Infectious Diseases

• Airborne transmission happens when infectious agents are carried by droplet nuclei or dust particles and inhaled by a susceptible person.
• Describe the innate immune system

  The innate immune system is the first line of defense of the immune system. It consists of the physical and chemical barriers as well as the cellular components- phagocytes. The physical barriers such as the skin and mucous membranes.

  The chemical barriers such as mucus, tears and saliva trap pathogens. It also consists of antimicrobial enzymes such as lysozymes and antimicrobial peptides such as defensins.
• What is the first response by the immune system to a pathogen?

  1. Ingestion of pathogens by phagocytes such as dendritic cells and macrophages
  2. Chemical barriers, antimicrobial peptides, antimicrobial enzymes, acidic pH and mucus, saliva and tears trap and kill pathogens
• Outline the role of antigen presenting cells

  Antigen presenting cells such as macrophages and dendritic cells link the innate immune system to the adaptive immune system when antigens from pathogens are presented to lymphoctes such as B cells and T cells to activate the adaptive immune response.
• Describe the inflammatory response

  Mast cells detect the injury and secrete histamine. Histamine is a signalling molecule that causes the blood vessels to dilate, increasing the flow of blood to the site of infection, promoting the recruitment of phagocytic cells to the site of infection. It also increases the permeability of the blood vessels near the site of infection of antimicrobial peptides.

  Phagocytes engulf and digests pathogens.

  Macrophages also secrete cytokines which has similar function.
• Describe the action of phagocytes

  Engulf the pathogens by phagocytosis and digests them with lysosomal enzymes
• Describe antigen presenting in APC

  1. After an APC engulfs the pathogen by phagocytosis, antigens from the surface of the pathogen are processed into short peptides.
  2. Peptides of antigen bind to MHC protein inside REr to form MHC-antigen complex
  3. The MHC-antigen complex is transported to the cell surface membrane of APC via vesicles
  4. Antigens on the cell surface membrane of APC are ready for presentation to T cells to activate T cells.
• Describe the adaptive immune system

  1. Highly specific
  2. Posseses immunological memory
  3. Undergoes clonal expansion upon activation
• Describe the role of T cells

  Activated T cells produce cytokines and undergo extensive clonal expansion and differentiation into effector T cells and memory T cells.
• Describe the role of helper T cells

  Helper T cells secrete cytokines which…

  1. Activate B cells to undergo clonal expansion and differentiation into plasma cells and memory B cells. The plasma cells secrete antibodies.
  2. Stimulate CD8+ cells to undergo clonal expansion and differentiation into cytotoxic T cells.
  3. Promote the recruitment of more monocytes, macrophages and helper T cells from the blood to the site of infection.
• Describe the role of cytotoxic T cells

  Cytotoxic T cells secrete enzymes(granzymes and perforins) which form pores in the infected cell’s cell surface membrane and digests the contents of the cell containing the virus, leading to lysis of the cell, killing the virally infected cell.
• Memory T cells persist long after an infection has been resolved
• Memory T cells quickly divide by mitosis, proliferate, and undergo differentiation to develop into large numbers of effector T cells upon re-exposure to the same antigen
• Memory T cells provide the immune system with immunological memory against past infections
• The number of antigen-specific memory T cells increases after an infection and can be rapidly reactivated if the same infectious agents are encountered again
• Increased number of memory T cells increases the chances of coming across Antigen-Presenting Cells (APCs)
• Faster response occurs for subsequent exposure to the same infectious agents, leading to highly efficient clearance of these agents
• Describe the activation of B cells

  B cells act as Antigen presenting cells.

  Helper T cells bind to MHC-antigen complex, providing a second activation signal to the B cells, secrete cytokines.
• Describe the structure of IgG antibody

  IgG has a globular structure with a quaternary structure held together by intermolecular ionic bonds, hydrophobic interactions, disulfide bonds and hydogen bonds between the R groups of amino acids.

  It consists of 4 polypeptide chains, 2 identical heavy chains and 2 identical light chains
• Role of IgG

  Bind to specific antigens of pathogens, preventing the pathogens from attaching to host cell receptor, this is known as neutralisation

  The Fc region binds to the Fc receptor on specific phagoctes and activate phagocytes so that phagocytosis of the pathogen occurs and the pathogen is ingested and killed. This is known as opsonisation.
• Constant region, Ch

  Presence of a hydrophobic membrane-anchoring sequence on the C-terminus allows the antibody to be anchored into the plasma membrane of the B cell.

  Soluble antibody lacks this hydrophobic sequence but has in place a hydrophilic sequence that allows for secretion.
• How is immunoglobulin coded for?

  The genes coding for immunoglobulin(Ig) are found at 3 gene loci and each locus is made up of multiple gene segments

  • A heavy chain (V,D,J,C)
  • Light chain (V,J,C)
• What are the two types of light chains?

  1. kappa chain (coded by Ig k locus on chromosome 2)
  2. lambda chain (coded by lg lambda locus on chromosome 22)
• How does antibody diversity arise?

  The random recombination of the multiple gene segments contributes to the vast numbers of heavy chain gene and light chain gene diversities. As any heavy chain can associate with any light chain, this contributes to antibody diversity.
• What 3 mechanisms give rise to antibody diversity

  1. somatic recombination
  2. somatic hypermutation
  3. class switching
• Define Somatic Recombination

  Somatic recombination is a form of DNA rearrangement whereby random gene segments are joined together randomly and some intervening sequences are enzymatically removed followed by rejoining of remaining sequences. Somatic recombination occurs prior to antigen contact during B cell development in the bone marrow.