Bubble Boy Disease Severe combined immunodeficiency (SCID) It is a genetic disorder in which the...

Bubble Boy DiseaseSevere combined immunodeficiency (SCID)

It is a genetic disorder in which the adaptive immune system is nonfunctional.

SCID is a severe form of heritable immunodeficiency. It is also known as the “bubble boy” disease because its victims are extremely vulnerable to infectious diseases and some of them, such as David Vetter, become famous for living in a sterile environment.

The human immunodeficiency virus (HIV) infects and destroys a particular type of white blood cells.

white blood cell

HIV

Over time, the immunity of the infected person may be seriously weakened, resulting in AIDS.

white blood cell

HIV

Patients usually die from infections that are harmless in healthy people.

white blood cell

HIV

What is immunity1

• Protects from pathogens and foreign molecules

– Parasites

– Bacteria

– Viruses

• Removes dead or damaged cells

• Attempts to recognize and remove abnormal cells

Immune System: Functions

9

• Incorrect responses

– Autoimmune disease (Type 1 diabetes)

• Overactive responses

– Allergies

• Lack of response

– Immunodeficiency disease (AIDS)

Immune System: Pathologies

26.1 Non-specific defence mechanisms

immune system ( 免疫系

統 )

pathogens

• provides body defence

Immune system

specific defence

mechanisms ( 特異性

防禦機制 )

non-specific defence

mechanisms ( 非特異性防

禦機制 )

• provide general protection against pathogens

• prevent the entry of all types of foreign substances

non-specific

Non-specific defence mechanisms

• include physical and chemical barriers

first line of defence ( 第一道防線 )


blood clotting

• include physical and chemical barriers


phagocytosis

inflammatory responses

• physical structures that prevent pathogens from entering the body

Physical barriers

• covers the whole body

Physical barriers1 Skin

layer of dead cells

- constantly worn away and replaced by new cells

2 Ciliated epithelium of the respiratory tract

Physical barriers

ciliated epithelial cell

closely packed cellsphysical barrier


Physical barriers

mucus-secreting cell

produces sticky mucus traps dust and pathogens


Physical barriers26.1 Non-specific defence mechanisms

cilia

beating action

moves dust and pathogens in mucus up from the bronchi to the pharynx


Physical barriers

dust and pathogens are swallowed or coughed out

cilia

beating action

• chemical secretions that may kill or stop the growth of pathogens

Chemical barriers

• secreted by sebaceous glands

1 Sebum

• a natural antiseptic ( 消毒劑 )

• kills pathogens on the skin

sebum

Chemical barriers

• contains hydrochloric acid

2 Gastric juice• secreted by gastric glands

• kills pathogens in the food in the stomach

gastric juice

Chemical barriers

3 Tears and saliva• secreted by tear glands

tears

Chemical barriers

3 Tears and saliva• secreted by salivary glands

Chemical barriers

breaks down the cell walls of certain bacteria on the conjunctiva and in the mouth cavity

Chemical barriers

• contain lysozyme ( 溶菌酶 )

3 Tears and saliva

4 Vaginal secretion

inhibits the growth of pathogens in the vagina

• acidic

Chemical barriers

Mucus is a chemical barrier that kills pathogens. mucus

In fact, mucus is a physical barrier that only traps pathogens without killing them.mucus

1 Examine a prepared slide of mammalian skin under a microscope using low power magnification or a skin model.

26.1

Identifying features of mammalian skin that are related to body defence

2 Identify the structures that are related to body defence.

prevents pathogens from entering through the wound

• blood clot ( 血凝塊 ) seals the wound and stops breeding

Blood clotting

• formation of a blood clot:

Blood clotting

- a blood vessel damaged

- blood platelets attracted to the wound

- blood platelets release chemicals

Blood clotting• formation of a blood clot:

insoluble fibrin ( 纖

維蛋白 )

soluble protein fibrinogen 　( 纖維蛋白原 )

Blood clotting

red blood cell

blood platelet

white blood cell

• formation of a blood clot:

- blood cells trapped in the net of fibrin

- blood clot dries to form a scab ( 痂 ) covering the wound

Blood clotting• formation of a blood clot:

• carried out by phagocytes ( 吞噬細胞 )

Phagocytosis

phagocyte

bacterium

Phagocytosis

pathogen phagocyte

nucleusenzymes

Phagocytosis1 A phagocyte engulfs a pathogen.

Phagocytosis2 The pathogen is digested by enzymes.

Phagocytosis3 The digested pathogen is released.

