Colloquium 2

• Infection


  The encounter, entry and multiplying of microorganisms behind the skin-mucous barrier of the host, followed by damage of the host's tissues
• Infectious process


  The process of overcoming the hosts' barriers, multiplication of the microorganism and damage of the host. The clinical manifestation of the infectious process is the infectious disease
• Colonisation


  The presence of microorganisms at a site of the body and doesn't necessarily lead to tissue damage, signs or symptoms of a disease
• Toxicosis


  The entry of microbial toxins in the host (botulism), if it is supported by infection it is called toxic infection e.g. tetanus, diphtheria
• Events of infectious disease

  1. Encounter

  2. Entry

  3. Spread

  4. Multiplication

  5. Damage

  6. Outcome

  
• Pathogenicity


  Generally determined sign of microbial species that shows their ability to cause damage
• Virulence


  The degree of pathogenicity as a quantitative individual sign
• Minimum infecting dose (MID)


  The minimum number of bacteria, required to produce clinical evidence of infection in a susceptible animal under standard conditions
• Minimum lethal dose (MLD)

  The minimum number of bacteria, required to kill 50 percent of susceptible animals, tested under standard conditions
• Factors affecting virulence


  • Chemical (e.g. phenol, hydrogen peroxide, bile)
  • Physical (e.g. UV rays)
  • Biological (e.g. passages through animals that are susceptible to the agent)
• Factors affecting pathogenicity


  • Adhesion/attachment
  • Mechanical action
  • Biofilm production
  • Invasiveness
  • Capsules which inhibit phagocytosis
  • Toxigenic products (exotoxins and endotoxins)
• Exotoxins


  e.g. botulinum (C. botulinum), C. diphtheriae toxin, tetanospasmin (C. tetani)
• Endotoxins


  aka LPS, e.g. N. menigitidis
• Factors supporting the spread of infection the epidemic process

  • Natural (e.g. water, air, food, soil)
  • Social (e.g. communal hygiene, transport)
  • Medicine (e.g. routine use of antibiotics and immunosuppressive drugs)
  • Sex (e.g. promiscuity)
  • Pets
  • Travel (e.g. journeys to tropical and subtropical countries)
  • Age (e.g. risk ages from new-borns and older persons)
  • Genetic background (e.g. malaria resistance among some people)
  • Nutrition, crowding and cultural factors
• Characteristics of infectious disease

  • Certain microbial causative agent
  • Incubation period
  • Specific symptoms
  • Epidemic spreading
  • Convalescent period
  • Carriage of causative agent
• Forms of infectious disease

  • According to origin (exogenous, iatrogenic, endogenous)
  • According to topic (focal, generalised)
  • According to microbial agent (bacteraemia, viremia, toxaemia, sepsis, pyaemia)
  • According to number of infectious agents (monoinfection, mixed infection)
  • According to secondary development (primary, secondary, reinfection, superinfection, relapse)
  • According to time course (acute, chronic, slow, carriage)
  • According to clinical course (unapparent, atypical, latent, manifested)

  
• Carrier


  A person who harbours microorganisms without suffering from the illness or symptoms of an infectious disease
• Epidemic process


  The biological circulation of pathogenic microorganisms among the population
• Epidemic


  Disease that spreads rapidly, involves many persons in an area at the same time. E.g. cholera, HAV etc which are waterborne diseases
• Endemic disease


  Occur regularly at low or moderate frequency, they are constantly present in a particular area e.g. cholera and typhoid fever
• Pandemics


  Global epidemics which spread through many areas of the world e.g. cholera, plague, COVID-19
• Characteristics of the epidemic process

  • Source of infection (living subject e.g. humans or animals)
  • Reservoir (all biological species which maintain the microbial agents in nature e.g. humans/antroponozones, animals (zoonozes) and other biological species)
  • Mechanisms of transmission (vectors, fomites, mechanical, biological, susceptible individuals)
• Natural/innate immunity


  Non-specific resistance that does not involve the production of Abs i.e. complement system, acute phase proteins, interferons and lysozyme

  
• Types of innate immunity

  • Species immunity
  • Different races
  • Individual immunity
• Acquired immunity


  Specific resistance that involves the production of specific Abs, the main cellular factors are T-Lys and B-Lys

  
• Types of acquired immunity

  • Naturally acquired, active immunity
  • Artificially acquired, active immunity
  • Artificially acquired, passive immunity
  • Naturally acquired, passive immunity
• Non-specific defences - the protective role of

  • Skin
  • Mucous membranes
  • Organs
  • Normal microbial flora
• Lysozyme


  Enzymes that damage bacterial cell walls, particular gram +ve bacteria. They are abundant in a number of secretions, such as tears, saliva, and mucus and are also present in cytoplasmic granules of Maf and PMNs
• Complement (CO)


  A complex of about 20 protein, grouped in 9 components, which form one of the triggered enzyme systems in serum. They produce a rapid amplified response to a stimulus, mediated by a cascade phenomenon where the product of one reaction is the enzymatic catalyst of the next
• Pathways of complement activation

  • Classical
  • Alternative
  • Lectin
• Complement system


  Two components for binding cell membranes and one for enzymatic cleavage of the next component
• Minor fragments


  Have chemotactic activities - bacteria can direct their movements according to certain chemicals in their environment
• Pathways of complement activation

  • Classical
  • Alternative
  • Lectin
• Classical pathway


  1. Activated by Ag-Ab complexes (IgG or IgM)

  2. Binding to the Fc portion of Ab that is bound to cell surface Ags or in an immune complex with soluble Ags

  3. Change in the Fc region of Ab reveals a binding site for C1q

  4. C1r and C1s bound to generate enzyme activity for C4 and C2

  5. C4b2a (C3 convertase) cleaves C3 into C3a and C3b

  6. C4b3b2a (C5 convertase) initiates the sequential attachment of C5, C6, C7, C8 and C9 known as MAC (membrane attack complex) which results in lysis
• Alternative pathway


  1. Activation of C3 and the generation of C3 convertase without Ag-Ab complex, C1, C2 or C4

  2. Endotoxins are the most important activators

  3. Initial cleavage of C3 happens continuously and spontaneously, generating low levels of C3b

  4. C3b uses factors B and D to produce the active enzyme C3bBb which becomes stabilised in the presence of factor B to form C5 convertase and then the lytic pathway continues as normal
• Lectin pathway


  1. Mannose-binding protein (MBP) binds non-reduced mannose, fucose and glucosamine on bacterial surfaces

  2. MBP replaces the C1q component and on binding bacterial surfaces, activates the MBP-associated serine protease which cleaves C4 and C2 to produce C3 convertase
• Interferons (INF)

  • A family of broad spectrum antiviral molecules, used for prevention and treatment of viral infections
  • 3 types; INF-α – produced by leucocytes, INF-β – produced by fibroblasts and INF-γ – produced immune lymphocytes and NK cells

  
• Cytokines


  • A group of non-antibody proteins that act as mediators between cells
  • Inflammatory cytokines (IL-1, IL-6) provoke an increased synthesis of particular serum protein in liver, termed as acute phase proteins (APP)
  • Many of them such as CRP (C- reaction protein) increase dramatically, while others show more moderate rises

  
• Phagocytosis


  Process of adherence of the microorganism to the phagocytic cells, engulfment and killing
• Phagocytes


  • Macrophages
  • Polymorphonuclear leucocytes/microphages