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Chapter 43. The Immune System. Innate and Acquired Immunity. Innate immunity Is present before any exposure to pathogens and is effective from the time of birth Involves nonspecific responses to pathogens Acquired immunity (also called adaptive immunity)

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Chapter 43 l.jpg

Chapter 43

The Immune System


Innate and acquired immunity l.jpg

Innate and Acquired Immunity

  • Innate immunity

    • Is present before any exposure to pathogens and is effective from the time of birth

    • Involves nonspecific responses to pathogens

  • Acquired immunity (also called adaptive immunity)

    • Develops only after exposure to inducing agents such as microbes, toxins, or other foreign substances

    • Involves a very specific response to pathogens


Summary of innate and acquired immunity l.jpg

INNATE IMMUNITY

Rapid responses to a

broad range of microbes

ACQUIRED IMMUNITY

Slower responses to

specific microbes

External defenses

Internal defenses

Skin

Phagocytic cells

Humoral response

(antibodies)

Mucous membranes

Antimicrobial proteins

Secretions

Inflammatory response

Invading

microbes

(pathogens)

Cell-mediated response

(cytotoxic

lymphocytes)

Natural killer cells

Summary of innate and acquired immunity


Innate immunity l.jpg

Innate Immunity

  • Innate immunity provides broad defenses against infection

  • A pathogen that successfully breaks through an animal’s external defenses soon encounters several innate cellular and chemical mechanisms that impede its attack on the body


External defenses l.jpg

External Defenses

  • Intact skin and mucous membranes

    • Form physical barriers that bar the entry of microorganisms and viruses

  • Certain cells of the mucous membranes produce mucus that traps microbes and other particles


First line respiratory defenses l.jpg

10m

First-line Respiratory Defenses

  • In the trachea, ciliated epithelial cells

    • Sweep mucus and any entrapped microbes upward, preventing the microbes from entering the lungs


Secretions l.jpg

Secretions

  • Secretions of the skin and mucous membranes

    • Provide an environment that is often hostile to microbes

  • Secretions from the skin

    • Give the skin a pH between 3 and 5, which is acidic enough to prevent colonization of many microbes

    • Also include proteins such as lysozyme, an enzyme that digests the cell walls of many bacteria


Internal cellular and chemical defenses l.jpg

Internal Cellular and Chemical Defenses

  • Internal cellular defenses depend mainly on phagocytosis

  • Phagocytes, types of white blood cells

    • Ingest invading microorganisms

    • Initiate the inflammatory response

  • Macrophages, a specific type of phagocyte

    • Can be found migrating through the body

    • Can be found in various organs of the lymphatic system


Phagocytic cells l.jpg

Pseudopodia

surround

microbes.

1

Microbes

Microbes

are engulfed

into cell.

2

MACROPHAGE

Vacuole

containing

microbes

forms.

3

Vacuole

Lysosome

containing

enzymes

Vacuole

and lysosome

fuse.

4

Toxic

compounds

and lysosomal

enzymes

destroy microbes.

5

Microbial

debris is

released by

exocytosis.

6

Phagocytic Cells

  • Phagocytes attach to their prey via surface receptors

    • And engulf them, forming a vacuole that fuses with a lysosome


Slide10 l.jpg

Interstitial fluid bathing the

tissues, along with the white

blood cells in it, continually

enters lymphatic capillaries.

1

Lymphatic

capillary

Interstitial

fluid

Fluid inside the

lymphatic capillaries,

called lymph, flows

through lymphatic

vessels throughout

the body.

2

Adenoid

Tonsil

Lymphatic vessels

return lymph to theblood via two largeducts that drain intoveins near the

shoulders.

4

Lymph

nodes

Blood

capillary

Spleen

Lymphatic

vessel

Tissue

cells

Peyer’s patches

(small intestine)

Within lymph nodes,

microbes and foreign

particles present in

the circulating lymph

encounter macro-

phages, dendritic cells,

and lymphocytes,

which carry out

various defensive

actions.

3

Appendix

Lymphatic

vessels

Masses of

lymphocytes and

macrophages

Lymph

node

  • The lymphatic system plays an active role in defending the body from pathogens


Antimicrobial proteins l.jpg

Antimicrobial Proteins

  • Numerous proteins function in innate defense

    • By attacking microbes directly or by impeding their reproduction

  • About 30 proteins make up the complement system

    • Which can cause lysis of invading cells and help trigger inflammation

  • Interferons

    • Provide innate defense against viruses and help activate macrophages


Inflammatory response l.jpg

Inflammatory Response

  • In local inflammation, histamine and other chemicals released from injured cells

    • Promote changes in blood vessels that allow more fluid, more phagocytes, and antimicrobial proteins to enter the tissues

  • 4 Classical Signs of Inflammation

    • Redness

    • Heat

    • Swelling

    • Pain


Major events in the local inflammatory response l.jpg

Blood clot

Pin

Pathogen

Macrophage

Blood

clotting

elements

Chemical signals

Phagocytic cells

Phagocytosis

Capillary

Red blood cell

Fluid, antimicrobial proteins,

and clotting elements move

from the blood to the site.

