stimulation of immune response to treat established infection, malignancy, other illness

• purified immunoglobulin fraction from serum
• Ab to Hep A, measles
• IV Ig used to replace with hypogammaglobinemic patients
• last 3-6 mnths

• tetanus Ig
• rabies Ig
• VZ Ig
• Hep B
• vaccinia Ig

Pooled from individuals with high titers of Ab to organism (usually post vaccination)

• anti-botulinum toxin
• snake antivenoms
• associated with serum sickness

• Palivizumab
  • px against RSV for at risk infants
  • humanized murine monoclonal Ab to F protein of RSV

• systemic immunity (mainly IgG, IgM)
  • route of admin: subQ, IM, intradermal
• mucosal immunity (primarily IgA)
  • also IgG, IgM
  • route of admin: oral, intranasal
• herd immunity
  • protect extending to unvaccinated segment of population when vaccination/protection reaches a certain threshold level

• Ag- any substance recognized by adaptive immune system to generate immune response
  • does generate Ab, but can induce humoral and/or cellular immunity
  • vaccine contains single (ex: hepB) or multiple (most others) Ag
• adjuvant- component that increase immune response to Ag
  • ex: aluminum hydroxide in DPT and Hep B vaccines
• others
  • excipients
  • preservatives
  • buffers

• Ab
  • neutralizing (mainly viral)
  • lytic via complement or ADCC
  • opsonization (encapsulated bacteria- Hib, pneumococcus, meningococcus)
  • inhibit adherence (B. pertussis)
  • inhibit surface enzymes (influenza neuroaminidase)
• cell medated: cytotoxic T cells to intracellular organisms (ex: TB)

• toxoids
• live organisms
• killed organisms
• subinit vaccines

• chemically treated toxin to eliminate toxicity but preserve antigenicity
• ex: tetanus, diphtheria

• Ag persistence in host for a more sustained Ab response
• non attenuated: vaccinia (for small pox)
• attenuated
  • oral polio
  • MMR
  • yellow fever
  • influenza
  • VZV
  • BCG
  • typhoid
  • rotavirus

• virus: inactivated polio, rabies, hep A, influenza
• bacteria: typhoid, pertussis

• purified capsular polysaccharide
  • N meningitis
  • S pneumoniae
  • Hib
• produced by recombinant DNA technology
  • Hep B surface Ag
  • HPV

• induction of Ab
  • neutralizing capcity
  • promote opsonophagocytosis
    • early reduction of pathogen load
    • clearance of extracellular pathogens
• induction of T cells
  • support Ab induction (T cell dependent Ag)
  • produce cytokine/cytolytic activities
• cloearnce of intracellular pathogens (essential role for Ab in current vaccines)

• effect
  • diminished virulence but maintained immunogenicity
  • originally done by culturing organism in lab and monitoring mutation that reduce virulence or ability to grow but maintain Ag
• danger- it could revert back to virulent strain
• new strategies
  • genetic modification
    • gene reassortment (ex: Rotavirus)
    • recombinant virus (experimental HIV and malaria vaccines)

1. local Ag deposition
2. recognition by innate immune system and dendritic cells
3. attractino of monocytes, macrophages, Ag presenting cells = local inflammatory focus
4. Ag uptake by dendritic cells or migration to lymphatics
5. migrate to draining lymph nodes
   • deltoid goes to axillary nodes
   • thigh goes to inguinal nodes
   • mainly local and unilateral LN activation

• no/minimal local deposition
• replication and dissemination
  • multifocal
  • general LN activation

1. early extrafollicular response
2. peak of Ab one week after Ag
   • B cells in germinal centers
   • more IgM than IgG
3. short lifespan of plasma cells in spleen/nodes
   • rapid initial Ab decline
4. long lived plasma cells in marrow (slower decline of Ab levels over yrs)

• need helper T cells
• long lasting immunity provided for by
  • long lasting plasma cells (bone marrow)
    • secrete Ab of highest affinity
  • specific memory B cells (secondary lymphoid organs)
    • resting, non dividing cells
    • few in blood

• memory B cells undergo rapid reactivation and differentiation into Ag secreting cells upon Ag contact
  • predominantly IgG response
• in vivo evolution of Ag specific memory B cells
  • natural exposure
  • mimicry of exposure (polysac injection)
  • booster vaccine injection

Kinetics of IgG response: rapid (day 2-7) with strong increase in serum IgG

• age (infants cant take polysac. vaccine- no T cell response, so no immunological memory)
  • elderly may have poor response to primary vaccination
• nutritional status
• immunosuppression
• genetic factors
  • MHC restriction
  • polymorphisms in molecules critical to B/T cell activation
• route of admin
  • Hep B vaccine not as immunogenic if injected into gluteal muscle as with deltoid
  • oral for GI mucosal immunity
  • intranasal
• interval between vaccine
  • minimal interveral btw primary and boost of 4 months
    • allow for maturation of memory B cells
    • higher secondary responses

• maternal IgG corss placenta
  • last until 6 months of age
  • premature infant may not acquire full complement of Ab from mother
  • maternal Ab may interfere with successful infant vaccination (ex: measles)
• vaccination of mother during pregnancy can induce Ab that may transfer to fetus
• newborn can response to some vaccines after birth
• cant respond to polysaccharaide vaccines until 2 years old
  • ex:tetanus toxoid, Hib