Inflammatory responsesAnimation

wound is infected

pathogens

1 Capillary increases its permeability.

Inflammatory responses

capillary

2 More phagocytes come out of the capillary.


phagocyte

3 Phagocytes engulf and digest the pathogens in the tissue.


carrying out phago-cytosis

• increased blood flow and accumulation of tissue fluid infected area becomes red, hot,

swollen and painful


inflammation ( 炎症 )

• pus ( 膿 ) may form inside the wound


- consists of the remains of killed pathogens and dead phagocytes

Tissue damage triggers the inflammatory response

Tissue injury; release ofchemical signals such as

histamine

1 2 3Dilation and increased leakinessof local blood vessels; migration

of phagocytes to the area

Phagocytes (macrophages andneutrophils) consume bacteria

and cell debris; tissue heals

Pin

Skin surface

Bacteria

Chemicalsignals

Whiteblood cell

Swelling

Phagocytes andfluid moveinto area

Phagocytes

The inflammation can disinfect tissues

and limit further infection

The inflammatory response mobilizes nonspecific defense forces

The lymphatic system becomes a crucial battleground during infection

It returns tissue fluid to the circulatory system It fights infections

Lymphatic system = lymphatic ducts and lymph nodes

Lymphatic system

Right lymphaticduct, entering

vein

Thoracicduct

Appendix

Tonsil

Lymph nodes

Thoracic duct,

entering vein

Thymus

Spleen

Bonemarrow Lymphatic

vessels

LYMPHATICVESSEL

VALVE

Bloodcapillary

Tissue cells

Interstitialfluid

LYMPHATICCAPILLARY

Masses oflymphocytes and

Macrophages

Primary lymph organs : Thymus and bone marrow

Secondary lymph organs : lymph nodes

This lymphatic vessel is taking up fluid from tissue spaces in the skin

• It will return it as lymph to the blood

– Lymph contains less oxygen and fewer nutrients than interstitial fluid

LYMPHATICVESSEL

VALVE

Bloodcapillary

Interstitialfluid

LYMPHATICCAPILLARY

Tissue cells

Lymph nodes are key sites for fighting infection

They are packed with lymphocytes and macrophages

Figure 23.3C, D

Masses oflymphocytes and

macrophages

Lymphocytes

Macrophages

Outer capsule oflymph node

1 Non-specific defence mechanisms prevent the entry of

.

all types of

foreign substances

2a The first line of defence includes and

barriers that prevent pathogens from entering the blood and other tissues.

physical chemical

• Covers the to prevent the entry of pathogens

Physical ChemicalBarrier: Skin

2b Possible entrance of pathogens:

Body surface

whole body

Method of prevention:

• An antiseptic that pathogens

Physical ChemicalBarrier: Sebum

killsMethod of prevention:

2b Possible entrance of pathogens:

Body surface

• Cells are packed to prevent the entry of pathogens

Physical

Chemical

Barrier: Ciliated

epithelium

2c Possible entrance of pathogens:

Respiratory tract

closelyMethod of

prevention:

• traps pathogens

Physical

Chemical

Barrier: Ciliated

epithelium

MucusMethod of

prevention:


Respiratory tract

beat to move the trapped pathogens upwards

Physical

Chemical

Barrier: Ciliated

epithelium

CiliaMethod of

prevention:


Respiratory tract

or coughed out

• The trapped pathogens are then

Physical

Chemical

Barrier: Ciliated

epithelium

swallowed

Method of

prevention:


Respiratory tract

• Contains to kill pathogens

Physical

Chemical

Barrier: Gastric juice

2d Possible entrance of pathogens:

Stomach

hydrochloric acidMethod of

prevention:

• Contains to kill pathogens

Physical

Chemical

Barrier: Tears

2e Possible entrance of pathogens:

Eyes

lysozymeMethod of

prevention:

• Contains lysozyme to kill pathogens

Physical

Chemical

Barrier:

2f Possible entrance of pathogens:

Mouth

Saliva

Method of

prevention:

• Acidity the growth of pathogens

Physical

Chemical

Barrier: Vaginal

secretion

2g Possible entrance of pathogens:

Vagina

inhibitsMethod of

prevention:

3 Pathogens can get into the body

seals blood clotting

through a wound on the skin. By , a blood clot is formed which the wound to prevent the entry of pathogens.

4 Phagocytosis is the process by which phagocytes pathogens.

engulf

in the infected area dilate, and capillaries there increase their .

5 In an inflammatory response, arterioles

permeability

More blood flows to the area and more come out of the capillaries to engulf and kill the pathogens in the tissues.

5phagoctyes

and result from the increased blood flow, and

6 Signs of inflammation:

Redness heat

and result from the accumulation of tissue fluid.swelling pain

Non-specific vs specific immunity

• adaptive immune response (應變性 ) / specific immunity

• Major characteristics of adaptive immune response

• 多樣性 (Diversity)

• 專一性（ specificity ）

• 記憶性（ memory ）

• 自我辨識（ self/non-self recognition ）

The Nature of ImmunityImmunity was originally used to indicate exemption from

taxes and this meaning still exits in the term "diplomatic

immunity".

