infectious diseases

• innate immune system:

  • mechanical barriers: skin, prevents penetration by pathogens
  • chemical barriers: lysozyme in saliva and tears that degrades peptidoglycan cell wall of bacteria, leads to lysis of bacteria
  • phagocytes: macrophages, dendritic cells, neutrophils, phagocytose pathogens, macrophages also induce inflammation via secretion of cytokines and chemokines
• neutrophils migrate to the site of infection, engulfs the pathogen and dies
• macrophages and dendritic cells can act as antigen presenting cells
• antigen presentation:

  1. antigen presenting cell forms pseudopodia and engulfs pathogen by phagocytosis
  2. fusion of phagocytic vesicles with lysosomes, hydrolysis of pathogen with hydrolytic enzymes
  3. antigens on pathogen is processed into peptides of antigens, loaded onto major histocompatibility (MHC) protein to form peptide:MHC complex
  4. peptide:MHC complex transported to the cell surface membrane for presentation to be recognised by naive T cells
• activation of T-cells:

  1. naive T cells have T cell receptors that are specific to antigen:MHC complex on an antigen presenting cell (APC)
  2. APC secretes cytokines that activate naive T cells
  3. naive T cells undergo clonal expansion and differentiation to form effector and memory T cells
• role of T helper cells:

  • secretes cytokines that activate specific naive B cells to become antibody-secreting plasma cells
  • stimulates macrophages to attack infected cells
• role of cytotoxic T cells:

  • secretes perforins to make pores in cell membrane of infected cells
  • secretes granzymes that enter infected cells via pores and activate enzymes that trigger apoptosis of infected cells
• role of memory T cells:

  • when re-exposed to the same pathogen, will recognise and mount a faster and stronger secondary immune response
• Activation of B cells:

  1. naive B cells have specific B cell receptors that recognises specific epitope and binds to a specific antigen
  2. BCR and antigen endocytosed into B cell, antigen processed into short peptides and attached to MHC proteins, forms peptide:MHC complex
  3. peptide:MHC complexes transported to cell surface membrane, recognised and bound by antigen-specific T helper cells, stimulating cytokine secretion from T-helper cell
  4. cytokines activate antigen-specific B cell to undergo clonal expansion and differentiation
• B cells differentiate into memory B cells and plasma cells
• role of plasma cells:

  • secretes antibodies that bind to pathogens, antibodies prevent attachment of pathogen to specific host cell receptor and gaining entry into host cell by endocytosis
  • opsonisation, binds antibodies to antigens on pathogens to mark pathogen for phagocytosis by macrophages
• structure of antibodies:

  • globular protein with quaternary structure, 4 polypeptide chains (2 heavy, 2 light)
  • light chain pairs with heavy chain, 2 heavy chains linked by disulfide bonds, hydrogen bonds, hydrophobic interactions, ionic bonds
• 2 Fragment of antigen-binding (Fab), each contains 1 antigen-binding site that binds to the epitope of antigen, prevents pathogen from attaching to host cell receptor and entering cell via endocytosis
• 1 Fragment crystallisable (Fc) region, binds to Fc receptor on phagocytes when bound to antigen to promote phagocytosis (opsonisation)
• Fab and Fc regions joined at hinge region, allows for flexibility and adopt a wide range of angles, can bind to epitopes spaced at variable distances apart
• VDJ recombination of heavy chain:

  1. rearrangement of D segment with J segment
  2. rearrangement of V segment with DJ segment
  3. transcription produces a pre-mRNA with VDJ exon and constant segments, RNA splicing for exon and constant segment to join
• VJ recombination of light chain:

  1. rearrangement of V segment with J segment
  2. transcription produces pre-mRNA, undergoes RNA splicing to join VJ segment with constant segment
• VDJ recombination allows for generation of many possible distinct antibody molecules, each with unique antibody binding sites
• VDJ recombination/somatic recombination takes place during B cell development in bone marrow
• somatic hypermutation: random point mutations in rearranged VDJ and VJ region

  • occurs in activated B cells outside bone marrow
  • occurs at a faster rate than normal mutations
• somatic hypermutation:

  1. activated B cells undergo clonal expansion, some undergo somatic hypermutation
  2. slight amino acid differences in variable regions of BCR
  3. can result in B cells with higher affinity B cell receptors on its cell surface membrane --> will be selected for clonal expansion and differentiation
  4. B cells can differentiate into plasma cells that secrete antibodies with higher binding affinity for specific antigen

  OR

  • results in B cells with low affinity B cell receptors
• class switching: different class antibodies contain different constant region of heavy chain

  • occurs in activated B cells in the presence of antigen
  • molecules released from T helper cells during B cell activation induces a B cell to switch synthesising a different class of antibody
  • rearrangement of variable region of heavy chain with constant region of another heavy chain
  • allows for expression of antibodies with the same antigen specificity by have different functions due to different constant region of heavy chain
• active immunity: produced by individual's own immune system in response to antigens introduced naturally or artificially
• passive immunity: antibodies are transferred to a recipient without participation from the recipient's immune system
• action of mycobacterium tuberculosis:

  1. macrophages phagocytose bacteria, forming phagosomes
  2. bacteria inhibits fusion of phagosome with lysosomes
  3. bacteria continue to multiply inside macrophages
  4. clustering of cells, forms a tubercle, cell death by necrosis takes place in the centre of the tubercle
  5. tubercle cavity enlarges, air filled cavity inside allows bacteria to multiply
  6. tubercle ruptures and releases bacteria
• bacteriostatic antibiotics inhibit growth or cell division of bacteria
• bacteriocidal antibiotics kills bacteria when they undergo binary fission
• penicillin is bacteriocidal
• penicillin acts on peptidoglycan in bacterial cell walls
• influenza virus targets epithelial cells in respiratory tract
• HIV targets T helper cells and macrophages