Immunodeficiency diseases

And
AIDS

- Dr. Sneh Acharya

 Immunodeficiency diseases

A. Primary immunodeficiency states

B. Secondary immunodeficiency states

 A. Primary immunodeficiency states

The primary immunodeficiency diseases are a group of disorders in

which the primary defect appears to be intrinsic to one or more
components of the immune system.
 Primary immunodeficiency states

B – Cell disorders T-cell disorders

1. Bruton’s 1. Di George syndrome
agammaglobulinemia
2. IgA deficiency Combined B & T cell disorders
3. Common variable 2. Severe combined
immunodeficiency immunodeficiency (SCID)
3. Wiskott-Aldrich syndrome
4. Ataxia-telengiectasia
• In some cases, a mild form may not find out
that they have PI until adulthood.

• In other cases, the disorder causes problems

in infancy and is found soon after birth.
 Signs and symptoms of PI
• Repeated infections:
– Ear infections
– Sinus infections
– Pneumonia
– Bronchitis
– Meningitis
– Skin infections
– Thrush or candidiasis
• Infections that last longer
• Infections that are hard to treat and do not respond to
antibiotics or require IV antibiotics
 Signs and symptoms of PI
• Severe infections: sepsis or abscesses (pus-
filled infections) of internal organs
• Infections that most people don’t get
(opportunistic infections)
• Lack of weight gain or growth in an infant
(failure to thrive)
• Digestive problems: chronic diarrhea
 A. Primary immunodeficiency states

X-linked agammaglobulinemia (Bruton's disease)

• Inability of pre-B cells to diff. into mature B-cells

• decrease in circulating B-cells, no germinal centers in LN,
rudimentary Peyer's patches
• recurrent bacterial infections (H. influ., Str. pneumon., Staph. aur.)
 A. Primary immunodeficiency states

Isolated deficiency of IgA

• most frequent (1:700)
• recurrent sinopulmonary infections, diarrhea
Thymic hypoplasia (DiGeorge's syndrome)
• Congenital malformation of 3rd and 4th branchial pouches(Facial
and heart disease, hypoparathyroidism- hypocalcemia)
• Vulnerability to viral, fungal and protozoal infections
Severe combined immunodeficiency (SCID)

• X-linked or autosomal recessive

• Combined B and T cell disorder
• Aka Boy in the bubble syndrome disease.
Wiskott-Aldrich syndrome

Combined B and T cell disorder

Triad of symptoms
Eczema;thrombocytopenia and sinopulmonary infections
Ataxia -telengiectasia
• Combined B &T cell
disorder.
• Cerebellar ataxia and
Telengiectasias of eye and
skin.
• Risk of lymphoma, leukemia
 B. Secondary immunodeficiency states

• More common.
• Seen in malnutrition, infection, cancer, renal disease,
malignancies
• Patients treated by immunosupressive drugs.
• AIDS
 AIDS
• Acquired Immunodeficiency Syndrome
• HIV is the virus that causes AIDS
• RETRO VIRUS
• Profound immuno-supression
• Leads to opportunistic infections, secondary
neoplasms, and neurologic manifestations
 Epidemiology
• Five groups of people
1. Homosexual Men: 50%
2. IV drug abusers: 20%
3. Hemophiliacs: 0.5%
4. Blood and Blood products? Organ Transplant:
1%
5. Heterosexual Men: 30%
6. Unknown cause: 5%
 Modes of HIV/AIDS Transmission

• Through Body Fluids

– Blood products
– Semen
– Vaginal fluids
– Breast Milk
o Through IV Drug Use
– Sharing Needles
• Without sterilization

o Through Sexual contact

o Mother-to-Baby
• Two genetically different forms of HIV:

- HIV-1 and HIV-2

- HIV-1 is the most common type associated

with AIDS in the United States, Europe, and
Central Africa
- HIV-2 : West Africa and India
• The virus core contains:

1. Major capsid protein p24

2. Nucleocapsid protein p7/p9
3. Two copies of viral genomic RNA
4. Three viral enzymes
- (protease, reverse transcriptase, and
integrase)
• 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.
• The HIV-1 RNA genome contains the gag, pol,
and env genes

• Several other accessory genes: tat, rev, vif, nef,

vpr, and vpu

• Regulate the synthesis and assembly of

infectious viral particles and the pathogenicity
of the virus.
• Pathogenesis:

The life cycle of HIV consists of:

- Infection of cells
- Integration of the provirus into the host cell
genome
- Activation of viral replication
- Production and release of infectious virus
• Uses the CD4 molecule as receptor and
various chemokine receptors as coreceptors

• Chemokine receptors (CCR5 and CXCR4)

• R5 strains use CCR5, X4 strains use CXCR4, and

some strains (R5X4) are dual-tropic.
• R5 strains preferentially infect cells of the
monocyte/macrophage lineage and are thus
referred to as M-tropic

• X4 strains are T-tropic, preferentially infecting

T cells
• The initial step in infection is the binding of
the gp120 envelope glycoprotein to CD4
molecules

• Leads to a conformational change that results

in the formation of a new recognition site on
gp120 for the coreceptors CCR5 or CXCR4.
Thank you