Immunology

• Cell Mediated Effector Responses

  • Kill virus infected cells
  • Kill bacteria infected cells
  • Kill tumor cells
  • Plays a role in transplant rejection
• Cytotoxic T cells (CTLs)


  Naive CTLs cannot kill target cells
• CTL Precursors or CTL-P

  1. Need TH cell and DC help to mature into killer CTLs

  2. Need help from a TH cell

  3. Need IL-2 for proliferation

  4. Need to induce killing granule formation

  5. Need Ag presented by a Licensed DC
• Licensed DC


  • DC that has been activated by TLRs
  • Induces CD80/86 expression
• CTL-P maturation


  Leads to CTL-P proliferation and differentiation into killer CTLs
• Killer CTLs


  • Have granules that contain perforin and granzymes
• Mechanism of CTL Killing

  1. CTL contacts target cell via TCR/CD3 to MHC Class I+Ag

  2. Forms a conjugate with the target

  3. CTL rearranges granules to focus at the target

  4. Perforin inserts into target cell membrane and polymerizes to form a pore

  5. Granzymes enter target cell through pore and induce apoptosis
• Fas-Fas Ligand Killing


  Fas on target cell is bound by Fas Ligand on CTL, activating caspases and inducing apoptosis
• NK Cells


  • 1st line of defense against viruses and intracellular bacteria
  • Secrete IFNgamma
  • Activate macrophages
  • Polarize TH cells to TH1
  • No TCR
• How NK Cells Recognize Targets

  1. NK cells have inhibitory receptors that bind to MHC Class I on target cell, blocking killing

  2. NK cells have activating receptors like NKG2D that bind to stress proteins on target cell, sending a kill signal
• Hypersensitivity


  An overreaction of the immune system
• Types of Hypersensitivity


  • Type I
  • Type II
  • Type III
  • Type IV
• Type I Hypersensitivity


  • Almost half of US population affected
  • IgE mediated allergies to pollen, foods, mold, insects, etc.
  • Many allergens are proteases that activate complement and disrupt epithelial barriers
• Stages of Type I Hypersensitivity

  1. Sensitization: Allergen induces TH2/TH9 response and IgE production

  2. Effector Response: Allergen binds IgE on mast cells, causing degranulation and release of mediators
• Immediate Response in Type I Hypersensitivity

  • Mast cell degranulation releases histamine, proteases, chemotactic factors
  • Results in inflammation, sneezing, coughing, vomiting, tissue damage
• Delayed Response in Type I Hypersensitivity

  • Eicosanoid production, cytokine release, chemokine release
  • Leads to stronger inflammation and recruitment of eosinophils, basophils, neutrophils
• Types of Type I Hypersensitivity

  • Allergic rhinitis
  • Allergic asthma
  • Food allergies
  • Atopic urticaria
  • Systemic anaphylaxis
• Anaphylaxis


  Widespread activation of mast cells, massive vascular permeability, airway constriction, can lead to death in 2-4 minutes
• Treatments for Type I Hypersensitivity

  Epinephrine, antihistamines, corticosteroids, anti-IgE monoclonal antibodies, desensitization immunotherapy
• Type II Hypersensitivity


  IgM or IgG antibodies to cell surface antigens, activate complement, ADCC, phagocytosis to destroy cells
• Type II Hypersensitivity


  • ABO blood group response, hemolytic disease of the newborn
• Prevention of Rh incompatibility

  Give Rhogam (anti-Rh IgG) to Rh- mother during pregnancy to prevent sensitization
• Type III Hypersensitivity


  Due to antigen-antibody immune complexes deposited in tissues, activate complement and induce inflammation
• Type III Hypersensitivity


  • Serum sickness
• Type IV Hypersensitivity


  Delayed type hypersensitivity, TH1/TH17 mediated, no antibodies involved
• Type IV Hypersensitivity


  • Poison ivy, nickel allergy, tuberculosis skin test
• Autoimmune disease


  Failure of tolerance to self, chronic disease with self antigen present
• Types of tolerance


  • Negative selection in thymus for T cells
  • Negative selection in bone marrow/spleen for B cells
  • Anergy for T cells
  • Regulatory T cells
  • Antigen sequestration
• Groups of autoimmune diseases

  • Organ specific
  • Systemic
• Organ specific autoimmune diseases

  • Hashimoto's thyroiditis
  • Type 1 diabetes
• Hypersensitivities


  TH1/TH17 cells/Cell Mediated Immunity
• Autoimmune Disease is a failure of Tolerance to self
• Tolerance


  A state of unresponsiveness to an Ag
• Autoimmune Disease


  Chronic Disease, Long term disease, Ag is always present=Self, 3-8% of people in the US
• Types of Tolerance


  • Negative Selection in the Thymus for T cells
  • Negative Selection in the Bone Marrow and Spleen for B cells
  • Anergy for T cells
  • Regulatory T cells
  • Ag Sequestration
• Anergy for T cells

  TCR/CD3 signal without CD28-CD80/86, Due to no inflammation to induce CD80/86 on APCs
• Regulatory T cells


  nTregs and pTregs
• Ag Sequestration


  Some Ags are never exposed to the Immune System, Blood-Brain Barrier, Anterior Chamber of the Eye, Can breach these barriers by Trauma or Inoculation
• Major Groups of Autoimmune Diseases

  • Organ Specific
  • Systemic
• Organ Specific Autoimmune Diseases

  • Often endocrine glands, Involves tissue specific Ag (not on other tissues)