Immunology

• Types of Infections


  • Bacteria
  • Viral
  • Protista
  • Fungi
  • Parasites
• 4 stairs of the immune system

  • Anatomic barriers
• A typical infection


  1. 1

  2. 2

  3. 3

  4. 4
• The complement


  • A triggered enzyme cascade
  • Three pathways
  • Functions: Opsonisation, Produce membrane attack complex (MAC), Enhance inflammatory process
• Deficiency of C1 inhibitor (hereditary or drug induced)

  Dermal and submucosal oedema that can be life-threatening if the airway is involved
• Innate Immunity


  • General recognition of bacteria, viruses, parasites
  • First line defence
  • Present in all individuals at all times
• Local infection


  1. Bacteria in tissue

  2. Complement activation

  3. Cytokine release (TNF-α, IL-1, IL-8)

  4. Activation of coagulation cascade

  5. Vasodilation

  6. Leakage of fluid into the tissue

  7. Clearing of infection

  8. Heat

  9. No of PMNs increased

  10. PMNs migrate into the tissue

  11. Constr. and relax. of blood vessels

  12. Small local clots produced

  13. Clots plugging capillaries
• DAMPs vs PAMPs


  • Damage associated Patterns vs Pathogens associated Patterns
  • Endogenous danger molecules vs "non-self" molecules
• 1. reactive protein


  • Promotes phagocytosis
  • Participates in opsonisation
  • Facilitates activation of the complement
  • Also new high-sensitivity CRP assays to assess cardiovascular risk
  • Also other (chronic) inflammatory diseases associated with (minute) changes in CRP levels
• The graph shows the CRP levels from two patients (green / blue) undergoing the same surgery


  What is the clinical difference between them?
• Systemic inflammatory response syndrome (SIRS)

  1. Ensuring hemodynamic stability

  2. Vasopressors and inotropes

  3. Primary source control

  4. Broad-spectrum antibiotics

  5. Glucocorticoids

  6. Blood glucose control
• Symptoms, Prevalence (in the UK, unless otherwise stated), Treatment
• The complement system


  • A triggered enzyme cascade
  • Three pathways
  • Functions: Opsonisation, Produce membrane attack complex (MAC), Enhance inflammatory process
• Sepsis with one or more end-organ failure

  severe sepsis
• Cells of the immune system

  • 1
  • 2
  • 3
  • 4
  • 6
  • 5
  • 7
  • 8
  • 9
  • 10
  • 11
  • 12
• Hemodynamic instability in spite of intravascular volume repletion

  septic shock
• Almost all septic patients have SIRS, but not all SIRS patients are septic
• SIRS: any two of these criteria

  • Body temperature over 38ºC or under 36ºC
  • Heart rate greater than 90 beats/minute
  • Respiratory rate greater than 20 breaths/minute or partial pressure of CO2 less than 32mmHg
  • Leucocyte count greater than 12000 or less than 4000 /µl or over 10% immature forms or bands
• There is more to sepsis than a cytokine storm
• Local infection


  1. Bacteria in tissue

  2. Complement activation

  3. Cytokine release

  4. TNF-α, IL-1, IL-8

  5. Activation of coagulation cascade

  6. Vasodilation

  7. Leakage of fluid into the tissue

  8. Clearing of infection

  9. Heat

  10. No of PMNs increased

  11. PMNs migrate into the tissue

  12. Constr. and relax. of blood vessels

  13. Small local clots produced

  14. Clots plugging capillaries
• Three main theories that explain immunological response in sepsis
• Adaptive Immunity is specific recognition of non-self, including other foreign human cells, develops immunological memory, also known as acquired immunity, includes humoral immunity and cell-mediated immunity
• Link between innate and adaptive immune system

  Macrophages, Dendritic cells, Neutrophils, Complement
• Antibody classes


  • IgM
  • IgG
  • IgA
  • IgD
  • IgE
• Antibodies


  • IgG
  • IgA
  • IgM
  • IgD
  • IgE
• Antibody properties


  • Heavy chain symbol
  • Molecular weight (approx. In daltons)
  • Serum concentration (mg/mL) (adult)
  • Serum half-life (days)
  • Percentage of total immunoglobulins in serum
  • Complement fixing capacity
  • Placental transfer to fetus
• IgM


  Blocks binding of toxins and adherence of microbes, Activates classical complement pathway, Destroys pathogens in early stages of B cell-mediated immunity, First antibody to appear in the immune response
• Antibody functions


  • Blocks binding of toxins and adherence of microbes
  • Provides majority of antibody-based immunity
  • Activates classical complement pathway
  • Can cross the placenta to protect the foetus
  • Opsonises antigen for phagocytic cells
  • Mediates killer activity of cells
  • Transported across mucous membranes, including gut
  • Involved in allergy, triggering release of histamine from mast cells and basophils
  • Provides protection against parasitic worms
  • Opsonisation of antigen for eosinophils
• Cytotoxic vs Helper T-cells

  • CD8 T cells: peptide + MHC class I
  • CD4 T cells: peptide + MHC class II
• IgG


  Blocks binding of toxins and adherence of microbes, Provides majority of antibody-based immunity, Subclasses 1, 2 and 3 activate classical complement pathway, Can cross the placenta to protect the foetus, Opsonises antigen for phagocytic cells, Mediates killer activity of null cells
• 1. cell types


  • Cytotoxic (killer) T cells
  • TH1 cells
  • TH2 cells
  • Treg cells
• 1. cell effector molecules


  • Perforin
  • Granzymes
  • Granulysin
  • IFNγ
  • GM-CSF
  • TNF-α
  • IL-4
  • IL-5
  • IL-13
  • Il-10
  • TGF-β
• IgA


  Blocks binding of toxins and adherence of microbes, Transported across mucous membranes, including gut, Has a secretory piece to protect against digestion
• Vaccines


  Protection against smallpox infection by vaccination with cowpox
• IgD


  Function unclear but may act as an antigen receptor on virgin B cells, Very low concentration
• B Sc Medical Sciences Dr Katja Vogt @katjetz [e-mail]
• IgE


  Low serum concentration because adsorbed onto mast cells, Involved in allergy, triggering release of histamine from mast cells and basophils, Cross-linking of IgE on mast cells by antigen mediates degranulation, Provides protection against parasitic worms, Opsonisation of antigen for eosinophils
• School of Medicine Dr Katja Vogt
• Edward Jenner (1749-1823) developed the smallpox vaccine
• Dr Katja Vogt