Chapter 22: The Lymphatic System

Biology 142 A&PR.L. Brashear-Kaulfers

Pathogens

• Microscopic organisms that cause disease:– viruses– bacteria– fungi– parasites

• Each attacks in a specific way

The Lymphatic SystemProtects us against disease

• Lymphocytes:• Lymphatic system cells respond to:

– environmental pathogens– toxins– abnormal body cells, such as cancers

What is the difference between nonspecific

and specific defense, and the role of lymphocytes in the immune response?

Specific Defenses

• Lymphocytes:– part of the immune response

• Identify, attack, and develop immunity to a specific pathogen

• Immunity- The ability to resist infection and disease

The Immune System

• All body cells and tissues involved in production of immunity:– not just lymphatic system

Nonspecific Defenses

• Block or attack any potential infectious organism

• Cannot distinguish one attack from another

Immunity: Nonspecific DefensesPLAYPLAY

Organization of the

Lymphatic System

Figure 22–1

What are the major components of the lymphatic system and their functions?

4 Parts of the Lymphatic System

1. Lymph: – a fluid similar to plasma– does not have plasma proteins

2. Lymphatic vessels (lymphatics): – network that carries lymph from

peripheral tissues to the venous system

3. Lymphoid tissues and lymphoid organs:

– found throughout the body

4. Lymphocytes, phagocytes, and other immune system cells

Function of the Lymphatic System

• To produce, maintain, and distribute lymphocytes-

**Lymphocyte Production:- Lymphocytes are produced:

– in lymphoid tissues (e.g., tonsils)– lymphoid organs (e.g., spleen, thymus)– and in red bone marrow

** Lymphocytes Distribution: – detect problems– travel into site of injury or infection

Lymphocyte Circulation

• From blood to interstitial fluid (lymph) through capillaries

• Returns to venous blood through lymphatic vessels

The Circulation of Fluids

• From blood plasma to lymph and back to the venous system

• Also transports hormones, nutrients, and waste products

Lymphatic Vessels• Are vessels that carry lymph • Lymphatic system begins with

smallest vessels: lymphatic capillaries (terminal lymphatics)

• Lymphatic Capillaries-• Differ from blood capillaries in 4

ways:– start as pockets rather than tubes– have larger diameters– have thinner walls– flat or irregular in section

Figure 22–2

Lymphatic Capillaries

Endothelial cells loosely bound together with overlapOverlap acts as one-way valve:

allows fluids, solutes, viruses, and bacteria to enterprevents return to intercellular space

Lacteals

• Are special lymphatic capillaries in small intestine

• Transport lipids from digestive tract

Figure 22–3

Lymphatic Vessels and Valves

Lymph Flow

• From lymphatic capillaries to larger lymphatic vessels containing one-way valves

• Lymphatic vessels travel with veins

Figure 22–4

Lymphatic Ducts and the Venous System

The Lymphatic System

• Is divided into: 1) Superficial lymphatics - located in:– skin– mucus membranes– serous membranes lining body 2) Deep lymphatics- Are larger vessels that

accompany deep arteries and veins

Superficial and Deep Lymphatics

• Join to form large lymphatic trunks • Trunks empty into 2 major

collecting vessels: – thoracic duct – right lymphatic duct

The Inferior Thoracic Duct • Collects lymph from:

– left bronchiomediastinal trunk– left subclavian trunk– left jugular trunk

• Empties into left subclavian veinThe Right Lymphatic Duct

• Collects lymph from:– right jugular trunk– right subclavian trunk– right bronchiomediastinal trunk

• Empties into right subclavian vein

Lymphedema

• Blockage of lymph drainage from a limb

• Causes severe swelling• Interferes with immune system

function

Why are lymphocytes important, and how are they

distributed in the body?