A ntigenic specificity To distinguish subtle difference among

antigens I mmunologic memory

A second encounter with the same antigen induces a heightened state of immune reactivity

D iversity To recognize billions of uniquely different

structures on foreign antigens S elf/nonself recognition

To respond only to foreign antigens

Characteristics of Adaptive immunity

26.2 Specific defence mechanisms

antigens ( 抗原 )

lymphocytes ( 淋巴細胞 )

B cells T cells

immune responses 　　( 免疫反應 )

activate

carry out

Two kinds of lymphocytes carry out the immune responseB cells secrete

antibodies that attack antigens

T cells attack cells infected with pathogens

LymphocytesBONE MARROW

Stem cell

Immaturelymphocytes

Viablood

Antigenreceptors

B cell

HUMORALIMMUNITY

CELL-MEDIATEDIMMUNITY

T cell

THYMUS

Viablood

OTHER PARTSOF THE

LYMPHATICSYSTEM

Lymph nodes,spleen, and otherlymphatic organs Final

maturation of B and T cellsin lymphatic

organ

and self antigens

• stimulate immune responses

Antigens

• two groups:

foreign antigens

- come from outside of the bodye.g. cell surface proteins of viruses

or toxins from bacteria

virussurface proteins

foreign antigens

• stimulate immune responses

Antigens

• two groups:

and self antigens

- produced by the person’s own body e.g. surface proteins on red blood cells

red blood cell

surface proteins

• immune system can usually recognize self antigens and does not attack them

Antigens

Antigens

humoral immune responses (HIR) ( 體液免疫反應 )

foreign antigens not yet entered the host cells

B cells

activate

carry out

• B cells are formed and mature in the bone marrow

Humoral immune responses

• B cells have antigen receptors that only bind with a specific antigen

Triggered by a specific antigen, a B cell differentiates into an effector cell

The effector cell is called a plasma cellThe plasma cell secretes antibodies

B cells are the main warriors of humoral immunity

Humoral immune responsesactivated by antigens and helper T cells

B cell

multiplies and differentiates into

memory B cell

plasma cell


plasma cell

Antibodies to act against antigens

produces

Humoral immune responses• antibody is a Y-shaped protein

molecule

polypeptide chains

disulphide bond

antigen-binding site

Antigens are molecules to which antibodies bind

Antigens have specific regions where antibodies bind to them

Antibody Amolecules

Antigen

Antibody Bmolecule

Antigenicdeterminants

Antigen-binding

sites


antigen-antibody complex

antigen

Humoral immune responses• production of antibodies is specific

- each type of antigen leads to the production of only one type of antibody

3D animation


1 Lysis ( 溶菌 )a Antibodies attach to pathogen and make holes in it.

Actions of antibodies

antibodies

pathogen (virus or bacterium)

Animation


1 Lysis ( 溶菌 )a Antibodies attach to pathogen and make holes in it.



1 Lysis ( 溶菌 )b Pathogen is lysed ( 被溶解 ) and killed.


hole


2 Help in phagocytosis

a Antibodies attach to pathogen.


pathogen

phagocyteantibody


b Phagocyte detects the antibodies and engulfs the pathogen.




c Pathogen is killed by phagocytosis.




3 Stick pathogens into clumps

- pathogens stuck together by antibodies and cannot reproduce or enter cells


pathogens

antibodies

Humoral immune responses26.2 Specific defence mechanisms

3 Stick pathogens into clumps

- pathogens stuck together by antibodies and cannot reproduce or enter cells



4 Neutralize toxins of pathogens

- antibodies act as antitoxins ( 抗毒素 ) to neutralize toxins


antibodies

toxins

Humoral immune responses26.2 Specific defence mechanisms

4 Neutralize toxins of pathogens


- antibodies act as antitoxins ( 抗毒素 ) to neutralize toxins

Binding of antibodies to antigens

inactivates antigens by

Neutralization

(blocks viral binding sites;

coats bacterial toxins)

Agglutination

of microbes

Precipitation of

dissolved antigens

Make holes in cell membrane

Virus

Bacterium

Bacteria

Antigen

molecules

Complement

molecule

Foreign cell Hole

Enhances

Phagocytosis

Macrophage

Cell lysis

Leads to

When an antigen enters the body, it activates only lymphocytes with complementary receptorsB and T cells multiply into clones of specialized

effector cells that defend against the triggering antigen

This is called clonal selection

Clonal selection musters defensive forces against specific antigens

Figure 24.7

Antigen molecules

Variety ofB cells in a lymph node

Cell growth

division, and

differentiation

Clone of manyeffector cells

secretingantibodies

Antibodymolecules

Antigen receptor(antibody oncell surface)

Endoplasmicreticulum

In the primary immune response, clonal selection produces memory cellsThese cells may confer lifelong immunity

The initial immune response results in a type of “memory”

When memory cells are activated by subsequent exposure to an antigen, they mount a more rapid and massive secondary immune response

Figure 24.8B

Unstimulated lymphocyte

First exposure to antigen

FIRST CLONE

Memory cells

Effector cellsSecond exposure to antigen

SECOND CLONE

More memory cells

New effector cells

Figure 24.9

PRIMARY RESPONSE

(initial encounter

with antigen)

