Unit 5 Early Innate Immunity

State how long it takes for early induced innate immunity to become activated and what it involves.

4 - 96 hours involves the recruitment of defense cells as a result of PAMPS binding to PRR

Function of inflammasome

A multiprotein complex that forms in macrophages as a result of PAMPs and DAMPs binding to their respective PRRs an DRRs that leads to an inflammatory response and the production of inflammatory cytokines

cytokines

A wide variety of intercellular regulatory proteins produced by many different cells in the body that ultimately control every aspect of body defense. Cytokines activate and deactivate phagocytes and immune defense cells, increase or decrease the functions of the different immune defense cells, and promote or inhibit a variety of nonspecific body defenses

Circulating phagocytes produce surface receptors that enabling them to squeeze out of the capillary and be attracted to the site of infection, produce PRRs, and increase metabolic and microbicidal activity. This best describes what step in phagocytosis?

Activation of phagocytes

Molecules located on the inner wall of endothelial cells that bind integrins on the surface of leukocytes to allow allowing leukocytes to firmly bind to the inner blood vessel wall, flatten out, and squeeze between the endothelial cells to leave the blood vessels and enter the tissue are called what?

Adhesion molecules

NK cells kill infected cells and tumor cells by

Apoptosis

Mechanism by which NK cells kill tumor cells and infected cells

Apoptosis, programmed cell suicide

Describe how an overactive TLR-4 receptor can increase the risk of SIRS in a person if Gram-negative bacteria enter the bloodstream

At that point the LPS-binding protein comes off and the LPS-CD14 bind to TLR-4. Interaction of LPS and CD14 with TLR-4 leads to an elevated synthesis and secretion of inflammatory cytokines such as IL-1, IL-6, IL-8, TNF-alpha, and platelet-activating factor (PAF).

During inflammation, integrins function to do what?

Bind leukocytes firmly to adhesion molecules on the inner wall of venules

During inflammation, integrins function to

Bind leukocytes firmly to adhesion molecules on the inner wall of venules.

Which is not a function of NK cells?

Bind to IgG on infected cells and tumor cells and kill them with lysosomes

What is the function of NK cells?

Bind to and kill infected cells and tumor cells that suppress MHC-I production and cannot be removed by CTLs Bind to and kill infected cells and tumor cells by antibody-dependent cellular cytotoxicity or ADCC.

The function of molecules such as MICA and MICB produced by stressed cells, cancer cells, and infected cells is to do what?

Bind to killer-activating receptors on NK cells to turn on their kill signal

The function of molecules such as MICA and MICB produced by stressed cells, cancer cells, and infected cells is to:

Bind to killer-activating receptors on NK cells to turn on their kill signal

Mannan-binding lectin (MBL), produced during the acute phase response, functions to:

Bind to mannose-rich glycans and stick microbes to phagocytes; activate the lectin pathway

C-reactive protein (CRP), produced during the acute phase response, functions to:

Bind to membrane phospholipids in microbial membranes and stick microbes to phagocytes; activate the classical complement pathway

How do NK cells kill infected cells and tumor cells?

By apoptosis

An acute phase protein that binds to phospholipids in microbial membranes, sticks the micobe to phagocytes, and activates the classical complement pathway is ___________________.

C-reactive protein

Movement of phagocytes toward an increasing concentration of some attractant such as PAMPs, C5a, chemokines, fibrin split products, kinins, and DAMPs best describes what step in phagocytosis?

Chemotaxis of phagocytes

____________ play(s) an important role in heart disease, Alzheimer's disease, diabetes, cancer, and tissue destruction from infections.

Chronic inflammation

____________ play(s) an important role in heart disease, Alzheimer's disease, diabetes,cancer, and tissue destruction from infections.

Chronic inflammation

During inflammation, what actually increases the permeability of venules?

Constriction of endothelial cells

__________ slows blood flow at the infection site to give more opportunity for leukocytes to adhere to the walls of the capillary and squeeze out into the surrounding tissue.

Constriction of smooth muscles around larger blood vessels

__________ slows blood flow at the infection site to give more opportunity for leukocytes to adhere to the walls of the capillary and squeeze out into the surrounding tissue.

Constriction of smooth muscles around larger blood vessels

interferons

Cytokines that prevent viral replication, activate a variety of cells important in body defense, and exhibit some anti-tumor activity

chemokines

Cytokines that promote inflammation by enabling white blood cells to adhere to the inner surface of blood vessels, migrate out of the blood vessels into the tissue, and be chemotactically attracted to the injured or infected site

Heat-shock proteins and altered membrane phospholipids are examples of what?

DAMPs

Molecules displayed on stressed, injured, infected, or transformed human cells that can also be recognized as a part of innate immunity. Examples include altered membrane phospholipids and heat shock proteins.

