Unit 3

Immunodeficiency
Diseases/HIV
MLAB 1335 – Immunology
Part Five – Immunodeficiency Diseases and HIV
 Immunodeficiency Disease
• Immunodeficiency is defined as
• Disorders where parts of the immune system are missing or dysfunctional
• Symptoms can be mild to severe with recurrent infections
• Two types
• Primary immunodeficiences – inherited dysfunctions of the immune system
• Most important demonstrate X-linked inheritance
• Secondary immunodeficiency – acquired as in AIDS, caused by HIV
• Current infections
• Cancers
• Autoimmune disorders
• Immunosuppressive drugs
 Primary Immunodeficiency
• Nine categories, we will focus on a few
• Defects in antibody-mediated immunity
• Recurrent infections with pyogenic bacteria
• Primarily in respiratory and intestinal tracts
• Examples include recurrent sinusitis and otitis media
• More severe problems if agammaglobulinemia
• Defects in T-cell mediated immunity
• Recurrent infections with intracellular pathogens
• Viruses, fungi, and intracellular bacteria
• Defects in phagocyte function
• Pyogenic bacterial infections, especially the skin
• Range from mild to lethal
 Secondary Immunodeficiency
• Secondary immunodeficiency – acquired as in AIDS, caused by HIV
• Current infections
• Cancers
• Autoimmune disorders
• Immunosuppressive drug therapy
• AIDS
• Acquired immunodeficiency syndrome
• Caused by the human immunodeficiency virus (HIV)
• A retrovirus – an RNA virus that inserts a DNA copy of its genome
into the host cell in order to replicate (make DNA from their RNA)
• Discovered by Luc Montagnier of France and Robert Gallo of US in
1983-1984.
• No cure
 HIV
• Infection in humans came from a chimpanzee in Central Africa from
contact with infected blood (hunting)
• May have jumped from chimpanzees to humans as early as 1800s
• Probably in the US in mid to late 1970s
• Symptoms – within 2 to 4 weeks after infection
• Fever
• Chills
• Rash
• Night sweats
• Muscle aches
• Sore throat
• Fatigue
• Swollen lymph nodes
• Mouth ulcers
HIV - Anatomy of the virus
 HIV - Structural Genes
• The genome of HIV has three main structural genes which code for
specific products
• gag – Codes for nucleocapsid and core proteins
• p55 – a precursor protein providing four core structural proteins
• p6, p9, p17 and p24
• env – Codes for viral envelope
• Glycoproteins gp160, gp120, and gp41
• pol – codes for enzymes necessary for HIV replication
• Reverse transcriptase p51
 HIV - Replication
• HIV attaches to the host-cell CD4 antigen
• Serves as a receptor for the virus by binding gp120 glycoprotein on the
outer envelope of HIV

• T-helper cells are the main target for HIV – highest number of CD4
molecules on their surface
• Bind with T-helper antigen with HIGH affinity

• After fusion, virus enters cell, uncoating occurs and exposes viral genome

• Reverse transcriptase produces complementary DNA from viral RNA

• THEN…
 HIV - Replication
• Double-stranded DNA is created and integrated into the host cell genome
as a provirus
• Can remain latent for long periods before replication

• Viral DNA is transcribed into genomic RNA; mRNA which sends message
to create viral proteins for assembly into new viral particles

• Virions acquire envelope when break out of host cell

• Viral replication occurs almost always in antigen-activated T-helper cells

• Replication occurs rapidly leading to a high rate of mutations

• This diversity LIMITS the host’s capability of mounting an immune response
HIV - Replication
HIV is seen at the arrows, infecting a T-helper cell
 HIV - Replication
• Viral production may slow down as the host’s immune response
develops
• Host produces neutralizing antibodies, prevents virus from infecting
close cells
• Host develops HIV-specific CTLs that lyse virus-infected target
cells
• Innate defenses also activated
• Can reduce level of HIV replication, not enough to eliminate
virus
• Due to virus capability to mutate and alter antigens
 HIV - Downfall of immune system
• HIV infection – decline in CD4 T-helper cells
• Results in immunodeficiency affecting cell-mediated and
humoral antibody responses to antigens
 HIV – course of disease
• If untreated HIV
• Acute phase of flu-like symptoms
• Latent, asymptomatic period – may last up to 10 years
• AIDS
• Profound immunosuppression
• Life-threatening opportunistic infections
• Malignancies
 HIV – course of disease
• HIV – positive patients classified in to one of five stages
• 0, 1, 2, 3, or unknown
• 0 – early infection
• 1, 2, or 3 – based on CD-4 T-cell count, if this information is missing,
then classified as unknown
• Stage 3 also indicated if presents with opportunistic infection
• CDC – Stage 1 – Acute HIV infection
• Stage 2 – Chronic HIV infection
• Stage 3 – Acquired Immunodeficiency Syndrome (AIDS)
 AIDS
• Stage 3 – AIDS
• Patients receive an AIDS diagnosis
when the CD4 cell count drops below
200 cells/mm3 or if they develop
opportunistic infections

• Patients with AIDS can have a

high viral load and can be VERY infectious

• Without treatment, patients with

AIDS survive ~ three years
 HIV - Testing
• Rapid antigen/antibody screening tests – ready in 30 minutes or less
• ELISA method, must confirm with high specialized testing if positive
• NAT – nucleic acid testing
• Three molecular methods
• Reverse-transcriptase PCR - a testing method that converts HIV RNA into cDNA
and then is amplified
• Real-time PCR method – amplifies a DNA sequence complementary to a portion
of the HIV RNA genome
• Branched chain DNA, which amplifies a labeled signal bound to a test plate
• Western Blot
• Used from 1985 to 2014, to confirm ELISA positives
• Identified specific amino-acid sequences in proteins
• Labor intensive
 HIV - Treatment
• Antiretroviral therapy (ART)
• Suppresses the virus’s replication
• Drugs such as nucleoside reverse transcriptase inhibitors
• Block HIV replication cycle
• Multiple drug therapy
• Combinations of at least two of the antiretroviral drug classes
• Vaccine?
• HIV rapidly mutates with no ideal animal model to study vaccine effects
Ending slide