Clotting begins.

1

Chemical signals released

by activated macrophages

and mast cells at the injury

site cause nearby capillaries

to widen and become more

permeable.

Neutrophils and macrophages

phagocytose pathogens and

cell debris at the site, and the

tissue heals.

Chemokines released by various

kinds of cells attract more

phagocytic cells from the blood

to the injury site.

4

2

3

Major events in the local inflammatory response


Natural killer cells l.jpg

Natural Killer Cells

  • Natural killer (NK) cells

    • Patrol the body and attack virus-infected body cells and cancer cells

    • Trigger apoptosis in the cells they attack


Invertebrate immune mechanisms l.jpg

Invertebrate Immune Mechanisms

  • Many invertebrates defend themselves from infection by many of the same mechanisms in the vertebrate innate response


Acquired immunity l.jpg

Acquired Immunity

  • Acquired immunity

    • Is the body’s second major kind of defense

    • lymphocytes provide specific defenses against infection


Antigens l.jpg

Antigen-

binding

sites

Epitopes

(antigenic

determinants)

Antibody A

Antigen

Antibody B

Antibody C

Antigens

  • An antigen is

    • Any foreign molecule that is specifically recognized by lymphocytes and elicits a response from them

  • A lymphocyte actually recognizes and binds to just a small, accessible portion of the antigen called an epitope


Antigen recognition by lymphocytes l.jpg

Antigen Recognition by Lymphocytes

  • The vertebrate body is populated by two main types of lymphocytes

    • B lymphocytes (B cells) and T lymphocytes (T cells) which circulate through the blood

  • The plasma membranes of both B cells and T cells

    • Have about 100,000 antigen receptor that all recognize the same epitope


B cell receptors for antigens l.jpg

Antigen-

binding site

Antigen-

binding

site

Disulfide

bridge

V

V

V

V

Variable

regions

Light

chain

C

C

Constant

regions

C

C

Transmembrane

region

Plasma

membrane

Heavy chains

B cell

Cytoplasm of B cell

(a)

A B cell receptor consists of two identical heavy

chains and two identical light chains linked by

several disulfide bridges.

B Cell Receptors for Antigens

  • B cell receptors bind to specific, intact antigens

  • Secreted antibodies are structurally similar to B cell receptors but aren’t anchored to a membrane


T cell receptors for antigens and the role of the mhc l.jpg

Antigen-

Binding site

Variable

regions

Constant

regions

Transmembrane

region

b chain

Plasma

membrane

a chain

Disulfide bridge

T cell

Cytoplasm of T cell

(b)

  • A T cell receptor consists of one

  • chain and one b chain linked by

    a disulfide bridge.

T Cell Receptors for Antigens and the Role of the MHC

  • Each T cell receptor consists of two different polypeptide chains

V

V

C

C


Slide21 l.jpg

  • T cells bind to small fragments of antigens

    • That are bound to normal cell-surface proteins called MHC molecules

  • MHC molecules

    • Are encoded by a family of genes called the major histocompatibility complex


Slide22 l.jpg

  • Infected cells produce MHC molecules

    • Which bind to antigen fragments and then are transported to the cell surface in a process called antigen presentation

  • A nearby T cell can then detect the antigen fragment displayed on the cell’s surface


Slide23 l.jpg

  • Depending on their source

    • Peptide antigens are handled by different classes of MHC molecules


Slide24 l.jpg

1

Infected cell

A fragment of

foreign protein

(antigen) inside the

cell associates with

an MHC molecule

and is transported

to the cell surface.

1

Antigen

fragment

2

Class I MHC

molecule

2

The combination of

MHC molecule and

antigen is recognized

by a T cell, alerting it

to the infection.

T cell

receptor

(a) Cytotoxic T cell

  • Class I MHC molecules, found on almost all nucleated cells of the body

    • Display peptide antigens to cytotoxic T cells


Slide25 l.jpg

1

Antigen-

presenting

cell

Microbe

A fragment of

foreign protein

(antigen) inside the

cell associates with

an MHC molecule

and is transported

to the cell surface.

1

Antigen

fragment

2

2

Class II MHC

molecule

The combination of

MHC molecule and

antigen is recognized

by a T cell, alerting it

to the infection.