DAMPs

Unique molecules displayed on stressed, injured, infected, or transformed human cells that can also be recognized as a part of innate immunity are known as what?

DAMPs

Function of danger-associated molecular patterns

Damage-associated molecular patterns are molecules displayed on stressed, injured, infected, or transformed human cells that can also be recognized as a part of innate immunity. Examples include altered membrane phospholipids and heat shock proteins

Function of danger recognition receptors

Danger recognition receptors are receptors in the cytosol of various body defense cells that recognize danger-associated molecular patterns.

Define DAMPs and give two examples

Danger-associated molecular patterns. Heat-shock proteins and altered membrane phospholipids

By blocking the acidification of the phagosome, some bacteria are better able to resist what step in phagocytosis?

Destruction by lysosomes.

Lysosomes fusing with phagosomes is the mechanism behind what step in phagocytosis?

Destruction of microbes by phagocytes

State 3 different ways the body deprives microorganisms of iron 2

During an infection there is decreased intestinal absorption of iron from the diet.

State 3 different ways the body deprives microorganisms of iron 1

During an infection there is increased synthesis of the human iron-binding proteins lactoferrin and transferrin which trap iron for use by human cells while making it unavailable to most microbe

During inflammation, diapedesis functions to

Enable phagocytes, inflammatory cells, and cytotoxic T-lymphocytes to leave the blood and enter the tissue

During inflammation, diapedesis functions to do what?

Enable phagocytes, inflammatory cells, and cytotoxic T-lymphocytes to leave the blood and enter the tissue.

During inflammation, selectins function to

Enable the leukocytes to roll along the inner wall of venules

During inflammation, selectins function to do what?

Enable the leukocytes to roll along the inner wall of venules.

Defense molecules such as IgG, C3b, C4b, CRP, and MBL are involved in what step in phagocytosis?

Enhanced attachment or opsonization by phagocytes.

Most tissue destruction associated with bacterial infections is a result of what?

Extracellular killing by phagocytes

T/ F Specific cytokines are typically produced by a specific type of cell in the body, interact with a specific type of cell, and carry out a specific function.

False

State what happens when either phagocytes are overwhelmed with microbes or they adhere to cells to large to be phagocytosed

If the phagocyte is overwhelmed with microorganisms, the phagocyte will empty the contents of its lysosomes by a process called degranulation in order to kill the microorganisms or cell extracellularly. These released lysosomal contents, however, also kill surrounding host cells and tissue.

Describe the mechanism behind fever

In response to toll-like receptors recognizing microbial products (pathogen-associated molecular patterns), activated macrophages and other leukocytes release proinflammatory cytokines such as TNF-alpha and Il-1 when their toll-like receptors bind pathogen associated molecular patterns. This stimulates the anterior hypothalamus of the brain to produce prostaglandins which lead to an increase in body temperature

State 2 benefits of fever.

Increasing the environmental temperature above the optimum growth temperature for many microorganisms. Since elevating the temperature of the body increases the rate of enzyme reactions in the body, this speeds up metabolism within the body. An increase in the rate of metabolism can increase the production and activity of phagocytes, speed up innate and adoptive immune responses, and enable faster tissue repair.

People with certain PRR polymorphisms that result in underactive PRRs are at risk for what?

Infection by specific pathogens due to a decrease innate immune response.

inflammation

Inflammation, as a result of vasosdilation and increased capillary permeability, enables phagocytes to leave the blood and enter the tissue at infected and injured sites

People with certain PRR polymorphisms that result in overactive PRRs are at risk for what?

Inflammatory damage by lower numbers of specific pathogens

Polymerization and then depolymerization of actin filaments send pseudopods out to engulf microbes and place them in phagosomes best describes what step in phagocytosis?

Ingestion of microbes by phagocytes.

Recognize stress induced molecules such as MICA and MICB on the surface of tumor cells or infected cells

Killer activating receptors

Recognize MHC-I molecules usually present on all nucleated cells of the body

Killer inhibitory receptors

Which is NOT a benefit of plasma leakage into the tissue during inflammation?

Leukocytes leave the blood and enter the tissue

Which is NOT a benefit of plasma leakage into the tissue during inflammation?

Leukocytes leave the blood and enter the tissue

Briefly describe the various beneficial effects of inflammation that are associated withwith diapedesis

Leukocytes leave the blood and enter the tissue for 1) phagocytosis (neutrophils, monocytes/macrophage, and eosinophils are phagocytes); 2) more vasodilation (basophils, neutrophils, and platelets promote inflammation); 3) killing of infected cells and cancer cells by cytotoxic T-lymphocytes (CTLs) and NK cells.

