IMMUNODEFICIENCY

IMMUNE SYSTEM

Innate immunity Adaptive immunity

The defenses against pathogenic Respond specifically to substances
microorganism that are present in and organisms
host who has not been previously
exposed to the pathogen

Complement Immunoglobulins
Natural Killer Cells T Lymphocytes
Phagocytic cells
DEVELOPMENT OF CELLS OF THE IMMUNE SYSTEM
Bone Marrow

Lymphoblasts

Bone marrow maturation Thymus

Regulator Effector
T cells T cells
B lymphocytes

Memory Cells Plasma Cells Helper Supressor Cytotoxic

T Cells T Cells T Cells

Antibodies

HUMORAL RESPONSES CELLULAR RESPONSE

 DEFINITION
Immunodeficiency disease is defects in one
or more components of the immune system,
can lead to serious and often fatal disorders.

1. Congenital (primary) immunodeficiencies

2. Acquired (secondary) immunodeficiencies
 CLINICAL SIGNIFICANCY
• Increased susceptibility to infection
(bacteria, viruses, other microorganisms)
• Increased susceptibility to certain types of
cancer
• Associated with an increased incidence of
autoimmunity
 CONGENITAL ID
CID are genetic defects that result in an
increased susceptibility to infection in infancy
and childhood.

• Defects in innate immunity

• Severe combined immunodeficiencies
• Defects in B cell development and
activation
• Defects in T lymphocyte activation and
function
• Multisystem disorders with
immunodeficiencies
 CLINICAL FEATURE OF CID
• Complement deficiencies result in recurrent
bacterial infections.
• Defective production of superoxide anion
(ROS) causes failure to kill phagocytosed
microbes.
• Severe combined immunodeficiencies
(SCID) affect both humoral and cell-mediated
immunity (B and T cells deficiencies).
Clinical features of CID
Child with congenital ID
Defects in B and T cell maturation
Severe combined immunodeficiency (SCID)

B cell immunodeficiency

T cell immunodeficiency
Defects in lymphocyte activation
and effector function
Therapeutic approaches for CID
• Passive immunization
• Bone marrow transplantation
• Gene therapy
 ACQUIRED ID
Acquired ID are not genetic abnormalities,
but acquired during life.

• Complications from malnutrition,

neoplasms and infections.
• Complications from drug therapies (eg:
immunosuppressive or cytotoxic drugs)
• Surgical removal of spleen
• HIV infection
Patient with tuberculosis
Structure of HIV
• Envelop
– gp 120
– gp41
• Enzym
– Reverse transcriptase
– Integrase
– Protease

• INucleus
– P17 (matrix)
– P24 (kapsid)
– P7/P9 (nucleocapsid)
 Structure of HIV

HIV is a member of the lentivirus family of animal retroviruses.

HIV-1 and HIV-2 have been identified.
HIV Genome
• HIV genome terdiri dari 2
strand RNA yg identik
• Viral genome mengkode
– Gag,pol&env mengkode
struktur, enzym & envelop
– Rev&tat mengkode
regulator protein
– Nef,vif,vpu&vpr mengkode
asesoris protein
 Transmission of HIV
• Sexual contact is the most frequent mode
of transmission (heterosexual,
homosexual)
• Mother to child transmission
• Infected blood or blood products.
• Shared needles by iv drug abusers
 Siklus Replikasi HIV
Ada 5 fase dalam replikasi virus HIV yaitu

 Binding and entry

 Reverse transcription
 Replication
 Budding
 maturation
 HIV LIFE CYCLE 2 Entry: Virus binds to a CD4 molecule and
one type of "coreceptor" (either CCR5 or
CXCR4). Receptor molecules are common
1 Free Virus on the cell surface. Then the virus fuses with
the cell.

CD4 Receptor
CCR5 Coreceptor
3 Penetration: virus empties CXCR4 Coreceptor
its contents into cell.
HIV RNA

4 Reverse Transcription: HIV DNA Human

single strands of viral RNA are DNA
used by the reverse
transcriptase enzyme to create HIV
double-stranded DNA. DNA

5 Integration: viral DNA is Human

inserted into the cell's own DNA
DNA by the integrase enzyme.
Chains of HIV
proteins
6 Transcription: When the 8 Budding:
infected cell divides, the viral
immature virus
DNA is "read" and long chains
pushes out of the
of proteins are made.
cell, taking some
cell membrane
with it. The
7 Assembly: sets of viral protease enzyme
proteins chains come together. starts processing
the proteins in the
newly forming
virus.
10 Maturation: the protease enzyme
10 Maturation:
finishes cutting the protease
HIV protein chainsenzyme
into finishes 9 Immature virus
cutting
individual HIV protein
proteins that chains
combineintotoindividual
make a proteins breaks free of the
that combine
new working virus.to make a new working virus. infected cell.
HIV replication cycle
 Progression of
HIV infection
HIV disease begins
with acute infection,
partly controlled by
the adaptive immune
response.
Advances to chronic
progressive infection
of peripheral
lymphoid tissues.
Clinical course of HIV disease
Patients with AIDS
 Mechanism of ID in HIV disease
• Loss of CD4+ T cells caused by direct
cytopathic effect of HIV
• Direct lysis of infected CD4+ T cells by
virus
• Functional defect of CD4+ T cells caused
by HIV
• The effects of HIV on macrophages,
dendritic cells etc
 Treatment and prevention of
AIDS
• Antiviral drugs (nucleoside analogues,
protease inhibitors, reverse transcriptase
inhibitors)
• Antibiotics
• Supportive treatment
• Vaccine against HIV (?)