Immunology

• Immunology


  The study of the immune system and its functions

  
• Importance of immunology


  • The immune system plays a crucial role in maintaining health by defending against pathogens and potentially harmful substances
  • When the immune system malfunctions, it can lead to diseases such as allergies and autoimmune disorders

  
• Immune system


  A complex network of cells, tissues, and organs that work together to defend the body against harmful foreign substances, such as bacteria, viruses, and toxins

  
• Components of the immune system


  • Innate immune system
  • Adaptive immune system

  
• Innate immune system


  • Provides a rapid response to infections
  • Non-specific and responds immediately to foreign substances

  
• Adaptive immune system


  • Provides a longer-term response that is specifically tailored to the invading pathogen
  • Needs priming and has immunological memory

  
• Cells of the immune system


  • Leukocytes (white blood cells)
  • Neutrophils
  • Macrophages
  • Monocytes
  • Dendritic cells
  • Natural killer cells
  • Lymphocytes (B cells and T cells)

  
• Tissues and organs of the immune system


  • Lymph nodes
  • Spleen
  • Thymus
  • Bone marrow
  • Mucosa-associated lymphoid tissue (MALT)
  • Gut-associated (GALT)
  • Bronchial-associated (BALT)
  • Skin-associated (SALT)

  
• Molecules of the immune system


  • Antibodies
  • Cytokines
  • Complement
  • Major histocompatibility complex (MHC) molecules
• Antigens


  Substances that stimulate an immune response, and can come from bacteria, viruses, and other foreign substances

  
• Antibodies


  Proteins produced by B cells in response to an antigen, which help neutralize or remove pathogens from the body
• Immune response


  A complex process that involves the activation of specific cells and the production of antibodies, regulated by signalling molecules and cytokines

  
• Vaccination


  A way to prevent or reduce the severity of infectious diseases by triggering an immune response to specific antigens without causing the disease itself

  
• Immune system disorders


  • An overactive immune system can lead to allergies and autoimmune diseases, while an underactive immune system can result in immunodeficiency disorders

  
• Innate immunity


  • The body's first line of defense against pathogens, non-specific and responds immediately to foreign substances

  
• Components of innate immunity


  • Phagocytes
  • Natural killer (NK) cells
  • Physical and chemical barriers (skin, mucus, antimicrobial secretions, bronchial cilia)
  • Inflammation
  • Complement system

  
• Inflammation


  Stops the spread of infection and promotes healing, with four cardinal signs: redness, heat, swelling, and pain
• Complement system


  A cascade of proteins that triggers inflammation, kills pathogens by cytolysis, and tags cells for destruction
• Innate immunity recognition molecules


  • MBP (Mannose-binding lectin)
  • Acute phase proteins
  • Pattern recognition receptors (PRRs)
  • Pathogen-associated molecular patterns (PAMPs)
  • Cytokine receptors
• Adaptive immunity


  • A specific immune response that occurs after exposure to an antigen, slower than innate immunity but has the advantage of memory and leads to a faster response upon re-exposure
• Passive immunity


  The transfer of antibodies from one individual to another, such as from mother to child during breastfeeding
• Antibody classes

  • IgG
  • IgM
  • IgA
  • IgD
  • IgE
• Antibody structure

  • ~12 domains, 2 heavy (H) and 2 light (L) chains, linked by disulfide bonds, flexible Y shape
• Antibody variable and constant regions

  • N-terminal domains = variable V, C-terminal domains = constant C, 5 H classes: M, G, A, E, D, V region has 6 hypervariable regions (3 per chain) => antigen-binding site
• Primary vs. secondary antibody response


  IgM initially responds while IgG concentrations develop later, antibody response is altered in the second exposure with IgG increase 2-10 times higher and developing much earlier, presence of "memory" lymphocytes following initial exposure
• Cytokines


  Proteins that facilitate immune cell communication to divide, differentiate, and secrete antibody, with at least 30 known cytokines such as IFNg and TNFa
• Key cytokines include TH1 - IFNg and TNFa activating macrophages or delayed-type hypersensitivity
• Adaptive Immunity


  Humoral and Cell-mediated Response
• Antibody response


  1. IgM initially responds

  2. IgG concentrations develops later

  3. Altered in the second exposure

  4. IgG increase to 2-10 times higher and develops much earlier

  5. Presence of "memory" lymphocytes following initial exposure
• Cytokines


  • Proteins, at least 30 known
  • IFNg - important macrophage activator
  • TNFa - important in inflammation
  • Act via cytokine receptor binding
• Key cytokines


  • TH1 - IFNg and TNFa activating macrophages or delayed hypersensitivity
  • TH2 - ILs activating B cells, IgE production
  • TH17 - IL-17 recruit neutrophils or autoimmunity
  • TREG - IL-10 and TGFb inhibit response, help maintain self-tolerance
• Immune Cascade


  • A series of reactions that occur in the body in response to a foreign substance
  • Involves the activation, recruitment, and action of various immune cells and molecules
  • Cells like macrophages, T cells, and B cells
  • Signalling molecules like cytokines and chemokines
  • Crucial for eliminating pathogens
  • Can also contribute to inflammation and tissue damage if not properly regulated

  
• Leukocytes (white blood cells)


  • Formed by hematopoiesis in bone marrow
  • Starts with multipotent hematopoietic stem cells
  • Cells develop into myeloid/lymphoid progenitor cells
• Myeloid cells (contribute to innate response)


  • Neutrophils
  • Eosinophils
  • Basophils
  • Mast cells
  • Monocytes
  • Dendritic cells
  • Macrophages
• NK cells


  • Contribute to innate response
  • Complete development in bone marrow
  • Large, contain granules
  • Primarily target infected, cancer cells
  • Kill target cells with cytotoxic granules
• B cells


  • Complete development in bone marrow
  • Bind to specific antigens (antigen presentation not needed)
  • Capable of phagocytosis, antigen presentation
  • Load antigens on major histocompatibility complex (MHC) II, display to T cells
  • T-cell activation--> B cells mature into plasma cells; secrete lots of antibodies/immunoglobulins
• T cells


  • Complete development in thymus
  • Responsible for cell-mediated immunity
  • Bind to specific antigens (antigen presentation needed)
  • Naïve T cells primed by antigen presenting cells (usually dendritic cells)
  • Generally categorized into CD4+ (helper) and CD8+ (cytotoxic) T cells
• Phagocytes


  • Reach around pathogens with cytoplasm, swallowing whole (phagosome)
  • Destroy some pathogens with cytoplasmic granules (phagosomes fuse with granules --> phagolysosomes; pH in vesicle drops killing pathogens)
  • Continue to swallow pathogens before oxidative burst
• Granulocytes


  • Contain granules in cytoplasm
  • All cells (except mast cells) polymorphonuclear
• Antigen-presenting cells


  Present antigens to T cells