AIDS &

Immunology

AIMS, JAIPUR

2.1. What is aids?

AIDS, the acquired immuno deficiency syndrome is a fatal illness caused by a
retrovirus known as the human immuno-deficiency virus (HIV) Which breaks down
the human immune system. The term aids refers only to the last stage of the HIV
infection. It can be called our modern pandemic.
In addition to CD4, the human immunodeficiency virus (HIV) requires a coreceptor
for entry target cells. The chemokine receptors CXCR4 and CCR5, members of the G
protein-coupled receptor super family, have been identified as the principal
coreceptors for T cell line-tropic and macrophage-tropic HIV-1 isolates, respectively.
The updated coreceptor repertoire includes numerous members, mostly chemokine
receptors and related orphans. These discoveries provide a new framework for
understanding critical features of the basic biology of HIV-1, including the selective
tropism of individual viral variants for different CD4 + target cells and the membrane
fusion mechanism governing virus entry. The coreceptors also provde molecular
perspectives on central puzzles of HIV-1 disease, including the selective transmission
of macrophage-tropic variants. The appearance of T cell line-tropic variants in many
infected persons during progression to AIDS, and deffering susceptibilities of
individuals to infection and disease progression. Genetic findings have yelded major
insights into the in vivo roles of individual coreceptors and their ligands; of particular
importance is the form, confers strong resistance to HIV-1 infection. Beyond
providing new perspectives on fundamental aspects of HIV-1 transmission and
pathogenesis, the coreceptors suggest new avenues for developing novel therapeutic
and preventative strategies to combat the AIDS epidemic immune ResponseOverview.

2.2. Innate immune response

The immune system protects the body from invading disease-causing organisms or
pathogens. Pathogens and other non-self molecules are antigens foreign molecules
recognized by the immune system, stimulating an immune response. The majority of
infections by pathogens occurs in mucous membranes of our body.

AIMS, JAIPUR

Innate defenses act immediately or within hours of a pathogens appearance in the

body innate defenses are nonspecific they target any pathogen. Innate defenses
include.

Skin, which excludes most pathogens from entering the body.

Cilia in mucous membranes, which sweep out airborne pathogens and dust.

Tears, nasal secretions and saliva, which contain, bacteria-destroying enzymes.

Phagocytic cells, called neutrophils, macrophages, and dendritic cells

Phagocytes (phage- = eating, cyte = cell) migrate to affected areas and engulf
pathogens. Neutrophils and macrophages are phagocytic white blood cells. This
migration of white blood cells causes the redness and inflammation associated with
infection. Some cells of innate immunity are of special importance for regulating our
immune response. These cells called dendritic cells or Langerhans cells can move
through out our body, and are particularly rich in our skin and mucus membranes of
our body that are exposed to foreign material, including our digestive systems,
airways, and sexual apparatuses. When dendritic cells encounter foreign material, they
also are phagocytic (eat the material), but have special receptors that allow them to
distinguish harmless and pathogenic (disease causing) organisms. However, these
cells carry fragments of pathogen to lymph nodes where they either prevent or
stimulate an adaptive immune response. The decision about which response to cause
depends on the foreign material (dangerous pathogens cause a dramatic response) and
whether cells of your own body are sending out danger or distress signals. The
significance of the dendritic that you ingest or harmless materials from environment,
or they can tell the rest of your immune system to make an adaptive immune
response.
Microscopic movie of macrophages ingesting a yeast( 567 kb)

2.3 Adaptive immune response

AIMS, JAIPUR

If innate immune cells (dendritic cells) decide that the material is dangerous (part of a
virus or bacteria), then they stimulate a specialized group of white blood cells causes
CD4+ helper T cells to become activated. CD4+ refers to a surface protein on this class
of T cells. Helper T cells can stimulate another group of white blood cells called B
cells to produce antibodies that bind that specific antigen and

