Term
The ____ is a multi-layer system of physical, chemical, and cellular defenses that are
ready for immediate activation by a pathogen. |
|
Definition
|
|
Term
|
Definition
| Physical; Chemical; Cellular |
|
|
Term
| Cellular part of innate consists of |
|
Definition
| Macrophages Neutrophils NK cells Dendritic cells |
|
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Term
| Physical barriers consists of |
|
Definition
Epithelial Cell Layers
Skin
Mucosa (GI, Respiratory, Urogenital)
Glandular Tissues (salivary, lacrimal,
mammary glands) |
|
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Term
| Chemical barriers consists of |
|
Definition
Acidity of the stomach
Anti-microbial molecules |
|
|
Term
Pathogens that breach barriers are confronted by
cells with ____receptors. Pathogens
can be phagocytosed or can face a barrage of antimicrobial
chemicals which kill them. |
|
Definition
|
|
Term
_______ are released that recruit
other cells including members of the adaptive arm. |
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Definition
|
|
Term
| the innate system is specific for what? |
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Definition
| Specific for molecules and molecular patterns associated with pathogens and molecules produced by dead and damaged cells… |
|
|
Term
| the diversity of the innate immune system consists of |
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Definition
| a limited number of conserved germ line encoded receptors...(while the adaptive his highly diverse) |
|
|
Term
| self and non-self recognition...the innate system is |
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Definition
| perfect ...there are no microbe self/ non self patterns in the host (while the adaptive can mess up and cause autoimmune disease) |
|
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Term
| The innate immune system's soluble components in the blood |
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Definition
| MANY anti microbial peptides, proteins and other mediators..(adaptive only has antibodies and cytokines.) |
|
|
Term
| the major cell types of the innate immune system are |
|
Definition
| the phagocytes (monocytes, macrophages, neutrophils)..natural killer cells...other leukocytes, epithelial cells and endothelial cells. |
|
|
Term
Neisseria gonorrhoeae, that causative agent of gonorrhea has ____that bind to specific glycoproteins
on the surface of epithelial cells in the mucous membrane of the urogenital tract. |
|
Definition
|
|
Term
Flu virus has ___that enables it to attach firmly to cells in the mucous membranes of
the respiratory tract, preventing the virus from being swept out by ciliated epithelial cells. |
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Definition
|
|
Term
The human skin produces a compound called _____ which is an antimicrobial protein that kills
E. coli but not microbes such as S. aureus. |
|
Definition
|
|
Term
___ immunity is the most ancient form of defense, found in all multicellular plants and animals, adaptive immunity is a much more recent evolutionary invention, having arisen
in vertebrates. |
|
Definition
|
|
Term
| The skin has an epidermis and a thicker layer, the ___ that contains__ |
|
Definition
epidermis. tiers of tightly
packed epithelial cells; its outer layer consists of mostly dead
cells filled with a waterproofing protein called keratin. Dermis made of connective tissue, blood
vessels, hair follicles, sebaceous glands, sweat glands, and scat-
tered myeloid leukocytes such as dendritic cells, macrophages,
and mast cells. |
|
|
Term
In place of skin, the respiratory, gastrointestinal, and urogenital tracts and the ducts of the salivary, lacrimal, and mammary glands are lined by strong barrier layers of ____ stitched together by tight junctions that prevent pathogens
from squeezing between them to enter the body. |
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Definition
|
|
Term
The ___ of these tissues (mucus, urine, saliva, tears, and milk) wash away potential invaders and also con-
tain antibacterial and antiviral substances. |
|
Definition
|
|
Term
___, the viscous fluid secreted by specialized cells of the mucosal
epithelial layers, entraps foreign microorganisms. |
|
Definition
|
|
Term
|
Definition
Mucosal/glandular secretions (e.g., tears, Cleaves glycosidic bonds of peptidoglycans in cell
saliva, respiratory tract) walls of bacteria, leading to lysis |
|
|
Term
Mucosal/glandular secretions (e.g., milk, Binds and sequesters iron, limiting growth of intestine mucus, nasal/respiratory and bacteria and fungi; disrupts microbial membranes;
