatory response.


Pathology Connection: Inflammation

• Has positive feedback loop; once it starts, will continue until turned off

–Too much inflammation, particularly in closed spaces (like brain, spinal cord, respiratory system and extremities), can cause serious damage



• Widespread (systemic) inflammation called anaphylaxis

–Causes widespread vasodilation, blood pressure plummets

–Can be fatal if not treated immediately

Many patients prone to anaphylaxis carry injectable epinephrine to treat acute reactions

–People allergic to insect stings, nuts, or shellfish may experience anaphylaxis



• Can be treated with several medications

–Nonsteroidal anti-inflammatory drugs (NSAIDS) like ibuprofen and naproxyn sodium

–Steroids

–Antihistamines (especially for allergic reactions)


Fever

• During infection, immune system releases cytokines that promote inflammation and immune responses

• One of cytokine targets in brain is hypothalamus, responsible for setting and maintaining body temperature


Fever

• Effect of cytokine is elevated temperature set point, or fever

• Rise in body temperature is deliberate attempt by immune system to destroy pathogens


Innate Immunity

• First, pathogens must get past physical and chemical barriers; most pathogens kept out by these barriers

• Presence of foreign antigen detected by neutrophils, which ingest foreign antigen, destroying it and releasing chemicals that attract other WBCs to site of infection, stimulating inflammation


Innate Immunity

• Release of cytokines and stimulation of inflammation attract macrophages and natural killer (NK) cells to infection site

• Macrophages phagocytize infected cells; NK cells use chemicals to destroy infected cells; both cells release chemicals to further stimulate inflammation, activate more immune cells, trigger complement cascade


Innate Immunity

• Pathogens are under attack from phagocytosis, noxious chemicals, membrane rupture, clumping, and even alteration to molecular structure

• Chemicals have signaled hypothalamus to raise body temperature and you run a fever


Innate Immunity

• Crude warfare, with innate immunity destroying anything non-self without surgical strikes or specific weapons; desperate attempt to defeat invaders, sometimes killing uninfected cells

• Activities of innate immunity stimulate adaptive immunity


Innate Immunity

• When phagocytic cells ingest pathogens, they display foreign antigen on cell membrane, essential for activation of B and T cells


Adaptive Immunity

• Fights specific pathogens; has memory, "learns" from experience, recognizes specific pathogens

• Because of adaptive immunity, immunizations are able to prevent illness

• Innate and adaptive immunity work hand in hand; one cannot do its job without the other


Lymphocyte Selection

• To function, lymphocytes must be able to recognize pathogens and ignore body's own tissues



• Lymphocytes must be selected through:

–Positive selection: T lymphocytes that recognize self-antigens are allowed to survive; T lymphocytes that do not recognize self-antigens are neglected and die

–Negative selection: destruction or deactivation of self-destroying lymphocytes



• Both positive and negative selection must work in order for immune system to function properly

• You must have lymphocytes that attack invaders but that don't attack you


Pathology Connection: Autoimmune Disorders

• Occur when immune system attacks some part of body; body fails to recognize "self" and destroys own tissues

• Most disorders treated with immunosuppressant drugs, but may not be successful, side effects can be severe



• Hundreds exist, each affecting different system:

–Rheumatoid arthritis (attacks joint linings)

–Multiple sclerosis (attacks myelin sheath in CNS)




– Lupus erythematosus (attacks every tissue, perhaps DNA)

–Type 1 diabetes (attacks beta cells in pancreas)




–Myasthenia gravis (attacks acetylcholine receptors in skeletal muscle)

–Graves' disease (attacks thyroid gland)

–Addison's disease (attacks adrenal gland)



• Rheumatoid arthritis (RA)

–Autoimmune disorder where synovial membranes of joints are attacked

– Leads to destruction of bone and cartilage in joints, weakening of soft tissue supporting joints

–Eventually can result in: joint collapse, fusion of bones, shortening of tendons, disfigurement (particularly of hands and feet)




–Symptoms (most patients have relapsing-remitting pattern of symptoms)

Joint stiffness

Symmetrical joint damage

Fatigue




–Symptoms (most patients have relapsing-remitting pattern of symptoms)

Fever

Systemic symptoms: anemia; dry eye; osteoporosis; lung, pericardial, and blood vessel inflammation; increased risk of heart attack




–Epidemiology

Juvenile and adult forms of disease

Women two to three times more likely than men to have RA

–Cause appears to be combination of genetics and some environmental trigger (virus, bacteria, or hormonal changes)




