Specific Internal Defenses

The Acquired (or Adaptive) Immune System

Adaptive immune response

Specific internal defenses, the final line of defense, comprise the adaptive immune response, in which immune cells selectively destroy the specific invading toxin or microbe and then “remember” the invader, allowing a faster response if it reappears in the future

skin, mucous membranesNonspecific External Barriers

phagocytic and natural killer cells,inflammation, fever

Innate Immune Response

If these barriers are penetrated,the body responds with

If the innate immune response is insufficient,the body responds with

cell-mediated immunity, humoral immunity

Adaptive Immune Response

The adaptive immune system consists of three major components Immune cells Tissues and organs Secreted proteins

Immune cells

several types of white blood cells, including macrophages and lymphocytes

Unique to the adaptive immune response are specialized white blood cells called lymphocytes

B cells and T cells are two types of lymphocytes that arise from dividing stem cells in the bone marrow and thymus

thymus

tonsils

bonemarrow

spleenthoracicduct

lymphvessels

lymphnodes

valve preventsbackflow

lymphnode

chamberspacked withwhite bloodcells

Tissues and organs lymph nodes: which contain masses of

macrophages and specialized white blood cells called lymphocytes

Thymus: is located beneath the breastbone, slightly above the heart, and is essential for development of T cells

Spleen: fist-sized organ located on the left side of the abdominal cavity - filters blood, exposing it to white blood cells that destroy microbes and aged red blood cells

Tonsils: are located in a ring around the pharynx Macrophages and other white blood cells in the tonsils directly destroy many invading microbes and often trigger an adaptive immune response

Secreted proteins

Cytokines: secreted by leukocytes, A large number of proteins in the blood, collectively

called complement, assist the immune system in killing invading microbes

Some cytokines and complement proteins are involved in both the innate and adaptive responses

For example, some cytokines stimulate innate immune responses such as inflammation, which activates fever

Antibodies: proteins produced by B cells and their offspring, help the immune system to recognize invading microbes and destroy them

All adaptive immune responses include the same three steps

1. Lymphocytes recognize an invading microbe and distinguish the invader from self

2. They launch an attack

3. They retain a memory of the invader that allows them to ward off future infections by the same type of microbe

How Does the Adaptive Immune System Recognize Invaders? To understand how the immune system recognizes invaders and

initiates a response, we must answer three related questions

1. How do lymphocytes recognize foreign cells and molecules?

2. How can lymphocytes produce specific responses to so many different types of cells and molecules?

3. How do they avoid mistaking the body’s own cells and molecules for invaders?

Antigens: The adaptive immune system recognizes invaders’ complex

molecules - ANTIGENS

Antigens: large, complex molecules are called, because they are “antibody generating” molecules that can provoke an immune response, including the production of antibodies

Bacteria and humans differ from one another because each contains specific, complex molecules that the other does not have

Antigens are often located on the surfaces of invading microbes

Many viral antigens become incorporated into the plasma membranes of infected body cells

Viral or bacterial antigens are also “displayed” on the plasma membranes of dendritic cells and macrophages that engulf them

Other antigens, such as toxins released by bacteria, may be toxins in the blood plasma, lymph, or other extracellular fluids

Antibodies Antibodies, produced only by B cells and their

offspring Y-shaped proteins composed of two pairs of peptide

chains: one pair of identical large (heavy) chains and one pair of identical small (light) chains

Both heavy and light chains consist of a constant region, which is similar in all antibodies of the same type, and a variable region that differs among individual antibodies

The light and heavy chains combine to form the two functional parts: the “arms” of the Y and the “stem” of the Y

The variable regions at the arm tips form sites that bind antigens

Each binding site has a particular size, shape, and electrical charge so that only certain molecules can fit in and bind to the antibody

The sites are so specific that each antibody can bind only a few, very similar, types of antigen molecules

antigen

Figure 36-6 Antibody structure

antigen

lightchain heavy

chain

Variable regions formantigen binding sites

Constant regions arethe same in all antibodiesof a given type

Antibodies Antibodies serve two functions in

the adaptive immune response

1. Recognizing foreign antigens and triggering the response against invaders

2. Helping to destroy the invading cells or molecules that bear antigens

B cell

antibody

antigen

mic

robe

T-cell receptors

T-cell receptors are found only on the surfaces of T cells

Every T cell produces T-cell receptors that differ from those of all other T cells

Variable regions, which form highly specific binding sites for antigens, protrude from the cell surface