• Lymphocytes• Make up 20–30% of circulating

leukocytes• Most are stored, not circulating

3 Classes of Circulating Lymphocytes

1. T cells: thymus-dependentMake up 80% of circulating lymphocytes

2. B cells: bone–marrow derived• Make up 10–15% of circulating

lymphocytes• Differentiate into plasma cells- Produce

and secrete antibodies (immunoglobin proteins)

3. NK cells:– natural killer cells

3 Main Types of T Cells1. Cytotoxic T cells-Attack cells infected

by viruses Produce cell-mediated immunity2. Helper T cells- Stimulate function of

T cells and B cells3. Suppressor T cells-Inhibit function of

T cells and B cells

Regulatory T Cells

• Are helper and suppressor T cells• Control sensitivity of immune

response

Other T Cells• Inflammatory T cells • Suppressor and inducer T cells

Antigens • Targets which identify any pathogen

or foreign compoundImmunoglobin Proteins (Ig’s)

Also called antibodies (Ab)• The binding of a specific antibody to

its specific target antigen initiates antibody-mediated immunity:- A chain of events which destroys the target compound or organism

Natural Killer (NK) Cells • Also called large granular

lymphocytes • Make up 5–10% of circulating

lymphocytes• Responsible for immunological

surveillance• Attack:

– foreign cells– virus-infected cells– cancer cells

Lymphocyte Distribution

• Tissues maintain different T cell and B cell populations

• Lymphocytes wander through tissues:– enter blood vessels or lymphatics for

transport – can survive many years

Figure 22–5

Production and Distribution of Lymphocytes

Lymphopoiesis

• Lymphocyte production involves:– bone marrow– thymus– peripheral lymphoid tissues

• Hemocytoblasts : In bone marrow, divide into 2 types of lymphoid stem cells

Lymphoid Stem Cells

• Group 1:– remain in bone marrow– produce B cells and natural killer cells

• Group 2:– migrate to thymus– produce T cells in environment

isolated by blood-thymus barrier

T Cells and B Cells

• Migrate throughout the body:– to defend peripheral tissues

• Retain their ability to divide:– is essential to immune system

function

Differentiation

• B cells differentiate:– with exposure to hormone interleukin-

7

• T cells differentiate:– with exposure to several thymic

hormones

• Interleukin-7 - A cytokine produced by stromal cells in bone marrow

What are the structures and functions of lymphoid

tissues and organs?

Lymphoid Tissues :Connective tissues

dominated by lymphocytes

Figure 22–6

Lymphoid Nodules

Lymphoid Nodule

• Areolar tissue with densely packed lymphocytes

• Germinal center contains dividing lymphocytes

Distribution of Lymphoid Nodules

• Lymph nodes• Spleen• Respiratory tract (tonsils)• Along digestive and urinary tracts

Mucosa-Associated Lymphoid Tissue (MALT)

• Lymphoid tissues associated with the digestive system:– aggregated lymphoid nodules:

• clustered deep to intestinal epithelial lining

• Appendix:– mass of fused lymphoid nodules

The 5 Tonsils

• In wall of pharynx:– left and right palatine tonsils– pharyngeal tonsil (adenoid)– 2 lingual tonsils

Lymphoid Organs

• Lymph nodes• Thymus • Spleen • Are separated from surrounding

tissues• By a fibrous connective-tissue

capsule

Figure 22–7

Lymph Nodes

• Range from 1–25 mm diameter

Afferent Lymphatic Vessels

• Carry lymph:– from peripheral tissues to lymph node

Efferent Lymphatic Vessels

Leave lymph node at hilus • Carry lymph to venous circulation

Lymph from Afferent Lymphatics

• Flows through lymph node in a network of sinuses:

• From subcapsular sinus:– contains macrophages and dendritic cells

• Through outer cortex:– contains B cells within germinal centers

• Through deep cortex:– dominated by T cells

• Through the core (medulla):– contains B cells and plasma cells– organized into medullary cords

• Into hilus and efferent lymphatics

Lymph Node

• A filter:– purifies lymph before return to

venous circulation

• Removes:– debris– pathogens– 99% of antigens

Antigen Presentation

• First step in immune response• Extracted antigens are

“presented” to lymphocytes:– or attached to dendritic cells to

stimulate lymphocytes

Lymphoid Functions

• Lymphoid tissues and lymph nodes:– distributed to monitor peripheral

infections– respond before infections reach vital

organs of trunk

Lymph Nodes of Gut, Trachea, Lungs, and Thoracic

Duct • Protect against pathogens in

digestive and respiratory systems

Lymph Glands • Large lymph nodes at groin and

base of neck • Swell in response to inflammation

Lymphadenopathy

• Chronic or excessive enlargement of lymph nodes may indicate infections, endocrine disorders, or cancer

