Merck Immune

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Immune Disorders

Biology of theImmune System

Overview of theImmune System

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Overview of the Immune

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Innate Immunity Acquired Im

Overview of the Immune System

The immune system is designed to defend the body against

foreign or dangerous invaders. Such invaders include
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microorganisms (commonly called germs, such as bacteria,

viruses, and fungi), parasites (such as worms), cancer cells, and

even transplanted organs and tissues (seeBiology of the Immune

System: Plan of Action). To defend the body against these

invaders, the immune system must be able to distinguish

between what belongs in the body (self) and what does not

(nonself or foreign). Any substances that are identified as

nonself, particularly if they are perceived as dangerous (for

example, if they can cause disease), stimulate an immune

response in the body. Such substances are called antigens.

Antigens include any substance that can be recognized by the

immune system.

Antigens may be contained within or on bacteria, viruses, other

microorganisms, or cancer cells. Antigens may also exist on

their ownfor example, as food molecules or pollen. A normal

immune response consists of recognizing a potentially harmful

foreign antigen, activating and mobilizing forces to defend

against it, and attacking it. If the immune system malfunctions

and mistakes self for nonself, it may attack the body's own

tissues, causing an autoimmune disorder, such as rheumatoid

arthritis, thyroiditis, or systemic lupus erythematosus (lupus).

Understanding the Immune System

Antibody (immunoglobulin that is produced by B cells a tightly binds to the antigen oftagging the invader for attacneutralizing it.

Antigen: Any substance thatimmune system can recogni

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arthritis

basophils

B lymphocytes

chemotaxis

cytokines

eosinophil

histocompatibility

human leukocyte antigens

immunoglobulin

lupus erythematosus

lymphadenitis

lymphocytes
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thus stimulate an immune response.

B cell (B lymphocyte): A white bloodcell that produces antibodies specific tothe antigen that stimulated theirproduction.

Basophil: A white blood cell thatreleases histamine (a substance

involved in allergic reactions) and thatproduces substances to attract otherwhite blood cells (neutrophils andeosinophils) to a trouble spot.

Cell: The smallest unit of a livingorganism, composed of a nucleus and

cytoplasm surrounded by a membrane.

Chemotaxis: The process of using achemical substance to attract cells to aparticular site.

Complement system: A group of

proteins that are involved in a series ofreactions (called the complementcascade) designed to defend the bodyfor example, by killing bacteria and otherforeign cells, making foreign cells easier

macrophages

monocytes

mucus

neutrophils

phagocyte

phagocytosis

systemic lupus erythematosus

thoracic

thyroiditis


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for macrophages to identify and ingest,and attracting macrophages and

neutrophils to a trouble spot.

Cytokines: Proteins that are secretedby immune and other cells that act asthe immune system's messengers tohelp regulate an immune response.

Dendritic cell: A cell that is derivedfrom white blood cells, resides intissues, and helps T cells recognizeforeign antigens.

Eosinophil: A white blood cell that killsbacteria, that kills other foreign cells too

big to ingest, that may help immobilizeand kill parasites, that participates inallergic reactions, and that may helpdestroy cancer cells.

Helper T cell: A white blood cell thathelps B cells produce antibodies against

foreign antigens, that helps killer T cellsbecome active, and that stimulatesmacrophages.

Histocompatibility: Literally,


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compatibility of tissue. Determined byhuman leukocyte antigens (see below)

and used to determine whether atransplanted tissue or organ will beaccepted by the recipient.

Human leukocyte antigens (HLA): Agroup of identification molecules that arelocated on the surface of all cells in a

combination that is almost unique foreach person, thereby enabling the bodyto distinguish self from nonself. Alsocalled the major histocompatibilitycomplex.

Immune complex: An antibody

attached to an antigen.

Immune response: The reaction of theimmune system to an antigen.

Immunoglobulin: An antibody.

Interleukin: A type of messenger(cytokine) secreted by some white bloodcells to affect other white blood cells.

Killer (cytotoxic) T cell: A T cell that


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attaches to infected cells and cancercells and kills them.

Leukocyte: A white blood cell, such asa monocyte, a neutrophil, an eosinophil,a basophil, or a lymphocyte (a B cell orT cell).

Lymphocyte: The white blood cell

responsible for acquired (specific)immunity, including producing antibodies(by B cells), distinguishing self fromnonself (by T cells), and killing infectedcells and cancer cells (by killer T cells).

Macrophage: A large cell that develops

from a white blood cell called amonocyte, that ingests bacteria andother foreign cells, that helps T cellsidentify microorganisms and otherforeign substances, and that is normallypresent in the lungs, skin, liver, andother tissues.

Major histocompatibility complex(MHC): A synonym for human leukocyteantigens.


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fragment.

Receptor: A molecule on a cell'ssurface or inside the cell that canidentify specific molecules, which fitprecisely in itas a key fits in its lock.

Regulatory (suppressor) T cell: Awhite blood cell that helps end an

immune response.

T cell (T lymphocyte): A white bloodcell that is involved in acquired immunityand that may be one of three types:helper, killer (cytotoxic), or regulatory.

