HIV/AIDS HIV/AIDS Rate per 100,000 people Plan for Tonight Unit 6 and 7 Work Immune Response HIV’s Interaction with the Immune System Difficulties with

HIV/AIDS

HIV/AIDS Rate per 100,000 people

• Plan for Tonight

• Unit 6 and 7 Work

• Immune Response

• HIV’s Interaction with the Immune System

• Difficulties with HIV Treatment/Vaccines

• Highly Active Antiretroviral Treatment (HAART)

• New Promising Treatments

Immune Response: Initial Infection

Pathogens (disease-causing bacteria or viruses or other organisms), for example

HIV, invade your body

Antigens (proteins on the surfaces of pathogens that can be recognized by antibodies)

Immune Response Step 1: Initial Recognition of Infection

Cell-Mediated Response Antibody-Mediated Response

Macrophage

B Cell # 146,883

B Cell# 34,599

MACROPHAGE are white blood cells that gobble up foreign invaders.

MHC Protein

B CELLS are white blood cells that produce antibodies. Each person can produce hundreds of millions of different B

Cells. Each type of B cell is genetically-unique and produces a unique antibody. Two B cells(out of hundreds of

millions) are shown here.

ANTIBODIES are Y-Shaped proteins. The ends of the arms of the Y have antigen-binding sites. Each different

type of antibody has a uniquely shaped antigen-binding site.

Immune Response Step 2: Phagocytosis of Pathogen


Macrophage

MACROPHAGE engulf (phagocytize) the pathogenic invader. After this, the macrophage kills

and breaks down the pathogen into pieces.

The B CELL that has an antibody that binds to antigen engulfs(phagocytizes) the antigen-antibody complex. After this, the B cell kills and

breaks down the pathogen into pieces.

B Cell # 146,883

Immune Response Step 3: Antigen-Presenting Cells


Antigen-Presenting

CellAntigen-Presenting

Cell

MACROPHAGE display parts of the pathogen alongside the MHC protein. At this point, the

macrophage is called an Antigen-Presenting Cell (or APC).

The B CELLdisplays parts of the pathogen alongside the MHC protein. At this point, this B cell is called an Antigen-

Presenting Cell (or APC).

Immune Response Step 4: Helper T Cell-APC Interaction


Antigen-Presenting


Cell

T Cell # 2,888,124

T Cell #492

HELPER T CELLS are another kind of white blood cell. There are hundreds of millions of different kinds of T Cells. Each is genetically

unique and each displays a unique form of the protein called T Cell Receptor protein. Shown

here are two of the hundreds of millions of different kinds of T Cells in a persons body.

Immune Response Step 5: Helper T Cell Stimulation


Antigen-Presenting


Cell

T Cell # 2,888,124

Binding of Helper T Cell to APC stimulates the APC to secrete Interleukin. Interleukin stimulates Helper T cells to rapidly reproduce. Since Helper

T Cell # 2,888,124 is locked on, it will be in an area of high Interleukin concentration. So among

all the Helper T Cells floating around the body, Helper T Cell # 2,888,124 will be the one to

reproduce rapidly and repeatedly.

Immune Response Step 5: Helper T Cell Proliferation


Antigen-Presenting


Cell

T Cell # 2,888,124

Huge numbers of T Cell # 2,888,124 are produced.

T Cell # 2,888,124

T Cell # 2,888,124T Cell # 2,888,124

T Cell # 2,888,124

T Cell # 2,888,124

T Cell # 2,888,124 T Cell # 2,888,124

Immune Response Step 6: Helper T Cell DifferentiationCell-Mediated Response Antibody-Mediated Response

Antigen-Presenting


Cell

T Cell # 2,888,124

Cytotoxic T Cells kill body cells infected by the pathogen.

MEMORY T Cell # 2,888,124

CYTOTOXIC T Cell # 2,888,124

HELPERT Cell # 2,888,124

CYTOTOXIC T Cell # 2,888,124CYTOTOXIC T Cell # 2,888,124

CYTOTOXIC T Cell # 2,888,124CYTOTOXIC T Cell # 2,888,124


MEMORY T Cell # 2,888,124MEMORY T Cell #

2,888,124MEMORY T Cell #

2,888,124

MEMORY T Cell # 2,888,124 HELPERT Cell #

2,888,124HELPERT Cell # 2,888,124



Memory T Cells are fairly inactive. They reproduce at a steady pace.

Helper T Cells interact with other white blood cells to propagate the immune response.