Antigen

Antigen receptoron a B cell

Antigen binding

to a B cell

Memory B cell

Antibody

molecules

Plasma cell

Cell growth,

division, and

differentiation

SECONDARY RESPONSE

(can be years later)

Cell division,

differentiation

Larger clone

of cells

Plasma cell

Antibody

molecules

Later

exposure

to

same antigen

Memory B cell

Clone ofcells

Cell-mediated immune response

cell-mediated immune responses (CMIR)

infected cells or cancer cells

T cells

stimulate

carry out

• T cells have receptors on their surface that fit a specific antigen

• T cells are formed in the bone marrow and mature in the thymus gland ( 胸腺 )


• several types: helper T cells, killer T cells and memory T cells


thymus gland

activated by infected cells or cancer cells

helper T cell

B cell

carries out HIR

T helper cells activate HIR

activates

T cell

lymphokines ( 淋巴激活

素 )

activate phagocytes

Cell-mediated immune responseactivated by infected cells or cancer cells

helper T cell

activatessecretes

destroys cells directly

memory T cell

killer T cell ( 殺手　T 細

胞 )


T cell

multiplies and differentiates

into

Cytotoxic T / killer T cells bind to infected body cells and destroy them by making hole in the cell membrane

Figure 24.13C

Cytotoxic T cell bindsto infected cell

1 2 3Perforin makes holes

in infected cell’s membraneInfected cell is destroyed

INFECTED CELL

Perforinmolecule

CytotoxicT cell

Foreignantigen

Holeforming

Killer T cells may attack cancer cells

The surface molecules of cancer cells are altered by the disease

Killer T cells may help prevent cancer

• immunological memory ( 免疫記憶 ): the ability of memory B cells and memory T cells to ‘remember’ the type of antigen from the previous exposure

Primary and secondary immune responses


• primary response occurs on the first exposure to an antigen

• secondary response occurs when the same antigen enters the body again

• usually slow / longer latent period• normally takes 3–14 days to

produce enough antibodies or cells

disease symptoms

• antigens have time to cause damage



• faster, stronger and lasts longer • memory cells multiply and differentiate

quickly into a larger number of plasma cells, killer T cells and memory cells

• kills the pathogen before it can multiply and cause a disease

0 7 14 21 28 35 days

conc

entr

atio

n of

an

tibod

ies

in b

lood

first exposure second exposure

primary response

secondary responserecovery

0 7 14 21 28 35 days


primary response


latent period ( 潛伏期 )

conc

entr

atio

n of

an

tibod

ies

in b

lood

0 7 14 21 28 35 days


primary response


concentration of antibodies

conc

entr

atio

n of

an

tibod

ies

in b

lood

0 7 14 21 28 35 days


primary response


period of existence of antibodies

conc

entr

atio

n of

an

tibod

ies

in b

lood

• immunity can be enhanced by vaccination

Principle of vaccination

introduction of vaccines ( 疫苗 ) into the body

Principle of vaccination• four types of vaccines:

1 Live, weakened pathogens

e.g. vaccines of measles, mumps, rubella

2 Killed pathogens

e.g. vaccines of poliomyelitis, rabies ( 狂犬病 )

• four types of vaccines:

3 Viral proteins

e.g. vaccine of whooping cough

4 Inactivated bacterial toxins

e.g. vaccines of diphtheria, tetanus


Vaccines　I# Many exotoxins can

be modified chemically so that they retain their antigenicity but are no

longer toxic. Such a modified exotoxin is

called a toxoid.

Vaccine　II# Most agents used for immunization are either

attenuated or inactivated pathogens or inactivated

forms of natural microbial products.

Alternative immunization strategies using

bioengineered molecules eliminate exposure to

microorganisms and, in some cases, even to

protein antigen. Application of these

strategies may provide safer and more targeted

vaccines.

• vaccine contains an antigen

• introduced into the body orally or by injection


- production of some antibodies and killer T cells

- production of memory cells that ‘remember’ the type of antigen

antigen in vaccine

primary response

stimulates


- production of a larger amount of specific antibodies and killer T cells in a shorter time

invasion by the same antigen

secondary response

stimulates


• makes use of the specificity and immunological memory

• protects the health of the community if a large number of people are vaccinated

• not completely without risk


• given by antibodies produced by our own plasma cells

Active and passive immunity

• acquired naturally when a person recovers from an infection

• acquired artificially by vaccination

• start of the immunity is relatively slow


• long lasting


• given by direct transfer of antibodies from immune persons

Active and passive immunity • occurs naturally in babies when:

- antibodies diffuse from mother’s blood to embryo’s blood in placenta


- babies are fed with breast milk

• occurs naturally in babies when:


• occurs artificially when:

- antibodies are injected for treatment of diseases

• immunity starts immediately

• lost after a short period of time when the antibodies break down

fusing B cells specific for a single antigenic determinant with easy-to-grow tumor cells

Connection: Monoclonal antibodies are powerful tools in the lab and clinic

Antigen injected

into mouse

Tumor cells grown

in culture

B cells

(from spleen)

Tumor cells

Cells fused to

generate hybrid

cellsSingle hybrid cell

grown in culture

AntibodyHybrid cell culture,

producing monoclonal antibodies

These cells are useful in medical diagnosis

– Example: home pregnancy tests

• They are also useful in the treatment of

certain cancers

Autoimmune diseases : The immune system turns against the body’s own molecules, including SLE (紅斑狼瘡 ), RA (類風濕性關節炎 ), type I diabetes, asthma, Crohn’s disease 孔羅氏症 (消化道瘜肉 ),….