immobilize it

preventing it from causing infection. Antibodies are specific for only one antigen. B
cells must interact with Helper T cells, other specialized white blood cells, to initiate
antibody production. An important concept is that once activated, memory cells are
produced that insure that a more rapid and stronger immune response can be made
upon re-exposure to the same pathogen. This is why vaccinations provide lasting
protection against disease. Memory helper T cells are labeled Preventing it CD4 +
CCR5+, to note that the chemokine receptor (CCR5) is present on the surface of the
helper T Cell. These cells migrate and reside in the mucus can enter and infect cells.
The surface of infected cells changes, and this change is recognized by T cells.
Cytotoxic T cells kill infected cells, preventing these cells from producing more
pathogen. Cytotoxic T cells must interact with Helper T cells to regulate destruction
of infected cells. Remember that eh dendritic cells must activate CD4 + helper T cells
before our bodies can produce B cells secreting pathogen specific antibodies or
cytotoxic T cells to destroy infected cells.)

AIMS, JAIPUR

Human immunodeficiency Virus (HIV) specifically attacks Helper T cells. Without an

adequate supply of Helper T cells, the immune system cannot signal B cells to
produce antibodies or Cytotoxic T cells to kill infected cells. When HIV has critically
depleted the Helper T cell population, the body can no longer launch a specific
immune response and becomes susceptible to many opportunistic infections. This
immunodeficiency is described in the name acquired immunodeficiency syndrome, or
AIDS. Recent work shows that the CD4 and CCR5 membrane proteins are targets for
HIV infection. Thus, our memory cells are rapidly infected and destroyed in the
mucus membranes of our tissues. We have only recently recognized that the memory
cell destruction occurs in the first several days after HIV infection, suggesting that
therapies should begin as soon as the infection is recognized.

2.4. Immunology and HIV

Immune systems response to HIV
HIV is stopped by innate defenses. HIV cannot penetrate unbroken skin. HIV is
transmitted through direct exchange of body fluids. Sexual intercourse is the most
common mode of transmission. Blood contact, such as through sharing needles for
intravenous injection or blood transfusion can also transmit HIV. Infected mothers can
pass HIV to their infants during pregnancy, birth and breastfeeding.
Additional information about HIV transmission
HIV transmitted through sexual activity enters the bloodstream via mucous
membranes lining the vagina, rectum and mouth. Macrophages and dendritic cells on
the surfaces of mucous membranes bind virus and shuttle it into the lymph nodes,
which contain high concentrations of Helper T cells (CD4+T cells)

AIMS, JAIPUR

Once HIV has entered the body, the immune system initiates anti-HIV antibody and
cytotoxic T cell production. However, it can take one to six months for an individual
exposed to HIV to produce measurable quantities of antibody. The immune response
is weakened as memory T cells (CD4+ CCR5+) are destroyed. This figure shows a
scanning EM picture of a dendritic cell interacting with helper T cells. This process
occurs in lymph nodes and regulates immune responses.

2.5. HIV mediated disease

HIV enters the body and binds to dendritic cells (orange cells with projections) which
carry the virus to CD4+ T cells in lymphoid tissue establishing the infection. Virus
replication accelerated production massive viremia and wide dissemination of virus
throughout the bodys lymphoid tissues. An immune response against virus causes
some projection but a chromic persistent infection is established.
The production of cytokines and cell divisions that regulate the immune response for
protection also cause HIV replication. There is a rapid turnover of CD4+ T

AIMS, JAIPUR

AIMS, JAIPUR

2.6. Infected cells produce massive amounts of virus

New copies of HIV bud from the surface of an infected Helper T cell
Enlarged View

2.7. Cellular immune responses of HIV

Cytotoxic lymphocyte production follows the rise of HIV in the blood.

HIV specific CD4+ T cells may be especially susceptible to attach and

destruction by HIV. HIV binds to CD-SIGN, a glycoporotein expressed on
dendritic cells. Migration of HIV bearing activated dendritic cells to helper T
cell areas of lymph nodes may specifically infect helper T cells specific for
HIV peptides.

Reductions in HIV specific helper T cells numbers may lead to decreased

activation and survival of cytotoxic CD8 T cells.

