Immunity

Chapter 38 Part 1

Impacts, IssuesFrankie’s Last Wish

Infection with a common, sexually transmitted virus (HPV) causes most cervical cancers – including the one that killed Frankie McCullogh

38.1 Integrated Responses to Threats

Immunity• The capacity to resist and combat infection by

pathogens such as viruses, bacteria, and fungi

In vertebrates, innate and adaptive immune systems work together to combat infection and injury

Evolution of the Body’s Defenses

Proteins in eukaryotic cell membranes have unique patterns that the body recognizes as self

Cells of multicelled eukaryotes have receptors that recognize nonself cues (PAMPs) on or in pathogens, and trigger defense responses

Innate Immunity

Binding of a receptor with a PAMP triggers immediate, general defense responses that are part of inborn innate immunity

Complement • Proteins that destroy microorganisms or flag them

for phagocytosis• An innate immune response

Adaptive Immunity

Adaptive immunity is a system of defenses that specifically targets billions of different antigens an individual may encounter during its lifetime

Antigen• PAMP or other molecule the body recognizes as

nonself that triggers an active immune response

Three Lines of Defense

1. Physical, chemical, and mechanical barriers• Keep pathogens outside the body

2. Innate immunity• General responses destroy invaders inside the

body before they become established

3. Adaptive immunity• Huge populations of white blood cells form to

target and remember a specific antigen

Mucus and Cilia: Physical Barriers

Comparing Innate and Active Immunity

The Defenders

White blood cells (leukocytes) specialized for different tasks carry out all immune responses• Phagocytes (neutrophils, macrophages,

dendritic cells)• Secretory cells (eosinophils, basophils, mast

cells • Lymphocytes (B and T lymphocytes, natural

killer cells)

The Defenders

All white blood cells secrete chemicals, including cell-to-cell signaling molecules (cytokines) that coordinate all aspects of immunity• Interleukins• Interferons• Tumor necrosis factors

White Blood Cells

Fig. 38-3a, p. 661

Fig. 38-3b, p. 661

Chemical Weapons of Immunity

38.1 Key Concepts Overview of Body Defenses

The vertebrate body has three lines of immune defenses • Surface barriers prevent invasion by ever-present

pathogens • General innate responses rid the body of most

pathogens • Adaptive responses specifically target pathogens

and cancer cells

38.2 Surface Barriers

Normal flora• Billions of microorganisms normally live on

human surfaces, including interior tubes and cavities of digestive and respiratory tracts

A pathogen can cause infection only if it enters the internal environment by penetrating skin or other protective barriers at the body’s surfaces

Some Normal Flora

Vertebrate Surface Barriers

Physical, chemical, and mechanical barriers keep microorganisms outside body tissues• Skin• Mucus and cilia• Lysozyme• Gastric fluid and bile salts• Normal flora• Urination

Vertebrate Surface Barriers

Skin

Healthy, intact skin is an effective surface barrier

Fig. 38-5, p. 663

skin surface

epithelial cells die and

become filled with keratin as they are

pushed toward skin surface

epidermis

dividing epithelial

cells

0.1 mm

38.3 Remember to Floss

Dental plaque• A thick, sticky biofilm of glycoproteins, bacteria,

and their products that contribute to tooth decay and gum disease (periodontitis)

Nine of every ten cardiovascular disease patients have serious periodontal disease

Oral bacteria associated with periodontitis are also found in atherosclerotic plaque

Plaque

38.2-38.3 Key Concepts Surface Barriers

Skin, mucous membranes, and secretions at the body’s surfaces function as barriers that exclude most microbes

38.4 Innate Immune Responses

Innate immune mechanisms nonspecifically eliminate pathogens that invade internal tissues before they become established• Phagocytes• Complement• Inflammation• Fever

Phagocytes

Macrophages• Large phagocytes that patrol interstitial fluid and

engulf and digest pathogens• Secrete cytokines when receptors bind to antigen• Cytokines attract more macrophages, neutrophils,

and dendritic cells to infection site

Complement

Complement proteins become activated when they encounter antigen• Cascading enzyme reactions concentrate

activated complement at infection site• Complement attracts phagocytes to infection site

and tags pathogens for destruction• Forms attack complexes that puncture bacteria• Helps mediate active immunity

