Immunology

• Fundamental lines of defence in the immune system


  • Innate immunity
  • Adaptive immunity

  
• Innate immunity


  First immunological mechanism for fighting against pathogens, rapid immune response initiated within minutes or hours, no immunologic memory

  
• Adaptive immunity


  Antigen-dependent and antigen-specific, has memory - enables the host to mount a more rapid and efficient immune response upon subsequent exposure to the antigen

  
• There is synergy between the innate and adaptive immune responses
• Defects in either the innate or adaptive system can provoke illness or disease, such as inappropriate inflammation, autoimmune disease, immunodeficiency disorders and hypersensitivity reactions
• Immune system


  Collection of cells, chemicals and processes that function to protect the skin, respiratory passages, intestinal tract and other areas from foreign antigens, such as microbes (bacteria, fungi and parasites), viruses, cancer cells and toxins

  
• Defensive barriers of innate immunity

  • Anatomic (skin and mucous membranes)
  • Physiological (temperature, low pH and chemical mediators)
  • Endocytic and phagocytic
  • Inflammatory

  
• Pattern recognition receptors (PRRs)

  Allow a limited range of immune cells to detect and respond rapidly to a wide range of pathogens that share common structures, known as pathogen associated molecular patterns (PAMPs)

  
• Examples of PAMPs


  • Bacterial cell wall components, such as lipopolysaccharides (LPS)
  • Double stranded ribonucleic acid (RNA) produced during viral infection
• Function of innate immunity

  Rapid recruitment of immune cells to sites of infection and inflammation through the production of cytokines and chemokines

  
• Key inflammatory cytokines


  • Tumour necrosis factor (TNF)
  • Interleukin 1 (IL-1)
  • Interleukin 6 (IL-6)
• Dysregulated production of inflammatory cytokines is often associated with inflammatory or autoimmune disease, making them important therapeutic targets
• Complement system

  A biochemical cascade that functions to identify and opsonized bacteria and other pathogens, rendering them susceptible to phagocytosis
• Phagocytosis


  A process by which immune cells engulf microbes and remove cell debris and also kill some pathogens and infected cells directly

  
• Cells involved in the innate immune response

  • Phagocytes (macrophages and neutrophils)
  • Dendritic cells
  • Mast cells
  • Basophils
  • Eosinophils
  • Natural killer (NK)
  • Innate lymphoid cells

  
• Neutrophils and Macrophages


  Phagocytic cells that share a similar function: to engulf (phagocytose) microbes and kill them through multiple bactericidal pathways
• Dendritic cells


  Phagocytose and function as antigen-presenting cells, initiating acquired immune response and acting as important messengers between innate and adaptive immunity

  
• Mast cells and Basophils


  Instrumental in the initiation of acute inflammatory responses, such as those seen in allergy and asthma
• Eosinophils


  Granulocytes that possess phagocytic properties and play an important role in the destruction of parasites that are often too large to be phagocytosed
• Natural killer (NK) cells

  Play a major role in the rejection of tumours and the destruction of cells infected by viruses

  
• Innate lymphoid cells (ILCs)

  Play a more regulatory role, selectively producing cytokines that help to direct the appropriate immune response to specific pathogens and contribute to immune regulation

  
• Adaptive immunity


  The development of adaptive immunity is aided by the actions of the innate immune system, and is critical when innate immunity is ineffective in eliminating infectious agents

  
• Primary functions of the adaptive immune system

  • The recognition of specific "non-self" antigens, distinguishing them from "self" antigens
  • The generation of pathogen specific immunologic effector pathways that eliminate specific pathogens or pathogen-infected cells
  • The development of an immunologic memory that can quickly eliminate a specific pathogen should subsequent infections occur

  
• Adaptive immune responses are the basis for effective immunisation against infectious diseases

  
• Cells of the adaptive immune system

  • Antigen-specific T cells
  • B cells which differentiate into plasma cells to produce antibodies

  
• T cells


  Derived from hematopoietic stem cells in bone marrow and mature in the thymus, express a series of unique antigen-binding receptors on their membrane, known as the T cell receptor (TCR)
• Antigen-presenting cells (APCs)


  Dendritic cells, macrophages, B cells, fibroblasts and epithelial cells that express major histocompatibility complex (MHC) proteins to present antigen fragments to T cells

  
• MHC class I


  Present endogenous (intracellular) peptides to T cells
• MHC class II


  Present exogenous (extracellular) peptides to T cells
• Stem cells


  • Can rapidly proliferate and differentiate if they receive the appropriate signals
• Antigen Presenting Cells (APCs)

  Dendritic cells, macrophages, B cells, fibroblasts and epithelial cells that allow T cells to recognise a specific antigen

  
• Major Histocompatibility Complex (MHC)


  A group of proteins expressed on the surface of APCs
• MHC Classes


  • Class I (HLA A, B and C) - found on all nucleated cells
  • Class II (HLA DP, DQ or DR) - found in certain immune system cells including macrophages, dendritic cells and B cells

  
• Class I MHC


  Present endogenous (intracellular) peptides to T cells
• Class II MHC


  Present exogenous (extracellular) peptides to T cells
• The MHC protein displays fragments of antigens (peptides) when a cell is infected with an intracellular pathogen or has phagocytosed foreign proteins or organisms
• T cells have a wide range of unique T Cell Receptors (TCRs) which can bind to specific foreign peptides
• During immune system development, T cells that would react to antigens normally found in our body are largely eliminated

  
• T cell activation


  1. T cell encounters an APC with the correct antigen fragments (peptides) bound to its MHC molecules

  2. MHC-antigen complex activates the TCR

  3. T cell secretes cytokines to further control the immune response

  
• Cytotoxic T cells (CD8+)


  Primarily responsible for destruction of cells infected by foreign agents, such as viruses, and the killing of tumour cells expressing appropriate antigens