–Diagnosis typically consists of: medical history, physical exam, imaging, and lab tests (leukocyte counts, erythrocyte sedimentation rate, test for presence of rheumatoid factor); no definitive test




–Treatment

Drugs

–Disease modifying anti-rheumatic drugs (DMARDs): injected gold, methotrexate (cancer drug), or plaquinil (malaria drug)

–Biological response modifiers (BRMs): suppress immune system by decreasing immune-enhancing chemicals




–Treatment

Lifestyle changes: stress reduction, moderate exercise, eating healthy

Assistive devices or surgery often necessary in severe cases



• Systemic lupus erythematosis (SLE)

– Immune system attacks body's connective tissue

–Symptoms

Fatigue

Depression or anxiety

Joint pain and stiffness

Atherosclerosis

Fever




–Symptoms

Heart problems

Kidney disease

Anemia

Chest pain

Swollen glands

Hair loss

Rashes (butterfly-shaped rashes on face)




–Course of disease may be chronic or show relapsing-remitting pattern

–Cause unknown; both genetics and environmental trigger probably necessary for onset




–Diagnosis (difficult because symptoms vary from patient to patient, no definitive test) typically includes:

Medical history

Imaging studies

Tissue biopsies




–Diagnosis (difficult because symptoms vary from patient to patient, no definitive test) typically includes:

Lab tests: blood counts, urinalysis, erythrocyte sedimentation rate, complement levels, testing for antinuclear antibodies




–Treatment

Drugs: NSAIDs, DMARDs, steroids, and immunosuppressants

BRM drugs also being investigated


Lymphocyte Activation

• Lymphocytes develop and mature when you are young; begin as undifferentiated cells, with potential to become anything

• During maturation process they become differentiated, growing to be specialized cells with special function



• Undifferentiated lymphocytes produced in bone marrow and some migrate to thymus, destined to become T cells



• Other lymphocytes develop and mature in bone marrow to become B cells

• Lymphocytes, once specialized, wait in lymph node for pathogen they recognize



• Can remain in suspended animation for long time

• Receive wake-up call, called lymphocyte activation, causing them to circulate combating pathogens



• When innate immune system phagocytizes infected cells they display pathogen's antigens on outside of cell, making them visible to specialized lymphocytes that then become activated and destroy them; beginning of adaptive immunity


Figure 14-6 Lymphocyte differentiation and activation.


Lymphocyte Proliferation

• You only have few lymphocytes that recognize each pathogen, but need hundreds of thousands to attack infection

• Reproduction of lymphocytes called lymphocyte proliferation



• Two types

–Proliferation of helper T cells

–Proliferation of all other types of lymphocytes



• Helper T cells help other lymphocytes; must be lots of these cells before other lymphocytes activated

• Helper T cells stimulated to divide by binding to antigen-displaying cells and by stimulation by cytokines

• Helper T cells continue to divide, then help proliferation of B cells and other types of T cells


Figure 14-7 Activation and proliferation of helper T cells.


Pathology Connection: HIV and AIDS

• Acquired immune deficiency syndrome (AIDS): immune deficiency disorder caused by infection with human immunodeficiency virus (HIV)



• AIDS characterized by severely decreased immune function; happens because HIV virus

–Directly kills helper T cells

–Destroys lymph nodes due to chronic infection

–Decreases amount of immune-enhancing chemicals in body



• HIV contracted through

–Sexual contact

–Sharing IV needles with infected drug user

–Use of blood products

–From mother to fetus in utero and in breast milk

–Accidental exposure to infected body fluids (rare)



• Symptoms

–Approximately four weeks after HIV infection, patients develop flulike symptoms due to body's attempts to fight off virus

– Immune system may continue to fight off disease for next 10 to 12 years without any obvious symptoms



• Symptoms

–Eventually, disease progresses to AIDS-related complex (ARC) or full-blown AIDS; symptoms may include

Enlarged lymph nodes, fatigue

Night sweats, weight loss, diarrhea

Opportunistic infections

CNS dysfunction

Some forms of cancer



• Diagnosis: medical history, low helper T-cell count (less than 200 cells/μl)



• Treatment

–Patients with HIV usually receive combination of antiviral drugs that block viral reproduction, keep virus from assembling new viruses, or block entrance of virus into cells

–Drug regimens are complicated, have severe side effects; infections treated appropriately


HIV Animation

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AIDS Video

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B Cell Action

• Antigen-displaying cells (ADCs) send out signal calling for weapons of adaptive immunity