Disorders of the immune system occur when

The body generates an immune response against itself (anautoimmune disorderseeAllergic Reactions and OtherHypersensitivity Disorders: Autoimmune Disorders).

The body cannot generate appropriate immune responsesagainst invading microorganisms (an immunodeficiencydisorderseeImmunodeficiency Disorders: Overview ofImmunodeficiency Disorders).

An excessive immune response to often harmless foreignantigens damages normal tissues (an allergic reactionseeAllergic Reactions and Other Hypersensitivity Disorders:Overview of Allergic Reactions).

Lines of DefenseThe body has a series of defenses. Defenses include physical

barriers, white blood cells, and molecules such as antibodies

and complement proteins.
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Physical barr iers:The first line of defense against invaders is

mechanical or physical barriers:

The skin

The cornea of the eyes

Membranes lining the respiratory, digestive, urinary, andreproductive tracts

As long as these barriers remain unbroken, many invaders

cannot enter the body. If a barrier is brokenfor example, if

extensive burns damage the skinthe risk of infection is

increased. In addition, the barriers are defended by secretions

containing enzymes that can destroy bacteria. Examples are

sweat, tears in the eyes, mucus in the respiratory and digestive

tracts, and secretions in the vagina.

White blood cel ls:The next line of defense involves certain

white blood cells (leukocytes) that travel through the

bloodstream and into tissues, searching for and attacking

microorganisms and other invaders. This defense has two parts:

innate and acquired immunity.

Innate (natural) immunity (seeBiology of the Immune System:

Innate Immunity) does not require a previous encounter with a

microorganism or other invader to work effectively. It responds

to invaders immediately, without needing to learn to recognize

them. Several types of white blood cells are involved:

Phagocytes ingest invaders. Phagocytes includemacrophages, neutrophils, monocytes, and dendritic cells.

Natural killer cells are formed ready to recognize and killcancer cells and cells that are infected with certain viruses.

Antigen-presenting cells help T cells (T lymphocytes)recognize invaders. Antigen-presenting cells consist ofdendritic cells (the most effective), macrophages, and Bcells.

Some white blood cells release substances involved ininflammation and allergic reactions, such as histamine.Some of these cells often act on their own to destroyinvaders.
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In acquired (adaptive or specific) immunity (seeBiology of the

Immune System: Acquired Immunity), lymphocytes (B cells and T

cells) encounter an invader, learn how to attack it, and

remember the specific invader so that they can attack it even

more efficiently the next time they encounter it. Acquired

immunity takes time to develop after the initial encounter with a

new invader because the lymphocytes must adapt to it.

However, thereafter, response is quick. B cells and T cells work

together to destroy invaders. Some of these cells do not directly

destroy invaders but instead enable other white blood cells to

recognize and destroy invaders.

Molecules:Innate immunity and acquired immunity interact,

influencing each other directly or through molecules that attract

or activate other cells of the immune systemas part of the

mobilization step in defense (seeBiology of the Immune System:

Activation and mobilization). These molecules include cytokines

(which are the messengers of the immune system), antibodies,

and complement proteins (which form the complement system).

These substances are not contained in cells but are dissolved in

a body fluid, such as plasma (the liquid part of blood).

Some of these molecules, including some cytokines, promote

inflammation. Inflammation occurs because these molecules

attract immune system cells to the affected tissue. To help get

these cells to the tissue, the body sends more blood to the

tissue. To carry more blood to the tissue, blood vessels expand

and become more porous, allowing more fluids and cells to

leave blood vessels and enter the tissue. Inflammation thus

tends to cause redness, warmth, and swelling. The purpose of

inflammation is to contain the infection so that it does not

spread. Then other substances produced by the immune system

help the inflammation resolve and damaged tissues heal.

Although inflammation may be bothersome, it indicates that the

immune system is doing its job. However, excessive or long-

term (chronic) inflammation can be harmful.
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Organs:The immune system includes several organs in

addition to cells dispersed throughout the body. These organs

are classified as primary or secondary lymphoid organs.

The primary lymphoid organs are the sites where white blood

cells are produced and/or multiply:

The bone marrow produces all the different types of whiteblood cells, including neutrophils, eosinophils, basophils,monocytes, B cells, and the cells that develop into T cells (Tcell precursors).

In the thymus, T cells multiply and are trained to recognizeforeign antigens and to ignore the body's own antigens. (Tcells are critical for acquired immunity.)

When needed to defend the body, the white blood cells are

mobilized, mainly from the bone marrow. They then move into

the bloodstream and travel to wherever they are needed.

Lymphatic System: Helping Defend Against I

The lymphatic system is a vital part of the immune system, alonmarrow, spleen, tonsils, appendix, and Peyer patches in the sm

The lymphatic system is a network of lymph nodes connected bsystem transports lymph throughout the body.

Lymph is formed from fluid that seeps through the thin walls of ctissues. This fluid contains oxygen, proteins, and other nutrientsof this fluid reenters the capillaries and some of it enters the lymlymph). Small lymphatic vessels connect to larger ones and eveThe thoracic duct is the largest lymphatic vessel. It joins with thereturns lymph to the bloodstream.