urogenital tracts) limits infectivity of some viruses |
|
Definition
|
|
Term
| Secretory leukocyte protease |
|
Definition
Skin, mucosal/glandular secretions Blocks epithelial infection by bacteria, fungi, inhibitor (e.g., intestines, respiratory, and urogenital viruses; antimicrobial
tracts, milk) |
|
|
Term
| S100 proteins, e.g psoriasin calprotectin |
|
Definition
| Skin, mucosal/glandular secretions (e.g., tears, saliva/tongue, intestine, nasal, respiratory and urogenital tracts) - Disrupts membranes, killing cells - Binds and sequesters divalent cations ... (e.g., manganese and zinc), limiting growth of bacteria and fungi |
|
|
Term
|
Definition
| Skin, mucosal epithelia (e.g., mouth, intestine, nasal/respiratory tract, urogenital tract) Disrupts membranes of bacteria; additional toxic effects intracellularly; kills cells. |
|
|
Term
| Surfactant proteins SP-A, SP-D |
|
Definition
| Secretions of respiratory tract, other mucosal epithelia Block bacterial surface components; promotes phagocytosis |
|
|
Term
| While some mammals have multiple ___, humans have only one. |
|
Definition
|
|
Term
| Anti microbial proteins and peptides at epithelial surfaces are produced by _____ |
|
Definition
cells in the epithelia of mucosal and glandular tissues; can also be increased by microbial or inflammatory stimuli; Many are also produced con-
stitutively in neutrophils and stored in granules; In addition, synthesis and secretion of many of these molecules may be induced by microbial components during
innate immune responses by various myeloid leukocyte populations (monocytes, macrophages, dendritic cells, and mast cells). |
|
|
Term
Another major class of antimicrobial components secreted by skin and other epithelial layers is comprised of
antimicrobial ____, generally less than 100 amino acids
long, which are an ancient form of innate immunity present
in vertebrates, invertebrates, plants, and even some fungi. |
|
Definition
|
|
Term
The main types of antimicrobial peptides found in humans
are ______ |
|
Definition
| alpha- and beta-defensins and cathelicidin |
|
|
Term
Defensins and cathelicidin LL-37 (the only cathelicidin expressed in humans) are secreted constitutively by ___ in many tissues, as
well as stored in neutrophil granules where they contribute to
killing phagocytosed microbes. |
|
Definition
|
|
Term
______ are typically less that 100 amino acids and are cationic (+ charged).
They kill rapidly and often disrupt microbial membranes or inhibit synthesis of DNA, RNA, or
proteins.
Various proteins are made that target bacteria, fungi or viruses. |
|
Definition
|
|
Term
|
Definition
Once pathogens penetrate the epithelial layers,phagocytic cells such as macrophages and dendritic
cells can take up the pathogens and degrade them.
The digested products are then released from the cell. In addition, small bits or antigens derived
from the pathogens can be presented to adaptive cells. |
|
|
Term
Bacterium becomes attached to membrane
evaginations called ____. |
|
Definition
|
|
Term
| Bacterium is ingested,forming ____. |
|
Definition
|
|
Term
| Phagosome fuses with ____. |
|
Definition
|
|
Term
| Bacterium is killed and then digested by ___. |
|
Definition
|
|
Term
Microbial invasion brings many ___of innate immunity into
play. |
|
Definition
|
|
Term
Microbes with surface components recognized by C-reactive protein (CRP), mannose-binding lectin (MBL), or surfactant proteins A or D (SP-A and SP-D) are bound by these _____ molecules, marking the microbes
for phagocytosis by neutrophils and macrophages. |
|
Definition
|
|
Term
The phagocytic cells recognize the
pathogens via _____ |
|
Definition
| pattern recognition receptors (PRRs). |
|
|
Term
Pathogens have _________ that are
recognized by various PRRs. |
|
Definition
pathogen-associated
molecular patterns (PAMPs) |
|
|
Term
_________ recognize and opsonize
pathogens. Opsonized pathogens are easily phagocytosed by macrophages and
dendritic cells.
Dendritic cells migrate to the lymph
nodes and carry intact or degraded
pathogens.In the lymph node the dendritic cells present antigen to T cells to initiate an adaptive response. |
|
Definition
Mannose binding lectin (MBL), C reactive protein (CRP) and complement
proteins......MBL and CRP are soluble
PRRs. |
|
|
Term
| Innate initiation of adaptive response |
|
Definition
| PRRs recognize PAMPs, +phagocytosis & signal paths, Dendritic cells to lymph nodes, carrying intact / degraded bugs; Antigen fragments on cell surface MHC proteins are recognized by T cells. Activated T cells initiate adaptive responses. |
|
|
Term
Common Opsonins _____.