Figure 22–8

The Thymus

The Thymus

• Located in mediastinum• Deteriorates after puberty:

– diminishing effectiveness of immune system

• Divisions of the Thymus Thymus is divided into 2 thymic lobes

• Septa divide lobes into smaller lobules

A Thymic Lobule

• Contains a dense outer cortex• And a pale central medulla

Thymus Hormones• Thymosins • Promote development of

lymphocytes

Lymphocytes

• Divide in the cortex• T cells migrate into medulla• Mature T cells leave thymus by

medullary blood vessels

Reticular Epithelial Cells in the Cortex

• Surround lymphocytes in cortex • Maintain blood-thymus barrier• Secrete thymic hormones that

stimulate:– stem cell divisions– T cell differentiation

Reticular Epithelial Cells in the Medulla

• Form concentric layers (Hassall’s corpuscles)

• The medulla has no blood–thymus barrier:– T cells can enter or leave bloodstream

Figure 22–9

The Spleen

3 Functions of the Spleen

1. Removal of abnormal blood cells and other blood components by phagocytosis

2. Storage of iron recycled from red blood cells

3. Initiation of immune responses by B cells and T cells:

– in response to antigens in circulating blood

Structure of the Spleen

• Attached to stomach by gastrosplenic ligament

• Contacts diaphragm and left kidney

• Splenic veins, arteries, and lymphatic vessels:– communicate with spleen at hilus

Structure of the Spleen• Inside fibrous capsule:

– Red pulp: contains many red blood cells

Contains elements of circulating blood plus fixed & free

macrophages

– White pulp: resembles lymphoid nodules

Trabecular Arteries

• Branch and radiate toward capsule• Finer branches surrounded by

white pulp• Capillaries discharge red blood

cells into red pulp

Splenic Circulation

• Blood passes through:– network of reticular fibers

• Then enters large sinusoids (lined by macrophages):– which empty into trabecular veins

Spleen Function

• Phagocytes and other lymphocytes in spleen:– identify and attack damaged and

infected cells– in circulating blood

Body Defenses• Provide resistance to fight infection,

illness, and disease• 2 categories of defenses:• nonspecific defenses = Always work the

same way , against any type of invading agent

• specific defenses = Protect against specific pathogens

• Depend on activities of lymphocytes• Specific resistance (immunity):

– develops after exposure to environmental hazards

7 Types of Nonspecific Resistance

1. Physical barriers2. Phagocytic cells3. Immunological surveillance4. Interferons5. Complement6. Inflammation7. Fever

Nonspecific and Specific Defenses

• Operate together to provide resistance to infection and disease

Figure 22–10

The 7 Nonspecific Defenses

The 7 Nonspecific Defenses • Physical Barriers -Keep hazardous materials

outside the body• Phagocytes -Attack and remove dangerous

microorganisms• Immunological Surveillance -Constantly

monitors normal tissues:– with natural killer cells (NK cells)

• Interferons -Trigger production of antiviral proteins in normal cells Antiviral proteins:– do not kill viruses– block replication in cell

The 7 Nonspecific Defenses

• Complement (C) Proteins -Form the complement system

Complements action of antibodies• Inflammation -Triggers a complex

inflammatory response• Fever -A high body temperature:

– increases body metabolism– accelerates defenses– inhibits some viruses and bacteria

Immunity: ComplementPLAYPLAY

What are the components

and mechanisms of each nonspecific defense?

