microbiology

1. What will you learn
today?

3. Outline
Immunodeficiency
Types of immunodeficiency
1. Primary
2. Secondary
AIDS HIV
• structure
• Infectivity
• Diagnostic methods
• HIV vaccines and their targets

4. Immune system
The immune system is a host defense system
comprising many biological structures and
processes within an organism that protects
against disease. It uses white blood cells and
special proteins to fight against foreign
proteins.

5. Immunodeficiency
The absence of a sufficient immune response is
called immunodeficiency.
or
A condition in which body is unable to produce
enough antibodies and specific immune
response against bacteria ,viruses ,often
resulting in infection or disease

6. Types of immunodeficiency
1. Congenital
2. Acquired
Congenital immunodeficiencies
The genetic inability of an organism to :
• Produce specific antibodies
• T cells
This is due to the individual genotype.
The absence of a number of inherited gene results in defective
immune system.
These are also called Primary immunodeficiency (PID) .

7. Primary immune deficiency
these inherited immune disorders resulting
from:
• genetic mutations, usually
• present at birth
• and diagnosed in childhood.
e.g DiGeorge syndrome is congenital ,do not
have thymus gland and lack cell mediated
immunity.

9. Disease Cells affected Immuniy
SCID T lymphocytes Humoral as well as
cellular
Bruton X linked
agammaglobuinemia
B-cells humoral
Digeorge
syndrome(thymic
hypoplasia
T cells Cell mediated
immunity
Wiskott Aldrich
syndrome
T cells eczema

10. Acquired immunodeficiency
• The inability obtained during the life of an individual to
• produce specific antibodies
• T cells.
. Secondary immunodeficiency (SID) – acquired
immunodeficiency
A result of disease
• environmental factors,
• such as HIV, malnutrition, or medical treatment (e.g.
chemotherapy)
• A variety of drugs,cancers,or infectious agents can result in
acquired immunodeficiency
• e.g AIDS

13. HIV (Human immunodeficiency virus)

14. Viral classification
Group: Group VI (ssRNA-RT)
Family: Retroviridae
Genus:Lentivirus
Species: Human immunodeficiency virus 1
Human immunodeficiency virus 2

15. Structure
• HIV ,of the genus Lentivirus , is retrovirus
• It has two identical strands of RNA,
• The enzyme reverse transcriptase
• An envelope of phospholipid.
• The envelope has glycoprotein spikes termed
gp120

16. Infectivity and pathogenicity of HIV
• There is strong association between HIV
infection and the immune system
• HIV is often spread by dendritic cells ,which
pick up the virus and carry it to lymphoid
organ.
• There it contacts cells of the immune
system,activate T cells and stimulate strong
immune response.

17. Incubation period
• The incubation period is HIV infection till
development of AIDS.
• It is from a few months to years or even more.
• 75% people infected wih HIV will develop AIDs at
the end.

18. Stages of infectiveness
Attachment
Fusion
Entry
Latent infection
Active infection
Release

19. Attachment
o The gp120 spike attaches to a receptor and to
a CCR5 or CXCR4 co-receptor on the cell.
o 65,000 of these receptors are found on CD4+ T
cells.
o monocytes and macrophages also carry CD4
molecules.

20. Fusion
The gp41 participates in fusion of the HIV with the cell.
Entry
 Following fusion the cell ,an entry pore is created.
 After entry,the viral envelope remains behind

 The HIV uncoats.
 Releasing the RNA core for directing synthesis of the new
viruses.
 RNA is transcribed into DNA by the enzyme reverse
transcriptase.

22. • Latent infection
• Viral DNA is integrated into cellular DNA and
forms a provirus .
• it remain in vacuoles witnin cell.
• it shelters it from immune system.

23. • Active infection
• The provirus is activated ,allowing it to control
the synthesis of new viruses which bud from
host cell
• Finally assembly takes place at the cell
membrane taking up the viral envelope
proteins as the virus buds from the cell.