Name at least 5 PAMPS associated with bacteria

Lipopolysaccharide in the gram-negative cell wall lipoteichoic acids in the gram-positive cell wall, peptidoglycan, flagellin, bacterial lipopeptides, N-formyl methionine, mannose-rich glycans, bacterial nucleic acid.

lymph nodules

Lymph nodules are unencapsulated masses of lymphoid tissue containing fixed macrophages and ever changing populations of B-lymphocytes and T-lymphocytes

Killer-inhibitory receptors on NK cells are able to recognize

MHC-I molecules on stressed cells

Killer-inhibitory receptors on NK cells are able to recognize what?

MHC-I molecules with self peptides on stressed cells

Name 2 endocytic PRRs.

Mannose receptors Dectin-1

Describe what causes most of the tissue destruction seen during microbial infections

Most tissue destruction associated with infections is a result of phagocytes emptying the contents of their lysosomes for extracellular killing.

Name 2 signaling PRRs found on the host cell cytoplasm.

NOD-2 RIG-1

Molecules shared by groups of related microbes that are essential for the survival of those organisms and are not found associated with mammalian cells are known as what?

PAMPs

Briefly describe the major difference between the effect of the cytokines produced in response to PAMPs that bind to cell surface signaling PRRs and endosomal PRRs.

PAMPs that bind to cell surface PRRs stimulate the synthesis of cytokines such as IL-1, TNF-alpha, and IL-8 that promote an inflammatory response in order to send defense cells and defense chemicals in the blood to the infected site. PAMPs that bind to endosomal PRRs stimulate the synthesis of cytokines called interferons that block viral replication within infected host cells.

State what is meant by pathogen-associated molecular patterns (PAMPs), and the role PAMPs play in inducing innate immunity.

Pathogen-associated molecular patterns are molecules unique to microorganisms that are not associated with human cells. They include LPS, peptidoglycan, lipoteichoic acids, mannose, flagellin, pilin, bacterial DNA, and viral double-stranded RNA.

Briefly describe two specific examples of how an improper functioning PRR can lead to an increased risk of a specific infection or disease.

People with chronic sinusitis that does not respond well to treatment have decreased activity of TLR-9 and produce reduced levels of human beta-defensin 2 and mannan-binding protein needed to initiate the lectin complement pathway Mutations in the gene coding for NOD2 that prevent the NOD2 from recognizing muramyl dipeptide make a person more susceptible to Crohns disease, an inflammatory disease of the large intestines

Briefly describe the various beneficial effects of inflammation that are associated with plasma leakage and with diapedesis

Plasma flows out of the blood into the tissue. This has the following benefits: 1) clotting factors cause fibrin clots to form to localize the infection, stop the bleeding, and chemotactically attract phagocytes; 2) antibodies enter the tissue to help remove or block the action of microbes; 3) proteins of the complement pathways to stimulate more inflammation (C5a, C3a, and C4a), stick microorganisms to phagocytes (C3b and C4b), chemotactically attract phagocytes ( C5a), and lyse membrane-bound cells displaying foreign antigens ( MAC); 4) nutrients enter the tissue to feed inflamed tissue; 5) lysozyme and beta-defensins enter the tissue to degrade peptidoglycan and cytoplasmic membranes; and 6) transferrin enters the tissue to deprive microbes of needed iron.

State what is meant by the phrase "Cytokines are pleiotropic, redundant, and multifunctional.

Pleiotropic - Act on # of different types of cells rather than single Redundant - # of different cytokines carry out the same function Multifunctional - cytokines are able to regulate a # of different functions

Function of endocytic pattern recognition receptors

Receptors found on the surface of phagocytes that promote the attachment of microorganisms to phagocytes and their subsequent engulfment and destruction

Function of pattern recognition receptors (PRRs)

Receptors on the surface of various body defense cells that recognize pathogen-associated molecular patterns

Function of signaling pattern recognition receptors

Signaling PRRs, once they bind pathogen-associated molecular patterns, promote the synthesis and secretion of intracellular regulatory molecules such as the cytokines, chemokines, and interferons that are crucial to initiating innate immunity and adaptive immunity.

Epitopes of glycolipid antigens are recognized by iNKT lymphocytes by way of their _______.

T-cell receptors (TCRs)

Name 2 signaling PRRs found on host cell surfaces.

TLR 2 TLR4 TLR5

Name 2 signaling PRRs found in the endosomes of phagocytic cells.

TLR-3 TLR-8 TLR-9

Briefly describe the mechanism behind the acute phase response

The binding of pathogen-associated molecular patterns to toll-like receptors stimulates macrophages and other cells to produce cytokines like TNF-alpha and Il-6. These cytokines are carried by the blood to the liver where they trigger the synthesis of acute phase proteins. The binding of these acute phase proteins to microbial surfaces promote opsonization and activate the complement system.