B Cell Action

• B cells

–Type of adaptive immunity (antibody mediated immunity); fight pathogens by making and releasing antibodies to attack specific pathogen

–B cells develop into plasma cells and memory B cells; make antibodies into bloodstream


B Cell Action

• Primary response: antibodies bind to antigens of infecting cells, destroying pathogen by

– Inactivating antigen (neutralization)

–Causing clumping of antigens (agglutination)


B Cell Action

• Primary response: antibodies bind to antigens of infecting cells, destroying pathogen by

–Activating complement cascade

–Releasing chemicals to stimulate immune system and enhance phagocytosis


B Cell Action

• Other B cells, memory B cells, stored in lymph nodes until they are needed at future date

• Secondary response: responsible for ability of adaptive immunity to improve with experience


Figure 14-8 The primary response causes B cells to produce memory B cells and a few antibodies. The second exposure causes the secondary response to produce more memory B cells and even more antibodies to fight the invaders. Now that the body has antibodies and

more memory B cells, the secondary response begins more rapidly after exposure, produces more antibodies, and lasts a longer time.


T Cell Action

• Four types:

–Helper T cells

–Cytotoxic T cells

–Regulatory T cells

–Memory T cells


T Cell Action

• Cytotoxic T cells

–Adaptive immune response known as cell-mediated immunity because cells directly responsible for death of pathogens or pathogen-infected cells

–Release cytokine called perforin, which causes infected cells to develop holes in their membranes and die


T Cell Action

• Cytotoxic T cells

–Release other cytokines that stimulate both innate and adaptive immunity, especially attracting macrophages to site of infection to dispose of cellular debris

–Response of cytotoxic T cells is primary response of cell-mediated immunity


T Cell Action

• Regulatory T cells

–Something must actively work to turn off response when threat is over or immune response could become rampant and out of control and thus cause damage

–Regulatory T cells are off-switch for immune system


T Cell Action

• Memory T cells

–Given rise from some T cells

– Like memory B cells, memory T cells responsible for secondary response, storing recognition of pathogen until next encounter


Immunity

• Acquire immunity in several different ways

–Natural active immunity: acquired in daily life

–Artificial active immunity: acquired during vaccinations


Immunity

• Acquire immunity in several different ways

–Babies acquire natural passive immunity to many pathogens via antibodies passed across placenta or during breast feeding

–Artificial passive immunity acquired when antibodies from one person injected into another to help fight infection


Figure 14-9 Cell-mediated immunity, primary, and secondary response.


Figure 14-10 Types of immunities.


The Big Picture

• Army of pathogens wants to invade body; first must get past body's barriers

• If invader gets inside body, series of weapons stimulated by non-self-antigen


The Big Picture

• Cells (neutrophils, macrophages, and basophils) stimulated

• Chemicals (cytokines) released that stimulate inflammation and phagocytosis


The Big Picture

• Macrophages and other cells which have ingested some of invaders move to lymphatic system and search lymph nodes, looking for T and B cells that will recognize intruder


The Big Picture

• Helper T cells activate and cause proliferation of B cells and cytotoxic T cells, as well as releasing chemicals to further stimulate phagocytosis and inflammation


The Big Picture

• Cytotoxic T cells activated and proliferate

• B cells produce antibodies that destroy invaders and further stimulate immune response

• Cytotoxic T cells destroy invaders directly and release chemicals that further stimulate immune response


The Big Picture

• Immune response, both innate and adaptive, will continue to be stimulated until feedback loop stopped, at least in part by regulatory T cells

• Memory B cells and T cells stored in lymph nodes for later use if another army of same types of pathogens invade


The Big Picture

• Macrophages and other phagocytic cells will clean up debris left by warfare waged by immune system and body will return to normal


Figure 14-11 The battle plan of the body's defenses.


Pathology Connection: Hypersensitivity Reactions

• Known as allergy; immune system mounts hyperactive response to foreign antigen, often treating harmless antigen, like grass or mold or insect bite, as invading pathogen



• Hypersensitivity reactions, such as hay fever, hives, skin rashes, or asthma generally mild and not life threatening



• Systemic hypersensitivity reactions (anaphylaxis) are life threatening

–Mast cells and basophils release immune-stimulating chemicals throughout body, causing widespread vasodilation

