Transcript The Body`s Response to HIV

The Body’s Response
to HIV
Topic 6.5
Specification- topic 6
 11 Explain how bacterial and viral infectious
diseases have a sequence of symptoms that may
result in death, including the diseases caused by
Mycobacterium tuberculosis (TB) and Human
Immunodeficiency Virus (HIV).
Incidence of HIV
Distribution of HIV and AIDS
 Which area has the highest incidence of HIV?
 Sub-Saharan Africa
 New infections reached a peak in 1999.Give reasons for this
reduction.
 Education about HIV prevention
 Access to condoms
 Access to medication
AIDS- what is it?
 What does AIDS stand for?
 Acquired immune deficiency syndrome
 What is a syndrome?
 A syndrome is a number of different symptoms, all with the same
cause
 What exactly is AIDS?
 The disease, which results from being infected with the virus:
basically the opportunistic diseases which the infected person
suffers from as the immune system becomes weaker
 What does HIV stand for? What is it?
 Human immunodeficiency virus. It is the pathogen causing AIDS.
HIV
HIV structure
 HIV is a retrovirus. What does this mean?
 An enveloped virus with RNA inside
 What’s the other name for the protein coat?
 Capsid
 What are the viral proteins inside the capsid?
 Reverse transcriptase, protease and integrase
 Describe the genetic material.
 Two identical copies of RNA
 Where does the envelope come from?
 Host cell, taken as virus leaves the host after it has been
replicated
HIV Life cycle
http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter24/animation__hiv_replication.html
HIV attaches to CD4 protein
 CD4 proteins are found on T helper cells
 The normal function of CD4 is to bind to the APC
 Then initiate an immune response
HIV Lifecycle
How does HIV get inside T-helper cells and
macrophages?
 GP 120 on HIV binds with a CD4 receptor
 the viral envelope fuses with the cell membrane
 The capsid protein uncoats - releasing the RNA
and viral enzymes into the cytoplasm
 Reverse transcriptase makes dsDNA from the viral
RNA
HIV Lifecycle
 Integrase inserts the dsDNA copy into the host DNA
 Host cell transcribes then translates the viral genes
 Viruses are assembled in the host cytoplasm
 The viruses bud off the host cell
6.5 The body’s response to
HIV and AIDS
 How does the increase in the number of viruses affect
the number of T-helper cells?
 They decrease because the viruses destroy the Thelper cells and infected T-helper cells are killed by
T-killer cells.
 How will this affect the specific immune system?
 Decrease in T-helper cells leads to B cells and T-killer
cells not being activated. Therefore fewer infected
cells are destroyed and less antibodies produced.
 Weakened immune system
The effect of infection
 T helper cell numbers decrease- Why? Give TWO reasons
 Some are killed by the virus during budding
 Some are killed by T killer cells because the infected cells present
the antigens on their surface- APCs
 What are the effects?Give at least FIVE effects.
 Fewer cytokines are produced
 Fewer B cells are activated
 Fewer antibodies are produced
 Fewer T killer cells are activated (activated by cytokines)
 Macrophage activity is reduced (also can be infected, they have
CD4 receptors)
The disease
 AIDS does not follow infection immediately
 The speed of the progression depends on many
factors like health, genetics, immune system
response, access to medication, and nutrition.
HIV develops into AIDS
The Acute Phase
 HIV antibodies appear after several weeks- these
are tested for to see if HIV positive. How are they
produced?
 Possible symptoms: fever, headache, swollen
lymph nodes, no symptoms
 Virus replicated and T cell number decreases
 T killer cells reduce viral replication but don’t
destroy the virus completely.
The chronic/latent phase
 Can last many years, especially with drug treatment:
Latency: a delay between infection and symtoms
 May be no symptoms
 What may be happening in the infected cells?
 DNA produced by reverse transcription
 DNA incorperated into host cell DNA
 Production of virus particles by protein synthesis
 Lysis of cells not happening on a large scale yet
 There might be a slight increase in number and length of
infections.
 Dormant diseases may reactivate, like TB
AIDS
 When the viral load increases and T cell number
decreases below a certain number, the person is
suffering from AIDS
 Normal T cell level: over 500 per mm3
 Under 200 per mm3: weakened immune system
 Opportunitstic infections may occur and may be
fatal eg. TB, pneumonia, flu
 Kaposi’s sarcoma, weight loss, dementia
AIDS
AIDS, acquired immune deficiency syndrome, is caused by infection with the human immunodeficiency virus,
HIV.
HIV infection occurs when the body fluid (blood, vaginal secretions and semen, but not saliva
or urine) of an infected person is transferred directly into the body of an uninfected person.
This can occur
through
unprotected sex.
This can occur when
sharing needles,
whether used illegally
or legally.
This can occur with
direct blood-to-blood
transfer through cuts
and grazes.
This can occur from
mother to child across
the placenta or in
breast milk.
HIV invades T helper cells and macrophages. The HIV gp120 molecules attach to their CD4 receptors allowing
the virus envelope to fuse with the host cell surface membrane, enabling the viral RNA to enter the cell.
Once inside, the virus uses reverse transcriptase to produce DNA from its RNA. The DNA is integrated into the
host’s DNA by another HIV enzyme, integrase. The viral DNA is transcribed and translated to produce new
viral proteins and assemble new viruses.
The new virus particles bud out of the T cell, taking some of the surface membrane with them as their
envelope, and killing the cell as they leave.
When a person is first infected by HIV, there is an acute phase of infection. There is rapid replication of the
virus and loss of T helper cells.
As the number of viruses increases, the number of host T helper cells decreases. Macrophages, B cells and
T killer cells are not activated and the infected person’s immune system becomes deficient.
The infected person may experience symptoms such as fever, sweats, headache, sore throat and swollen
lymph nodes, or they may have no symptoms.
The virus continues to reproduce rapidly, but the numbers are kept in check by the immune system.
T killer cells recognise the infected T helper cells and destroy them.
There may be no symptoms during this chronic phase, but there can be an increasing tendency to suffer
various infections which are slow to go away. Dormant diseases such as TB and shingles can reactivate.
The chronic phase can last for years, especially if combined with drug treatment.
An increased number of viruses in circulation (viral load) and a declining number of T helper cells indicate
the onset of AIDS, the disease phase.
The weakened immune system makes the patient more prone to opportunistic infections such as
pneumonia and TB. There may also be significant weight loss, dementia (memory and intellect loss) and the
cancer Kaposi’s sarcoma. AIDS is usually fatal.
DNA review
Structure
1.
Polynucleotide
2.
Nucleotide: phosphate group, deoxyribose sugar, nitrogenous base
3.
A = T G=C
4.
Bonds between the complementary bases in the two strands : hydrogen
5.
Bonds between the phosphate group of one nucleotide and the deoxyribose of the neighbouring
nucleotides in the same strand: Phosphodiester
6.
Double stranded twisted into a helix
7.
Gene: a length of DNA containing all the bases needed to code for one polypeptide chain.
Replication
1.
Semi-conservative
2.
DNA replication: Strands unwinds and unzips, new nucleotides line up with the complementary
bases on both strands and DNA polymerase forms phosphodiester bonds between the nucleotides
forming the polymer.
Compare RNA and DNA
1.
Differences between DNA and RNA: double/single stranded, type of sugar (deoxyribose/ribose),
thymine replaced by uracil
2.
Types of RNA in animal cells: mRNA, tRNA, rRNA
Protein synthesis
Protein Synthesis