Immunodeficiency diseases : Immune components are lacking, and infections recur. Innate immune deficiency : Severe combined immunodeficiency

(SCID) Acquired immune deficiency : AIDS

Physical and emotional stress may weaken the immune system

Connection: Malfunction or failure of the immune system causes disease

Arthritis X-ray

RA is an autoimmune disorder in which your own body mistakenly attacks healthy tissue, causing inflammation and damage to your joints.

About 1% of the US population suffers from RA. Patients usually develop the signs and symptoms of the disease between the ages of 35 and 50,

with women affected 2 to 3 times more often than are men.

Allergies are abnormal sensitivities to allergens in the surroundings

Connection: Allergies are overreactions to certain environmental antigens

Allergen

(pollen grain)

B cells make

antibodies

Antigenic

determinant

SENSITIZATION: Initial exposure to allergen

Antibodies

attach to

mast cell

B cell

(plasma cell)Histamine

Mast

cell

Allergen binds to

antibodies on

mast cell

Histamine is

released, causing

allergy symptoms

LATER EXPOSURE TO SAME ALLERGEN

Allergy-causing fungal spores

Figure 24.17x

The AIDS virus attacks helper T Cells This cripples both cell-mediated and humoral

immunity

So far, AIDS is incurableDrugs and vaccines offer hope for the future

Practicing safer sex could save many lives

Connection: AIDS leaves the body defenseless

Acquired immune deficiency syndrome (AIDS) is epidemic throughout much of the world

14,000 people are infected with the AIDS virus every dayHIV is the virus that causes AIDSHIV is transmitted mainly

in blood and semen Former L.A. Laker Magic

Johnson is one of 900,000 Americans who are HIV-positive

The Continuing Problem of HIV

AIDS is an immunodeficiency disease caused by a virus

In 1981, increased rates of two rare diseases, Kaposi’s sarcoma, and pneumonia caused by a protozoan P. carinii, were the first signals of a new threat to humans, later known as acquired immunodeficiency syndrome, or AIDS.Both conditions were previously known to occur

mainly in severely immunosuppressed individuals.People with AIDS are susceptible to opportunistic

diseases.

Kaposi’s　Sarcoma

Unusual tumor arising from blood or lymphatic vessels in multiple locations

Tumor began to appear in young men with HIV○ 2000 time higher than period

before HIV○ So common among AIDS

patients became AIDS-defining condition

Causative agent - Pneumocystis carinii

Tiny fungus formerly considered a protozoan

Differs from many fungi in cell wall components○ Consequently resistant to many fungal

medications

Pathogenesis Spores of organism are inhaled into lung

○ Attach to alveolar wallsAlveoli fill with fluid, mononuclear cells

and organisms Alveolar walls become thickened and

scarred. Interferes with free passage of oxygen

Pneumocystosis( 肺孢子蟲病 )

In 1983, a retrovirus, now called human immunodeficiency virus (HIV), had been identified as the causative agent of AIDS.

With the AIDS mortality close to 100%, HIV is the most lethal pathogen ever encountered.Molecular studies reveal that the virus probably

evolved from another HIV-like virus in chimpanzees in central Africa and appeared in humans sometimes between 1915 and 1940.○ These first rare cases of infection and AIDS went

unrecognized.

Two major strains HIV-1 and HIV-2.HIV-1 is the more widely distributed and more

virulent.

Both strains infect cells that bear CD4 molecules, especially helper T cells and also macrophages, some lymphocytes and some brain cells.

HIV　infected　cells:　　Among　the　susceptible　WBCs,　　what　do　they　have　in　common?

CD4 functions as the major receptor for the virus.Other HIV receptors present on the surface of some

WBCs are implicated:

• Clues: Some people who are innately resistant to HIV-1 owe their resistance to defective chemokine receptors. chemokines – chemicals secreted by WBC when signaling with one another.

• What is your conclusion?

The entry of the virus requires not only CD4 on the surface of the susceptible cells but also a second protein molecule, a co-receptor. Defective chemokine receptor prevents HIV from binding and infecting cells.

What is your conclusion?

Once inside a cell, HIV RNA is reverse-transcribed, and the product DNA is integrated into the host genome.This directs the production of new virus particles.Because a retrovirus exists integrated in the host

genome of the infected cell, immune responses fail to eradicate it from the body.

