This document summarizes secondary immunodeficiency states and acquired immunodeficiency syndrome (AIDS). It describes AIDS as being caused by the human immunodeficiency virus (HIV) which leads to immunosuppression and opportunistic infections. The virus is transmitted through unprotected sex, blood transfusions, from mother to child, and sharing of infected needles. HIV infects immune cells like CD4+ T cells and macrophages. This results in loss of CD4+ T cells and ultimately immune system failure putting individuals at risk for infections and cancers.

1. Secondary[Acquired]
Immunodeficiency states

2.  may arise as complications of :-
infections ; malnutrition ; aging ; or side effects of
immunosuppression, irradiation , chemotherapy.
Acquired Immunodeficiency Syndrome (AIDS) :
 caused by retrovirus Human Immunodeficiency Virus
(HIV).
 characterized by profound immunosuppression that
leads to opportunistic infections, secondary neoplasms,
and neurologic manifestations.

3.  The virus is transmited via:
1. Unprotected sex with someone who is infected.
2. Transfusion of contaminated blood
or blood products ; skin grafts or organ transplants
taken from someone who is infected.
3. From a mother who is infected to her baby , this
can occur during pregnancy, at birth , and through
breast feeding.
4. Sharing unsterilized injection equipment that has
previously been used by someone who is infected
as in drug addicts.

4. Properties of HIV:
 HIV is retrovirus ( RNA containing virus ) that can
convert its genetic material into DNA by means of
enzyme reverse transcriptase which enables it
to become integrated into DNA of its host cells.
 Two genetically different but related forms of HIV,
called HIV-1 and HIV-2.
Structure of HIV:
 HIV virion is spherical and contains a cone-shaped core
surrounded by a lipid envelope derived from the host
cell membrane .

5.  The virus core contains:
(1) major capsid protein ( p24 ).
(2) nucleocapsid protein ( p7/p9 ).
(3) two copies of genomic RNA.
(4) three viral enzymes (protease , reverse transcriptase ,
and integrase).

6.  p24 is the most readily detected viral antigen and,
is the target for antibodies that are used for
diagnosis of HIV infection.
 The viral core is surrounded by a matrix protein
called p17, which lies underneath the virion
envelope.
 Studding the viral envelope are two viral
glycoproteins ( gp120 and gp41 ) which are critical
for HIV infection of cells.

7. HIV- structure

8. Pathogenesis of HIV Infection and AIDS:
there are two major targets of HIV infection:
immune system and central nervous system.
Immune system:-
 This results from infection and severe loss of
CD4+ T cells as well as impairment in function
of surviving CD4+ T cells.
 macrophages and dendritic cells are also targets of
HIV infection.
 HIV envelope contains two glycoproteins, surface
( gp120 ) that is non-covalently attached to
transmembrane protein ( gp41 ).

9.  The initial step in infection is binding of gp120.
 This binding leads to a conformational change that
results in formation of a new recognition site on
gp120 for coreceptors CCR5 ( on macrophage ) or
CXCR4 (on CD4+ T cells ).
 The next step involves conformational changes in
gp41 , these changes result in insertion of a fusion
peptide at tip of gp41 into cell membrane of target
cells .
 After fusion, the virus core containing HIV genome
enters cytoplasm of cell.

10.  Once internalized, the RNA genome of virus undergoes
reverse transcription, leading to formation of cDNA
(proviral DNA) .
 In quiescent T cells, HIV cDNA may remain in cytoplasm.
 In dividing T cells, the cDNA , enters the nucleus and
is then integrated into host genome.
 After this integration, the provirus may remain locked
into chromosome for months or years, and hence the
infection becomes latent.
 Alternatively, proviral DNA may be transcribed, with
formation of complete viral particles that bud from cell
membrane.

