chapter 22: the lymphatic system and immunity bio 211 lecture instructor: dr. gollwitzer 1

Chapter 22: The Lymphatic System and Immunity

BIO 211 LectureInstructor: Dr. Gollwitzer

1

• Today in class we will discuss:– Body defenses and the components, mechanisms and

functions of:• Nonspecific defenses

– Physical Barriers– Phagocytes– Immunological surveillance– Interferons– Complement system– Inflammatory response– Fever

• Specific defenses– Immune response

» T cells» B cells» Types of immunity» Properties of immunity

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Immune System

• A physiological system that includes several organ systems– Primary = lymphatic system– Plus components of integumentary,

cardiovascular, respiratory, digestive, and other anatomic systems

– e.g., interactions between lymphocytes and Langerhans cells of skin important in defenses against skin infections

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Immune System

• Specialized sensory “megaorgan”• Enables us to detect things that are foreign

or cannot be seen with the naked eye (microbes, allergens…)

• Allows us to fight (defend against) pathogenic microbes while normal flora left alone

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Body Defenses• Physical and chemical barriers that prevent or

slow entry/progress of infectious organisms• 2 Types of defenses– Nonspecific defenses– Specific defenses

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Body Defenses• Nonspecific defenses– NOT unique– Against any invading agent– Many different threats elicit same response– Present from birth (innate)– e.g., physical barriers, phagocytic cells,

immunological surveillance, interferons, complement, inflammation, fever

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Body Defenses• Specific defenses (AKA: Adaptive defenses)– Protect against specific threats (e.g., one type of

bacterium or virus)– Develop after birth as a result of exposure– Depend on activities of lymphocytes– Result in specific resistance or immunity = ability

to resist infection and disease through activation of specific defenses

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Nonspecific Defenses

Figure 22-11

Nonspecific Defenses:Physical Barriers

• Keep pathogens from entering body– Epithelial linings

• Skin surface layers with keratin and desmosomes water resistant, impregnable wall

– Epithelial accessory structures (e.g., hair, cilia)• Protect against mechanical abrasion• Prevent hazardous contact with skin

– Epithelial secretions• Mechanical barrier, e.g., mucous in respiratory tract, stomach• Antibacterial, e.g. sebum (oily secretion from sebaceous gland),

lysozyme enzyme in tears• Flushing action (tears, urine, mucus in respiratory tract)

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Nonspecific Defenses:Phagocytes

• Perform “police,” “first-responder,” “janitorial” services in peripheral tissues

• First line of cellular defense– Roving cells on look-out for foreign invaders– Remove pathogens and cell debris (cell eaters)– Often attack and remove invaders before lymphocytes

aware of them• Attracted to chemicals (chemotaxis)– Chemicals released:

• From damaged body cells• By pathogens into surrounding fluids, e.g., cytokines

• Move out of bloodstream by squeezing between endothelial cells (diapedesis)

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• Must be activated• Respond to invasion by foreign compounds or

pathogens in several ways– Engulf pathogen or foreign object and destroy with

lysozymes– Bind or remove pathogen from interstitial fluid but not

able to destroy without assistance from other cells– Destroy pathogen by releasing:

• TNF (tumor necrosis factor), NO (nitric oxide), or H2O2 (hydrogen peroxide)

• Brief lifespan for active phagocytes(30 min – 1 hr)

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• 2 Classes of phagocytes– Microphages (“small eaters”)– Macrophages (“big eaters”)

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Nonspecific Defenses:Microphages

• Circulating neutrophils and eosinophils that leave bloodstream and enter injured or infected tissues

• Neutrophils– Abundant, quick, mobile– Engulf pathogens or cellular debris

• Eosinophils– Much rarer cells– Target foreign compounds or pathogens (antigens)

coated with antibodies, e.g., allergens

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Nonspecific Defenses:Macrophages

• Large, actively phagocytic cells derived from monocytes

• Spend very little time in blood• 2 Types– Fixed/resident macrophages• Permanent cells in certain tissues, e.g.,

– Microglia in CNS, Kupffer cells in liver, alveolar macrophages in lungs

– Free macrophages• Mobile; travel throughout body through tissues or

blood14

Nonspecific Defenses: Immunological Surveillance

• Immune system programmed to ignore cells of own body (e.g., intestinal bacteria) unless they become abnormal