Complement components binds to LPS on the surface of pathogens.
Complement components can also bind to the Fc portion of antibodies that are bond to pathogens.
H-ficolin binds to carbohydrates on the surface of pathogens. |
|
Definition
| Mannose binding lectin binds to carbohydrates on the surface of pathogens |
|
|
Term
that they can be expressed by
microbes whether or not the microbes are pathogenic disease); hence some researchers have started to use the
more general term ____ |
|
Definition
microbe-associated molecular patterns
(MAMPs). |
|
|
Term
___from the
Greek word for “to make tasty” |
|
Definition
|
|
Term
Once bound to microbe surfaces, opsonins are recognized by membrane
opsonin ___ on phagocytes, activating phagocytosis |
|
Definition
|
|
Term
MBL (and other collectins), ficolins, and C1q share structural features, NS similar polymeric structures with
collagen-like shafts, but have recognition regions with different ______ |
|
Definition
|
|
Term
| As a result of their structural similarities, all are bound by the ____ |
|
Definition
|
|
Term
Another opsonin, C-reactive protein (CRP), recognizes phosphorylcholine and carbohydrates on bacteria, fungi,
and parasites, and is then bound by ____ for IgG found on most phagocytes |
|
Definition
|
|
Term
| Fc receptors also are important for the opsonizing activity of ___ and some IgG antibody subclasses |
|
Definition
|
|
Term
After binding specifically to antigens on microbe surfaces, the Fc regions of
these antibodies can be recognized by specific __, triggering phagocytosis. |
|
Definition
|
|
Term
|
Definition
mannose binding lectin binds to carbohydrates on the surface of pathogens
Compliment components bind to LPS on the surface of pathogens
Complement components can also bind to the Fc portion of antibodies that are bound to pathogens.
H-ficolin binds to carbohydrates on the surface of pathogens |
|
|
Term
Phagocytosed microbes are killed by chemicals within the phagolysosome. This includes hydrolytic
enzymes, anti-microbial peptides (_________), low pH, reactive oxygen and nitrogencompounds. |
|
Definition
| definisins and cathelicidins |
|
|
Term
| In the cytoplasm of _____several enzymes transform molecular oxygen into highly reactive oxygen species that scavenge electrons and break bonds in the molecules of the pathogens. |
|
Definition
| neutrophils, macrophages, and dendritic cells |
|
|
Term
______ can interact with NO to produce various reactive nitrogen species.
People with chronic granulomatous disease have a defect in NADPH oxidase. They have less ability
to destroy pathogens. |
|
Definition
|
|
Term
Oxidative attack on the phagocytosed microbes, which occurs in neutrophils, macrophages, and dendritic cells,
employs highly toxic reactive oxygen species (ROS) and reactive nitrogen species (RNS), which damage intracellu-
lar components. The reactive oxygen species are generated by the phagocytes’ unique NADPH oxidase
enzyme complex (also called ___ ), which is activated when microbes bind to the phagocytic receptors. |
|
Definition
|
|
Term
___ allow Gram positive and Gram negative bacteria to be recognized by
pattern recognition receptors. |
|
Definition
| Conserved molecular patterns |
|
|
Term
| _____ were the first family of PRRs to be discovered. ___ recognized many types of pathogen molecules. |
|
Definition
|
|
Term
(DAMPs) and “don’t eat me” signals
expressed by _____ |
|
Definition
|
|
Term
“eat me” signals, such
as ____ |
|
Definition
|
|
Term
“don’t eat me” signal, the protein ___.___, expressed on many cell
types throughout the body, is recognized by the SIRP-alpha receptor on macrophages, which transmits signals that inhibit phagocytosis. |
|
Definition
|
|
Term
tumors use elevated __ expression to evade tumor surveillance
and phagocytic elimination by the immune system. Increased
expression of CD47 on all or most human cancers is correlated with tumor progression, probably because the CD47
activates SIRP-1alpha-mediated inhibition of the phagocytosis
of tumor cells by macrophages |
|
Definition
|
|
Term
___ are transmembrane proteins that contain several leucine rich repeats.
Several leucine rich repeats are found in the extracellular ligand binding domain.
