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Body Defenses

Immune System

Part 2

What do the specific defenses

include?

Third line of defense

Helps protect us against specific pathogens when

nonspecific defenses fail

Helps protect us against cancer

Depends on the action of B and T cells

(remember that these are lymphocytes)

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Adaptive Immune Defenses

When innate defenses have failed to prevent

an infection, the adaptive line of defense

comes into play.

How Adaptive Defenses Works

Adaptive defenses respond to antigens

Molecules the immune system recognizes as foreign

to the body.

Adaptive defenses primarily depend on the action

of B and/or T lymphocytes

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Lymphocytes B cells remain in the bone

marrow to mature

“B” for “bone marrow”

T cells migrate to the

thymus, to mature

“T” for “thymus”

Maturation of a B or T cell

involves becoming immuno-

competent, meaning that it

can recognize, by binding, a

specific molecule or antigen.

What are the types of B and T

cells?

• B cells produce plasma cells and memory

cells.

– Plasma cells produce specific antibodies.

– Memory cells are ready to produce

antibodies in the future.

What are the types of B and T

cells?

• T cells regulate immune response;

produce various types of T cells.

– Cytotoxic T (Tc) cells kill virus-infected and

cancer cells.

– Helper T (TH) cells regulate immunity.

– Memory T (Tc and TH) cells are ready to kill

in the future.

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Lymphocytes

During the maturation process, B and T cells that

bind too strongly to the body’s own cells are

eliminated in order to minimize an immune response

against the body’s own tissues (autoimmune

diseases)

Cells that react weakly to the body’s own cells, but have

highly specific receptors on their cell surfaces that allow

them to recognize a foreign molecule, or antigen, remain.

Process occurs during fetal development and continues

throughout life.

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Lymphocytes

The specificity of this receptor is determined by the

genetics of the individual.

Once they are immunocompetent, the T and B cells

will migrate to the spleen and lymph nodes where

they will remain until they are called on during an

infection.

B cells are involved in the humoral immune response,

which targets pathogens in blood and lymph.

T cells are involved in the cell-mediated immune response,

which targets infected cells.

Third line of defense: Antibody-

mediated immunity by B cells

Each B cell has a unique receptor called a BCR that binds a specific antigen.

This binding plus cytokines secreted by helper T cells result in clonal expansion in which this B cell makes copies of itself.

Most of the cells produced are plasma cells that secrete antibodies.

Memory cells are also made.

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B Cells and Antibody-Mediated

Immunity

The clonal selection model states that an

antigen selects, then binds to the B-cell

receptor of only one type of B cell, and then

this B cell produces multiple copies (clones)

of itself.

Memory Cells

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B Cells and Antibody-Mediated

Immunity

The receptor on a B cell is called a B-cell receptor.

Receptor is an antibody (immunoglobulin)

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B Cells and Antibody-Mediated

Immunity

B Cells Become Plasma Cells and Memory B Cells

After initially binding an antigen to the B cell receptor, a B

cell internalizes the antigen and presents it on MHC class II.

MHC major histocompatibility complex antigen (“self”)

A helper T cell recognizes the MHC class II- antigen

complex and activates the B cell by secreting cytokines.

As a result, memory B cells and plasma cells are made.

Plasma cells secrete antibodies and eventually undergo

apoptosis (programmed cell death).

Memory B cells remain in the body and rapidly initiate

maturation and antibody production if the same antigen

enters the body at a later date.

Antibody-mediated immunity by

B cells

antigens

B cell B-cell

receptor

(BCR)

a. Activation: When a B cell receptor binds to an antigen

activation occurs.

antigen cytokines

from T cells

b. Clonal expansion – During clonal expansion, cytokines secreted by

helper T cells stimulate B cells to clone mostly into plasma cells or memory cells.

c. Apoptosis – Apoptosis, or programmed cell death, occurs to plasma cells

left in the system after the infection has passed.

Apoptosis

Plasma cells

Memory B cells

Figure 7.7 B cell clonal selection.

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The basic unit that composes antibody molecules is a Y-shaped protein.

The trunk of the Y is a constant region that determines the class of the antibody.

The ends of the arms (Y) are the variable regions where specific antigens bind.

Structure of antibodies

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Antibodies

Structure of an Antibody

Antibodies = immunoglobulins.