Physical Barriers • Outer layer of skin• Hair• Epithelial layers of internal

passageways• Secretions that flush away materials:

– sweat glands, mucus, and urine

• Secretions that kill or inhibit microorganisms:– enzymes, antibodies, and stomach acid

2 Classes of Phagocytes• Microphages: neutrophils and

eosinophils• Leave the bloodstream• Enter peripheral tissues to fight

infections• Macrophages: large phagocytic cells

derived from monocytes• Distributed throughout body• Make up monocyte–macrophage

system (reticuloendothelial system)

Activated Macrophages

• Respond to pathogens in several ways:

– engulf pathogen and destroy it with lysosomal enzymes

– bind to pathogen so other cells can destroy it

– destroy pathogen by releasing toxic chemicals into interstitial fluid

2 Types of Macrophages

• Fixed macrophages - also called histocytes: Microglia:– found in central nervous system

Kupffer cells:– found in liver sinusoids

• Stay in specific tissues or organs:– e.g., dermis and bone marrow

• Free macrophages -Travel through blood stream

• Special free macrophages:– alveolar macrophages (phagocytic dust cells)

3 Functional Characteristics of Free Macrophages and

Microphages• Move through capillary walls

(emigration)• Are attracted or repelled by

chemicals in surrounding fluids (chemotaxis)

Phagocytosis begins:– when phagocyte attaches to target

(adhesion)– and surrounds it with a vesicle

Figure 22–11

Natural Killer Cell Function

Immunological Surveillance is carried out by Natural killer (NK) cells

NK Cell Function

• Identifies and attaches to abnormal cell (non-selective)

• Golgi apparatus in NK cell:– forms perforin vesicles

• Vesicles release perforin (exocytosis)

• Perforin lyses abnormal cell membrane

NK Cells attack: cancer cells and

cells infected with viruses1) Cancer Cells -with tumor specific

antigens: – are identified as abnormal by NK cells– some cancer cells avoid NK cells

(immunological escape)

2) Viral Infections : Cells infected with viruses:– present abnormal proteins on cell

membranes– allow NK cells to identify and destroy them

Interferons

• Proteins (cytokines) released by activated lymphocytes and macrophages-

• Cytokines - Chemical messengers released by tissue cells:– to coordinate local activities– to act as hormones to affect whole

body

3 Types of Interferons

1. Alpha interferons:– produced by leukocytes– stimulate NK cells

2. Beta interferons:– secreted by fibroblasts– slow inflammation

3. Gamma interferons:– secreted by T cells and NK cells– stimulate macrophage activity

Figure 22–12

Complement Activation

Complement:Plasma contains 11 special complement (C) proteins:

that complement antibody action

Complement Activation

• Complements work together in cascades

• 2 pathways activate the complement system– classical pathway– alternative pathway

The Classical Pathway

• Fast method• C1 binds to antibody molecule

attached to antigen (bacterium)• Bound protein acts as enzyme:

– catalyzes chain reaction

The Alternative Pathway• Slow method• Exposed to antigen:

– factor P (properdin)– factor B– and factor D interact in plasma

• ** Both pathways end with:– conversion of inactive complement

protein (C3)– to active form (C3b)

4 Effects of Complement Activation

1. Stimulation of inflammation2. Attraction of phagocytes3. Enhancement of phagocytosis by

opsonization: – complements working with antibodies

(opsonins)

4. Destruction of target cell membranes:– 5 complement proteins join to form

membrane attack complex (MAC)

Inflammation

• Also called inflammatory response • A localized response• Triggered by any stimulus that kills

cells or injures tissue

Cardinal Signs and Symptoms

• Swelling (tumor)• Redness (rubor)• Heat (calor)• Pain (dolor)

3 Effects of Inflammation

1. Temporary repair and barrier against pathogens

2. Retards spread of pathogens into surrounding areas

3. Mobilization of local and systemic defenses:

– and facilitation of repairs (regeneration)

Figure 22–13

Inflammation and Tissue Repair

Inflammation and Tissue Repair

• Injured cells release:– prostaglandins– proteins– potassium ions

• Changes interstitial environment and stimulates mast cells

• Mast cells release:– histamine (increases capillary

permeability)– heparin (inhibits clotting

Inflammation and Tissue Repair

• Increased blood flow:– raises local temperature– causes area to swell, redden, and

become painful

• Blood clot forms around damaged area, isolating it

• Complements:– break down bacteria– attract phagocytes

Inflammation and Tissue Repair

• Activated neutrophils attack debris and bacteria

• Phagocytes and foreign proteins:– activate body’s specific defense

system

• Macrophages clean up pathogens and cell debris

• Fibroblasts form scar tissue

Products of Inflammation

• Necrosis:– local tissue destruction in area of

injury

• Pus:– mixture of debris and necrotic tissue

• Abscess:– pus accumulated in an enclosed

space

Fever - A maintained body temperature above 37°C (99°F)