The intracellular domain is the TIR domain.
In mice the lps gene codes for a mutant form of
TLR4. Mice with this mutation are resistant to
LPS.
In fact TLR4 is the pattern recognition receptor
that recognizes LPS, which is a pathogen
associated molecular pattern. |
|
Definition
|
|
Term
| The intracellular domain is the TIR domain. TIR = Toll/IL-1 receptor domain and is so named because it is ____ to the TLRs and IL-1 receptors. |
|
Definition
|
|
Term
| TL4 induces the expression of ___ |
|
Definition
|
|
Term
| In fact __ is the pattern recognition receptor that recognizes LPS, which is a pathogen associated molecular pattern. |
|
Definition
|
|
Term
| It has been well established that TLRs recognize the ____ |
|
Definition
| pathogen associated molecular patterns (PAMPs). |
|
|
Term
TLRs can also recognize DAMPs.
DAMPS are damage associated molecular patterns that are present on normal cells that have somehow been damaged.
DAMPs can be recognized by PRRs on phagocytes.
DAMPS allow phagocytes to know ___ |
|
Definition
| what cells are should be targeted for phagocytosis. |
|
|
Term
____ include heat shock and chromatin proteins, fragments of extracellular matrix components, and oxidized LDLs and amyloid-beta.
Self nucleic acids bound to anti-DNA or antichromatin antibodies can be recognized by TLRs.
These complexes can be endocytosed and recognized by endosomal/lysosomal TLRs. |
|
Definition
|
|
Term
TLRs can interact with extracellular ____ or intracellular ___ within the endosome or
lysosomal compartments. |
|
Definition
|
|
Term
TLRs are membrane-spanning proteins that share a common structural element
in their extracellular region called __ |
|
Definition
leucine-rich repeats
(LRRs) |
|
|
Term
TLRs that recognize PAMPs on the outer surface are found on the plasma membrane, where they can bind these PAMPs In contrast, TLRs that recognize internal microbial components —are found in endosomes and
lysosomes. Unique among the TLRs, TLR4
and induce responses __ |
|
Definition
move from the plasma membrane to endosomes/
lysosomes after binding LPS or other PAMPs. |
|
|
Term
how does binding of a specific pathogen evoke an appropriate response
for that pathogen? |
|
Definition
Signaling through TLRs utilizes many of the principles and some of the signaling molecules described
in Chapters 3 and 4, along with some unique to pathways activated by TLRs (and by other PRRs, described below). |
|
|
Term
An important example of a shared component is the transcrip-
tion factor __.__ is key for inducing many innate and inflammatory genes, including those encoding defensins; enzymes such as iNOS; chemokines; and cytokines such as the proinflammatory cytokines TNF-α, IL-1, and
IL-6, produced by macrophages and dendritic cells. |
|
Definition
|
|
Term
| The particular signal transduction pathway activated by a TLR dimer following PAMP binding are largely determined by the TLR and by the initial protein adaptor that binds to the TLR’s cytoplasmic domain. this region is called the _____ |
|
Definition
TIR domain (from Toll/IL-1
receptor), referring to the similarity noted earlier between the
cytoplasmic domains of TLRs and IL-1 receptors |
|
|
Term
| TIR domains of all TLR dimers serve as ___for the TIR domains of adaptors that activate the downstream signaling pathways. |
|
Definition
|
|
Term
The two key ____ are MyD88 (Myeloid
differentiation factor 88) and TRIF (TIR-domain-containing
adaptor-inducing IFN- β factor) |
|
Definition
|
|
Term
___are a second family of surface PRRs.
often expressed in plasma membrane of monocytes, macrophages, dendritic cells, neutrophils, B cells, and T cells. They recognize _____The CLRs recognize sugar moieties such as a mannose, fucose, and glucans.
CLRs promote phagocytosis.
Dectin-1 is an example of a CLR. |
|
Definition
C-type Lectin Receptors (CLRs)
carbohydrate components of fungi,mycobacteria, viruses, parasites, and allergens such as peanut allergens. |
|
|
Term
Retinoic acid-inducible Gene –I-like Receptors (RLRs)
RLRs are soluble PRRs that reside in the cytosol of many cell types.