26. • CLADES OF HIV
• Based on sequencing of the viral genome
,there are three HIV-1 groups
• 1. M(main)
• 2. O(outlier)
• 3.N(non M or O)

27. Stages of HIV infection
• The progress of HIV infection can be divided
into three clinical phases:
• Phase 1: acute stage, the first few weeks after
transmission
• Phase2:clinical latency, or chronic stage
• Phase 3:AIDS

28. Phase 1
• The number of viral RNA molecules per
milliliter of blood plasma may reach more
than 10 million in the first week.
• Billions of the CD4+ T cells may be infected
within couple of weeks .
• infection is asymptomatic or cause
lymphadenopathy

30. Phase 2
• The number of CD4+ T cells decline steadily
• HIV replications continues but at a relatively low
level,
• controlled by CD8+ T cells and occur in lymphatic
tissue.
• Serious disease symptoms become apparent ,e.g
persistent infection by the yeast candida albicans
in
• mouth,throat,vagina.fever and persistent
diarrhea

31. Phase 3
• Clinical AIDS emerges ,usually within 10 years of
infection.
• CD4+ T cell counts are below 350 cells/ ul -200 cells /ul.
• A person with HIV is considered to have progressed to
AIDS when:
1) The number of their CD4 cells falls below 200 cells per
cubic millimeter of blood (200 cells/mm3).
2) They develop one or more opportunistic infections
regardless of their CD4 count.

34. • If AIDS does develop, it means that the immune system is
weakened to the point where it can no longer fight off most
diseases and infections. That makes the person vulnerable to a wide
range of illnesses, including:
• • pneumonia
• • tuberculosis
• • oral thrush, a fungal infection in the mouth or throat
• • cytomegalovirus (CMV), a type of herpes virus
• • cryptococcal meningitis, a fungal infection in the brain
• • toxoplasmosis, a brain infection caused by a parasite
• • cryptosporidiosis, a
• • an infection caused by an intestinal parasite
• • cancer, including Kaposi’s sarcoma (KS) and lymphoma

36. HIV and AIDS:
• What’s the connection?
• To develop AIDS, a person has to have
contracted HIV. But having HIV doesn’t
necessarily mean that someone will develop
AIDS.

37. HIV transmission
HIV is transmitted through bodily fluids that include:
• blood
• breast milk
• semen
• vaginal and rectal fluids
• by sharing needles, syringes, and other items for
injection drug use
• by sharing tattoo equipment without sterilizing it
between uses
• during pregnancy, labor, or delivery from a woman
to her baby

39. HIV does NOT spread through
• skin-to-skin contact
• hugging, shaking hands, or kissing
• air or water
• sharing food or drinks, including drinking
fountains
• saliva, tears, or sweat (unless mixed with the
blood of a person with HIV)
• sharing a toilet, towels ,bedding
mosquitoes and other insect

40. Diagnostic methods
• ELISA:has the standard procedure for detecting
HIV antibodies.it is most sensitive
• QraQuick test:it uses oral swab of fluid.
• Western Blot test:it is confirmatory test for
positive sreening test.
• APTIMA assay detects the RNA of HIV-1 and
should be easy to read.it is used for early
detection of HIV.
• PVL Plasma viral load detects viral RNA use PCR
or nucleic acid hybridization

41. • Hiv vaccines
• The rapid mutation rate of HIV makes it difficult to develop
a vaccine that is effective against all mutational variants of
the virus that appear during the course of an infection.
• Virus has developed clades that differ from one geographic
area to another and required an appropriate vaccine.
• Cells infected by HIV ,are not susceptible to attack by CTLs.
• There is also proviruses and latent viruses that are
immunologically invisible and no vaccine is effective in this
case.
• There is no single case in which immune system has
eradicated the HIV virus.

42. Targets of anti HIV drugs
• Nucleoside reverse transcriptase inhibitor
• Non nucleoside reverse transcriptase inhibitor
• Protease inhibitors
• Fusion inhibitors
• Integrase inhibitors
• Maturation inhibitors

43. Nucleoside reverse transcriptase inhibitor
• These are analogs of nucleosides and cause
termination of the synthesis of viral DNA by
competitive inhibition .
Non nucleoside reverse transcriptase inhibitor
• These inhibit reverse transcription but are not analogs
of nucleic acid.
Protease inhibitors
• Virus makes use of certain protease enzyme that cut
proteins into pieces which reassembled into the coat of
new HIV particles .Drugs inhibit these enzymes

44. Fusion inhibitors
• For infection to occur ,virus attach to the cells CD4
receptors ,an interplay between the gp120 spike on the
virus and the coreceptors must occur ,and finally there
must be a fusion with the cell to allow viral entry into the
cell.
• Fusion inhibitor targets the gp41 region of viral envelope.
Integrase inhibitors
• Integrase is an enzyme that integrated cDNA and
chromosome to form the HIV provirus.Integrase inhibitors
inhibit this integration.
• .

45. Highly activated antiretroviral
therapy(HAART)
• This therapy consist of administering drug
combinations .
• one of the most common combination is two
nucleoside analog reverse transcriptase
inhibitors plus either a non nucleoside analog
inhibitor or protease inhibitor.
• patients are required to take 40 pills per day
on a complex schedule.