• Pyrogens - Any material that causes the hypothalamus to raise body temperature:– circulating pathogens, toxins, or

antibody complexes

• Endogenous Pyrogens : Interleukin-1 (IL-1)– pyrogen released by active

macrophages– a cytokine

Figure 22–14

Forms of Immunity

Specific Defenses

• Specific resistance (immunity):– responds to specific antigens– with coordinated action of T cells and

B cells

T Cells

• Provide cell-mediated immunity• Defends against abnormal cells

and pathogens inside cells

B Cells

• Provide antibody-mediated immunity

• Defends against antigens and pathogens in body fluids

Forms of Immunity• 1) Innate Immunity:

– present at birth

• 2) Acquired Immunity:– after birth

Active:– antibodies develop after exposure to

antigen

Passive:– antibodies are transferred from another

source

Active Immunity

• Naturally acquired:– through environmental exposure to

pathogens

• Induced:– through vaccines containing

pathogens

Passive Immunity

• Naturally acquired:– antibodies acquired from the mother

• Induced:– by an injection of antibodies

4 Properties of Immunity1. Specificity- Each T or B cell:

– responds only to a specific antigen, ignores all others

2. Versatility-The body produces many types of lymphocytes:

– each fights a different type of antigen (Ag)– active lymphocyte clones itself to fight specific Ag

3. Memory-Some active lymphocytes (memory cells):

– stay in circulation– provide immunity against new exposure

4. Tolerance- Immune system ignores “normal” antigens

What are the differences between cell-mediated

(cellular) immunity and antibody-mediated (humoral) immunity?

Figure 22–15 (Navigator)

The Immune Response

The Immune Response

• 2 main divisions:– cell mediated immunity (T cells)– antibody mediated immunity (B cells)

Immunity: Cell-Mediated ImmunityPLAYPLAY

What are the types of T cells and their functions

in the immune response?

What are the types of T cells and their functions in the immune response?

1) Cytotoxic T Cells= also called Tc cells

• Attack cells infected by viruses• Responsible for cell-mediated immunity2) Helper T Cells= also called Th cells

• Stimulate function of T cells and B cells3) Suppressor T Cells = also called Ts cells

• Inhibit function of T cells and B cells

Antigens and MHC Proteins

Antigens and MHC ProteinsPLAYPLAY

Figure 22–16a (Navigator)

Antigen Recognition

• T cells only recognize antigens that are bound to glycoproteins in cell membranes

Figure 22–16b

Antigen Presentation

MHC Proteins

• The membrane glycoproteins that bind to antigens

• Genetically coded in chromosome 6:– the major histocompatibility complex

(MHC)– differs among individuals

2 Classes of MHC Proteins• Class I: found in membranes of all nucleated

cells• Pick up small peptides in cell and carry them

to the surface:– T cells ignore normal peptides– abnormal peptides or viral proteins activate T

cells to destroy cell

• Class II: found in membranes of antigen-presenting cells (APCs)– found in lymphocytes Antigenic fragments:– from antigenic processing of pathogens – bind to Class II proteins – inserted in cell membrane to stimulate T cells

Antigen-Presenting Cells (APCs)

• Responsible for activating T cells against foreign cells and proteins

Phagocytic APCs :• Free and fixed macrophages:

– in connective tissues

• Kupffer cells:– of the liver

• Microglia:– in the CNS

Pinocytic APCs

• Langerhans cells:– in the skin

• Dendritic cells:– in lymph nodes and spleen

What are the mechanisms

of T cell activation and the differentiation of the major classes of T cells?