AIMS, JAIPUR

Mode of
Transmission

AIMS, JAIPUR

Mode of Transmission:
Basic modes of transmission area) Sexual transmission Any vaginal, oral or anal sex can spread AIDS. Every single act of unprotected
intercourse with an HIV infected person exposes the uninfected partner to the risk of
infection. The size of risk is affected by a no. of factors, including the presence of
STD, the sex & age of the uninfected, the type of sexual act, the stage of illness of the
infected partner & the virulence of the HIV strain involved. Women are more
vulnerable to HIV infection because a larger surface is exposed, & semen contains
higher concentration of HIV than vaginal or cervical fluids.
b) Blood contactIt is transmitted by contaminated by transfusion of whole blood cells, platelets &
factors VII & IX derived from human plasma. Contaminated blood is highly infected
when introduced in large qty. directly in the blood stream. It can be spread by
contaminated needle, syringe or any skin piercing instruments.
c) Maternal-fetal transmission: mother to child transmission It may pass from an infected mother to her fetus, through the placenta or to her infant
during delivery or by breast feeding.
Incubation period Not certain few months to 6yr

AIMS, JAIPUR

10

Epidemiological
Factors

AIMS, JAIPUR

11

4. Epidemiologic features:
4.1. Agent factor
4.1.1. agent
Firstly it was called (the virus) lymphadenopathy - associated virus (LAV).
Taxonomy gave it a new name: human immuno-deficiency virus (HIV)
Diameter-1/10,000th of a millimeter. It is a protein capsule containing 2 short strands
of genetic material (RNA) & enzymes the virus replicates in actively dividing T4
lymphocytes & can remaining lymphoid cells in a latent state that can be activated.
The virus has the unique ability to destroy human T4 helper T4 cells, a subset of the
human T-lymphocytes.
It is able to spread through the body it can pass through the BBB & can then destroy
some brain cells (cause of some neurological & psychomotor abnormalities). HIV
mutates rapidly new strains are continually developing.
There are two types of HIV: HIV 1(most common) & HIV2 (more recently
recognized in West Africa.
The virus is easily killed by heat & inactivated by ether, acetone, ethanol (20%) &
beta propiolactone but resistant to ionizing radiation & UV light.
4.1.2. Reservoir of infection
Once a person is infected, it remains in the body life long.
4.1.3. Source of infection
The virus has been found in greatest concentration in blood, semen, & CSF.
4.2. HOST FACTOR:
4.2.1. ageMostly in sexually active persons (20 to 49 yrs.).
4.2.2. sexAIMS, JAIPUR

12

Mostly in homosexual & bisexual men & in multiple sexual partners, anal intercourse
& male homosexuality. Higher rate of HIV infections is found in prostitutes.

4.2.3. High risk group

Male homosexuals & bisexuals, heterosexual partners (including prostitute) IV drug
abusers, transfusion) recipients of blood & blood products hemophiliacs & clients of
STD.
4.3. ImmunologyOwing to HIV infection a gradual depletion in a specialized group of white blood
cells (Lymphocytes) called T-helper or T4 cells is occur.
(T4 cells-CD4+ lymphocytes or CD4 cells.) these cells play a key roll in regulating the
immune system.
HIUV selectively infects T helper cells apart from several other cells in immune
system such as B-cells microphages & nerve cells. When the virus reproduces, the
infected T-helper cells are destroyed, so AIDS patients tent to have low overall WBC
count. Where as healthy individuals have twice as many helper cells or suppressor
cells, in the AIDS patients the ration is reversed. It may be an indicator of reduced
cellular immunity. One of the most striking features of aids patient is PROFOUND
LYMPHOPENIA, with a total lymphocyte count often below 500cmm. It is the
alternation in T cell function i.e. responsible for the development of NEOPLASM, the
development of opportunistic infection, or the inability to mount a delayed type
hypersensitivity response. The lack of an obvious immunological response by the host
to the virus in one of the problems confronting scientists. That is, those with
antibodies to HIV usually have too few HIV antibodies, and these antibodies are also
ineffective against the virus.