http://www.wellcome.ac.uk/Education-resources/Education-andlearning/Resources/Animation/WTX057748.htm
 What is the definition of a gene?
 A section of DNA made up of nucleotides which
codes for one to several proteins. Sequences at
beginning and end start and stop transcription.
 How do you switch on a gene?
 Activator proteins bind to DNA promoter sites.
 Which enzyme makes the RNA strand?
 RNA polymerase
 Where does transcription take place?
 In the nucleus
Protein Synthesis
 Which nucleotide replaces thymidine when making an RNA strand?
 Uracil
 What is RNA splicing?
 Between transcription and translation, non-coding introns are removed
and the exons, sections that are to be expressed, are left to produce one
or more proteins.
 What process happens next?
 Translation
 Where does it happen?
 In the cytoplasm on the ribosomes/RER
 Give an example of a start and stop codon.
 Start: AUG Stop: UGA, UAA, UAC
Transcription- more detail
 http://www.wisc-online.com/objects/index_tj.asp?objID=AP1302– first 4 slides
 Where does it take place?
 What is produced?
 How is it produced? Make a list of key words and then describe
the process
 Anti-sense strand
 Template strand
 sense strand
 Coding strand
 Uracil.
 Base pairing rule
 Hydrogen bonds
 Free RNA nucleotides
 RNA polymerase
 Phosphodiester bonds
mRNA splicing
 mRNA can be modified, 1 gene can give rise to
several related proteins.
 Exons: expressed regions of DNA.
 Introns: found between expressed regions, noncoding regions
 Use introns for STRs for DNA fingerprinting
RNA Splicing
Translation- more detail
 Where

does it take place?
http://www.wisc-online.com/objects/index_tj.asp?objID=AP1302
 What
is produced?
 How is it produced? Make a list of key
words and then describe the process
 mRNA
 Specific amino acid
 Ribosome subunits
 Peptide bond
 Start codon
 Condensation
 Two tRNA molecules
 Ribosome moves along
the mRNA one codon at
a time
 Anticodon
 Complementary base
pairing
 Stop codon
 Q 2.21-2.25
Post-translational
modification
 What is post translation modification?
 additional groups are added to polypeptide chains
after translation.
 Give examples of groups:
 carbohydrates (glycoproteins)
 Lipids (lipoproteins)
 Haem groups (haemoglobin)
Nature of the genetic code
TUND:
 Triplet: 3 bases code for 1 amino acid
 Universal: the code is the same in all living
organisms
 Non-overlapping: the start or end of one triplet is
not involved in the previous or next.
 Degenerative: there is often more than one code
for an amino acid, often the first 2 letters are the
same.
EXTRA Transcription
 In the nucleus
 mRNA is produced from DNA code
 mRNA forms on the template strand also called
antisense strand
 mRNA is a copy of the other strand (except T
replaced by U)-known as the sense strand or
coding strand.
 http://www.wisc-online.com/objects/index_tj.asp?objID=AP1302 – first 4 slides