Lymph also transports foreign substances (such as bacteria), cadamaged cells that may be present in tissues into the lymphaticfor disposal. Lymph contains many white blood cells.

All substances transported by the lymph pass through at least osubstances can be filtered out and destroyed before fluid is returlymph nodes, white blood cells can collect, interact with each otgenerate immune responses to foreign substances. Lymph nodeis tightly packed with B cells, T cells, dendritic cells, and macropmicroorganisms are filtered through the mesh, then identified ancells.


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Lymph nodes are often clustered in areas where the lymphatic vessels branch off, such as theneck, armpits, and groin.

The secondary lymphoid organs include the spleen, lymph

nodes, tonsils, appendix, and Peyer patches in the small

intestine. These organs trap microorganisms and other foreign

substances and provide a place for mature cells of the immune

system to collect, interact with each other and with the foreign

substances, and generate a specific immune response.

The lymph nodes are strategically placed in the body and are

connected by an extensive network of lymphatic vessels, which

act as the immune system's circulatory system. The lymphaticsystem transports microorganisms, other foreign substances,

cancer cells, and dead or damaged cells from the tissues to the

lymph nodes, where these substances and cells are filtered out

and destroyed. Then the filtered lymph is returned to the

bloodstream.


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Lymph nodes are one of the first places that cancer cells can

spread. Thus, doctors often evaluate lymph nodes to determine

whether a cancer has spread. Cancer cells in a lymph node can

cause the node to swell. Lymph nodes can also swell after an

infection because immune responses to infections are

generated in lymph nodes. Sometimes lymph nodes swell

because bacteria that are carried to a lymph node are not killed

and cause an infection in the lymph node (lymphadenitis).

Plan of ActionA successful immune response to invaders requires recognition,

activation and mobilization, regulation, and resolution.

Recogni t ion:To be able to destroy invaders, the immune

system must first recognize them. That is, the immune system

must be able to distinguish what is nonself (foreign) from what is

self. The immune system can make this distinction because all

cells have identification molecules on their surface.

Microorganisms are recognized because the identification

molecules on their surface are foreign. In people, the most

important self-identification molecules are called human

leukocyte antigens (HLA) or the major histocompatibility

complex (MHC). HLA molecules are called antigens because if

transplanted, as in a kidney or skin graft, they can provoke an

immune response in another person (normally, they do not

provoke an immune response in the person who has them).

Each person has an almost unique combination of HLAs. Each

person's immune system normally recognizes this unique

combination as self. A cell with molecules on its surface that are

not identical to those on the body's own cells is identified as

being foreign. The immune system then attacks that cell. Such a

cell may be a microorganism, a cell from transplanted tissue, or

one of the body's cells that has been infected by an invading

microorganism or altered by cancer. (HLA molecules are what

doctors try to match when a person needs an organ transplant.)


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Some white blood cellsB cells (B lymphocytes)can

recognize invaders directly. But othersT cells (T

lymphocytes)need help from other cells of the immune system

(called antigen-presenting cells). These cells ingest an invader

and break it into fragments. The antigen fragments from the

invader are combined with HLA molecules as they are

assembled in the antigen-presenting cell. The combination of

antigen fragments and HLA molecules is moved to the cell's

surface. T cells that come into contact with the antigen-

presenting cell can then learn to recognize the invader's antigen

fragments. T cells are then activated and can begin fighting the

invaders that have that antigen.

How T Lymphocytes Recognize Antigens

How T Cells Recognize Antigens
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T cells are part of the immune surveillance system. They travel through the bloodstream andlymphatic system. When they reach the lymph nodes or another secondary lymphoid organ,they look for foreign substances (antigens) in the body. However, before they can fullyrecognize and respond to a foreign antigen, the antigen must be processed and presented tothe T cell by another white blood cell, called an antigen-presenting cell. Antigen-presentingcells consist of dendritic cells (which are the most effective), macrophages, and B cells.

Activation and mobi l ization:White blood cells are activated

when they recognize invaders. For example, when the antigen-

presenting cell presents antigen fragments bound to HLA to a Tcell, the T cell attaches to the fragments and is activated. B cells

can be activated directly by invaders. Once activated, white

blood cells ingest or kill the invader or do both. Usually, more

than one type of white blood cell is needed to kill an invader.

Immune cells, such as macrophages and activated T cells,


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release substances that attract other immune cells to the trouble

spot, thus mobilizing defenses. The invader itself may release

substances that attract immune cells.

Regulation:The immune response must be regulated to

prevent extensive damage to the body, as occurs in

autoimmune disorders. Regulatory (suppressor) T cells help

control the response by secreting cytokines (chemical

messengers of the immune system) that inhibit immune

responses. These cells prevent the immune response from

continuing indefinitely.

Resolution:Resolution involves confining the invader andeliminating it from the body. After the invader is eliminated, most

white blood cells self-destruct and are ingested. Those that are

spared are called memory cells. The body retains memory cells,

which are part of acquired immunity, to remember specific

invaders and respond more vigorously to them at the next

encounter.

Last full review/revision March 2013 by Peter J. Delves, PhD

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