Immunodeficiencies HIV/AIDS

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Immunodeficiencies HIV/AIDS
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Immunodeficiencies

• Due to impaired function of one or more
  components of the immune or inflammatory
  responses.
• Problem may be with
• B cells
• T cells
• phagocytes
• or complement

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• Immunodeficiencies may be
• Congenital (primary)
• Caused by a genetic abnormality
• Acquired (secondary) more common
• Normal physiologic changes aging
• Severe malnutrition or selective deficiency
• Caused by another illness Diabetes Cancer Vira
  l infection

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Main cause is disruption of lymphocyte
function Stem cell defect Prevent normal
lymphocyte development and total failure of
immune system Lymphoid organ dysfunction preve
nts maturation of B or T cells or final
maturation of B cells lack of specific class
of immunoglobulins
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Hallmark Tendency to develop unusual or
recurrent, severe infections. Deficiencies in T
cells suggested by recurrent infections with
viruses, fungi and yeast. Deficiencies in B
cells suggested by recurrent infections with
certain bacteria or viruses affected by humoral
immunity
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Routine treatment

• No live vaccines
• Be aware breaks in skin for routine blood tests
  can cause septicemia
• At risk for Graft-versus-Host disease

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Acquired Immunodeficiencies Nutritional
deficiencies Iatrogenic drugs
immunosuppressive therapy chemotherapy and
radiation Trauma esp. burns Stress
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HIV/AIDS

• Human immunodeficiency virus
• Acquired immunodeficiency syndrome
• Two forms HIV1 and HIV-2
• High mortality rate
• Asymptomatic carriers
• Logarithmic increase in number of patients
• Medical community cannot control spread

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Transmission

• Sexual transmission
• Contaminated needles sharing
• Blood products
• Transplacental or nursing

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History

• Probably arose in central Africa before 1931
• Believed to be a monkey virus mutated to affect
  humans
• Found Abs against HIV in serum samples taken in
  1960s
• First cases reported 1980s in male homosexuals

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• In 1995, the number 1 cause of death for ages 25
  44 in U.S.
• Heterosexual transmission is increasing in the
  U.S. and is the most common route of transmission
  outside of the U.S.
• Greater than 50 of cases are women

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High Risk Individuals

• Homosexual/bisexual men
• I.V. drug abusers
• Recipients of blood products
• Female partners of bisexual men/ I.V. drug
  abusers
• Children of infected mothers

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• Health care workers are at risk
• Nurses
• Clinical lab techs
• Most HIV workers infected off duty
• TAKE PRECAUTIONS !!!

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Pathogenesis

• Retrovirus RNA plus reverse transcriptase,
  integrase and protease
• Attachment Binds to CD4 receptors (TH) and
  chemokine receptors gp 120 or gp 41
• Internalization RNA enters the cell
• Reverse transcriptase converts RNA ?DNA
• Integrase inserts viral DNA into Host DNA

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• Viral DNA is transcribed into mRNA
• mRNA is translated into protein polyprotein
• Cleavage of polyprotein into usable proteins
• Viruses are assembled
• Host cell is killed as viruses are released
• BUT helper T cells are replaced and viruses are
  killed, but CD4 cells decrease over time.

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Helper T cells

• Coordinate the response of both B and T cells
• Patients susceptible to infections and
  malignancies
• Normally 600 - 1200 /mm3
• Category1 gt 500 cells/ µL
• Category 2 200- 499 cells/ µL
• Category 3 lt 200 cells/ µL (AIDS)

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Clinical Manifestations

• Category A no symptoms or persistent generalized
  lymphadenopathy or symptoms of primary HIV
  infection
• Category B symptoms of immune deficiency not
  serious enough to be called AIDS
• Category C person has AIDS defining illness
  (chart 15-2)

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Clinical manifestations

• Infection - serologically negative
• In seven days followed by acute phase in 30-70
  of people lasts a few days - 2 weeks resembles
  influenza or mononucleosis sore throat, muscle
  aches, fever, swollen glands, rash, headache
  or meningitis

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• Seroconversion occurs 3 17 weeks after
  infection HIV proteins can be detected in the
  blood
• Seropositive patients have anti-HIV Abs
  circulating
• Following infection through blood products, in
  general see anti-HIV Abs in 4-7 weeks
• Following infection through sexual exposure, it
  may take 6-14 months for detection of anti-HIV
  Abs (one case - years)

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Window period time between infection, Ab
detection An infected person can infect others
within 2 weeks of initial HIV exposure, at a time
well before anti-HIV Abs can be detected.
Average time from initial infection to AIDS is
about 10 years, though this rate of development
is lengthening with new treatments available.
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• Chronic phase can last for years
• Asymptomatic
• Viral load decreases
• Chronic lymphadenopathy
• orofacial herpes zoster, oral candidiasis
• B cells make antibodies, but are ineffective
• Gradual drop in T4 cells no symptoms until
  below 200/mm3

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• Crisis phase ARC AIDS-related complex
• CD4 count lt 200 cells/ µL
• Long lasting fever lt 3 months
• Malaise
• Diarrhea
• Weight loss and wasting syndrome
• Multiple opportunistic infections
• Persistent viral or fungal infections of the skin
• Without therapy death in 2-3 years

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AIDS Related Diseases

• AIDS To be positive for AIDS requires positive
  lab test and clinical symptoms -Unusual
  infections or neoplasms
• Kaposis sarcoma
• Non-Hodgkins lymphoma
• Wasting syndrome
• AIDS dementia complex

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AIDS Related Diseases

• Fungal
• Candidiasis
• Cryptococcus
• Viral
• Herpes simplex
• Herpes zoster
• Cytomegalovirus

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Opportunistic infections

• Pneumocystis carinii pneumonia
• Toxoplasmosis gondii
• Mycobacterium avium intracellulare
• Mycobacterium tuberculosis

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Treatment

• Expensive 1,200 -1,500 / month if healthy
• Cocktail of 3 different meds

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Treatment

• Restore immune function
• Hasnt been easy or successful
• Bone marrow transplant, immunomodulators,
  transfusions
• Prevent viral replication
• Reverse transcriptase inhibitors (AZT)
• Protease inhibitors
• Integrase inhibitiors
• Maturation inhibitors
• Fusion inhibitors - newest

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Difficulties with Vaccines

• HIV is antigenically variable
• Antibodies are not protective
• Can be transmitted by cell to cell contact
• Animal models are protected species

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Other problems

• Viral DNA incorporated into host cell DNA
• Virus mutates as the virus replicates