An Overview of the Immune Response

Figure 22–15 (Navigator)

Antigen Recognition

• Inactive T cell receptors:– recognize Class I or Class II MHC

proteins– recognize a specific antigen

• Binding occurs when MHC protein matches antigen

CD Markers• Also called cluster of differentiation

markers:– in T cell membranes– molecular mechanism of antigen

recognition– more than 70 types:

• designated by an identifying number

CD3 Receptor Complex• Found in all T cells

CD8 Markers • Found on cytotoxic T cells and

suppressor T cells• Respond to antigens on Class I MHC

proteins CD4 Markers• Found on helper T cells• Respond to antigens on Class II MHC

proteins• CD8 or CD4 Markers - Bind to CD3

receptor complex• Prepare cell for activation

Costimulation

• For T cell to be activated, it must be costimulated:– by binding to stimulating cell at

second site– which confirms the first signal

2 Classes of CD8 T Cells

• Activated by exposure to antigens on MHC proteins:– one responds quickly:

• producing cytotoxic T cells and memory T cells

– the other responds slowly:• producing suppressor T cells

Figure 22–17 (Navigator)

Activation of Cytotoxic T Cells

Also called killer T cells Seek out and immediately destroy target cells

Actions of Cytotoxic T Cells

1. Release perforin:– to destroy antigenic cell membrane

2. Secrete poisonous lymphotoxin:– to destroy target cell

3. Activate genes in target cell:– that cause cell to die

Slow Response

• Can take up to 2 days from time of first exposure to an antigen, for cytotoxic T cells to reach effective levels

Memory Tc Cells

• Produced with cytotoxic T cells• Stay in circulation• Immediately form cytotoxic T cells:

– if same antigen appears again

Suppressor T Cells

• Secrete suppression factors • Inhibit responses of T and B cells• After initial immune response• Limit immune reaction to single

stimulus

Activation of Helper T Cells

Figure 22–18

Helper T Cells - Activated CD4 T cells divide into:

active helper T cells:

secrete cytokines

memory T cells:remain in reserve

4 Functions of Cytokines

1. Stimulate T cell divisions:– produce memory T cells– accelerate cytotoxic T cell maturation

2. Attract and stimulate macrophages

3. Attract and stimulate NK cells4. Promote activation of B cells

Figure 22–19

Pathways of T Cell Activation

KEY CONCEPT • Cell-mediated immunity involves close

physical contact between activated Tc cells and foreign, abnormal or infected cells

• T cell activation usually involves:– antigen presentation by phagocytic cell– costimulation by cytokines from active

phagocytes

• Tc cells may destroy target cells through local release of cytokines, lymphotoxins, or perforin

What are the mechanisms

of B cell activation and the differentiation of

plasma cells and memory B cells?

B Cells

• Responsible for antibody-mediated immunity

• Attack antigens by producing specific antibodies

• Millions of populations, each with different antibody molecules

Immunity: Antibody-Mediated ImmunityPLAYPLAY

B Cell Sensitization

• Corresponding antigens in interstitial fluids bind to B cell receptors

• B cell prepares for activation• Preparation process is sensitization

Figure 22–20 (Navigator)

B Cell Sensitization and Activation

PLAYPLAY

During sensitization, antigens are:

taken into the B cell, processed,reappear on surface, bound to Class II MHC protein

Helper T Cells• Sensitized B cell is prepared for

activation, but needs helper T cell activated by same antigen

B Cell Activation• Helper T cell binds to MHC complex:

– secretes cytokines that promote B cell activation and division

B Cell Division

• Activated B cell divides into:– plasma cells -Synthesize and secrete

antibodies into interstitial fluid

Memory B cells- Like memory T cells remain in reserve to respond to next infection

Figure 22–21a, b

Antibody Structure What is the

structure of an antibody, and what types

of antibodies are found in body fluids and secretions

Antibody Structure

• 2 parallel pairs of polypeptide chains: – 1 pair of heavy chains – 1 pair of light chains

• Each chain contains:– constant segments – variable segments-Determine specificity of

antibody molecule

5 Heavy-Chain Constant Segments

• Determine 5 types of antibodies:– IgG– IgE– IgD– IgM– IgA

Binding Sites

• Free tips of 2 variable segments:– form antigen binding sites of antibody

molecule– which bind to antigenic determinant

sites of antigen molecule

Figure 22–21c, d

Antibody Function

•Antigen–Antibody Complex = An antibody bound to an antigen

A Complete Antigen

• Has 2 antigenic determinant sites• Binds to both of antigen binding

sites of variable segments of antibody

• Exposure to a complete antigen leads to:– B cell sensitization– immune response