AIMS, JAIPUR

13

Diagnosis of AIDS

AIMS, JAIPUR

14

6. DUAGBISUS IF AIDS:
Hiv testing tells you if you are infected with the Human Immunodeficiency Virus
(HIV) which causes AIDS. These tests look fir antibodies to HIV. Antibodies are
proteins produced by the immune system to flight a specific germ.
Test

Normal Range

Glucose

65-125

6.1. Clinical
6.1.1. WHO case definition for AIDS surveillance
Major signs. Wt. loss>= 10% of body wt.
. Chronic diarrhea for more than 1 month
. prolonged fever for more than 1 month (intermittent or constant)
Minor signs-

. Persistent cough for more than 1 month

. generalized pruritic dermatitis
. history of herpes zoster
. Oropharyngeal candiasis

AIMS, JAIPUR

15

. chronic progressive or disseminated herpes simplex infection

. generalized lymphodenopathy
. Cryptococcal meningitis, Kaposi sarcoma may be present.

6.1.2. WHO case definition for AIDS surveillance

. Wt. loss>= 10% of body wt.
. chronic diarrhea for more than 1 month
. prolonged fever for more than 1 month (intermittent or constant)
Kaposi sarcoma
Cryptococcal meningitis
. neurological impairment
. Candiasis of the esophagus
. Clinically diagnosed life threatening or recurrent episodes of pneumonia, with or
without etiological confirmation
. invasive cervical cancer

6.2. LABORATORY DIAGNOSIS

Types of HIV Antibody Tests:
6.2.1. Rapid HIV antibody tests: Where the standard HIV antibody testing
procedure requires up to two wee. There are several HIV antibody tests being used
today. All testing options are not available in all areas. Contact your local health
department for the tests available in you area.
6.2.2. Standard blood test or Screening Tests: It is was the first HIV antibody test
developed and made available, and is the most widely used.
Two different tests are commonly applied. At first a sensitivity test (ELISA) is used to
detect the HIV-antibodies, while a second confirmatory test (WESTERN BLOT) is
used to weed out any false positive result. It is based on detecting specific antibody to
viral core protein(p24) & envelop glycoprotein (gp41)
6.2.3. Virus isolation test: HIV can be recovered from cultured lympholcytes.

AIMS, JAIPUR

16

* several laboratory markers: e.g. absolute CD4 cell lymphocytes count. As the
count decreases, the risk of opportunistic infection increases. For a healthy person it is
more than 950 CD4 cells/ul. (USA makes CD cells count below 200 in an HIV
infected person a definition of AIDS)
6.2.4. Oral mucosal transudate test: This test, an alternative to the standard blood
test, uses a specially treated pad placed in a persons mouth and gently rubbed
between the lower cheek and gum. The pad collects an oral fluid called oral mucosal
transudate (OMT). This fluid contains HIV antibodies in an HIV infected person. This
test does not test for HIV in saliva.
6.2.5. Urine HIV antibody test: The urine HIV-1 testing method is a painless, nonevasive option for getting an HIV antibody test. This test uses the urine EIA (ELISA)
and urine Western Blot technks for result, the repid test gives results in 5-60 minutes.
For rapid blood testing the fingertip is cleaned with alcohol and pricked with a lancet
to get a small drop of blood. The blood is collected with a specimen loop and
transferred to a vial, where it is mixed with a developing solution, for oral testing oral
fluid specimens are obtained by swabbing gums with test devices and placed in a
solution. In as little as 20 minutes, the test device will indicate if HIV-1 antibodies aer
present in the solution.
Although the result of rapid screenings will be reported in point-of-care settings, as
with all screening tests for HIV, if the test gives a reactive test result, that result must
be confirmed with an additional specific test.
To determine which type of rapid testing is being performed, call the organization
directly.
6.3.6. Home Testing Kit: This do-it-yourself test kit uses the same technology as the
standard blood test. Individual blood samples are collected at home and mailed to a
laboratory. Test results are provided over the telephone. The serum home testing kit is
available at many drug stores. Currently there is only one FDA approved home
sample collection.
6.3.7. Viral load tests: Measure the amount of virus in the bloodstream. They can
generally predict how quickly HIV will damage the immune system. In effect, these
tests predict the loss of CD4+ cells: the higher the number, the greater the risk of
AIMS, JAIPUR