• Normal tissues constantly monitored by natural killer (NK) cells looking for:– Abnormal cells (cancer cells with tumor-specific

antigens)– Cells infected with viruses

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• NK cells– Lymphocyte “spy system” in peripheral tissue– Recognize/respond to wide variety of proteins on

cell membranes• vs. T cells or B cells that can be activated only by

exposure to a specific antigen at a specific site on a cell membrane

– Respond immediately on contact with abnormal cell• Much more rapidly than T or B cells whose activation is

complex and time consuming16


• NK cell– Attaches to abnormal cell– Producess protein (perforin) that creates large

pores in cell membrane lyses cell– Especially important opponent for cancer cells

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Fig. 22-12

How NK Cells Kill Cellular Targets

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Nonspecific Defenses:Interferons

• Small protein chemical messengers (type of cytokine) produced by:– Macrophages– Cells infected with viruses– Activated lymphocytes

• Interfere with spread of disease– Coordinate local defenses against viral infection– Stimulate macrophages and NK cells– Signal WBCs and lymphatic system (“tattle tales”)

• Increase resistance of cells to viral infections– Trigger production of antiviral proteins that inhibit

replication within cells19

Nonspecific Defenses:Complement System

• System of 11 blood proteins that interact in a chain reaction (cascade)

• Assists (complements, supplements) antibodies in destroying pathogens– Begins when first complement protein (C1) binds

to antibody (Ab) attached to its specific antigen– Ends with pore formation and lysis of target cell

membrane

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Figure 22–12, 7th edition

Complement System

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Nonspecific Defenses:Complement System

• Attracts phagocytes to injury or infection (via chemotaxis)

• Enhances phagocytosis of antibody-antigen (pathogen) complex

• Stimulates inflammation– Enhances histamine release by mast cells

(basophils in tissues)• Increases local inflammation and accelerates blood flow

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Nonspecific Defenses:Inflammation

• Local tissue response to injury or infection• Stimulus– Anything that changes cell and alters chemical

composition of interstitial fluid– Anything that kills cells, damages CT fibers, or

injures tissue– e.g., impact, abrasion, chemical irritation, infection

by pathogens, extreme temperatures

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• Stimulus causes mast cells – Histamine– Heparin

• – Local vasodilation increased blood flow

redness and heat– Increased capillary permeability blood proteins

into injured tissue local swelling– Stimulation of pain receptors pain

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• Inflammatory response– Walls off region, slows spread of injury/ pathogens

from site– Combats infection by activating: • Phagocytes• Complement• Specific defenses

– Performs temporary repair and prevents access of other pathogens

– Mobilizes regeneration (permanent repair)

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Figure 22-15 26

Nonspecific Defenses:Fever

• High body temperature (>99 F)• Caused by pyrogens– = Proteins released by macrophages that can raise body

temperature– Affect temperature-regulating center in hypothalamus

• Stimuli for pyrogens– Pathogens– Bacterial toxins– Antigen-antibody complexes

• Act directly as pyrogens• Stimulate release of pyrogens by macrophages

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Nonspecific Defenses:Fever

• Beneficial phenomenon– Increases body’s metabolic rate so more enzyme

made to fight infection– Inhibits pathogenic enzymes– Stimulates cell repair

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Specific/Adaptive Defenses:The Immune Response

• Immunity– Specific resistance to injury and disease caused by

foreign compounds, toxins, or pathogens

• Provided by coordinated effort of 2 types of lymphocytes: T and B cells

• Lymphocytes– Respond to presence of specific antigens– “Organize” the defense

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Figure 22-17 30

Specific Defenses:The Immune Response

• T cells (thymus-dependent)– Initiate, maintain, control the immune response– Responsible for cell-mediated immunity– Defend against abnormal cells and pathogens inside

cells (do not respond to pathogens in body fluids)– 3 Major types of T cells• Cytotoxic• Helper• Suppressor

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• B cells (bone marrow-derived)– Responsible for antibody-mediated (humoral)

immunity– Differentiate into plasma cells that produce

antibodies– Defend against antigens and pathogens in body

fluids (antibodies can’t cross cell membranes)