Even more challenging : frequent mutational changes that occur in each round of virus replication.

Give two reasons why it is difficult to remove the virus from our body?

Give　two　reasons　why　it　is　difficult　to　remove　HIV　from　our　body?

•Because a retrovirus exists integrated in the host genome of the infected cell,

immune responses fail to eradicate it from the body.

•Even more challenging : frequent mutational changes that occur in each

round of virus replication.

Because a retrovirus exists integrated / hidden in the host genome of the infected cell, immune responses fail to eradicate it from the body.

Even more challenging : frequent mutational changes occur in each round of virus replication fools our immune system – render immunologic memory and immune specificity ineffective.

Give　two　reasons　why　it　is　difficult　to　remove　HIV　from　our　body?

The body is then engaged in a Prolonged battle against HIV.(1) The immune response diminishes the initial viral

load, but HIV continues to replicate in lymphatic tissue.

(2) Viral load gradually rises as HIV is released from lymphatic tissue and helper T cell levels decrease. Consequence?

The body is then engaged in a Prolonged battle against HIV.(1) The immune response diminishes the initial viral

load, but HIV continues to replicate in lymphatic tissue.

(2) Viral load gradually rises as HIV is released from lymphatic tissue and helper T cell levels decrease. Consequence?

This results in extensive loss of humoral and cell-mediated immunity.

After an initial peak, virus levels in the blood fall as

anti-HIV antibodies,

produced 1 to 12 months after

infection, rise.

After the early drop in HIV levels in the blood, the virus continues to be produced by cells in the lymph nodes,

causing structural and functional damage.

In time, the concentration of HIV in the blood increases as a result of :

the breakdown of lymphatic tissue function and diminishing responses to the infection because of

the depletion of helper T cells.

The time required for an HIV infection to progress to severe

helper T cell depletion and AIDS varies greatly, but it currently averages

about ten years.

A person who is HIV-positive will have blood tested positive for the presence of antibodies to the virus.

However, a HIV-negative blood test result does not completely guarantee a safe blood supply, WHY?

because an infected individual may require several weeks to 6 months (window period) before anti-HIV antibodies become detectable.

After the early drop in HIV levels in the blood, the virus continues to be produced by cells in the lymph nodes, causing structural and functional damage.In time, the concentration of HIV in the blood

increases as a result of :the breakdown of lymphatic tissue function and

diminishing responses to the infection because of the depletion of helper T cells.

The time required for an HIV infection to progress to severe helper T cell depletion and AIDS varies greatly, but it currently averages about ten years.During most of this time, the individual exhibits

only moderate hints of illness, such as swollen lymph nodes and occasional fever.

How do you think doctors can monitor the progress of the disease?

by measuring changes in the level of T cells, although measures of viral load are a better

indicator of disease prognosis and of the effectiveness of anti-HIV treatment.

The time required for an HIV infection to progress to severe helper T cell depletion and AIDS varies greatly, but it currently averages about ten years.During most of this time, the individual exhibits

only moderate hints of illness, such as swollen lymph nodes and occasional fever.

How do you think doctors can monitor the progress of the disease?

by measuring changes in the level of T cells. Or measures of viral load - a better indicator of disease prognosis

and of the effectiveness of anti-HIV treatment.

At this time, HIV infection cannot be cured, and the progression to AIDS cannot be prevented.

New, expensive drug therapies can slow this progression.

Suggest how these drugs might work:

Combinations of these drugs (a cocktail) decrease viral load and therefore allow the number of helper T cells to rise.

slow viral replication by 1) inhibiting DNA synthesis, 2) inhibiting reverse transcriptase, and 3) protein synthesis inhibitors

At this time, HIV infection cannot be cured, and the progression to AIDS cannot be prevented.

New, expensive drug therapies can slow this progression.

Suggest how these drugs might work:

Combinations of these drugs (a cocktail) decrease viral load and therefore allow the number of helper T cells to rise.

slow viral replication by

•- inhibiting DNA synthesis,

•- inhibiting reverse transcriptase, and

•- protein synthesis inhibitors

Highly　Active　Anti-retroviral　therapy　(HAART)

Reverse transcriptase inhibitors and protease inhibitors, provide a "one-two punch," interrupting HIV's replication cycle at different points and reducing the virus in many cases to undetectable levels.

HOW ANTI-HIV DRUGS WORK Entry inhibitors bind to the

proteins on the outside of the HIV virus　and　stop　it　from　entering　the　target　cell　(Fuzeon　only).

Nucleoside reverse transcriptase inhibitors stop HIV copying its genes into the cell.　Nucleosides　are　the　building　block　for　genes.　The　drugs　supply　faulty　versions　of　these　building　blocks　(drugs　include　abacavir,　AZT,　ddI,　3TC).

Non-nucleoside reverse transcriptase inhibitors also block the gene-copying process.　They　disable　the　enzyme　that　controls　it　(drugs　include　nevirapine　and　efavirenz).

