imid 2

• Koch' postulates 


  establish the cause of infectious diseases

  1. microorganisms should be found in every case of disease
  2. microorganisms should be grown in vitro in pure culture for several generations
  3. same disease must be produced
  4. microorganisms should be isolated from infected hosts
• Koch Postulates do not work when

  1. Microorganisms are not culturable
  2. No animial model
  3. microbe only one part of disease
  4. hosts are infected but not having symptoms
• primary pathogen


  microbe can produce disease in a healthy human by generating virulence factors to breach host defense
• opportunistic pathogen


  microbe capable of producing disease only in hosts who are immunocompromised
• stages of bacterial pathogenesis

  transmission, adherence to cell surfaces, colonization, exit
• vertical transmission


  transmission from mother to offspring via breast milk, birth canal, transplacental
• horizontal transmission


  human to human contact
• ex of horizontal transmissions

  direct contact (STD) , respiratory aerosol, respiratory droplets, indirect contact, fecal-oral contact
• mobile genetic elements

  plasmids, bacteriophages and pathogenicity islands

  move from one cell to another
• pathogenicity islands

  genomic islands with genes that encode for virulence factors causing disease
• genomic islands


  large groups of genes in bacterial chromosome from horizontal gene transfer
• adherence factors

  attach to host receptor pili and binding is highly specific to determine type of cell bacterium can attach
• colonization

  microbes multiply and deal with host defenses by competing with normal microbiota, avoid secretory IgA, rapid pili turnover, and producing siderophores to bind to iron
• siderophores

  iron-binding molecules to obtain iron and enhance disease
• how humans limit iron binding during colonization

  use transferrin and lactoferrin to sequester iron limiting bacterial growth
• type III secretion system (injectisome)

  alters cytoskeleton structure to induce uptake of bacterial cells by inducing non phagocytotic cells to engulf them via endocytosis and rearrange host cell actin to cause membrane ruffling
• membrane ruffling

  encloses bacteria to cause disease
• M cells


  antigen serving cells used to transport material through intestinal barrier, when infected bacteria induce M apoptosis by binding to the base of mucosal epithelial cells and induce uptake
• avoiding destruction by phagocytes by preventing contact w phagocytes

  C5a peptidase degrades C5a to avoid contact
• avoiding destruction by phagocytes by toxin release to damage phagocytes

  Membrane damaging toxins forms pores in cell membranes

  Ex: Streptolysin O
• avoiding destruction by phagocytes by preventing opsonization

  avoiding recognition by phagocytes by producing capsules that block C3b deposition blocking the activation of phagocytes or fc receptors bind to fc region to mask from phagocytes
• inhibiting phagosome lysosome fusion

  avoid proteases and lipases in lysosome to avoid exposure and destruction
• avoiding destruction by phagocytes by escaping from phagosome into cytoplasm


  use pore-forming proteins to escape before fusion
• other mechanisms for immune evasion

  avoiding killing by complement by serum resistant bacteria and avoiding recognition by antibodies (humoral) by using IgA protease to cleave antibodies and antigenic variation
• antigenic variation

  alter surface antigen to avoid detection and allows bacteria to stay ahead of antibody production
• endotoxins

  gram negative LPS that contains Lipid A which is released following cell lysis triggering inflammatory response and the activation of complement cascade sometimes resulting in septic shock,

  heat stable- not destroyed by autoclaving
• peptidoglycans

  gram positive bacteria that can trigger sepsis and septic shock but less potent than endotoxins
• exotoxins

  produced by gram positive and gram negative bacteria that can secrete proteins locally or systemically and used to generate antibodies

  grouped according to tissues they affect or structure and MOA
• membrane damaging toxins

  cytotoxins that disrupt eukaryotic cytoplasmic membranes to cause lysis
• pore-forming toxins


  a type of membrane damaging toxins that insert into membranes form pores and cause hemolysins
• A-B toxins

  A-active subunit is toxic normally the enzyme B - binds to cell and determines what cell type will be infected
• superantigen

  stimulate Th cells leading to a cytokine storm and override by binding to MHC II and falsely activating Th to release cytokines
• indirect damages of immune responses

  inflammation and adaptive immunity by activating complement cascade (Ab-Ag complex) or molecular mimicry which can all result in tissue damage
• human microbiota


  population of microbes that inhabit internal and external epithelial surfaces of healthy humans
• microbiome project

  uses rRNA sequencing to characterize the human microbiome and the role it plays in human health and diseases
• microbiome in human health and diseases

  provides instruction to developing immune system, confers susceptibility or resistance to pathogen, and contributes to nutrition and health
• bacterial interference

  compete for sit for attachment and nutrients which limits colonization and growth
• skin flora

  a complex microbiome the exposed dry environment is not good for bacteria, the moist area can support large microbial regions
• aerobic bacteria on skin

  Staphylococcus epidermis and Staphylococcus aureus
• anaerobic bacteria on skin

  hair follicles, sweat, sebaceous glands

  Cutibacterium acnes