A Hapten

• Also called partial antigen • Must attach to a carrier molecule

to act as a complete antigen

Dangers of Haptens• Antibodies produced attack both

hapten and carrier molecule• If carrier is “normal”:

– antibody attacks normal cells– e.g., penicillin allergy

Table 22–1

5 Classes of Antibodies

5 Classes of Antibodies

• Also called immunoglobins (Igs)• Are found in body fluids• Are determined by constant

segments• Have no effect on antibody

specificity

7 Functions of Antigen–Antibody Complexes

1. Neutralization of antigen binding sites2. Precipitation and agglutination:

– formation of immune complex

3. Activation of complement4. Attraction of phagocytes5. Opsonization:

– increasing phagocyte efficiency

6. Stimulation of inflammation7. Prevention of bacterial and viral adhesion

KEY CONCEPT• Antibody-mediated immunity involves the

production of specific antibodies by plasma cells derived from activated B cells

• B cell activation usually involves:– antigen recognition, through binding to

surface antibodies, costimulation by a Th cell

• Antibodies produced by active plasma cells bind to target antigen and:– inhibit its activity or destroy it– remove it from solution– promote its phagocytosis by other defense

cells

Figure 22–22

Primary and Secondary Responses

• Occur in both cell-mediated and antibody-mediated immunity

Primary and Secondary Responses to Antigen

Exposure• First exposure:

– produces initial response (Primary)

• Next exposure:– triggers secondary response– more extensive and prolonged– memory cells already primed

The Primary Response • Takes time to develop• Antigens activate B cells• Plasma cells differentiate• Antibody titer slowly rises• Peak response:

– can take 2 weeks to develop– declines rapidly

• IgM:– is produced faster than IgG– is less effective

The Secondary Response• Activates memory B cells:

– at lower antigen concentrations than original B cells

– secrete antibodies in massive qualities

Effects of Memory B Cell Activation• IgG:

– rises very high and very quickly– can remain elevated for extended time

• IgM:– production is also quicker– slightly extended

KEY CONCEPT

• Immunization produces a primary response to a specific antigen under controlled conditions

• If the same antigen appears at a later date, it triggers a powerful secondary response that is usually sufficient to prevent infection and disease

Figure 22–23

Summary of the Immune Response

• Specific and nonspecific defenses

Figure 22–24

Body Responses to Bacterial Infection

Figure 22–25

Combined Immune System Responses

Combined Responses to Bacterial Infection

• Neutrophils and NK cells begin killing bacteria

• Cytokines draw phagocytes to area• Antigen presentation activates:

– helper T cells– cytotoxic T cells

• B cells activate and differentiate• Plasma cells increase antibody levels

Combined Responses to Viral Infection

• Similar to bacterial infection• But cytotoxic T cells and NK cells

are activated by contact with virus-infected cells

Table 22–2

Summary: Cells of the Immune System

KEY CONCEPT • Viruses replicate inside cells, whereas

bacteria may live independently• Antibodies (and administered

antibiotics) work outside cells, so are primarily effective against bacteria rather than viruses

• Antibiotics cannot fight the common cold or flu

• T cells, NK cells, and interferons are the primary defense against viral infection

What is the origin, development, activation, and regulation of normal

resistance to disease?

Immune System Development

• Fetus can produce immune response or immunological competence:– after exposure to antigen– at about 3–4 months

Development of Immunological Competence

• Fetal thymus cells migrate to tissues that form T cells

• Liver and bone marrow produce B cells

• 4-month fetus produces IgM antibodies

Before Birth

• Maternal IgG antibodies:– pass through placenta– provide passive immunity to fetus

After Birth• Mother’s milk provides IgA

antibodies:– while passive immunity is lost

Normal Resistance

• Infant produces IgG antibodies through exposure to antigens

• Antibody, B-cell, and T-cell levels slowly rise to adult levels:– about age 12

Table 22–3

Hormones of the Immune System

6 Groups of Hormonal Cytokines

1. Interleukins2. Interferons3. Tumor necrosis factors4. Chemicals that regulate

phagocytic activities5. Colony stimulating factors6. Miscellaneous cytokines

What are the origins of autoimmune disorders,

immunodeficiency diseases, and allergies,

and what are some examples of each?