T cell

receptor

Helper T cell

(b)

  • Class II MHC molecules, located mainly on dendritic cells, macrophages, and B cells

    • Display antigens to helper T cells


Lymphocyte development l.jpg

Bone marrow

Lymphoid

stem cell

Thymus

T cell

B cell

Blood, lymph, and lymphoid tissues

(lymph nodes, spleen, and others)

Lymphocyte Development

  • Lymphocytes arise from stem cells in the bone marrow

  • Newly formed lymphocytes are all alike but they later develop into B cells or T cells, depending on where they continue their maturation


Testing and removal of self reactive lymphocytes l.jpg

Testing and Removal of Self-Reactive Lymphocytes

  • As B and T cells are maturing in the bone and thymus

    • Their antigen receptors are tested for possible self-reactivity

  • Lymphocytes bearing receptors for antigens already present in the body

    • Are destroyed by apoptosis or rendered nonfunctional


Clonal selection of lymphocytes l.jpg

Clonal Selection of Lymphocytes

  • In a primary immune response

    • Binding of antigen to a mature lymphocyte induces the lymphocyte’s proliferation and differentiation, a process called clonal selection


Clonal selection of b cells l.jpg

Antigen molecules

bind to the antigen

receptors of only one

of the three B cells

shown.

Antigen molecules

B cells that

differ in

antigen

specificity

Antigen

receptor

The selected B cell

proliferates, forming

a clone of identical

cells bearing

receptors for the

selecting antigen.

Some proliferating

cells develop into

short-lived plasma

cells that secrete

antibodies specific

for the antigen.

Some proliferating cells

develop into long-lived

memory cells that can

respond rapidly upon

subsequent exposure

to the same antigen.

Antibody

molecules

Clone of memory cells

Clone of plasma cells

Clonal selection of B cells

  • Generates a clone of short-lived activated effector cells and a clone of long-lived memory cells


Secondary immune response l.jpg

1

Secondary response to anti-

gen A produces antibodies

to A; primary response to anti-

gen B produces antibodies to B

Day 1: First

exposure to

antigen A

4

Primary

response to

antigen A

produces anti-

bodies to A

2

Day 28:

Second exposure

to antigen A; first

exposure to

antigen B

3

104

103

Antibody concentration

(arbitrary units)

102

Antibodies

to A

Antibodies

to B

101

100

35

28

21

42

49

56

0

14

7

Time (days)

Secondary immune response

  • Memory cells facilitate a faster, more efficient response


Humoral and cell mediated immunity l.jpg

Humoral and cell-mediated immunity

  • Acquired immunity includes two branches

    • The humoral immune response involves the activation and clonal selection of B cells, resulting in the production of secreted antibodies

    • The cell-mediated immune response involves the activation and clonal selection of cytotoxic T cells


Acquired immune response l.jpg

Cell-mediated immune response

Humoral immune response

First exposure to antigen

Antigens displayedby infected cells

Antigens engulfed and displayed by dendritic cells

Intact antigens

Activate

Activate

Activate

Secreted

cytokines

activate

B cell

HelperT cell

CytotoxicT cell

Gives rise to

Gives rise to

Gives rise to

Active and memory helperT cells

Memory cytotoxicT cells

Active cytotoxicT cells

MemoryB cells

Plasmacells

Defend against infected cells, cancer cells, and transplanted tissues

Secrete antibodies that defend againstpathogens and toxins in extracellular fluid

Acquired immune response


Activated cytotoxic t cell l.jpg

The granzymes initiate apoptosis within the

target cells, leading to fragmentation of the

nucleus, release of small apoptotic bodies,

and eventual cell death. The released

cytotoxic T cell can attack other target cells.

The activated T cell releases perforin

molecules, which form pores in the

target cell membrane, and proteolytic

enzymes (granzymes), which enter the

target cell by endocytosis.

A specific cytotoxic T cell binds to a

class I MHC–antigen complex on a

target cell via its TCR with the aid of

CD8. This interaction, along with

cytokines from helper T cells, leads to

the activation of the cytotoxic cell.

Cytotoxic T cell

Released

cytotoxic

T cell

Perforin

Cancer

cell

Granzymes

Apoptotic

target cell

TCR

CD8

Class I MHC

molecule

Pore

1

3

3

2

1

2

Target

cell

Peptide

antigen

Cytotoxic

T cell

Figure 43.16

Activated cytotoxic T-cell

  • The activated cytotoxic T cell secretes proteins (perforin and granzymes) that destroy the infected target cell


Humoral immunity l.jpg

Humoral Immunity

..\images and movies\anim0066-mov_humoral_im.mov


Antibody classes l.jpg

IgM

(pentamer)

First Ig class produced after initial exposure to

antigen; then its concentration in the blood declines

Promotes neutralization and agglutination of

antigens; very effective in complement activation

(see Figure 43.19)