Y-shaped molecules with two arms.

Each arm has a heavy and a light polypeptide chain.

These chains contain variable and constant regions.

The antigen combines with the antibody in the variable

regions in a lock-and-key manner.

Structure of antibodies

Figure 7.8 The structure of an antibody. b: Courtesy Dr. Arthur J. Olson, Scripps Institute

C C

Antigen binds

to binding site.

heavy

chain

light

chain Shape of antigen fits

shape of binding site.

antigen

antigen-binding

sites

a.

b.

C = constant V = variable

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Classes of Antibodies

Classes of Antibodies

There are five different classes of circulating

antibodies:

IgG

IgM

IgA

IgD

IgE

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Monoclonal Antibodies

Every plasma cell derived from the same B

cell secretes antibodies against a specific

antigen.

These are monoclonal antibodies.

Monoclonal antibodies can be made outside

the body, and are being used to:

Diagnose certain conditions or infections

Deliver drugs

Treat cancers.

We make monoclonal antibodies (derived

from plasma cells that originated from the

same B cell) in glassware outside the body

(in vitro).

This is done through fusion of plasma cells

with myeloma cells that allow them to divide

indefinitely.

This fusion results in a cell called a

hybridoma.

How do we make monoclonal

antibodies?

Figure 7.9 The production of

monoclonal antibodies.

How do we make monoclonal

antibodies?

antibody plasmacell

antigen

cancerous myelomacell hybridomacell

monoclonal antibody

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Fig. 7.13

What are the characteristics of

T cells?

• Cell-mediated immunity against virus-infected

cells and cancer cells

• Produced in bone marrow, mature in thymus

• Antigen must be presented in groove of an HLA

(MHC) molecule

• Cytotoxic T cells destroy nonself antigen-

bearing cells

• Helper T cells secrete cytokines that control the

immune response

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T Cells and Cell-Mediated

Immunity

T cells:

Directly attack diseased cells and cancer cells.

Other T cells release cytokines that stimulate both

innate and adaptive defenses.

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Clonal Expansion

T cells have specific TCRs (T Cell Receptors).

An activated T cell undergoes clonal

expansion producing many copies of itself.

The two classes of MHC proteins are called

MHC I and MHC II.

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How T Cells Recognize an

Antigen

Each T cell bears a specific receptor. Antigen must be presented by an antigen-presenting cell

(APC), such as a macrophage.

A piece of a phagocitized pathogen is displayed in the

groove of a major histocompatibility (MHC) protein on the

APC’s surface.

Human MHC proteins are called human leukocyte

antigens (HLAs).

MHC proteins are self proteins that mark the cell as part

of a particular individual.

The T cell can compare the antigen and self protein side

by side in the plasma membrane of the antigen-

presenting cell and destroy cells carrying foreign

antigens.

Third line of defense: Cell-

mediated immunity by T cells

The T cell will specifically recognize the combination of the HLA protein and the piece of antigen.

Clonal expansion will occur leading to mostly helper T cells, cytotoxic T cells, and a few memory T cells.

After an infection has passed, helper and cytotoxic T cells undergo apoptosis, leaving memory cells.

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Fig. 7.14

Memory T cells remain in the

body to initiate an immune

reaction to a previous

antigen in the case of

another exposure.

Cell-mediated immunity by

T cells T-cell receptor (TCR)

bacterium

T cell

Activation

Clonal expansion Macrophage

Memory T cell

Cytotoxic T cell

Apoptosis

self antigen

(MHCI)

cytokines

Figure 7.10 The clonal selection model for T cells.

T cells

Helper T cells

Secrete cytokines that

help many immune

cells function.

HIV, the virus that

causes AIDS, infects

helper T cells, making

HIV-infected

individuals susceptible

to opportunistic

infections.

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T cells

Cytotoxic T cells

are responsible for cell-

mediated immunity,

causing virus-infected cells

or tumor cells to undergo

apoptosis and die.

have vacuoles containing

granzymes and perforins.

Perforins punch holes in

target cells, followed by

granzymes that cause the

cell to undergo apoptosis.

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Immunity

Immunity is the ability to combat diseases and cancer.

It can be brought about naturally through an infection or artificially through medical intervention.

There are 2 types of immunity, active and passive.