Complement Attack Complexes

Fig. 38-7a, p. 664

A In some responses, complement proteins become activated when antibodies (the Y-shaped molecules) bind to antigen—in this case, antigen on the surface of a bacterium.

activated complement

antibody molecule

Fig. 38-7b, p. 664

B Complement also becomes activated when it binds directly to antigen.

activated complement

bacterial cell

Fig. 38-7c, p. 664

C By cascading reactions, huge numbers of different complement molecules form and assemble into structures called attack complexes.

activated complement

Fig. 38-7de, p. 664

D The attack complexes become inserted into the target cell’s lipid envelope or plasma membrane. Each complex makes a large pore form across it.

attack complex that causes a pore to form through the lipid bilayer of the bacterium

E The pores bring about lysis of the cell, which dies because of the severe structural disruption.

Inflammation

Inflammation• A local response to tissue damage characterized

by redness, warmth, swelling and pain, triggered by activated complement and cytokines

• Mast cells release histamine, increasing capillary permeability

• Phagocytes and plasma proteins leak out, attack invaders, form clots, and clean up debris

Inflammation Response to Bacterial Infection

Fig. 38-8, p. 665

A Bacteria invade a tissue and release toxins or metabolic products that damage tissue.

B Mast cells in tissue release histamine, which widens arterioles (causing redness and warmth) and increases capillary permeability.

C Fluid and plasma proteins leak out of capillaries; localized edema (tissue swelling) and pain result.

D Complement proteins attack bacteria. Clotting factors also wall off inflamed area.

E Neutrophils and macrophages engulf invaders and debris. Macrophage secretions kill bacteria, attract more lymphocytes, and initiate fever.

Stepped Art

Fever

Fever• A temporary rise in body temperature – above the

normal 37°C (98.6°F) – that often occurs in response to infection

• Cytokines stimulate brain cells to release prostaglandins, which act on the hypothalamus

• Fever enhances the immune response by speeding up metabolism and phagocyte activity

• Fever over 40.6°C (105°F) can be dangerous

38.4 Key Concepts Innate Immunity

Innate immune responses involve a set of general, immediate defenses against invading pathogens

Innate immunity includes phagocytic white blood cells, plasma proteins, inflammation, and fever

38.5 Overview of Adaptive Immunity

Vertebrate adaptive immunity adapts to different antigens it encounters during its lifetime

Lymphocytes and phagocytes interact to effect four defining characteristics: Self/nonself recognition, specificity, diversity, and memory

Self/Nonself Recognition

Self versus nonself recognition• Each kind of cell or virus has a unique identity

MHC markers• Plasma membrane self-recognition proteins

T cell receptors (TCRs)• Antigen receptors that recognize MHC markers

as self, antigens as nonself

Specificity and Diversity

Specificity • Defenses are tailored to target specific antigens

Diversity• There are potentially billions of different antigen

receptors on T and B cells

Memory

Memory• The capacity of the adaptive immune system to

remember an antigen• If the same antigen appears again, B and T cells

make a faster, stronger response

First Step – The Antigen Alert

Once a B or T cell recognizes and binds to a specific antigen, it begins to divide by mitosis• All descendent cells recognize the same antigen

T cells do not recognize an antigen unless it is presented by an antigen-presenting cell• Macrophages, B cells, and dendritic cells digest

particles and display antigen-MHC complexes

Cell Types

Effector cells• Differentiated lymphocytes (B and T cells) that act

at once to fight infection

Memory cells• Long-lived B and T cells reserved for future

encounters with the same antigen

Antigen Processing

Fig. 38-9a, p. 666

cell engulfs an antigen-bearing particle

Fig. 38-9b, p. 666

antigen–MHC complexes become displayed on

cell surfaceendocytic vesicle forms

MHC markers bind fragments of particle

particle is digested into bits

lysosome fuses with endocytic vesicle

Stepped Art

Two Arms of Adaptive Immunity

Antibody-mediated immune response• B cells produce antibodies that bind to specific

antigen particles in blood or interstitial fluid

Cell-mediated immune response• Cytotoxic T cells and NK cells detect and destroy

infected or altered body cells

Interactions Between Antibody-Mediated and Cell-Mediated Responses

Intercepting and Clearing Out Antigen

After engulfing antigen-bearing particles, dendritic cells or macrophages migrate to lymph nodes, where T cells bind and initiate responses