– Leads to dangerously low blood pressure and heart failure



• Systemic hypersensitivity reactions (anaphylaxis) are life threatening

–Hives and respiratory distress may also accompany anaphylactic reaction



• Hypersensitivity reactions

–Mast cells found throughout the body

– If overstimulated in eyes, cause red and runny eyes

– If overstimulated in lungs, cause allergic asthma




–Other immune cells involved in allergic reactions: basophils, B cells, eosinophils, and macrophages

– Increased inflammation and release of immune-stimulating chemicals




–Many patients with one type of allergy suffer from others; example: patients with asthma also have hay fever

–For some patients, mild allergy may progress to more severe form




–Atopic march: early exposure to allergen may cause skin reaction, for example; later exposures cause allergic rhinitis and later exposures cause asthma or even anaphylaxis



• Diagnosing allergies is difficult

–Blood test may show increased immune activity, but may not pinpoint allergen

–Exposing patient's skin or blood sample to suspected allergens may help find allergen, but tests are often inconclusive



• Treatment

–Best treatment is avoidance of allergen; if patient allergic to common substance like grass, mold or pollen, might not be possible

–Medications can be used if allergen unavoidable


Figure 14-12 Allergic rhinitis.


Allergic Rhinitis Video

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EpiPen Video

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Common Disorders of the Immune System

• Lymphoma

–Etiology: uncontrolled proliferation of lymphocytes (30 different types)

–Signs and symptoms: enlarged lymph nodes, fever, weight loss, and other vague symptoms



• Lymphoma

–Diagnostic tests: biopsy, imaging, and bone marrow tests

–Treatment: chemotherapy, radiation, antibody therapy, stem cell or bone marrow transplant



• Tonsillitis

–Etiology: inflammation of tonsils due to bacterial or viral infection

–Signs and symptoms: sore throat, swollen tonsils, fever, upper respiratory symptoms, swollen lymph glands, visible coating or spots on the tonsils, and upset stomach



• Tonsillitis

–Diagnostic tests: examination showing inflamed tonsils, rule out bacterial infection

–Treatment:

If bacterial, treat with antibiotics

If viral, rest and fluids until virus runs its course

If swollen tonsils impair breathing, tonsillectomy may be necessary



• Leukemia

–Etiology: excess production of white blood cells, causes decreased function of WBCs, RBCs, and platelets

–Signs and symptoms: increased infection, anemia, bleeding, bruising, fatigue, and weight loss



• Leukemia

–Diagnostic tests: CBC, genetic testing, and bone marrow biopsy

–Treatment, depending on type: chemotherapy, stem cells, and bone marrow transplant



• Hodgkin's disease

–Etiology: cancer of lymph nodes, effecting white blood cells—most common in people 5–35 years of age; a type of lymphoma




–Signs and symptoms: painless swelling of lymph node early symptom (often in neck), fever, night sweats, weight loss, weakness, fatigue, and itching; respiratory symptoms may occur with chest involvement




–Diagnostic tests: biopsy, various types of x-rays, ultrasound, and lymphangiograms

–Treatment: possibly chemotherapy and radiation depending on age and stage



• Rheumatoid arthritis

–Etiology: destruction joints by immune system

–Signs and symptoms: swollen painful joints, fatigue, anemia, and cardiovascular abnormalities



• Rheumatoid arthritis

–Diagnostic tests: blood tests, and imaging studies

–Treatment: DMARDs, BRMs, lifestyle changes; difficult to treat effectively



• Lupus

–Etiology: destruction of many different body tissues by immune system

–Signs and symptoms: swollen painful joints, fatigue, anemia, and cardiovascular abnormalities



• Lupus

–Diagnostic tests: blood tests, and imaging studies

–Treatment: DMARDs, BRMs, lifestyle changes; difficult to treat effectively



• HIV/AIDS

–Etiology: infection of helper T cells by HIV causes decreased numbers of T cells eventually leading to severe immune deficiency

–Signs and symptoms: flulike symptoms in early stages, opportunistic infections and some forms of cancer in full-blown AIDS



• HIV/AIDS

–Diagnostic tests: medical history, very low helper T-cell counts; AIDS diagnosis made when helper T-cell counts less than 200 μl



• HIV/AIDS

–Treatment: drug cocktails designed to prevent infection from progressing to full-blown AIDS, treatment of opportunistic infections when they develop



• Severe combined immune deficiency (SCID)

–Etiology: severe decreased T cell production (and sometimes other cells) caused by number of different genetic defects

–Signs and symptoms: repeated opportunistic or severe infections in babies, fatal if untreated



• Severe combined immune deficiency (SCID)