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• Types of immunity– Innate immunity• Present at birth (genetically determined)• Does not require exposure to antigen or antibody

production• Diseases that are species specific

– Acquired/Adaptive immunity• Not present at birth• Produced by prior exposure to specific antigen or

antibody production• 4 types

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Figure 22-14, 7th edition 34

Specific Defenses: Acquired Immunity

• Active immunity– Appears after exposure to an antigen– Requires active response by body, i.e., antibody

production (immune response)– Two types• Naturally acquired (active) immunity

– Through environmental exposure to pathogens

• Induced (active) immunity– Through vaccines containing dead/inactive pathogens or antigens– Antibody production stimulated before possible future exposure

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Specific Defenses: Acquired Immunity

• Passive immunity– Requires no response by body– Produced by transfer of antibodies from one

individual to another– Two types• Natural passive immunity

– Antibodies acquired from mother during development (across placenta) or in early infancy (through breast milk)

• Induced passive immunity– Antibodies (developed in another body) administered via injection– e.g., IG injected into Rh- mother after first Rh+ baby; antirabies

virus antibodies injected into person bitten by rabid animal, antivenom…snake bite

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• Properties of immunity that enable body to respond with a specific defense – Specificity– Versatility– Memory– Tolerance

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Specific Defenses:4 Properties of Immunity

• Specificity– Specific defenses activated by one specific antigen• Immune response targets that antigen ONLY

– Each T and B lymphocyte has receptors that bind to only one specific antigen and ignore all others

– T or B cells will destroy or inactivate that antigen without affecting other antigens or normal tissues

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• Versatility– Ability of immune system to confront any antigen any time– Results from large diversity of lymphocytes in body

• During development, cell differentiation in lymphatic system produces millions of different lymphocyte populations (each has several 1000 identical cells)

• Each lymphocyte population responds to a different antigen

– Several 1000 lymphocytes not enough to overcome pathogenic invasion, but begin dividing when activated in presence of appropriate antigen

– Produce more lymphocytes with same specificity clone

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• Memory– Lymphocytes remember antigens they’ve

encountered before– During initial response to antigen, lymphocytes

undergo repeated cycles of cell division– Produce 2 types of cells• Activated lymphocytes that attack antigen invader• Memory cells that remain inactive until exposed to same

antigen again at a later time

– After second exposure, response is faster, stronger, and lasts longer than first time

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• Tolerance– Immune system• Ignores “normal” (self) antigens• Attacks foreign (nonself) antigens

– Can also develop in response to chronic (long-term) exposure to antigen in environment; lasts only as long as exposure continues

– Failure autoimmune diseases

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• Today in class we will discuss:– The immune process• Antigens• T cells• B cells• Types of immune responses

– Cell-mediated immunity• Antigen presentation• Antigen recognition• T cell activation• Destruction/elimination of target cell/antigen

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Immune Response Process• Antigen– = Foreign substance capable of inducing antibody

production– Triggers immune response– Activates• Phagocytes activation of T cells• B cells

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Immune Response Process• T cells– Initiate, maintain, control immune response– Carry out direct physical/chemical attack on

antigen– Stimulate activation of B cells

• B cells– Mature into plasma cells that produce antibodies– Antibodies in bloodstream bind to/attack antigen

antigen-antibody complex that is eliminated from system

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Figure 22-17 45

Immune Responses• 2 types– Cell-mediated immunity

(T cells)– Antibody-mediated (humoral) immunity

(B cells)

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Immune Responses• Cell-mediated immunity– Involves T cells– Process• Antigen presentation• Antigen recognition• T cell activation• Destruction/elimination of target cell/antigen

(cytotoxic T cells)

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T Cells and Cell-mediated Immunity

• Antigen presentation– = Process whereby foreign antigen is displayed

(“presented”) on cell membrane– Requires combining foreign antigen + glycoprotein

(e.g., MHC protein)

Antigen = foreign peptide that has potential to induce antibody formation

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• MHC proteins– Membrane glycoproteins– Synthesis controlled by group of genes called the

major histocompatability complex (MHC)– Bind antigens– Differ among individuals– Two classes of MHC proteins• MHC I• MHC II

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• MHC I proteins– Continuously being formed in all normal, healthy

cells that have a nucleus

• MHC II proteins– In:• Antigen-presenting cells (APCs)

