Transcript Immune Response: Initial Infection

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
Antigens (proteins on the
surfaces of pathogens that can
be recognized by antibodies)
Pathogens (disease-causing bacteria or
viruses or other organisms), for example
HIV, invade your body
Immune Response Step 1: Initial Recognition of Infection
Cell-Mediated Response
Antibody-Mediated Response
MHC Protein
Macrophage
MACROPHAGE are white blood cells that gobble
up foreign invaders.
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.
B Cell# 34,599
B Cell # 146,883
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.
Immune Response Step 2: Phagocytosis of Pathogen
Cell-Mediated Response
Antibody-Mediated Response
Macrophage
MACROPHAGE engulf (phagocytize) the pathogenic
invader. After this, the macrophage kills and breaks
down the pathogen into pieces.
B Cell # 146,883
The B CELL that has an antibody that binds
to antigen engulfs(phagocytizes) the antigenantibody complex. After this, the B cell kills and
breaks down the pathogen into pieces.
Immune Response Step 3: Antigen-Presenting Cells
Cell-Mediated Response
Antibody-Mediated Response
Antigen-Presenting
Cell
Antigen-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 AntigenPresenting Cell (or APC).
Immune Response Step 4: Helper T Cell-APC Interaction
Cell-Mediated Response
Antibody-Mediated Response
Antigen-Presenting
Cell
Antigen-Presenting
Cell
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
Cell-Mediated Response
Antibody-Mediated Response
Antigen-Presenting
Cell
Antigen-Presenting
Cell
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
Cell-Mediated Response
Antibody-Mediated Response
Antigen-Presenting
Cell
Antigen-Presenting
Cell
Huge numbers of T Cell # 2,888,124
are produced.
Immune Response Step 6: Helper T Cell Differentiation
Cell-Mediated Response
Antibody-Mediated Response
Antigen-Presenting
Cell
Antigen-Presenting
Cell
Cytotoxic T Cells kill body cells
infected by the pathogen.
Memory T Cells are fairly inactive. Helper T Cells interact with other white blood
They reproduce at a steady pace.
cells to propagate the immune response.
Immune Response Step 7: Helper B Cell Stimulation
Cell-Mediated Response
Antibody-Mediated Response
Antigen-Presenting
Cell
Antigen-Presenting
Cell
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 Proliferation
Cell-Mediated Response
Antibody-Mediated Response
Antigen-Presenting
Cell
Antigen-Presenting
Cell
B Cell # 146,883
B Cell # 146,883
B Cell # 146,883
B Cell # 146,883
B Cell # 146,883
B Cell # 146,883
B Cell # 146,883
B Cell # 146,883
B Cell # 146,883
Many copies of B Cell 146,883 are
produced.
Immune Response Step 9: Helper B Cell Differentiation
Cell-Mediated Response
Antibody-Mediated Response
Plasma B Cell
#146,883
Plasma B Cell
Plasma B Cell
Plasma B Cell
#146,883
#146,883
#146,883
Plasma B CellPlasma B Cell
#146,883
#146,883
Antigen-Presenting
Cell
Plasma B Cells produce and secrete
large quantities of antibodies. This
helps to fight the current infection.
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.
Memory B Cell
# 146,883
Memory B Cell
# 146,883
Memory
B Cell
Memory B Cell
# 146,883
Memory B Cell
Memory B Cell
# 146,883
# 146,883
# 146,883
Immune Response Step 10: Immunity
Memory B Cell
# 146,883
Memory B Cell
# 146,883
Memory
B Cell
Memory B Cell
# 146,883
Memory B Cell
Memory B Cell
# 146,883
# 146,883
# 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 reinfection (so you don’t feel like you’re sick).
Human Immunodeficiency Virus
Cell-Mediated Response
Antibody-Mediated Response
Antigen-Presenting
Cell
Antigen-Presenting
Cell
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
2. HIV penetrates into
host cell
1. HIV attaches to the
T Cell Receptor
6. Many new viral
particles are
produced. Some
are mutants.
4a. HIV cDNA can
insert into host
chromosome
5. Viral proteins are made and
must be cut apart by Protease
Enzymes to be activated.
3. HIV’s RNA genome
is liberated.
4. cDNA of the HIV genome
is made by the enzyme
Reverse Transcriptase
Difficulties with HIV Treatment/Vaccines
6. Many new viral
particles are
produced. Some
are mutants.
4. cDNA of the HIV genome
is made by the enzyme
Reverse Transcriptase
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
Bone marrow from mutant
person was transplanted
into an HIV-infected
person. After two years,
the bone marrow recipient
appears to be HIV-free.
A few rare mutant people
appear to have T Cell
Receptors that HIV cannot
attach to.
New Promising Treatment: Next Step
Isolate gene for mutant T
Cell Receptor.
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.
Introduce mutant T Cell
Receptor gene into bone
marrow of HIV-infected
people (must also remove
the native T Cell Receptor
gene).