IMMUNE RESPONSE TO COMPLEMENT SYSTEM

• Immune response


  The process on how the body defends itself when harmful or foreign agents are present

  
• Immune response is also defined as the reaction of cells when foreign agents are present in the body

  
• Types of immune response

  • Primary
  • Secondary

  
• Primary immune response

  1. Lag phase

  2. Log phase

  3. Plateau/Stationary phase

  4. Decline phase
• Primary immune response


  • Response when the body encounters the antigen for the first time
  • IgM is the primary response antibody

  
• Secondary immune response

  • Response when an individual is re-exposed to the same antigen
  • Involves memory
  • Faster reaction
  • Shorter lag phase
  • IgG is the predominant antibody

  
• COVID vaccine - first dose is primary response, second dose is secondary response
• Booster shots are given in the decline phase to boost antibody levels
• Factors influencing immune response

  • Age (weaker in geriatrics and pediatrics)
  • Overall health status (healthier individuals have faster response)
  • Dose and route of antigen administration (higher dose and IV route elicit stronger response)
  • Genetic control (MHC determines self vs non-self)

  
• Major Histocompatibility Complex (MHC)


  • Group of genes associated with transplantation antigen and the immune response
  • Molecular basis for T cell discrimination between self and non-self

  
• Utilities of MHC

  • Responsible for graft/transplant rejection
  • Determine histocompatibility of transplanted tissue
  • Trigger transplant rejection if recipient recognizes MHC as foreign
• MHC class restrictions


  • Main role is antigen presentation
  • T cells can only respond to antigens combined with MHC molecules
  • MHC class I presents cytoplasmic antigens to CD8+ T cells
  • MHC class II presents extracellular antigens to CD4+ T cells

  
• MHC class I antigens

  • HLA-A
  • HLA-B
  • HLA-C
  • B2-microglobulin
  • HLA-E
• MHC class II antigens

  • HLA-DP
  • HLA-DQ
  • HLA-DR
• Microlymphocytotoxicity test


  1. Uses typing sera with anti-HLA antibodies

  2. Adds patient's lymphocytes

  3. Adds complement to activate and lyse cells with matching HLA antigens

  
• Mixed lymphocyte culture

  1. Uses donor lymphocytes (inactivated) and patient lymphocytes (active)

  2. Adds radioactive thymidine to measure lymphocyte reaction

  3. Indicates class II compatibility between donor and recipient

  
• Foreign antigen

  Bubutasin niya yung membrane ng cells hanggang matigok
• Only dead cells will take up the stain (positive result)

  
• MHC CLASS II


  • Restricted to immunocompetent cells of the immune system
  • Present in macrophages, B cells, & dendritic cells
  • Processed extracellularly derived antigens and presented to CD4 positive cells
  • Important in antigen presentation and interaction between immunocompetent cells

  
• Includes

  • HLA-DP
  • HLA-DQ
  • HLA-DR
• 2 LETTERS ANTIGEN
• MIXED LYMPHOCYTE CULTURE

  1. Donor lymphocyte & Patient "Responder" lymphocyte is used

  2. Donor - inactivated/irradiated

  3. Patient - active/live (will exhibit the reaction)

  4. Radioactive Thymidine is added to the recipient lymphocyte (way of measuring the response)

  
• BLASTOGENESIS REACTION/MIXED LYMPHOCYTE REACTION


  Cellular response showing lymphocytes from 2 individuals to undergo BLAST TRANSFORMATION when cultured in vitro

  
• Blastogenesis Reaction


  Indication of incompatibility
• Higher reaction rate = More incompatible (donor against patient lymphocyte)
• MLC REACTION


  The GREATER the amount of reaction in the recipient cells, the MORE FOREIGN are the MHC Class of the donor cells
• MHC CLASS III


  • Minor MHC antigens (cells is not involved)
  • Involves proteins and complement components
• Includes

  • C2
  • C4
  • Factor B "C3 Proactivator"
• Importance of HLA Typing:
• HLA-B27: ANKYLOSING SPONDYLITIS
• HLA-DR2: GOODPASTURE'S SYNDROME
• HLA-DR3: SYSTEMIC LUPUS ERYTHEMATOSUS
• HLA-DR4: RHEUMATOID ARTHRITIS
• Role of MHC in Immune Regulation (Homeostasis)


  1. Macrophages initially ingest foreign materials (from plasma) and present them to T lymphocytes in a process that relies on MHC antigens on the macrophage and Ag receptor on the T lymphocytes

  2. T helper cells stimulate B lymphocytes to produce antibodies against the processed antigen

  3. T suppressor cells (CD8 positive cells) limit the antibody response (immune regulation)

  
• CD4 vs CD8

  • CD4 (T helper cells): Stimulate / activates the immunity
  • CD8 (T suppressor/cytotoxic cells): Slows down / shut down immune response
• Acquired Immunodeficiency Syndrome (AIDS)
• Systemic Lupus Erythematosus (SLE)
• Complement System


  • A set of "non-specific" serum proteins that play a role in cytolytic destruction of cellular antigen by specific antibody
  • The end result of complement system is cytolysis
  • Activity of the complement system is possible in the presence of antibodies
  • It is called complement because in the presence of these protein systems, the activity of antibodies to eliminate or destroy the cell antigen is promoted

  
• Ways to Inactivate Complement System

  • Heat Inactivation (Heating)
  • Use of anticoagulants (EDTA and citrate)
• Contributions of Complement System to Biological Reaction

  • Chemotaxis (Chemotaxins)
  • Immune Adherence
  • Kinin Activator
  • Anaphylatoxins
  • Virus Neutralization
  • Opsonization (Opsonins)