People that lack the enzyme oxidase in the cytoplasmic membrane of their phagocytes due to a genetic disorder are more susceptible to infection. Why might this be?

Their phagocytes cannot produce reactive oxygen species (ROS) that kill microbes.

State 3 different ways the body deprives microorganisms of iron 3

There is prior stationing of lactoferrin at common sites of microbial invasion such as in the mucous of mucous membranes, and the entry of transferrin into the tissue during inflammation.

Describe the 4 processes that make up the inflammatory mechanism.

These agents cause 1) contraction of endothelial cells in venules for increased capillary permeability; 2) contraction of smooth muscles around larger blood vessels to slow blood flow around the infection site so that leukocytes and defense chemicals can leave the blood and enter the tissue; 3)activation of adhesion molecules on the inner wall of the capillaries that bind to integrins on leukocytes to enable diapedesis. Inflammation enables plasma and leukocytes to leave the blood and enter the tissue; and 4) activation of the coagulation pathway causes fibrin clots to physically trap the infectious microbes and prevent their entry into the bloodstream.

T/F Part of innate immunity is the body trapping or eliminating iron so as to make it unavailable for bacteria. Iron is a cofactor required for certain bacterial enzyme reactions

True

T/F Type I interferons block viral replication in infected host cells primarily by triggering the production of antiviral proteins that degrade both viral mRNA and host cell mRNA.

True

t/f Some bacteria are able to successfully compete for iron by having receptors for human iron chelating proteins and taking in that bound iron.

True

Name the two cytokines that are most important in stimulating acute inflammation.

Type 2 interferons inflammatory cytokines

Describe specifically how type I interferons are able to block viral replication within an infected host cell.

Type I interferons, produced by virtually any virus-infected cell, provides an early innate immune response against viruses. Interferons induce uninfected cells to produce enzymes capable of degrading mRNA. These enzymes remain inactive until the uninfected cell becomes infected with a virus. At this point, the enzymes are activated and begin to degrade both viral and cellular mRNA. This not only blocks viral protein synthesis, it also eventually kills the infected cell.

Bacterial capsules best help bacteria block what step in phagocytosis?

Unenhanced attachment.

A multiprotein complex that forms in macrophages as a result of PAMPs and DAMPs binding to their respective PRRs and DRRs that leads to an inflammatory response and the production of inflammatory cytokines is called what?

an inflammasome

LPS, porins, teichoic acids, peptidoglycan, mycolic acid, and flagellin are common PAMPs associated with what?

bacteria

NKT cells promote both innate and adaptive immunity and may also regulate immune responses by way of the ____________ they produce once activated

cytokines

Found on the surface of phagocytes, these receptors promote the attachment of microorganisms to phagocytes.

endocytic PRRs

TNF-alpha, IL-1, and chemokines are examples of cytokines that promote what?

inflammation

Signaling PRRs found on cell surfaces tend to stimulate the synthesis of what?

inflammatory cytokines

Tissue fluid picks up microbes, enters the lymph vessels as lymph, and then enters _________________ where antigens are exposed ever-changing populations of circulating to B-lymphocytes and T-lymphocytes.

lymph nodes

Unencapsulated masses of lymphoid tissue containing fixed macrophages and ever changing populations of B-lymphocytes and T-lymphocytes and located in the respiratory and gastrointestinal tracts describes what?

lymph nodules

An acute phase protein that binds to mannose in microbial walls, sticks the micobe to phagocytes, and activates the lectin pathway is ___________________.

mannose-binding lectin

These receptors promotes the synthesis and secretion of intracellular regulatory molecules such as cytokines.

signaling PRRs

Blood carries microorganisms to ___________ where antigens are exposed to ever-changing populations of circulating to B-lymphocytes and T-lymphocytes.

the spleen

Cytokines that block viral replication and kill infected host cells are known as what?

type I interferons

Signaling PRRs found in the membranes of the endosomes (phagolysosomes) tend to stimulate the synthesis of what?

type-1 interferons

Name at least 2 PAMPS associated with viruses.

viral genomes, viral double-stranded RNA, viral single-stranded RNA.

DNA, double-stranded RNA, and single-stranded RNA are common PAMPs associated with what?

viruses

Briefly describe the healing stage of inflammation.

ytokines stimulate a proliferation of endothelial cells and fibroblasts. The endothelial cells form a fine network of new capillaries into the injured area to supply blood, oxygen, and nutrients to the inflamed tissue. The fibroblasts deposit the protein collagen in the injured area and form a bridge of connective scar tissue to close the open, exposed area.