J chain

Most abundant Ig class in blood; also present in

tissue fluids

IgG

(monomer)

Only Ig class that crosses placenta, thus conferring

passive immunity on fetus

Promotes opsonization, neutralization, and agglutination

of antigens; less effective in complement activation than

IgM (see Figure 43.19)

Present in secretions such as tears, saliva, mucus,

and breast milk

IgA

(dimer)

Provides localized defense of mucous membranes by

agglutination and neutralization of antigens (see

Figure 43.19)

J chain

Secretory

component

Presence in breast milk confers passive immunity on

nursing infant

IgE

(monomer)

Triggers release from mast cells and basophils of

histamine and other chemicals that cause allergic

reactions (see Figure 43.20)

IgD

(monomer)

Present primarily on surface of naive B cells that have

not been exposed to antigens

Acts as antigen receptor in antigen-stimulated

proliferation and differentiation of B cells (clonal

selection)

Transmembrane

region

Antibody Classes

  • The five classes of immunoglobulins


Active immunity l.jpg

Active Immunity

  • Active immunity

    • Develops naturally in response to an infection

    • Can also develop following immunization (vaccination)

    • In immunization a nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory for that microbe


Passive immunity l.jpg

Passive Immunity

  • Passive immunity, which provides immediate, short-term protection

    • Is conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk

    • Can be conferred artificially by injecting antibodies into a nonimmune person


Tissue transplantation l.jpg

Tissue transplantation

  • The immune system’s ability to distinguish self from nonself limits tissue transplantation

    • The immune system can attack cells from other individuals

    • Transplanted tissues are usually destroyed by the recipient’s immune system


Tissue and organ transplants l.jpg

Tissue and Organ Transplants

  • MHC molecules

    • Are responsible for stimulating the rejection of tissue grafts and organ transplants

  • The chances of successful transplantation are increased

    • If the donor and recipient MHC tissue types are well matched

    • If the recipient is given immunosuppressive drugs


Problematic immune responses l.jpg

Problematic Immune Responses

  • Exaggerated, self-directed, or diminished immune responses can cause disease

  • If the delicate balance of the immune system is disrupted

    • The effects on the individual can range from minor to fatal consequences


Allergies l.jpg

Allergies

  • Allergies are exaggerated (hypersensitive) responses to certain antigens called allergens

  • In localized allergies such as hay fever

    • IgE antibodies produced after first exposure to an allergen attach to receptors on mast cells

  • The next time the allergen enters the body it binds to mast cell–associated IgE molecules

  • The mast cells then release histamine and other mediators that cause vascular changes and typical symptoms


The allergic response l.jpg

IgE

Allergen

Histamine

1

3

2

Granule

Mast cell

Degranulation of the cell,

triggered by cross-linking of

adjacent IgE molecules,

releases histamine and other

chemicals, leading to allergy

symptoms.

1

IgE antibodies produced in

response to initial exposure

to an allergen bind to

receptors or mast cells.

2

3

On subsequent exposure to the

same allergen, IgE molecules

attached to a mast cell recog-

nize and bind the allergen.

The allergic response


Anaphylactic shock l.jpg

Anaphylactic shock

  • An acute allergic response sometimes leads to anaphylactic shock

    • A whole-body, life-threatening reaction that can occur within seconds of exposure to an allergen


Autoimmune diseases l.jpg

Autoimmune Diseases

  • In individuals with autoimmune diseases

    • The immune system loses tolerance for self and turns against certain molecules of the body

  • Examples

    • Systemic lupus erythematosus

    • Multiple sclerosis

    • Insulin-dependent diabetes

    • Rheumatoid arthritis


Immunodeficiency diseases l.jpg

Immunodeficiency Diseases

  • An inborn or primary immunodeficiency

    • Results from hereditary or congenital defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses

  • An acquired or secondary immunodeficiency

    • Results from exposure to various chemical and biological agents


Inborn primary immunodeficiencies l.jpg

Inborn (Primary) Immunodeficiencies

  • In severe combined immunodeficiency (SCID)

    • Both the humoral and cell-mediated branches of acquired immunity fail to function


Acquired secondary immunodeficiencies l.jpg

Acquired (Secondary) Immunodeficiencies

  • Acquired immunodeficiencies range from temporary states to chronic diseases

  • Growing evidence shows that physical and emotional stress can harm immunity


Acquired immunodeficiency syndrome aids l.jpg

Acquired Immunodeficiency Syndrome (AIDS)

  • People with AIDS are highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapse

  • Because AIDS arises from the loss of helper T cells both humoral and cell-mediated immune responses are impaired


Hiv infection l.jpg

1µm

HIV Infection

  • The loss of helper T cells results from infection by the human immunodeficiency virus (HIV)

Infected T-cell releasing HIV particles (gray)


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