During an infection, lymph nodes swell due to accumulation of T cells

Antibody-antigen complexes bound by complement are cleared by the liver and spleen

The Lymphatic System

Fig. 38-11, p. 667

lymph node, midsection

(thymus gland)

spleen

38.6 Antibodies and Other Antigen Receptors

Antigen receptors on B and T cells have the potential to recognize billions of different antigens

Antibody• Y-shaped antigen receptor (protein), made only by

B cells, that binds only to the antigen that prompted its synthesis

• Activates complement, facilitates phagocytosis, or neutralizes pathogens or toxins

Antibody Structure

Fig. 38-12b, p. 668

binding site for antigenvariable region (dark green) of heavy chain

binding site for antigen

variable region of light chain

constant region of light chain

constant region (bright green) of heavy chain, including a hinged region

Five Classes of Antibodies

Constant regions determine 5 classes of antibodies (immunoglobins IgG, IgA, IgE, IgM, and IgD), each with different functions

B cell receptors are membrane-bound IgM or IgD antibodies

Five Classes of Antibodies

Making Antigen Receptors

Genes that encode antigen receptors occur in several segments on different chromosomes

Different versions are randomly spliced together during B or T cell differentiation, producing about 2.5 billion different combinations

T cells mature in the thymus, which stimulates production of MHC and T cell receptors

Antigen Receptor Diversity

38.7 The Antibody-Mediated Immune Response

Antibody-mediated immune response• Antigen activates naïve B cells and dendritic cells• Naïve T cell binds to APC and differentiates into

effector and memory helper T cells• Helper T cells bind antigen-MHC complexes on

activated B cell and secrete cytokines• B cell differentiates into effector B cells, which

produce antibodies targeting a specific antigen, and memory B cells

Antibody-Mediated Immune Response

Fig. 38-14, p. 670

Stepped Art

A

naive B cell

B cell

complement

A The B cell receptors on a naïve B cell bind to a specific antigen on the surface of a bacterium

dendritic cell

B

bacterium

antigen- presenting dendritic

cell

B The dendritic cell engulfs the same kind of bacterium that the B cell encountered.

D cytokines

D Antigen receptors of one of the effector helper T cells bind antigen-MHC complexes on the B cell.

E

memory B cell

effector B cell

E The cytokines induce the B cell to divide, giving rise to many identical B cells.

FF The effector B cells begin making and secreting huge numbers of IgA, IgG, or IgE.

C The antigen-MHC complexes on the antigen-presenting cell are recognized by antigen receptors on a naïve T cell.

naive T cell

effector helper T

cell

memory helper T cell

C

Clonal Selection and Memory Cells

Only B cells with receptors that bind antigen divide (clone) and differentiate into effector and memory B cells

First exposure (primary response) produces memory B and T cells; secondary response is stronger and faster

Clonal Selection and Memory Cells

Fig. 38-15a, p. 671

antigen

Antigen binds only to a matching B cell receptor.

mitosis

clonal population of effector B cells

Many effector B cells secrete many antibodies.

Fig. 38-15b, p. 671

B cell with bound antigen

mitosis

primary immune response

effector cells memory cells

mitosis

secondary immune response

effector cells memory cells

Primary and Secondary Immune Response

38.8 The Cell-Mediated Response

Cell-mediated immune response• Dendritic cell ingests altered body cell, displays

antigen-MHC complexes, migrates to lymph node• Naïve helper T and cytotoxic T cells bind to APC • Activated helper T divides and differentiates into

memory and effector cells; cytokines signal division of activated cytotoxic T cells

• Cytotoxic T cells circulate and touch-kill altered body cells

Primary Cell-Mediated Response

Fig. 38-17, p. 672

Stepped Art

dendritic cell

A

antigen- presenting dendritic

cell

A A dendritic cell engulfs a virus-infected cell.

naive cytotoxic

T cell

C

activated cytotoxic

T cell

C Receptors on a naïve cytotoxic T cell bind to the antigen-MHC complexes on the surface of the dendritic cell.

D

cytokines

memory cytotoxic

T cell

effector cytotoxic

T cell

D The activated cytotoxic T cell recognizes cytokines secreted by the effector helper T cells as signals to divide.

