Exam 1: Immunity to Infection

Question 1

Classes of Bacteria

Answer 1

• Gram-positive: thick peptidoglycan layer
• Gram negative: thin peptidoglycan layer plus presence of lipopolysaccharide (LPS)
• Extracellular bacteria:
  
  • Include majority of bacteria
  • Causes inflammation
  • Produces toxins
• Intracellular bacteria:
  
  • Facultative ⇒ can survive and replicate both inside and outside of host cells
  • Obligate intracellular ⇒ must replicate within cells
  • Many uniquely adapted to survive in macrophages cause chronic infections
  • Activate and sustain immune response against host tissue

Question 2

Viruses

Answer 2

• Obligate intracellular pathogens
• Uses normal host molecules for attachment and entry
• Naked or enveloped
• Cause disease in many ways including:
  
  • Direct cell lysis
  • Inciting host immune response
  • Transformation of host cells

Question 3

Fungi

Answer 3

• Eukaryotic organisms
• Some replicate inside, outside, or both
• Immunodeficient may acquire severe infections

Question 4

Parasites

Answer 4

• Unicellular and multicellular eukaryotic organisms
• Accounts for more morbidity and mortality than any other class of microorganism
• Some intracellularly and some extracellularly
  
  • Some with both stages

Question 5

Innate Immunity

Answer 5

Provides early protection.

Present prior to exposure to infectious agents.

Not enhanced by repeated exposure.

Does not discriminate.

• Exterior Defenses
  
  • Skin, mucosal epithelium, lysozyme, acidic environments
• Interior Defenses
  
  • Infection or trauma ⇒ inflammation
    
    • Non-specific response aimed at clearing tissue of foreign/dead material and tissue regeneration
  • Phagocytes ⇒ primary mediators

Question 6

TLR-4

Answer 6

• LPS-LPS binding protein complex binds to CD14 on macrophages
• Activated CD14 associated with TLR-4
• Signaling through TLR-4 leads to activation of NFkB (transcription factor)
• Results in pro-inflammatory cytokine release

Question 7

Immunity to Extracellular Bacteria

Answer 7

Innate: principal mechansims complement, phagocytosis (neutrophils), and inflammation.

Aquired: Humoral immunity functions to eliminate bacteria or neutralize toxins.

• Neutralizing Ab
  
  • Inhibits attachment
  • Binds toxins & inactivates
• Opsonizing Ab
  
  • IgG enhances phagocytosis ± C3b
    
    • Important against encapsulated, gram + bacteria
• Complement activation
  
  • Classical pathway
    
    • Lysis of gram neg bacteria
    • C3b opsonization of gram pos bacteria
    • Inflammation

Question 8

Immunity to Intracellular Bacteria

Answer 8

Innate: phagocytosis by macrophages (inactivated), may result in limited killing or inhibition of replication, but cannot control infection.

Acquired: cell-mediated immunity by CD4 and CD8 T cells.

• CD4⁺ T cell activation → T_h1 effectors due to IL-12
  
  • T_h1 cells secrete IFN-γ which activate macrophages to kill most intracellular bacteria
• CD8⁺ T cell → cytotoxic T cells
  
  • Lyse infected macrophages
  • Allow bacteria to be phagocytized by activated macrophages which can kill some
• Activated macrophages
  
  • Activated by IFN-γ, TNF-α, and other cytokines
  • Become effector cells which can kill via ROI, RNI, lysozyme & other antimicrobial peptides, secretion of cytokines
  • May lead to chronic inflammation, tissue damage, & granuloma formation

Question 9

Leprosy

Answer 9

Differences among individuals in the strength and character of immune response to organism may directly affect disease progression and clinical outcome:

• Th1 response results in tuberculoid form
  
  • restricted growth of organsims
  • tissue distruction by immune system
  • less severe form
  • responds to treatment
• Th2 response results in lepromatous form
  
  • unrestricted growth of organisms
  • extensive damage
  • may require life long treatment

Question 10

Bacterial Evasion Strategies

Answer 10

• exotoxins - leukocidins that kill or impair phagocytes
• IgA protease - inactivates IgA
• capules or slimes - prevents phagocytosis
• prevention of phagosome-lysome fusion
• escape from the phagosome

Question 11

Viral

Innate Immunity

Answer 11

1. Type I IFNs mediated inhibition of infection
   
   • Produce a local and transient anti-viral effect on neighboring cells
2. NK cells mediated lysis of virally infected cells

Question 12

Two major groups of interferons are…

Answer 12

Interferon α ⇒ made by dendritic cells and macrophages

Interferon β ⇒ made by many cells types including fibroblasts

Question 13

Viral

Adaptive Immunity

Answer 13

Both humoral and cell mediated immunity is involved in the resolution and resistance to viral infections:

• Humoral
  
  • Neutralizing IgG
    
    • Prevent viral attachment and entry
    • Only effective during extracellular stage
      
      • Cytopathic (lytic) viruses before entry or after release
  • sIgA
    
    • May neutralize viruses in mucosa
  • Complement
    
    • Promotes phagocytosis
    • May directly lyse
• Cell mediated
  
  • Virus specific CD⁸⁺ T-cells
    
    • Recognize cytosolic endogenously processed viral Ag on MHC I
    • Lysed by CTL
    • Full activation of CTL requires co-stimulation by cytokines from activated CD⁴⁺ T cells

Question 14

Only ___ mechanisms can eradicate an established viral infection.

Answer 14

cell-mediated immunity

(e.g. CD⁸⁺ T-cells and NK cells)

Question 15

Viral

Evasion Strategies

Answer 15

• Downregulation of MHC I
• Virokines
• Viroreceptors

Question 16

Immunity to Fungi

Answer 16

Innate: phagocytes are the most important innate defense against fungi via ROI, NRI, and lysosomal enzymes.

Acquired: cell mediated immunity, specifically Th1 mediated granulomatous responses control many opportunistic and systemic fungal infections.

Frequently causes host cell injury due to granulomas.

Question 17

Immunity to Parasites

Answer 17

Wide range of pathogens from intracellular organisms to worms.

Diverse immune response.

• Acquired
  
  • For intracellular pathogens of macrophages:
    
    • Th1 responses most important
  • For worm (helminth) infections:
    
    • Th2 resulting in IgE
    • Activation of eosinophils important
  • Malaria
    
    • Combo of immune responses required to eliminate still not fully understood
• Evasion strategies:
  
  • Cuticle formation
  • Antigenic variation