–Diagnostic tests: genetic testing

–Treatment, depending on underlying genetic problem: enzyme replacement, complete sterile environment, bone marrow transplant, stem cells, gene therapy; most types difficult to treat



• Allergies

–Etiology: overreaction of immune system to typically harmless antigens, such as mold, pollen or animals

–Signs and symptoms, depending on severity: upper respiratory symptoms, asthma, skin rashes, and anaphylaxis



• Allergies

–Diagnostic tests: medical history, elimination of suspected culprits, skin tests, and blood tests

–Treatment: avoidance, antihistamines, allergy shots, steroids, and epinephrine


Pharmacology Corner

• Anti-inflammatory drugs: decrease inflammation

–Nonsteroidal anti-inflammatory drugs (NSAIDS); examples: aspirin, naprosyn, ibuprofen, celecoxib, and many others

Relieve pain and inflammation by inhibiting hormones called prostaglandins


Pharmacology Corner

• Anti-inflammatory drugs: decrease inflammation

–Nonsteroidal anti-inflammatory drugs (NSAIDS); examples: aspirin, naprosyn, ibuprofen, celecoxib, and many others

Side effects can include formation of stomach ulcers


Pharmacology Corner

• Steroids

–Examples: prednisone, cortisone

–Administered systemically (orally or by injection); can have dangerous side effects if used for long periods of time


Pharmacology Corner

• Steroids

–Topical steroids, applied to skin or nasal passages; effective for treating skin inflammation and upper respiratory symptoms due to allergies

– Inhaled steroids used to control asthma symptoms

–Topical and inhaled steroids do not have severe side effects associated with oral or injected steroids


Pharmacology Corner

• Drugs for allergies

–Antihistamines: decrease mast cell activation; work well, but may cause severe drowsiness

–Cytokine blockers

–Blockers of antibodies that mediate allergies

–Topical steroids (inhalers or nasal sprays)


Pharmacology Corner

• Drugs for allergies

–Patients with anaphylactic reactions to common allergens may be required to carry EpiPen for emergencies.

–Shot of epinephrine constricts blood vessels, stimulates heart, opens air passages, decreasing effects of anaphylactic reactions and giving patient time to get to medical care


Pharmacology Corner

• Drugs for autoimmune disorders

–Disease modifying antirheumatic drugs (DMARDs)

Examples:

–Immunosuppressants (Cyclosporine, an antirejection drug for transplant patients)

–Gold shots

–Methotrexate (chemotherapy drug)

–Antimalarial medications


Pharmacology Corner

• Drugs for autoimmune disorders

–Disease modifying antirheumatic drugs (DMARDs)

Mechanism of action not well understood

Highly toxic


Pharmacology Corner

• Biological response modifiers (BRMs)

–Given to patients who have used DMARDs unsuccessfully

–Suppresses immune system by decreasing immune-enhancing chemicals or inhibiting proliferation of cells


Pharmacology Corner


–Examples:

Drugs that inhibit tumor necrosis factor (TNF), a cytokine: etarnercept (EnbrelTM), infliximab (RemicaideTM), adalimumab (HumiraTM)

Anakinra (KineretTM)—inhibits interleukin-1

Rituximab (RituxanTM)—inhibits B cells


Pharmacology Corner


–Side effects may include

Increased risk of infection

Increased risk of some forms of cancer

– Less toxic than DMARDs; do better job at decreasing fatigue in RA patients


Snapshots from the Journey

• Lymphatic system handles transport for immune system and houses lymphocytes; consists of lymph capillaries, vessels, trunks, and ducts containing lymphatic fluid and lymph nodes, which house WBCs



• Lymph nodes concentrated in several regions of body: cervical, axillary, inguinal, pelvic, abdominal, thoracic, and supratrochlear; patches in areas where pathogens most likely to enter; tonsils, adenoids, spleen, and thymus all contain lymphatic tissue



• Fluid leaking from blood capillaries enters tissue fluid and flows into lymph capillaries

• Fluid carried through lymph capillaries to lymph vessels to lymph nodes

• In nodes, any pathogen destroyed by WBCs



• Fluid then flows from nodes to vessels to lymphatic trunks to collecting ducts and into either right or left subclavian vein, returning fluid to bloodstream

• Cancer cells may use this "highway" to spread to other parts of the body



• Thymus gland and spleen are lymphatic organs; spleen contains blood sinuses and removes dead and dying RBCs as well as pathogens; thymus is birthplace of T lymphocytes



• Immune system function based on ability to recognize cell surface molecules called antigens; immune system must ignore self-antigens and respond to non-self antigens