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Acquired Immunity

Immunity can be brought about artificially by

medical intervention.

Active Immunity

Sometimes develops naturally after infection with a

pathogen.

Ex. Chicken Pox, Mumps, Measles

Can also be induced.

Vaccines

Active immunity

The individual’s body makes antibodies against a particular antigen.

This can happen through natural infection or through immunization involving vaccines.

Primary exposure is shorter-lived and slower to respond while a secondary exposure is a rapid, strong response.

This type of immunity is usually long-lasting.

It depends on memory B and T cells.

Immunization: A type of active

immunity

Figure 7.12 How immunizations cause active immunity.

Pla

sm

a a

nti

bo

dy

co

nc

en

tra

tio

n

Time (days)

high

low

30 60 90 120 150 180 0

primary response secondary response

second exposure

to vaccine

first exposure

to vaccine

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Immunization: A type of

active immunity

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Table 7A

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Passive Immunity

Passive immunity occurs when an individual is

given antibodies from an outside source.

Nursing passes antibodies from mother to child.

Get shot of gamma globulins after exposure to

disease

Anti-venom for snake bite

Passive immunity is temporary.

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How can the immune system

harm the body?

Allergies

Tissue rejection

Immune system disorders

Allergies

Allergies are hypersensitivities to harmless substances such as pollen, food, or animal hair.

An immediate allergic response is caused by the IgE antibodies that attach to mast cells and basophils. When allergens attach to these IgE molecules, histamine is released and we see allergy symptoms.

An immediate allergic response that occurs when the allergen enters the bloodstream is anaphylactic shock, in which the blood pressure drops and is life-threatening.

Delayed allergic responses (such as the reaction to poison ivy) are initiated by memory T cells.

Tissue rejection

Tissue rejection can occur when cytotoxic T cells respond to tissue that is not recognized as “self.”

This can be controlled by giving patients immunosuppressive drugs and by transplanting organs that have the same MHC proteins in the donor and recipient.

Currently, we are trying to grow organs in the lab that can be transplanted with less rejection.

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Disorders of the immune system

Autoimmune disease A disease in which cytotoxic T cells or antibodies

attack the body’s own cells as if they were foreign

Examples

Myasthenia gravis -neuromuscular junctions do not

work properly.

Multiple sclerosis - the myelin sheath of the nerve

fibers is broken down.

Systemic lupus erythematosus - various symptoms

eventually leading to death from kidney damage.

Rheumatoid arthritis - the joints are affected.

Disorders of the immune system

Immunodeficiency disease A disease in which the immune system is

compromised and thus unable to defend the body against disease

Examples: AIDS and SCID

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Cytokines and Immunity

Cytokines, including interferon, are signaling

molecules produced by T lymphocytes,

macrophages and other cells which are used in an

attempt to promote the body’s ability to recover from

cancer.

Interferon and interleukins have been used as

immunotherapeutic drugs.

Interleukin antagonists are used to prevent

transplant rejection.

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Fig. 7.10

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Hypersensitivity Reactions

Sometimes the immune system responds in a

manner that harms the body.

Allergies

Allergic responses occur when the immune system

reacts vigorously to substances not normally recognized

as foreign.

Immediate allergic responses are due to the activity of

antibodies.

Symptoms can vary from mild, coldlike symptoms, to

anaphylactic shock, which is an immediate allergic

response that occurs because an allergen has entered

the bloodstream.

The immunoglobulin IgE appears to be responsible.

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Hypersensitivity Reactions

Allergies

Delayed allergic responses, such as contact dermatitis,

are due to the activity of T cells.

Skin test for TB is a classic example of a delayed

allergic response – redness and swelling don’t show

for a few days.

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Other Immune Problems

Transplant rejection

Occurs when cytotoxic T cells bring about the destruction

of foreign tissue in the body.

Immunosuppressive drugs act by inhibiting the response of

T cells to cytokines.

Xenotransplantation is the use of animal organs instead

of human organs in transplant patients.

Genetic engineering can make these organs less

antigenic to humans.

Laboratory grown urinary bladders have been

successfully used in human transplantations.

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Other Immune Problems

Transplant rejection

In individuals with severe combined immunodeficiency

disease (SCID), both antibody- and cell-mediated

immunity is lacking or severely reduced.

AIDS is an example of an acquired immune deficiency.

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