Protease inhibitors disable protease, an enzyme which plays a key role in the formation of the new virus　(drugs　include　amprenavir,　lopinavir,　ritonavir,　nelfinavir).

HAART　reduce　the　virus　in　many　cases　to　undetectable　levels.

• Even though ARV drugs are getting more powerful in inhibiting the effects of HIV, one must remember that these do not cure HIV infection and AIDS.

• Individuals who are on HAART can still transmit the virus to other people.

protease inhibitors

When　the　(HIV)　replicates,　it　does　not　make　perfect　copies　of　itself　but　rather,　creates　new　strains　in　the　process.　This　means　that　an　HIV+　person　actually　has　many　different　strains　of　the　virus　inside　his/her　system.　　

Suggest why the ‘cocktail treatment’ is preferred rather than a single drug?

168

Suggest why the ‘cocktail treatment’ is preferred rather than a single drug?

• New strains of HIV which are resistant to the effects of a particular antiretroviral (ARV) drug may appear and then replicate quickly.

• For a treatment regimen to be effective over the long term, it has to include more than one ARV drug at a time. Taking two or more ARV drugs concurrently, known as combination therapy, can vastly reduce the rate at which drug resistance develops.

• HIV evolve quickly because it has a very short life cycle and high mutation rate.

Transmission of HIV requires the transfer of body fluids containing infected cells, such as semen or blood, from person to person:

Transmission of HIV

• Unprotected sex (that is, without a condom) among male homosexuals

• and transmission via nonsterile needles (typically among intravenous drug users)

• However, transmission of HIV among heterosexuals is rapidly increasing as a result of unprotected sex with infected partners.

So far, only one case of HIV transmission by kissing has been reported, and both individuals had bleeding gums.

Transmission of HIV from mother to child can occur during fetal development or during nursing. Mother-to-child transmission accounts for more than 90% of all HIV infections in infants and children worldwide.

HIV screening has virtually eliminated blood transfusions as a route of transmission in developed countries.

HIV　is　not　transmitted　by　casual　contact.

河南爱滋病村

马深义一家住在中国河南上蔡县文楼村，他的家庭就是爱滋病的受害者。他们一家五口人，有四人感染了艾滋病，只有 9 岁的大女儿是健康的。《好死不如赖活着》没有故事、没有情节、没有背景音乐、没有字正腔圆的叙述、没有宏大的场面，整部影片就是在纪录这个家庭的日常生活。影片的镜头从 2001年的春末夏初开始，历经盛夏、深秋、严冬，一直到春节，近距离地拍摄了马深义一家面对爱滋病和死亡的人生经历。

As of 2000 the Joint United Nations Program on AIDS estimates that 30 to 40 million people worldwide are living with HIV or HIV/AIDS.Of these, approximately 70% reside in sub-

Saharan Africa.The number of people with AIDS is expected to

grow by nearly 20% per year.

The best approach for slowing the spread of HIV is to educate people about the practices that transmit the disease, such as using nonsterile needles and having sex without a condom.

Any individual who has sex with a partner who had unprotected sex with another person during the past two decades risks exposure to HIV.

HIV on a lymphocyte

Figure 24.18x2

HIV budding collage ( 大雜燴 )

No approved vaccine

Most people infected are unaware

Virus on surfaces can be inactivated with commercially available disinfectants and heat at 56°C for more that 30 minutes

Knowledge of transmission greatest tool for control

Use of condoms not 100% effective but have been shown to decrease transmission

Avoidance of practices that favor HIV transmission

HIV Prevention and Treatment

Currently no approved vaccines In theory, vaccine could be used in two ways:

HIV vaccine prospects

Prevention vaccine

Immunize uninfected individuals against disease

Therapeutic vaccine

Boost immunity of those already infected

•get around HIV variability

•Be effective in preventing direct spread of HIV from cell to cell

Successful vaccine must

• Be capable of turning into disease-causing strain

• Be oncogenic – cancer causing

• Stimulate an autoimmune response

Successful vaccine must NOT

Vaccine trial in humans has been undertaken for at least 10 experimental vaccines

All have failed and prospects do not look

favorable

A monumental safe-sex message in Paris


Pope says condoms are not the solution to Aids - they make it worse


Pope Benedict stressed that the Roman Catholic Church is in the forefront of the

battle against Aids. The Vatican encourages sexual abstinence to fight

the spread of the disease.

Pope says condoms are not the solution to Aids - they make it worse


2 million people die of Aids each year.

14,000 people get infected with HIV every day.

