Exam 1: Immunity to Infection Flashcards
Classes of Bacteria
- Gram-positive: thick peptidoglycan layer
- Gram negative: thin peptidoglycan layer plus presence of lipopolysaccharide (LPS)
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Extracellular bacteria:
- Include majority of bacteria
- Causes inflammation
- Produces toxins
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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
Viruses
- 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
Fungi
- Eukaryotic organisms
- Some replicate inside, outside, or both
- Immunodeficient may acquire severe infections
Parasites
- 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
Innate Immunity
Provides early protection.
Present prior to exposure to infectious agents.
Not enhanced by repeated exposure.
Does not discriminate.
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Exterior Defenses
- Skin, mucosal epithelium, lysozyme, acidic environments
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Interior Defenses
- Infection or trauma ⇒ inflammation
- Non-specific response aimed at clearing tissue of foreign/dead material and tissue regeneration
- Phagocytes ⇒ primary mediators
- Infection or trauma ⇒ inflammation
TLR-4
- 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
Immunity to Extracellular Bacteria
Innate: principal mechansims complement, phagocytosis (neutrophils), and inflammation.
Aquired: Humoral immunity functions to eliminate bacteria or neutralize toxins.
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Neutralizing Ab
- Inhibits attachment
- Binds toxins & inactivates
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Opsonizing Ab
- IgG enhances phagocytosis ± C3b
- Important against encapsulated, gram + bacteria
- IgG enhances phagocytosis ± C3b
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Complement activation
- Classical pathway
- Lysis of gram neg bacteria
- C3b opsonization of gram pos bacteria
- Inflammation
- Classical pathway
Immunity to Intracellular Bacteria
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.
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CD4+ T cell activation → Th1 effectors due to IL-12
- Th1 cells secrete IFN-γ which activate macrophages to kill most intracellular bacteria
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CD8+ T cell → cytotoxic T cells
- Lyse infected macrophages
- Allow bacteria to be phagocytized by activated macrophages which can kill some
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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
Leprosy
Differences among individuals in the strength and character of immune response to organism may directly affect disease progression and clinical outcome:
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Th1 response results in tuberculoid form
- restricted growth of organsims
- tissue distruction by immune system
- less severe form
- responds to treatment
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Th2 response results in lepromatous form
- unrestricted growth of organisms
- extensive damage
- may require life long treatment
Bacterial Evasion Strategies
- 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
Viral
Innate Immunity
-
Type I IFNs mediated inhibition of infection
- Produce a local and transient anti-viral effect on neighboring cells
- NK cells mediated lysis of virally infected cells
Two major groups of interferons are…
Interferon α ⇒ made by dendritic cells and macrophages
Interferon β ⇒ made by many cells types including fibroblasts
Viral
Adaptive Immunity
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
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sIgA
- May neutralize viruses in mucosa
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Complement
- Promotes phagocytosis
- May directly lyse
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Neutralizing IgG
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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
- Virus specific CD8+ T-cells
Only ___ mechanisms can eradicate an established viral infection.
cell-mediated immunity
(e.g. CD8+ T-cells and NK cells)
Viral
Evasion Strategies
- Downregulation of MHC I
- Virokines
- Viroreceptors
Immunity to Fungi
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.
Immunity to Parasites
Wide range of pathogens from intracellular organisms to worms.
Diverse immune response.
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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
- For intracellular pathogens of macrophages:
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Evasion strategies:
- Cuticle formation
- Antigenic variation
