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 respons 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
- Exterior Defenses
- Skin, mucosal epithelium, lysozyme, acidic environments
- Interior Defenses
- Infection or trauma causes inflammation
- non-specific response aimed at clearing tissue of foreign/dead material and tissue regeneration
- Phagocytes primary mediators
- Infection or trauma causes 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.
- neutralizing Ab
- inhibits attachtment
- Binds toxins & inactivates
- opsonizing Ab: IgG enchances phagocytosis with or without C3b
- encapsulated, gram + bacteria
- complement activation
- classical pathway
- lysis of gram neg bacteria
- C3b opsonization of gram pos bacteria
- inflammation
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.
- CD4+ T cell activation → Th1 effectors due to IL-12
- Th1 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
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
Immunity to Viruses
Innate: includes inhibition of infection by Type I IFNs which produce a local and transient anti-viral effect on neighboring cells and NK cells mediated lysis of virally infected cells.
Acquired: both humoral and cell mediated immunity is involved in the resolution and resistance to viral infections.
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Humoral
- neutralizing IgG prevent viral attachment and entry
- Ab only effective during extracellular stage
- Or for cytopathic (lytic) viruses after release from cell and before going into another cell
- IgA may neutralize viruses in mucosa
- Complement promotes phagocytosis and may directly lyse
- neutralizing IgG prevent viral attachment and entry
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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 require com-stimulation by cytokines from activated CD4+ T cells
- virus specific CD8+ T cells recognize cytosolic endogenously processed viral Ag on MHC I
- Only cell mediated but not humoral immune mechanisms can eradicate an established viral infection.
- Evasion strategies:
- downregulation of MHC I
- virokines and 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 oppotunistic 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