CountryPeople living

with HIV/AIDS

Adult (15-49) rate %

Women with

HIV/AIDS

Children with

HIV/AIDS

AIDS deaths

Orphans due to AIDS

Cameroon 610,000 5.3 320,000 54,000 37,000 330,000

Chad 210,000 3.4 110,000 23,000 11,000 120,000

Congo 77,000 3.4 40,000 7,900 5,100 51,000

Ghana 260,000 1.8 140,000 27,000 18,000 160,000

Kenya 1,500,000 6.3 760,000 180,000 80,000 1,200,000

Mozambique 1,400,000 11.5 760,000 130,000 74,000 670,000

Nigeria 3,300,000 3.6 1,700,000 360,000 220,000 2,500,000

South Africa 5,600,000 17.8 3,300,000 330,000 310,000 1,900,000

Total sub-Saharan Africa 22,500,000 5.0 12,100,000 2,300,000 1,300,000 14,800,000

Notes

Adults in this page are defined as men and women aged over 15, unless specified otherwise.

Children are defined as people under the age of 15, whilst orphans are children aged under 18 who have lost one or both parents to AIDS.

Sub-Saharan Africa HIV & AIDS statistics (2010)

There is no single perfect solution to the problem of Aids

Telling people to abstain doesn’t make everyone abstain

Telling people NOT to use condom undermines the effort of the fight against AIDs and makes a serious global public health problem in places where AIDs is

rapidly spreading e.g. Africa

Botswana, 23.9% of adults between 15 and 49 are HIV positive; Swaziland, where 26.1% of adults have HIV;

1 Antigens are substances that stimulate , activate the immune system to produce , and combine with specific antibodies.

immune responses

antibodies


to act against specific antigens that have not yet entered host cells.

2 Humoral immune response uses antibodies


them.

of pathogens anda Antibodies may attach to the

3 How antibodies act against pathogens:

antigens


lyse

phagocytes the pathogens more easily.

b Antibodies may help theengulf



, preventing them from reproducing or entering cells.

c Antibodies may help pathogens stick into clumps



which neutralize the toxins secreted by pathogens.

d Antibodies may act as antitoxins



cells.

4 Cell-mediated immune response uses to destroy cells infected with specific antigens and

T cells


cancer

5 Compare B cells and T cells:


B cells T cells

Formed in Bone marrow

Mature in Bone marrow Thymus gland

- which produce to act against

antigens that have not yet entered host cells



Plasma cellsantibodies

B cells give rise to:

- which ‘remember’ the type of and are responsible for the secondary response



Memory B cellsantigen

B cells give rise to:

- which destroy infected cells or cancer cells directly

- which can activate other T cells and B cells



Helper T cells

Killer T cells

T cells give rise to:

- which ‘remember’ the type of antigen and are responsible for the secondary response



Memory T cellsT cells give rise to:



B cells T cellsResponsible for

CMIRHIR

6 Distinguish primary and secondary responses:


Primary response Secondary response

Effected by stimulation of B cells and T cells

Effected by stimulation of memory B cells

memory T cellsand



latent period

( response)

latent period

( response)

Longer

slower

Shorter

faster




amount

of antibodies and

killer T cells

produced

amount of

antibodies and killer T

cells produced

Smaller Larger




Lasts for a Lastsshort longer

period of time


pathogens, killed pathogens, or inactivated bacterial toxins.

, which contains an , into the body. A vaccine may contain live and

7a Vaccination is the introduction of a vaccine


antigen

weakenedviral proteins

of the specific defence mechanisms. The vaccine produces a response.

and Vaccination makes use of the7b

specificity


immunological

memory

primary

Any subsequent invasion by the same in the vaccine will produce a response, giving enhanced immunity to the disease.

antigen


secondary

7b

8 Distinguish active immunity and passive immunity:


own plasma cells immune persons

Active immunity Passive immunity

Antibodies are produced by our

Antibodies are transferred from


from an infectionrecovers

andplacenta

breast-feeding



Acquired naturally when a person

Acquired naturally through the diffusion of antibodies in the


vaccination injection



Acquired artificially by (for disease prevention)

Acquired artificially by of antibodies (for the treatment of diseases)


slow fast



Start of immunity is Start of immunity is


longer short



Lasts Lasts for a period of time

What is immunity?1Immunity is the ability of the body to resist a disease.

Which type of white blood cell is 2

Helper T cells are necessary to activate the defensive reactions of the body.

necessary to activate the defensive reactions of the body?

How does a low level of those white3With only a low level of helper T cells, few B cells and T cells are activated to carry out immune responses.

blood cells lead to weakened immunity?

Body defence

non-specific defence

mechanisms

consists of

specific defence mechanisms

non-specific defence mechanisms

physical barriers

include

chemical barriers

blood clotting

phagocytosis

inflammatory response

physical barriers

chemical barriers

form

first line of defence

phagocytosis

phagocytes

carried out by

specific defence mechanismsinclude

humoral immune response

cell-mediated immune response

T cellscarried out by

helper T cellssome are

carried out by

B cells

activate

T cells

lymphokinescan secrete

phagocytes

activate

T cellsmultiply and differentiate into

killer T cells

memory T cells

B cellsmultiply and differentiate into

memory B cells

plasma cells

antibodies

produce

memory B cells

responsible for

immunological memory

memory T cells

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