Both antibodies and T-cell receptors play crucial roles in helping to destroy invading microbes

The immune system can recognize millions of different antigens

The adaptive immune system recognizes and responds to millions of potentially harmful antigens

B and T cells randomly synthesize millions of different antibodies and T-cell receptors

At any given time, the human body contains perhaps 100 million different antibodies and even more T-cell receptors

The immune system distinguishes self from non-self

The body manufactures thousands of different proteins, including MHC proteins that are unique to you

These proteins can stimulate powerful immune responses in other people’s bodies: that is, they can act as antigens

This is why transplants are often rejected, unless the transplant recipient takes drugs to suppress the immune response

If the immature immune cells contact antigens that bind to their antibodies or T-cell receptors, they undergo apoptosis, or programmed cell death, in which they essentially commit cellular suicide

Therefore, the immune system distinguishes self from non-self by retaining only those immune cells that do not respond to the body’s own molecules

Not all self-reactive B and T cells are eliminated in this way

One of the functions of regulatory T cells is to prevent any remaining self-reactive lymphocytes from attacking the body and causing an autoimmune disease

the Adaptive Immune System Attacks Invaders

The invading microbe usually includes a handful of different antigens, each capable of binding only to a few antibodies or T-cell receptors

Your immune system contains millions of B and T cells, each bearing antibodies or T-cell receptors that differ from the antibodies or T-cell receptors of every other immune cell in your body

The benefit to having millions of unique immune cells is that almost any invader will provoke an adaptive immune response

The drawback to having very small numbers of cells that can recognize any given invader is that a handful of cells isn’t enough to kill the invaders immediately It usually takes 1 to 2 weeks to mount a good immune response

to the first exposure to an invading microbe, as the responding cells multiply and differentiate

The adaptive immune system simultaneously launches two types of attack against microbial invaders1. Humoral immunity

2. Cell-mediated immunity

Humoral immunity produced by antibodies dissolved in the blood

provided by B cells and the antibodies that they secrete into the bloodstream

When a microbe enters the body, the antibodies on a few of these B cells can bind to antigens on the invader

Antigen-antibody binding causes these B cells to multiply rapidly

The daughter cells differentiate into two cell types

1. Memory B cells, which do not release antibodies, but play an important role in future immunity to the invader that stimulated their production

2. Plasma cells, which become enlarged and packed with rough endoplasmic reticulum, which synthesizes huge quantities of antibodies

These antibodies are released into the bloodstream

antibodies antigens

Invadingantigens bindto antibodieson one B cell(dark blue)

The B cell“selected” by theantigen multipliesrapidly

A large cloneof geneticallyidentical B cellsis produced

TheseB cellsdifferentiateinto plasmacells andmemoryB cells

plasma cell

endoplasmicreticulum

Plasma cellsrelease antibodiesinto the blood

memory Bcell

antibodies

Humoral immunity Antibodies in the blood combat invading molecules or microbes

in three ways 1. The circulating antibodies may bind to a foreign molecule, virus, or cell and

render it harmless by a process called neutralization

2. Antibodies may coat the surface of invading molecules, viruses, or cells and make it easier for macrophages and phagocytes to destroy them

3. When antibodies bind to antigens on the surface of a microbe, the antibodies interact with complement proteins that are always present in the blood

Antibodies bind to antigens on amicrobe and promote phagocytosis bymacrophages

antibodyantigen

microbe

microbe

macrophage

Cell-mediated immunity

Cell-mediated immunity is produced by cytotoxic T cells, which attack virus-infected body cells and cells that have become cancerous

When a cell is infected by a virus, some pieces of viral proteins are brought to the surface of the infected cells and “displayed” on the outside of the plasma membrane

When a cytotoxic T cell with an appropriate matching T-cell receptor binds to a viral antigen, the cytotoxic T cell passes through pores, killing the infected cell

If the infected cell is killed before the virus has finished multiplying, then no new viruses are produced, and the viral infection cannot spread to other cells

Cancer cells often display unusual proteins on their surfaces that cytotoxic T cells recognize as foreign, and can be killed by the same mechanism

cytotoxic T celldying cancer cell

Helper T cells enhance both humoral and cell-mediated immune responses

B cells and cytotoxic T cells require assistance from helper T cells

Helper T cells bear receptors that bind to antigens displayed on the surfaces of dendritic cells or macrophages that have engulfed and digested invading microbes