– Present only when cell actively processing foreign antigen

• Lymphocytes (B cells and helper T cells)NOTE: these cells also have MHC I proteins

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• Antigen-presenting cells (APCs)– Phagocytic APCs• Free and fixed macrophages in CT

– Engulf and break down foreign cells (bacteria or cancer) and viruses

– Foreign antigens– e.g., microglia in CNS, Kuppfer cells in liver

– Nonphagocytic APCs• Remove foreign antigens from their surroundings by

pinocytosis• e.g., Langerhans cells of skin, dendritic cells of lymph

nodes and spleen

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• Antigen presentation (continued)– As MHC proteins are formed they pick up small

peptides/antigens from cytoplasm– Carry them to cell membrane– Peptide/antigen-MHC protein complex inserted into

cell membrane– Peptide/antigen “presented” to circulating T cells

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Figure 22-18a 53

Figure 22-18b 54


• Antigen recognition– Circulating T cells (inactive) have receptors for:• A specific antigen-MHC I or MHC II protein complex

– If membrane-bound peptide normal, ignored by circulating T cells

– If peptide abnormal (from cancer cell) or foreign (from bacteria or virus that infected cell) and circulating T cell contains appropriate antigen-MHC protein complex, membrane-bound complex will be noticed (“recognized”) by T cell

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T Cells and Cell-mediated Immunity• Antigen recognition (continued)– MHC I protein with foreign antigen• Recognized by cytotoxic T cells and suppressor T cells• Tells immune system “I’m an abnormal/infected cell – kill

me!” (= cytotoxicity)– MHC II protein with foreign antigen• Recognized by helper T cells• Tells immune system “I’m an active APC. This antigen is

dangerous – get rid of it.”

• T cell will bind to antigen-MHC protein receptor on cell membrane

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Antigen Recognition by and Activation of Cytotoxic T Cells

57Figure 22-19, (Steps 1-3)

Antigen Recognition by and Activation of Cytotoxic T Cells

58Figure 22-19, (Steps 4)


• T cell activation– Must occur before immune response can begin– When T cell released from antigen-MHC protein

receptor on cell membrane it is “activated”– Activated T cell divides to produce:• Active cells (cytotoxic, helper T cells)• Memory cells

– Reserve (“sleeper”) cells– Immediately become active T cells when antigen appears a

second time

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Antigen Recognition and Activation of Helper T Cells

Antigen Recognition by CD4 T Cell

Foreign antigen

Antigen-presentingcell (APC)

Class II MHC APC

Antigen

T cell receptor

Costimulation

CD4 protein

TH cell

InactiveCD4 (TH)

cell

Figure 22-20, (Part 1 of 2) 60

Antigen Recognition and Activation of Helper T Cells

CD4 T Cell Activation and Cell Division

Memory TH cells(inactive)

Active TH cells

Cytokines

Active helper T cells secretecytokines that stimulate both

cell-mediated andantibody-mediated immunity.

Cytokines

Cytokines

Figure 22-20, (Part 2 of 2) 61


• End result– Activated cytotoxic T cells (Fig 22-19)• Destroy abnormal or infected cells that “display” its target

antigen and MHC I protein (cytotoxicity)

– Activated helper T cells (Fig 22-20)• Secrete cytokines when exposed to cells that “display” its

target antigen and MHC II protein• Cytokines interact with sensitized B cells (see Fig 22-22)

• Summary of T cell activation (Fig 22-21)

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Figure 22–21

Pathways of T Cell Activation

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• Today in class we will discuss:– Antibody-mediated immunity• T cells• B cell activation• Antibodies and their classification• Primary response in antibody-mediated immunity• Secondary response in antibody-mediated immunity

– Body responses to• Bacterial infection• Viral infection

– Immune disorders– Aging and the immune response

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Immune Responses• Antibody-mediated (humoral) immunity– Involves B cells– Process• B cell sensitivation• B cell activation (by helper T cells)• Antibody production (by plasma cells)• Destruction/elimination of target antigen-antibody

complex

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B Cells and Antibody-mediated Immunity

• B cell sensitization– Each B cell carries its own antibody molecules on its

cell membrane– As it migrates through tissues, it finds appropriate

antigen that binds to its antibodies = “sensitization” (like antigen presentation in T cells)• Usually occurs in lymph node nearest site of

infection/injury

– Antigens brought into B cell and appear on cell membrane bound to MHC II proteins