E E The new cytotoxic T cells circulate through the body.

B

effector helper T

cell

memory helper T

cell

B Receptors on a naïve helper T cell bind to antigen-MHC complexes on the dendritic cell.

naive helper T

cell

Cytotoxic T Cells

Cytotoxic T cells touch-kill cells displaying antigen-MHC markers; perforin and proteases puncture cells and kill them by apoptosis

Fig. 38-18b, p. 673

cytotoxic T cell

cancer cell

Natural Killer Cells

Cytokines secreted by helper T cells also stimulate natural killer (NK) cell division

Unlike cytotoxic T cells, NK cells can kill infected cells that are missing all or part of their MHC markers

38.5-38.8 Key Concepts Adaptive Immunity

In an adaptive immune response, white blood cells destroy specific pathogens or altered cells

Some make antibodies in an antibody-mediated immune response; others destroy ailing body cells in a cell-mediated response

38.9 Allergies

Allergy • An immune response to a typically harmless

substance (allergen)• First exposure stimulates production of IgE,

which becomes anchored to mast cells and basophils

• Later exposure stimulates secretion of histamine and cytokines that initiate inflammation

• Anaphylactic shock is a severe and potentially fatal allergic reaction

Allergies: Annoying or Life-Threatening

38.10 Vaccines

Immunization• The administration of an antigen-bearing vaccine

designed to elicit immunity to a specific disease

Vaccine (active immunization) • A preparation containing an antigen that elicits a

primary immune response

Passive immunization• Administration of antibodies; no immune response

Smallpox Vaccine

Edward Jenner created the first vaccine against smallpox, which has now been eradicated

Recommended Immunizations

38.11 Immunity Gone Wrong

Misdirected or compromised immunity is sometimes the result of mutation or environmental factors

The outcome is often severe or lethal

Autoimmune Disorders

Sometimes lymphocytes and antibodies fail to discriminate between self and nonself

Autoimmune response• An immune response that is misdirected against

the person’s own tissues• Rheumatoid arthritis, Graves’ disease, multiple

sclerosis

Immunodeficiency

In immunodeficiency, the immune response is insufficient to protect a person from disease

Primary immune deficiencies are present at birth• SCIDs, ADA

Secondary immune deficiency results from exposure to an outside agent, such as a virus• AIDS

Gene Therapy

Primary immunodeficiency is the result of mutation; Cindy Cutshwall was successfully treated for ADA, a type of severe combined immunodeficiency (SCID), using gene therapy

38.12 AIDS Revisited—Immunity Lost

Acquired immune deficiency syndrome (AIDS) • A group of disorders resulting from a failure of the

immune system due to HIV infection• Includes rare cancers and infections caused by

normally harmless microorganisms

Human immunodeficiency virus (HIV)• A retrovirus that attacks specific cells of the

immune system, including helper T cells

T Cells and AIDS

Global HIV and AIDS Cases

Transmission and Treatment

Common modes of HIV transmission• Unprotected sex, mother to child, shared syringes

HIV testing• Antibodies are found in blood, saliva or urine

Drugs• There is no cure; protease inhibitors and reverse

transcriptase inhibitors can slow its progress

Prevention

Vaccines• Experimental vaccines are mostly ineffective or

risky; the virus’ high mutation rate is an obstacle

Education• The best option for preventing the spread of HIV

is teaching people how to avoid being infected

The Global AIDS Program

The global battle continues; researchers are using several strategies to develop an HIV vaccine

38.9-38.12 Key Concepts Immunity In Our Lives

Vaccines are an important part of any health program

Failed or faulty immune mechanisms can result in allergies, immune deficiencies, or autoimmune disorders

The immune system itself is a target of human immunodeficiency virus (HIV)

Animation: Inflammatory response

Animation: Complement proteins

Animation: Antibody-mediated response

Animation: Clonal selection of a B cell

Animation: Immune memory

Animation: Cell-mediated response

Animation: Antibody structure

Animation: Cell mediated response

Animation: Gene rearrangements

Animation: Human lymphatic system

Animation: Immune responses

Animation: Innate defenses

ABC video: Food Allergy Increase

Video: HPV vaccine

Video: Gene therapy