RLRs are critical sensors of___They recognize___They distinguish viral from cellular RNA on the basis of particular structural features not
shared by normal cellular RNA, such as double stranded regions of the RNA, virus-specific motifs, and 5’ modifications. |
|
Definition
viral infection.
viral RNAs from RNA viruses such as influenza, measles, and West Nile virus. |
|
|
Term
___ are nucleotide oligomerization domain/leucine-rich repeat containing receptors. NLRa are cytosolic proteins activated by intracellular PAMPs and substances that alert cells to
damage or danger (DAMPS).
They play a beneficial role in activating innate immunity and inflammatory responses.
They can also trigger inflammation that causes extensive tissue damage and disease. All NLRs have a _____NLRCs also have a CARD domain.
NRLPs have pyrin domains.
NLRBs have BIR domains. |
|
Definition
Nod-like Receptors (NLRs)
leucine rich repeat domain and a nuclear binding domain. |
|
|
Term
Some NLRs assemble into an __ that activates proteases necessary for converting the inactive procytokine forms of IL-1 and IL-18 into the mature forms that are
secreted by cells.
A variety of activators can induce NLR mediated inflammasome formation. |
|
Definition
|
|
Term
Proteins of innate immunity are
expressed following activation and
signaling of ___. |
|
Definition
|
|
Term
Inflammatory Response (IR)is a localized tissue response to injury characterized by pain,heat, redness and swelling.IR includes altered patterns of blood flow, an influx of
phagocytic and other immune cells, removal of foreign antigens, and healing of damaged tissue.
Tissue damage releases vasoactive and chemotactic factors:
Vasodilation increases blood flow
into the area leading to calor
(heat), rubor (redness), tumor
(swelling), and dolor (pain).
Leukocyte migration occurs by
extravasation. (continued) |
|
Definition
Phagocytes recognize DAMPs and PAMPs via
PRRs and become activated.
Molecular mediators that help to expand the inflammatory response are released.
Cytokines secreted by various cells regulate the development and behavior of immune effector cells.
Chemokines act as chemo-attractants to
attract new cells to the site of inflammation. |
|
|
Term
| Pathogen evasion of innate and inflammatory responses |
|
Definition
Avoid detection by PRR
Block PRR signaling pathways, preventing activation of responses
Prevent killing or replication inhibition |
|
|
Term
The innate immune system activates and regulates the adaptive immune responses. + delivers the pathogen to the lymphoid tissues where T and B cells can recognize it and respond.
____ serve as sentinels in epithelial tissues. They use their PRRs to recognize microbes.___ then carry the microbes to the lymphoid tissues such as lymph nodes or MALTs.
There __ can transfer or present to the cell surface bound to MHC Class II proteins.___ also receive a maturation signal when their PRRs engaged the microbes. This maturation signal causes the ___ to increase their expression of MHC molecules. __ are increase expression of CD80 and CD86 which are costimulatory molecules that are recognized by the T cells the ___ will present antigen to. |
|
Definition
|
|
Term
Interactions Between the Innate and the Adaptive Microbial PAMs (?Polyacrylamide) bind and activate distinct PRRs on dendritic cells. This induces production of various cytokines and other mediators.
These cytokines and mediators interact with receptors on naïve CD4+ T cells that are in the process of being activated by antigen-derived peptides bound to dendritic MHC Class II proteins and by interactions with costimulatory molecules such as CD80 and CD86.
The particular cytokines to which a T cell is exposed induces it to turn on genes for certain
cytokines, determining the T cell’s functional phenotype. |
|
Definition
|
|
Term
| What mechanisms have evolved to allow pathogens to evade the innate system and the inflammatory response? |
|
Definition
avoid detection by PRR prevents it from being seen by TLR..
Blocks PRR signal path
Prevent from killing or replicating. |
|
|
Term
|
Definition
collagen domain CD 91 calreticulin
Complement CR1
Immunoglobulin FC receptor Fc alpha R specific to IgA antibodies bound to antigen
Fc gamma R specific to IgG |
|
|
Term
|
Definition
Mannose binding lectin binds to carbohydrates on the surface of pathogens.
Complement components binds to LPS on the surface of pathogens.
Complement components can also bind to the Fc portion of antibodies that are bond to pathogens.
H-ficolin binds to carbohydrates on the surface of pathogens |
|
|