Immune Response Step 7: Helper B Cell StimulationCell-Mediated Response Antibody-Mediated Response

Antigen-Presenting


Cell

T Cell # 2,888,124





HE

LP

ER

T C

ell # 2,888,124




HELPER T CELL #2,888,124 binds to the antigen-presenting B cell (#146,883)

since this B cell displays the same antigen-MHC complex. This binding stimulates Helper T Cell to secrete

Cytokines. Cytokines stimulate B cells to rapidly reproduce. Since B cell

146,883 is locked on, it will be the one to rapidly reproduce. Thus, the B Cell

that produces the antibody that binds to the current infectious agent is the one

that proliferates.

Immune Response Step 8: Helper B Cell ProliferationCell-Mediated Response Antibody-Mediated Response

Antigen-Presenting


Cell

T Cell # 2,888,124





HE

LP

ER

T C

ell # 2,888,124




Many copies of B Cell 146,883 are produced.

B Cell # 146,883

B Cell # 146,883B Cell # 146,883

B Cell # 146,883

B Cell # 146,883

B Cell # 146,883

B Cell # 146,883

B Cell # 146,883B Cell # 146,883

Immune Response Step 9: Helper B Cell DifferentiationCell-Mediated Response Antibody-Mediated Response

Antigen-PresentingCell

HE

LP

ER

T C

ell # 2,888,124

Plasma B Cells produce and secrete large quantities of antibodies. This helps to fight the current infection.

Memory B Cell # 146,883

Plasma B Cell#146,883











Memory B Cells are fairly inactive. They reproduce at a steady rate and will be present if the body is ever re-infected

with the same pathogen.

Immune Response Step 10: Immunity

Memory B Cell # 146,883Memory B Cell

# 146,883





If the body is ever again infected with the same pathogen, then the particular Memory T Cells and Memory B Cells that specifically recognize and bind this pathogen are already present. So steps 1-5 and 7-8 won’t have to happen. This makes for a faster immune response upon

re-infection (so you don’t feel like you’re sick).


2,888,124


2,888,124MEMORY T Cell #

2,888,124





Human Immunodeficiency VirusCell-Mediated Response Antibody-Mediated Response

Antigen-Presenting


Cell

T Cell # 2,888,124





HE

LP

ER

T C

ell # 2,888,124




HIV infects Helper T Cells. When HIV infects a person’s body, that stimulates an

immune response. This causes an increase in Helper T Cells. But this increase in

Helper T Cells is an increase in hosts as far as HIV is concerned.

HIV Multiplication

T Cell # 2,888,124

1. HIV attaches to the T Cell Receptor

T Cell # 2,888,124

2. HIV penetrates into host cell

T Cell # 2,888,124

3. HIV’s RNA genome is liberated.

T Cell # 2,888,124

4. cDNA of the HIV genome is made by the enzyme Reverse Transcriptase

T Cell # 2,888,124

5. Viral proteins are made and must be cut apart by Protease Enzymes to be activated.

T Cell # 2,888,124

6. Many new viral particles are produced. Some are mutants.

4a. HIV cDNA can insert into host chromosome

Difficulties with HIV Treatment/Vaccines

T Cell # 2,888,124

4. cDNA of the HIV genome is made by the enzyme Reverse Transcriptase

T Cell # 2,888,124

6. Many new viral particles are produced. Some are mutants.

Reverse transcriptase has a very high mutation rate. Drug-resistant and vaccine-resistant strains develop rapidly.

Random mutations occur. Among these mutants a few may be resistant to an anti-HIV drug. When that drug is used, non-resistant strains will be killed off and that will leave the drug-resistant strain as the survivor.

Highly Active Antiretroviral Drug Therapy (HAART)

One or two different nucleoside analogs that inhibit the action of Reverse Transcriptase

AND

One or two different protease inhibitors that inhibit the action of retroviral protease enzyme.

Pros: Highly effective. Unlikely that a cell will incur enough random mutations that make it resistant to all of the drugs all at once.

Cons: Expensive. Difficult dosage regimen that many people fail to maintain (missed doses increase risk of drug-resistant HIV strains). Some have side effects.

New Promising Treatment

T Cell Mutant

A few rare mutant people appear to have T Cell Receptors that HIV cannot attach to.

Bone marrow from mutant person was transplanted into an HIV-infected person. After two years, the bone marrow recipient appears to be HIV-free.

New Promising Treatment: Next Step

T Cell Mutant

A few rare mutant people appear to have T Cell Receptors that HIV cannot attach to.

Transfuse genetically-altered bone marrow stem cells back into the bones of the HIV-infected patient. Should be a “permanent” treatment with little risk of immunological rejection since they are the person’s own cells.

Isolate gene for mutant T Cell Receptor.

Introduce mutant T Cell Receptor gene into bone marrow of HIV-infected people (must also remove the native T Cell Receptor gene).

Documents

HIV/AIDS HIV/AIDS Rate per 100,000 people Plan for Tonight Unit 6 and 7 Work Immune Response HIV’s Interaction with the Immune System Difficulties with