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Figure 22-22

The Sensitization and Activation of B Cells

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• B cell activation– Sensitized B cell on “standby” until it meets

appropriate, activated helper T cell– T cell• Recognizes antigen-MHC protein complex• Binds to it• Secretes cytokines

– Cytokines stimulate B cell activation

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• B cell activation (continued)– B cell divides to form:• Activated B cells

– Become plasma cells» Produce antibodies specific for that antigen

• Memory B cells– Remain in reserve to deal with subsequent injuries/infections

that involve same antigen

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• Antibodies (immunoglobulins, Igs)– Found in body fluids, not cells– Y-shaped, 2 parallel pairs of polypeptide chains– 5 classes determined by structural differences• IgG = largest, most common; only one that crosses the

placenta• IgE = important in allergic responses• IgD = helps B cells• IgM = first Ab produced during immune response, then

declines when IgG increases• IgA = found in glandular secretions (mucus, tears, saliva)

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Figure 22-23 71

Table 22–1

5 Classes of Antibodies

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• Immune response– Occurs after exposure to an antigen– 2 types of responses• Primary• Secondary

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• Primary response– Initial response– Develops slowly, takes 1-2 weeks to peak after exposure

• Antigen must activate appropriate B cells, which then differentiate into plasma cells

– IgM is first antibody to appear• Provides immediate, limited defense that fights infection until IgG can

be produced– Concentrations of IgM and IgG relatively low and do not

remain elevated• Plasma cells have short life spans• Production of new cells inhibited by suppressor T cells

– May not prevent an infection

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Figure 22-24, 7th edition 75


• Secondary response– Response after second exposure– More extensive and prolonged; more effective defense– Due to large numbers of memory B cells primed for arrival of

antigen (may last > 20 years!)– When same antigen appears a second time, memory B cells

differentiate into plasma cells that secrete huge quantities of IgG antibodies

– IgG antibody activity stays elevated for extended period– Response very adequate for preventing infection– Effectiveness of secondary response is basic principle behind

use of immunization to prevent disease

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Figure 22-24b, 7th edition 77


• Antibody molecule binds to corresponding antigen molecule antigen-antibody complex

• Elimination of antigen-antibody complex– Destroyed by phagocytes– Destroyed by complement system– Complexes may be insoluble and precipitate– Form large complexes through agglutination

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Figure 22-26

Overall Summary of Defense Mechanisms

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Figure 22–24 80

Body Responses to Bacterial Infection

Figure 22-27

Responses to Bacteria & Viruses

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Key Concepts

• Viruses replicate inside cells• Bacteria may live independently• Antibodies (and antibiotics) work outside cells,

so are primarily effective against bacteria rather than viruses

• Antibiotics can’t fight common cold or flu (caused by viruses)

• Primary defense against viral infection– NK cells, interferon, T cells

82

Immune Disorders• Allergies – over-reaction of immune system;

anaphylaxis = most extreme form• Autoimmune diseases – produce (auto)antibodies

against own tissues– Rheumatoid arthritis (connective tissue and joints)– Thyroiditis (anti-thyroglobulin)– Insulin-dependent diabetes mellitus (pancreas)

• Immunodeficiency diseases – problems with:– Development of lymphoid tissues (genetic)– Viral infection (AIDS – interferes with helper T cells)– Treatment with immunosuppressive drugs (steroids,

antineoplastics) or radiation83

Aging and the Immune Response• Immune system less effective• Some effects may be related to involution of thymus

and decreased thymic hormones• T cells less responsive to antigens so fewer cells

respond to infection• B cells less responsive so Ab levels don’t increase as

quickly increased susceptibility to viral and bacterial infections (Note: reason vaccinations for flu, pneumonia recommended for elderly persons)

• Decreased immune surveillance (NK cells) tumor cells aren’t eliminated as effectively increased cancer rate

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chapter 22: the lymphatic system and immunity bio 211 lecture instructor: dr. gollwitzer 1

Documents

body defensesphysical

nonspecific defensesfigure

damaged body cellsby

specific threats

phagocytic cells

respiratory tract

foreign compounds

foreign object