Immunity to Bacteria

Question 1

What makes bacteria and fungi differ from viruses?

Answer 1

• pathogenic bacteria and fungi are free living - don’t usually enter cells
• reproduce on mucous surfaces

Question 2

Examples of pathogenic bacteria

Answer 2

• Mycobacterium tuberculosis - TB (infects macrophages in lung)
• Mycobacterium leprae - Leprosy
• Salmonella enterica - food poisoning
• Listeria monocytogenes - food poisoning
• Brucella abortus - triggers abortion in cows

Question 3

TB

Answer 3

• common in HIV patients whom are not on HAART anti-viral treatments
• infects macrophages in lungs - hypersensitivity response forms nodules (tubercles) - chronic inflammation
• treatment - antibiotic (months)
  
  • Isoniazid (rifampin + Pyrazinamide + Ethambutol)

Question 4

Gram + Bacteria

Answer 4

• streptococcus pneumonias (lungs)

Question 5

Gram - bacteria

Answer 5

• helicobacter pylori (gastric ulcers)
• mycobacteria (TB)
• spirochetes (treponema pallidum) - syphilis
• susceptible to lysis by complement
• peptidoglycan degradation by lysozyme

Question 6

Adaptive immune responses to extracellular micro-organsims

Answer 6

• neutralisation
• opsonisation and fc-receptor mediated phagocytosis
• inflammation
• lysis of microbe
• macrophage activation - phagocytosis
• ab response

*don’t have to kill cell but rather the bacteria itself

Question 7

Gram + cell wall

Answer 7

• increased amount of peptidoglycan

Question 8

Gram - wall

Answer 8

• 2 membranes
  
  • inner cytoplasmic membrane
  • small peptoglycan layer in between
  • outer membrane
• main component - LPS

Question 9

Bacterial Cell Wall Differences

Answer 9

Question 10

Role of Ab

Answer 10

• neutralisation of toxins - e.g. Tetanus toxoid from clostridium tetani
• secretory IgA (sIgA) - protection of mucosal surfaces
  
  • sIgA dimers secreted onto intestinal lumen surface by plasma cells
  • prevents new luminal invasion by same pathogen
• binding of Fe by lactoferrin - required for bacterial growth

Question 11

How do macrophages and DCs recognise bacteria?

Answer 11

• PRRs
• mannosyl-fucose receptors - bind sugars on surface of microbes
• CD14r - remove microbes coated with LPS
• Fcr - bind abs to pathogens - IgG, IgM, IgA
• Complement receptor CR1/CD35 - binds complement microbes

Question 12

Abs that are capable of activating complement

Answer 12

• IgM
• IgG1
• IgG3
• promotes complement mediated lysis of bacteria
• promotes opsonisation of bacteria and fungi - phagocytosis

Question 13

Main mechanisms for removing bacteria

Answer 13

• abs
• phagocytosis

Question 14

Cationic proteins & Lysosomal enzymes

Answer 14

• Defensins, Cathepsin G, Lysosome, Lactoferrin
• O2-dependant killing

Mechanism:

• alkaline environment required for cationic proteins in phagosome
• when phagosome fuses with lysosome - acidification - acidic environment required for lysosomal enzymes

Question 15

Describe killing of pathogens by phagocytosis

Answer 15

• production of RO intermediates (ROI)
  
  • hydroxyl radical
  • H202
  • hypochlorous acid
  • NO
  • Superoxide anion

Question 16

Evasion mechanism of bacteria

Answer 16

• secretion of anti-chemotaxis signals
• capsule that inhibits phagocytosis - strep pneumoniae
• inhibition of phagosome/lysosome fusion and acidification - m.tuberculosis
• production of catalase - breakdown H202
• blocks IFNy effects - mycobacterium
• Impaired MHC - salmonella
• tough outer coat scavenges free radicals - mycobacterium

*only way to kill this type of bacteria is by antibiotics

Question 17

Sepsis

Answer 17

• body’s response to infection damages its own tissues
• predisposition to infection - young to old age, immunosuppressive diseases, cancer, immunosuppressive medications, diabetes
• Treatment : timely initiation of appropriate antibiotic therapy
  
  • not treated in time - increased LPS, inflamm response (cytokine storm) - irreversible
• circulatory collapse and disseminated intravascular coagulation
  
  • NF-endothelial cell adhesion
  • activation of clotting and complement cascades - microthrombi formation
• massive vasodilation - loss of plasma volume
• shock from dramatic drop in bp - organ failure
• important trigger
  
  • LPS on gram - bacteria (TLR4 binds to LPS)
  • monocytes respond by cytokine storm - TNFa, IL-1, IL-6

Question 18

Drug used to counteract vasodilation in sepsis

Answer 18

• noradrenaline - vasopressor
  
  • contacts blood vessels and raises bp

Question 19

Therapies under investigation for sepsis

Answer 19

• LPS removal via polymyxin B haemo-perfusion
• anti-TNF-a mabs

*anti-sepsis medication is time critical

Question 20

Immunity to Fungi

Answer 20

• mainly NFs, macrophages and DCs
• through TLRs and Dectin-1
  
  • Dectine-1 binds to β-glucan on surface of Candida albicans
  • TH17 response

Superficial mycosis