17

damage to your immune system. Using effective treatments can greatly reduce the
level of HIV and slow its rate of disease progression.
6.3.8. CD4+ cell count tests: measure the level of CD4+ cells, a certain type of white
blood cell. These tests can measure the decline of your immune health. However,
taking medicine can slow the decline of your immune health. In fact, many people
who start anti-HIV therapy experience a significant increase in their CD4+ cell
counts.
For long periods, often several years, the body copes effectively with HIV in many
people. The number and percentage of CD4+ cells fall, but slowly. During this period,
most people feel normal and suffer no obvious ill effects. Despite this, most
researchers believe that damage is still being done to the immune system. Many
scientists believe that early intervention during this time may have the greatest
impact, though others remain skeptical. They believe the possible side effects from
early treatment might outweigh its benefits.
Without treatment, the body slowly loses its ability to fight infections. Some
infections, like Pneumocystis jiroveci pneumonia (sometimes called PCP), become
likely when CD4+ cell counts fall below 300 or 200. Minor infections can occur at
counts above 300. other life-threatening infections become more likely when the
count falls below 100 to 50.

AIMS, JAIPUR

18

6.4. The Bottom Line

HIV testing generally looks for HIV antibodies in the blood, or saliva or urine. The
immune system produces these antibodies to fight HIV. It usually takes two tot three
months for them to show up. In rare cases, it can take longer than three months.
During this window period you may not test positive for HIV even if you are
infected. Normal HIV tests dont work for newborn children of HIV-infected mothers.
In many places, you can get tested anonymously for HIV. Once you test positive and
start to receive health care for HIV infection, your name may be reported to the
Department of Health. These record are kept confidential.
A positive test result does not mean that you have AIDS. If you test positive, you
should learn more about HIV and decide how to take care of you health.

AIMS, JAIPUR

19

Life Cycle of HIV

AIMS, JAIPUR

20

7.1 The HIV Life Cycle

7.1.1. Introduction
In order for viruses to reproduce, they must infect a cell. Viruses are not technically
alive: they are sort of like a brain with no body. In order to make new viruses, they
must hi-jack a cell, and use it to make new viruses. Just as you body is constantly
making new skin cells, or new blood cells, each cell often makes new proteins in
order to stay alive and to reproduce it. Viruses hide their own DNA in the DNA of the
cell, and then, when the cell tries to make proteins, it accidentally makes new viruses
as well. HIV mostly infects cells in the immune system.
7.1.2. Infection: Several different kinds of cells have proteins on their surface that are
called CD4 receptors. HIV searches for cells that have CD4 surface receptors, because
this particular protein enables the virus to bind to the cell. Although HIV infects a
variety of cells, its main target is the T4-lymphocyte (also called the T-helper cell),
a kind of white blood cell that has lots of CD4 receptors. The T4-cell is responsible
for warning your immune system that there are invaders in the system.
7.1.3. Replication: Once HIV binds to a cell, it hides HIV DNA inside the cells
DNA: this turns the cell into a sort of HIV factory.
7.1.4. Definitions:
There are a few things you need to know in order to understand HIV infection.
DNA: DNA is like the blueprint for building living cells.
Enzymes: Enzymes are like the workers of a cell. They build new proteins, transport
materials around the cell, and carry out other important cellular functions.
RNA: RNA is like the construction boss. Cells use RNA to tell enzymes how to build
a specific part of a cell. To make a new protein, enzymes will copy a specific part of

AIMS, JAIPUR

21

the DNA into a piece of RNA. This RNA is then used by other enzymes to build a
new protein or enzyme.
Proteins: The building blocks that are used to make living things.
Nucleus: A small package inside the cell where the genetic material is kept.