• Immune system divided into two separate but interdependent parts: innate and adaptive immunity

• Innate immunity: nonspecific, has no memory, cannot get better with experience; adaptive immunity: specific, has memory, improves with experience



• Barriers prevent pathogens from getting into body; can be either physical or chemical; skin and tears are examples of barriers

• Immune system uses dozen or more different types of cells to combat pathogens



• All of these cells are leukocytes or modified leukocytes; some are part of innate immunity and some are part of adaptive immunity

• Functions range from phagocytosis, chemical stimulation of other cells, and antigen display to antibody secretion and direct destruction of pathogens



• Cancer of these cells, which leads to excessive production in bone marrow, is known as leukemia

• Immune response stimulated by variety of chemicals including cytokines, and complement



• Inflammation (redness, heat, swelling, and pain) associated with infection is a powerful tool in immune system's arsenal

• During inflammation, WBCs are stimulated and attracted to site of infection to destroy pathogens and clean up cellular debris



• Inflammation is two-edged sword, with too much causing more damage than infection



• Fever, like inflammation, is deliberate attempt by body to destroy pathogen

• Chemicals trick hypothalamus into raising body temperature set-point in attempt to make things too hot for pathogens



• Innate immune mechanisms are triggered by presence of foreign antigens in body

• Mechanisms hold off infection and stimulate adaptive immune mechanisms



• Adaptive immunity uses T and B lymphocytes to fight off specific pathogens

• Lymphocytes must be selected during development to recognize foreign antigens but to ignore own antigens



• In order to fight pathogen, lymphocytes must be activated by binding with antigen-displaying cells

• Then, once activated, lymphocytes must proliferate, making thousands of copies of themselves



• Helper T cells required for activation of most types of lymphocytes; if lymphocytes continue to recognize body tissues, autoimmune disorder may result

• Rheumatoid arthritis (RA) is autoimmune disorder in which immune system attacks lining of synovial joints



• Systemic illness that involves many joints at once and may also cause damage to heart, eyes and lungs



• Systemic lupus erythematosis (SLE) is more generalized autoimmune disorder in which immune system attacks connective tissue, and even DNA; it is a systemic illness causing joint, heart, and kidney damage



• HIV, virus which causes AIDS, infects and destroys helper T cells; when HIV infection progresses to full-blown AIDS, helper T cell numbers drop so low that activation and proliferation of T and B cells is negatively affected



• With AIDS, adaptive immunity ceases to function and patients are at increased risk of rare infections or may become seriously ill from infections not usually dangerous in people with healthy immune systems



• B cells control antibody-mediated immunity; they are activated by binding to antigen-presenting cells and helper T cells

• Once B cells begin to proliferate, they either become plasma cells or memory B cells



• Plasma cells secrete antibodies during primary response; these antibodies help destroy pathogens by binding to antigens on infected cells

• Memory B cells are stored for next time pathogen is met, to mediate secondary response



• Cytotoxic T cells control cell-mediated immunity, directly killing infected cells

• Cytotoxic T cells, like B cells, are activated by helper T cells

• Some T cells become memory T cells and mediate secondary response if pathogen met again



• Regulatory T cells are one of off-switches for immune system; not very much known about them, as they were discovered within the last decade



• Innate and adaptive immunity work together, complementing one another

–One stimulates the other in large positive feedback loop

– If either stops working, whole system breaks down


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Case Study: Ray's Story

• Remember Ray, the daredevil who broke his neck in the pool and injured his spinal cord? He was treated with steroids as soon as he arrived at the hospital.

–Why?

–What benefit did physicians hope steroids would have for spinal cord injury patients?


Case Study: Ray's Story

• Remember Ray, the daredevil who broke his neck in the pool and injured his spinal cord? He was treated with steroids as soon as he arrived at the hospital.

–Since the time Ray was injured, doctors have begun experimenting with treating injuries like Ray's by inducing hypothermia. How might making Ray's body very cold have helped treat his injury?


Case Study: Maria's Story

• Maria was diagnosed with diabetes mellitus when she was 12 years old. After not taking care of herself in her teen years, she had been doing much better until recently. Though she is following all of her doctor's advice, her diabetes is currently not well controlled.



• What is the cause of her diabetes?

• How is the immune system involved?

• It has been suggested that Maria have a pancreas transplant to relieve her symptoms. If she accepts this treatment option, how might her immune system continue to be a problem?



• What kind of drugs may she have to take after the transplant to prevent problems?

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