Immune Disorders• Autoimmune disorders- A malfunction of

system that recognizes and ignores “normal” antigens

Activated B cells make autoantibodies against body cells

• Immunodeficiency disease- Thyroiditis

Rheumatoid arthritis Insulin-dependent diabetes mellitus• Allergies -

Immunodeficiency Diseases 1. Problems with embryological

development of lymphoid tissues:– can result in severe combined

immunodeficiency disease (SCID)

2. Viral infections such as HIV:– can result in AIDS

3. Immunosuppressive drugs or radiation treatments:

– can lead to complete immunological failure

Allergies

• Inappropriate or excessive immune responses to antigens

• Allergens:– antigens that trigger allergic reactions

4 Categories of Allergic Reactions

• Type I:– immediate hypersensitivity

• Type II:– cytotoxic reactions

• Type III:– immune complex disorders

• Type IV:– delayed hypersensitivity

Type I Allergy (1)• Also called immediate hypersensitivity• A rapid and severe response to the

presence of an antigen• Most commonly recognized type of allergy• Includes allergic rhinitis (environmental

allergies) • Sensitization leads to:

– production of large quantities of IgE antibodies

– distributed throughout the body

• Second exposure leads to:– massive inflammation of affected tissues

Type I Allergy (2)

• Severity of reaction depends on:– individual sensitivity– locations involved

• Allergens in blood stream may cause anaphylaxis

Anaphylaxis• Can be fatal• Affects cells throughout body• Changes capillary permeability:

– produce swelling (hives) on skin• Smooth muscles of respiratory

system contract:– make breathing difficult

• Peripheral vasodilatation:– can cause circulatory collapse

(anaphylactic shock)

Antihistamine Drugs

• Block histamine released by MAST cells

• Can relive mild symptoms of immediate hypersensitivity

Stress and the Immune Response

• Glucocorticoids:– secreted to limit immune response – long-term secretion (chronic stress):

• inhibits immune response• lowers resistance to disease

Functions of Glucocorticoids

• Depression of the inflammatory response

• Reduction in abundance and activity of phagocytes

• Inhibition of interleukin secretion

Aging and the Immune Response

• Immune system deteriorates with age, increasing vulnerability to infections and cancer

4 Effects of Aging on Immune Response

1. Thymic hormone production:– greatly reduced

2. T cells:– become less responsive to antigens

3. Fewer T cells reduce responsiveness of B cells

4. Immune surveillance against tumor cells declines

Figure 22–27

Integration with Other Systems

Nervous and Endocrine Systems Interact with thymic hormonesAdjust sensitivity of immune

Disorders of the Lymphatic System

• 3 categories affect immune response:– disorders resulting from:

• an insufficient immune response• an inappropriate immune response• an excessive immune response

SUMMARY (1)• Divisions of the lymphatic system:

– lymphatic vessels (lymphatics)– lymph– lymphoid tissues and organs

• Types of lymphocytes: – T cells– B cells– NK cells

• Lymphoid tissues and organs:– Nodules nodes– MALT thymus– spleen

SUMMARY (2)

• 7 nonspecific defenses:– physical barriers– phagocytes– immunological surveillance– interferons– complement– inflammation– fever

SUMMARY (3)• Specific defenses:

– cell-mediated immunity– antibody mediated immunity

• Forms of immunity: – innate or acquired– active or passive

• Properties of immunity:– specificity, versatility, memory,

andtolerance

SUMMARY (4)

• T cells and cell-mediated immunity:– antigen presentation– MHCs and APCs– antigen recognition– CD8 T cell activation– CD4 T cell activation

SUMMARY (5)

• B cells and antibody-mediated immunity:– sensitization– plasma cells and memory B cells– antibody structure– antigen–antibody complex– 5 classes of immunoglobins

SUMMARY (6)

• Primary and secondary responses to antigen exposure

• Hormones and the immune system:– interleukins, interferons, TNFs, and CSFs

• Immune disorders• Effects of aging on the immune

response