7.2. The HIV Life Cycle

Step 1: Binding
A virus consists of an outer envelope of protein, fat and sugar wrapped around a set of
genes (in the case of HIV, genetic information is carried as RNA instead of DNA) and
special enzymes.
HIV has proteins on its envelope that are strongly attracted to the CD4+ surface
receptor on the outside of the T4-cell. When HIV binds to a CD4+ surface receptor, it
activates other proteins on the cells surface, allowing the HIV envelope to fuse to the
outside of the cell.
Entry can be clocked by entry inhibitors
Step 2: Reverse Transcription
HIVs genes are carried in two strands of RNA, while the genetic material of human
cells is found in DNA. In order for the virus to infect the cell, a process called
reverse transcription makes a DNA copy of the viruss RNA.
After the binding process, the viral capsid (the inside of the virus which contains the
RNA and important enzymes) is released into the host cell. A viral enzyme called
reverse transcription makes a DNA copy of the RNA. This new DNA is called
proviral DNA
Reverse transcription can be blocked by : Necleoside Reverse Transcriptase
Inhabitors (NRTIs), and Non-Nucleoside Reverse

AIMS, JAIPUR

22

Step 3: Intergration
The HIV DNA Is then carried to the cells nucleus (center), where the cells DNA is
kept. Then, another viral enzyme called integrase hides the proviral DNA into the
cells DNA. Then, when the cell tries to make new proteins, it can accidentally make
new HIVs
Intergration can be blocked by integrase inhibitors, a new class of drugs that are in
the earliest stage of research .

Step 4: Transcription
Once HIVs genetic material is inside the cells nucleus, it directs the cell to produce
new HIV.
The strands of viral DNA in the nucleus separate, and special enzymes create a
complementary strand of genetic material called messenger RNA or mRNA
(instructions for making new HIV)
Transcription can be blocked by antisense antivirals or transcription inhibitors
(TIs), new classes of drugs that are in the earliest stage of research.
Entry can be blocked by entry inhibitors
Step 5: Translation
The mRNA carries instructions for making new viral proteins from the nucleus to a
kind of workshop in the cell. Each section of the mRNA corresponds to a protein
building block for making a part of HIV.
As each mRNA strand is processed, a corresponding string of proteins is made. This
process continues until the mRNA strand has been transformed or translated into
new viral proteins needed to make a new virus.

AIMS, JAIPUR

23

Seep 6: Viral Assembly and Maturation

The final step begins with the assembly of new virus. Long strings of proteins are cut
up by a viral enzyme called protease into smaller proteins. These proteins serve a
variety of functions; some become structural elements of new HIV, while others
becomes enzymes, such as reverse transcriptase.
Once the new viral particles are assembled, they bud off the host cell, and create a
new virus. The virus then enters the maturation stage, which involves the processing
of viral proteins. Maturation is the final step in the process and is required for the
virus to become infectious.
With viral assembly and maturation completed, the virus is able to infect new cells.
Each infected cell can produce l a lot of new viruses.
Viral assembly can be blocked by Protease Inhibitors (PIs). Maturation, a new
target of companies developing anti-HIV drugs, may be blocked using Maturation
Inhibitors picture of HIV budding from a T-cell, HIV, or human immuno-deficiency
virus, is the virus that causes AIDS, acquired immuno-deficiency syndrome.
Specifically, HIV is a virus that continually weakens the immune system so the body
can no longer combat infections like diarrhea, pneumonia, tumors, and other common
illnesses. A person can be HIV positive for years before the onset of AIDS, after
which the typical life expectancy is about 3 years. HIV is known as a retrovirus,
which is a virus made up of RNA. With a disease like HIV, the RNA strand is used as
a template for replication through DNA. HIV can only be transmitted through the
exchange of bodily fluids. In particular HIV is spread through sexual intercourse,
sharing of needles, trough the birth canal of an infected mother, or any other exchange
of blood that my occur accidentally. The only 100% safe prevention of HIV
transmission sexually is abstinence, so it is import to get tested prior to having
intimate relations. Today, bloods at hospitals used in transfusion are tested rigorously
in order to prevent the spread of HIV.

AIMS, JAIPUR

24

As long as one person is an HIV carrier, than the disease can potentially be transferred
to someone else. If you suspect you may have contracted HIV, see a doctor right
away. All people with HIV should see a doctor regularly for proper treatment.

AIMS, JAIPUR

25

Treatment

AIMS, JAIPUR

26

AIMS, JAIPUR

27