11.  Such productive infection, when associated with
extensive viral budding, leads to cell death.
 Early in course of HIV infection, the immune system
can replace the dying T cells.
 Later in course of disease, renewal of CD4+ T cells
cannot keep up with loss of these cells.
 Despite the fact that macrophages allow viral
replication, they are quite resistant to cytopathic
effects of HIV, in contrast to CD4+ T cells.
Thus, macrophages may be reservoirs of infection.

12.  two types of dendritic cells are also targets of HIV
infection: mucosal and follicular dendritic cells.
 patients with AIDS also display profound abnormalities
of B-cell function
Central Nervous System:
 It is a major target of HIV infection.
 Macrophages and microglia (cells in central nervous
system that belong to monocyte and macrophage
lineage) are predominant cell types in brain that are
infected with HIV.
 HIV is carried into brain by infected monocytes.

13. Natural History of HIV Infection:
Three phases recognized:-
(1) Early , acute retroviral syndrome.
(2) Middle, chronic phase.
(3) Final , full-blown AIDS.
 Early , acute retroviral syndrome ( phase 1):
 high level of virus production, viremia, and
widespread seeding of lymphoid tissues.
 however, is readily controlled by development
of antiviral immune response.
 Clinically: nonspecific symptoms, including sore throat,
myalgia , fever, rash, weight loss, and fatigue,
resembling a flulike syndrome.

14. Middle chronic phase ( phase 2 ):
 represents a stage of relative containment of virus,
associated with period of clinical latency.
 The immune system is largely intact, but there is
continuous HIV replication, predominantly in lymphoid
tissues, which may last for several years.
 Patients are either asymptomatic or develop
persistent generalized lymphadenopathy.

15.  Final phase ( phase 3 ), full-blown AIDS :
 Its progression to AIDS, characterized by a breakdown
of host defense, a dramatic increase in plasma virus,
and clinical disease.
 Typically the patient presents with long-lasting fever
(>1 month), fatigue, weight loss, and diarrhea.
 After a variable period: serious opportunistic infections,
secondary neoplasms, or clinical neurologic disease
(grouped under the AIDS indicator diseases ), and
the patient is said to have developed AIDS.

16. Clinical Features of AIDS:
 Opportunistic infections:
 account for the majority of deaths in patients with
AIDS.
 Approximately 15% to 30% of HIV-infected people
develop pneumonia caused by opportunistic fungus
P. carinii .The risk of developing this infection is
extremely high in individuals with fewer than
200 CD4+ cells/µL.
 other opportunistic infections are caused by Candida,
cytomegalovirus, atypical and typical mycobacteria,
Cryptococcus neoformans, Toxoplasma gondii, and
herpes simplex virus.

17.  Neoplasms :
 Kaposi sarcoma (KS) ; non-Hodgkin B-cell lymphoma ;
cervical cancer in women ; and anal cancer in men.
 It is estimated that 25% to 40% of HIV-infected
individuals will eventually develop malignancy.
 KS is composed of mesenchymal (spindle) cells that
form blood vessels; the proliferation of these cells is
driven by a variety of cytokines and growth factors that
are derived from tumor cells , and from HIV-infected
T cells. it is strongly linked to infection of tumor cells
by KS-associated herpesvirus (KSHV).

18.  Central nervous system:
 90%of patients demonstrate some form of neurologic
involvement at autopsy ; and 40% to 60% have
clinically manifest neurologic dysfunction.
 These include : self-limited meningoencephalitis ;
aseptic meningitis ; vacuolar myelopathy ;
peripheral neuropathies ; and most commonly
a progressive encephalopathy designated clinically
as (AIDS-dementia complex ).

19. Morphology:
 Biopsy specimens from enlarged lymph nodes in
early stages of HIV infection reveal marked follicular
hyperplasia.
 With disease progression, B-cell proliferation subsides
and gives rise to severe follicular involution.
The follicles are depleted of cells.
The germinal centers may become hyalinized.
These lymph nodes are atrophic and small and
may harbor numerous opportunistic pathogens.
 Lymphoid depletion is not confined to lymph nodes;
in later stages of AIDS, the spleen and thymus also
appear to be "wastelands."

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