Pharmacy-Immunology 19

Primary & Acquired

Immunodeficiency
Saber Hussein
 Objectives
• Know the types of primary (congenital)
immunodeficiency that result of:
– Defects in B and T lymphocytes maturation
– Defects in lymphocytes activation and function
– Defects in innate immunity
– Lymphocyte abnormalities associated with other diseases
• Know the acquired (secondary) immunodeficiency
syndrome (AIDS) in regard of:
– Structure and biology of HIV
– Clinical features of HIV infection and pathogenesis of AIDS
– AIDS therapeutic and vaccination strategies
 Features of immunodeficiency diseases
• Diagnostic features and clinical manifestations of immune
deficiencies affecting components of the immune system
• Different diseases, and even different patients with the same
disease, may show considerable variation

(Extracellular
bacterial infections)

Fig12-1
 Congenital immunodeficiencies

• Primary Immunodeficiencies are congenital

diseases caused by genetic defects that inhibit
maturation of B or T cells or interfere with
functions of immune components
• Prevalence: 1 in 500 American and European
• Hallmark of immunodeficiencies’ consequences:
– Infections that could be mild or severe, start in early
childhood or in adulthood
 Congenital immunodeficiencies caused by defects in
lymphocyte maturation
• Autosomal SCID (severe combined immunodeficiency) caused by:
– ADA (adenosine deaminase) & PNP (purine nucleoside
phosphorylase) deficiency prevent maturation of:
• Stem cell  pro-B cell
• Pro-B cell  pre-B cell
• Stem cell  pro-T cell
• Pro-T cell  pre-T cell
– RAG (recombination activating gene) deficiency prevents
maturation of:
• Pro-B cell  pre-B cell
• Pro-T cell  pre-T cell
• X-linked SCID:
– Signaling IL-2Rg chain (c is common in IL receptors of IL-2, IL-
4, IL-7, IL-9, IL-15) deficiency interferes with
• Pro-T cell  pre-T cell [see Fig12-2, next slide]
 Fig12-
2:Congenital
Fig12-2:Congenital
immunodeficiencies
immunodeficienci
es
 Features of congenital immunodeficiencies
caused by defects in lymphocyte maturation

Fig12-3
 Features of congenital immunodeficiencies
caused by defects in lymphocyte maturation

Fig12-3
Congenital Fig12-4 :
immune- Sites where immune responses
may be blocked
deficiencies
associated
with defects
in
lymphocyte
activation
and effector
functions
• Congenital immunodeficiencies may be caused by genetic defects in
the expression of molecules required for
– Ag presentation to T cells,
– T or B lymphocyte antigen receptor signaling,
– helper T cell activation of B cells and macrophages, and
– differentiation of antibody-producing B cells.
Congenital immunodeficiencies associated with defects in
lymphocyte activation and effector functions

Fig12-4: Features of some of resulting deficiency disorders

Congenital immunodeficiencies caused by
defects in innate immunity

Fig 12-5
Congenital immunodeficiencies caused by
defects in innate immunity

Fig 12-5
Acquired (secondary) immunodeficiency
diseases
Fig 12-6
 Fig 12-8
HIV life cycle
HIV life cycle
The pathogenesis of
HIV-AIDS
• The stages of HIV
disease correlate with 12-9
a progressive spread
of HIV from the
initial site of infection
to lymphoid tissues
throughout the body.
• The immune response
of the host
temporarily controls
acute infection but
does not prevent
establishment of
chronic infection of
cells in lymphoid
tissues.
The pathogenesis 12-9
of HIV-AIDS
• The host’s immune
response temporarily
controls acute
infection
• But establishment of
chronic infection of
cells in lymphoid
tissues succeeds
• Cytokines produced
in response to HIV and
other microbes serve
to enhance HIV
production and
progression to AIDS
 The clinical course of HIV disease
• Blood-borne HIV virus (plasma viremia) is detected
early after infection
• It may be accompanied by systemic symptoms typical of
acute HIV syndrome
• The virus spreads to lymphoid organs, but
• plasma viremia falls to very low levels (only detectable
by sensitive reverse transcriptase polymerase chain
reaction (rtPCR) assays) & stays this way for many years
• CD4+ T cell counts steadily decline during this clinical
latency period, because of
– active viral replication and
– T cell destruction in lymphoid tissues
• As the level of CD4+ T cells falls, there is increasing risk
of infection and other clinical components of AIDS
[See next slide, Fig 12-10 ]
The clinical course of HIV disease
Fig 12-10