Term
Innate Immunity: an evolutionary view
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Definition
-All multicellular organisms have defense mechanisms against microbial and viral infections
-For vertebrates, innate and adaptive immunity
-Vertebrate innate immune elements are closely related to components of immunity in invertebrates
-Innate immunity retains importance as:
-A first line of defense, slowing growth of infectious agents until adaptive immunity kicks in
-A means of directing adaptive immunity
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Term
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Definition
-The ability of pre-existing or rapidly inducible host effector systems to combat infectious agents against which the host has not been previously immunized
-Provides time for host to elicit specific immunity to the invading pathogen, by retarding replication and dissemination
-Essential for the control of many common infections early after infection (4-7 dpi)
-Participate in the removal of pathogens that have been targeted by an adaptive immune response
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Term
Recognition mechanisms of innate immunity |
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Definition
-Innate immune mechanisms have evolved to focus on components of pathogens that can not easily be changed and are broadly expressed molecules characteristic of broad groups of microbes
-pathogen-associated molecular patterns, or PAMPs
-recognized by host pattern recognition receptors, or PRRs
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Term
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Definition
-Internal epithelia called mucosal because they secrete viscous fluid, mucus (contains many glycoproteins called mucins)
-Mucus coats microorganisms and can prevent their adherence to epithelium
-In respiratory tract, mucus flow driven by beating of cilia on epithelial cells
-In gut, peristalsis keeps both food and infectious agents moving through the body
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Term
Chemical barriers: Antimicrobial peptides |
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Definition
-Generally small peptides (fewer than 100 amino acids)
-Often highly amphipathic in nature
-Expressed by epithelial cells in select locations to prevent bacterial colonization
-Expressed by neutrophils to contribute to killing of microbes after phagocytosis
-Three major groups:
a-defensins
b-defensins
cathelicidins
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Term
Mechanism of defensin killing of microbes |
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Definition
-Defensins are highly amphipathic and positively charged
-Their (+)-charged regions interact with the (-)-charged phospholipids of microbial membranes
-They insert their hydrophobic regions into the membrane and oligomerize to form pores
-Disrupts the normal function of the membrane
-Allow entry of other effector molecules of immune defense
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Term
Microbiological barriers: Protection afforded by normal flora |
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Definition
-Normal flora found along epithelial surfaces are nonpathogenic bacteria that are present continuously but cause no harm to the host
-Compete with pathogenic microorganisms for nutrients and for attachment sites on epithelial cells
-Can produce antimicrobial substances
-Antibiotic treatment kills pathogenic and nonpathogenic bacteria; thus overuse of antibiotics can allow replacement of normal flora with pathogenic bacteria
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Term
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Definition
-One of three populations of phagocytic cells
-Monocytes migrate from the blood and develop into Mφs
-Many tissues have resident Mφs and in some tissues they are given unique names:
nKupffer cells in the liver
nmicroglial cells in the CNS
nalveolar Mφ in the lungs
Mφ-derived cytokines are critical in coordinating innate responses to a variety of microbes
A major effector function of Mφs is phagocytosis of particles (bacteria, yeast, etc.) or pinocytosis of viruses
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Term
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Definition
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-Neutrophils are phagocytic cells that are able to ingest and kill most microbes in the blood
-Can migrate from blood to tissues, if needed
-Are short lived cells but the most numerous cells of the immune system
-Neutrophils are critically important in resistance to some microbes (e.g., gram + bacteria): hereditary deficiencies in neutrophil function lead to overwhelming bacterial infections
-Neutrophil numbers in the blood can be increased by a wide variety of conditions (extreme exercise, infection, severe psychological stress, inflammation)
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Term
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Definition
-Phagocytic and macropinocytic cells (ingest large amounts of surrounding extracellular fluid)
-Specialized to take up antigen (self and nonself), process it, and present it for recognition by T lymphocytes
-Immature DCs migrate from the blood to reside in tissues
-In the absence of pathogens, immature cells continuously migrate from the tissues bearing self antigens and induce tolerance
-Upon encountering a pathogen, they rapidly mature and express costimulatory molecules; they then migrate to lymph nodes and activate adaptive immune responses
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Term
Natural killer (NK) cells |
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Definition
-Small percentage of total lymphocytes
-Kill cells infected with certain viruses
-Produce interferon-gamma for early anti-bacterial activity
-Activated by various Mφ-derived cytokines to more effectively lyse target cells
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Term
Functions of pattern-recognition receptors |
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Definition
-Phagocytic receptors
-Chemotactic receptors (guide cells to sites of infection)
-Induce effector molecules that contribute to the induced response of innate immunity
-Induce molecules that influence the initiation and nature of subsequent adaptive immune response– Toll-like receptors
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Term
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Definition
-13 mammalian family members currently known
-Evolutionarily conserved transmembrane receptors that are thought to function only as signaling receptors
-Recognize constituents of microbial cell walls or pathogen-specific nucleic acids
-TLR interaction with pathogen induces Mjs to synthesize and secrete cytokines and lipid mediators, initiating inflammation
-TLR interaction with pathogen induces DCs to produce and display co-stimulatory molecules that eventually lead to the induction of adaptive immunity
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Term
Recognition by TLRs can occur intracellularly |
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Definition
-Microbial nucleic acids are recognized by TLRs localized to intracellular membranes
-These TLRs are thought to encounter their ligands in phagosomes or endosomes
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Term
Individuals can have genetic defects in TLR pathways |
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Definition
-Heritable IRAK4 deficiency:
-Have been 18 identified individuals; 8 died in early childhood
-Susceptible to recurrent and invasive bacterial infections
-Surprisingly, patients are not overly susceptible to viral infections
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Term
Interferon provides a critical defense against virus infection |
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Definition
-Interferons (IFNa, b, and g) are induced by viruses and inhibit viral replication
-Type I IFN (IFNa and IFNb) is produced by most cells upon viral infection and its major function is defense against viruses
-Type II IFN (IFN g) functions in defense against intracellular infections by microbes and parasites as well as against viruses
-Mice genetically deficient in receptors for both type I and type II IFN exhibit increased susceptibility to infections by a wide range of viruses
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Term
IFN regulatory factors (IRFs) induce the production of type I IFN |
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Definition
•Type I IFNs are produced in two distinct ways:
•By innate immune cells detecting the presence of viruses through TLRs
•By infected cells detecting intracellular virus replication
-one product is PKR.
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Term
Individuals can have genetic defects in IFN pathways |
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Definition
-IFNGR defect: Very rare inherited disorder that causes persons to be more susceptible to certain types of bacteria, esp. those that cause tuberculosis
-Very rare cases of reported STAT-1 deficiency (fatal): Infants highly susceptible to both bacterial and viral infections and usually die from viral infections
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