When its receptor binds an antigen, a helper T cell multiplies rapidly, and its daughter cells differentiate and release cytokinins that stimulate cell division and differentiation in both B cells and cytotoxic T cells

A summary of humoral and cell-mediated immune responses

Targets invaders outside cells (e.g.,viruses, bacteria, fungi, protists, andtoxins)

HUMORAL IMMUNITY

Stimulate both humoral and cell-mediated immunity by releasingcytokines

HELPER T CELLS

Targets defective body cells (e.g.,infected cells and cancer cells),transplants

CELL-MEDIATED IMMUNITY

infected cell

Viral antigenspresented on thesurfaces ofdendritic cells ormacrophages,and infected cells

T-cell receptors bindto viral antigens

cytotoxicT cellhelper T cell

dendritic cellor macrophage

virusviralantigen

cytokines

B-cell antibodies bindto viral antigens andstimulate the B cells todivide and differentiate

antibody

B cell

Cytokines released byhelper T cells stimulate Bcells and cytotoxic T cells

plasmacell

memoryB cell

memoryhelperT cell

memorycytotoxic

T cell

cytotoxicT cell

Plasma cells secreteantibodies into theblood and interstitialfluid

Memory cells conferfuture immunity to thisspecific virus but notto any other microbes

Cytotoxic T cellsrelease pore-formingproteins that destroyinfected cells

infectedcell

Memory B cells and Memory T cells

After recovering from a disease, you remain immune to that particular microbe for many years, perhaps a lifetime

Some of the daughter cells of the original B cells, cytotoxic T cells, and helper T cells that responded to the original infection differentiate into memory B cells and memory T cells that survive for many years

If the body is reinvaded by the same type of microbe, the memory cells recognize the invader and mount an immune response

Animation: Humoral Versus Cell-Mediated Immunity

Adaptive Immune System Memory

Memory B cells rapidly produce a clone of plasma cells, secreting antibodies that combat this second invasion

Memory T cells produce clones of either helper T cells or cytotoxic T cells specific for the “remembered” invader

Each memory cell responds so quickly and so largely in a second infection, the body fends off the attack before the person suffers any symptoms—they have become immune

Acquired immunity confers long-lasting protection against many diseases such as smallpox, measles, mumps, and chicken pox

Figure 36-12 Acquired immunity

firstexposure

interval:monthsor years

secondexposure

time since exposure (weeks)0 1 2 3 0 1 2 3

immuneresponse

(amount ofantibody

produced)

How Does Medical Care Assist the Immune Response?

The battle against disease, for most of human history, was fought by the immune response alone

Currently, the immune response has a powerful assistant

Medical treatment

Antibiotics and vaccinations are two very important medical tools

Antibiotics Antibiotics slow down microbial reproduction

Antibiotics are chemicals that help to combat infection by slowing down the multiplication of bacteria, fungi, or protists

The occasional mutant microbe that is resistant to an antibiotic will pass on the genes for resistance to its offspring; resistant microbes thrive while susceptible microbes die off

Eventually, many antibiotics become ineffective in treating diseases

Antibiotics are not effective against viruses because they target metabolic processes that viruses do not possess

Drugs are now available that target different stages of the viral cycle of infection, including attachment to a host cell, replication of viral parts, assembly of new viruses within the host cell, and the release of these viruses to infect more body cells

Antiviral drugs are available to treat HIV, herpes virus (cold and genital sores), and the flu virus

Vaccines A vaccine stimulates an immune response by exposing a person to antigens

produced by a pathogen

Vaccines often consist of weakened or killed microbes, or some of the pathogen’s antigens, usually synthesized using genetic engineering techniques

Exposure to these antigens results in the body producing an army of memory cells that confer immunity against living microbes of the same type

HIV and AIDS AIDS is caused by human immunodeficiency viruses (HIV) that

undermine the immune system by infecting and destroying helper T cells, which stimulate both the cell-mediated and humoral immune responses

AIDS does not kill people directly, but AIDS victims become increasingly susceptible to other diseases as their helper T-cell populations decline

HIV enters a helper T cell and hijacks the cell’s metabolic machinery, forcing it to make more viruses, which then emerge, taking an outer coating of T-cell membrane with them

Helper T-cell levels continue to decline over time and without treatment, and eventually the immune response becomes too weak to overcome routine infections

At this time, the person is considered to have AIDS

The life expectancy for untreated AIDS victims is 1 to 2 years

Animation: HIV: The AIDS Virus