Specific Defenses to Microbes

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Specific Defenses to Microbes

• T Cells and Cellular Immunity

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Humoral Immunity

• Humoral immunity is due to antibodies made by B
  cells (neutralization, opsonization, complement
  activation, ADCC)
• Eliminates extracellular pathogens
• Works with phagocytes and complement
• Can be passively transferred

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Cellular Immunity

• Cellular immunity is due to T cells
• Eliminates intracellular pathogens, transplanted
  tissue, cancer
• Kills infected host cells
• Helps macrophages kill phagocytosed pathogens
• Difficult to passively transfer

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EffectorT Cells
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Antigen binding --gt activation/proliferation --gt
effector cells memory cells
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• T cells are either CD4 (helper) or CD8
  (cytotoxic)
• CD4 T cells bind antigen on MHC II
• CD8 T cells bind antigen on MHC I

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Antigen Presenting Cells

• Professional APC present extracellular antigen on
  MHC II
• Dendritic cells (DC)
• Macrophages
• B cells
• All cells can present intracellular antigen on
  MHC I

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MHC Molecules
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MHC Proteins

• MHC proteins tissue typing antigens
• Class I MHC is on all cells (except RBC),
  presents antigen to Tc (CD8)
• Class II MHC is on professional APC, presents
  antigen to Th1 and Th2 cells (CD4)

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TCR

• TCR is not secreted it is always membrane-bound
• TCR diversity is also generated by gene cutting
  and splicing

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TCR Antigen Binding
TCR binds MHC antigen peptide CD4 binds MHC II
CD8 binds MHC I
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T Cell Development

• TCR are generated randomly in T cells developing
  in the thymus
• TCR must bind MHC I or MHC II for the T cell to
  survive
• Because T cells are selected for their ability to
  bind self MHC, foreign MHC (transplants) trigger
  T cell rejection
• Immature T cells binding too tightly to self
  peptide on self MHC are killed

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IL-2 is a cytokine that signals cells to divide
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T Cell Immunity

• Tc (cytotoxic T cells CTL CD8) recognize and
  kill virus-infected host cells
• Th1 cells ( CD4) signal infected macrophages to
  kill pathogens in their phagosomes
• Th2 cells ( CD4) signal B cells to divide and
  make antibodies

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Cytotoxic T Cell (CTL)

• CTL go to the infection site and find and kill
  virus-infected cells
• They kill by releasing perforin (makes pores in
  target cell) and granzymes (cause apoptosis)
• CTL also kill tumor cells

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Cytotoxicity
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Th1 Cells Activate Macrophages to Kill Pathogens
They Have Engulfed
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Skin Testing for Th1 Function TB Test

• Also called Delayed-Type Hypersensitivity (TB
  test)
• Inject small amount of antigen to form bubble
  under skin

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Skin Testing for Th1 Function

• Macrophages bind antigen, send cytokines to
  attract memory Th1 cells
• Activated Th1 activate Macrophages ? inflammation
  and antigen removal

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B Cell Activation

• Antigen signal Th2 signal
• B cells need T cell help to make IgG and IgA and
  IgE, memory cells

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T-Independent Antigens

• Polysaccharide with repeating epitopes - capsules
• B cells divide and make IgM without Th2 cell help
• Infants cannot make good TI response to HiB, need
  vaccine

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Vaccination

• Stimulate with harmless but similar antigen to
  generate memory cells and antibody
• Vaccine types commonly used in US
• Whole Cell
• Live attenuated (weakened) virus
• Killed virus
• Subunit/Toxoid
• Recombinant
• Generate active immunity

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Whole Cell Vaccines
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Live Attenuated Virus

• Can replicate in host
• Induces CTL and antibodies
• Unsafe for immunosuppressed people
• Examples
• Sabin polio
• MMR
• Chickenpox

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Inactivated Virus or Bacterium

• Cannot replicate in host
• Safe, induces neutralizing antibodies
• Examples
• Salk polio
• Rabies
• Influenza
• Hepatitis A Virus (HAV)
• Pneumococcal vaccine (adult)

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Subunit Vaccines
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Subunit Vaccines

• Parts of pathogen
• Safe, generate antibodies
• Examples
• Pertussis (acellular)
• Haemophilus influenzae B (HiB)
• Pneumococcal pneumonia (infants)
• Meningococcal meningitis

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Toxoid Vaccines

• Inactivated toxin molecules
• Safe, generate neutralizing antibodies
• Examples
• diphtheria
• tetanus
• anthrax

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Recombinant Vaccine

• Examples Hepatitis B Virus (HBV), HPV
• Usually require multiple exposures

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DNA Vaccine
None currently used in humans or animals several
under development
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