Innate Immunity I

Question 1

Our early and rapid system of defense against pathogens and other events or substances considered to be dangerous

Answer 1

Innate Immunity

Question 2

Consists of molecules that recognize foreign or unusual molecules in the body, and molecules or cells that respond to this perceived threat by eliminating or neutralizing the perceived threat

Answer 2

Innate Immunity

Question 3

Innate Immunity is the initial response to microbes that acts to prevent, control and eliminate

Answer 3

Infection

Question 4

stimulates the subsequent adaptive immune response and can influence the nature of the response to tailor it to the specific type of microbe

Answer 4

Innate Immunity

Question 5

Innate immunity can also recognize some products of damaged or dead host cells and can eliminate those cells and initiate tissue repair, often without causing

Answer 5

Inflammation

Question 6

Innate immunity is always

Answer 6

Functional

Question 7

Key molecules of innate immunity are encoded in the

-Thus are NOT the products of antigen-specific genetic rearrangements

Answer 7

Genome

Question 8

Does not result in specific memory of antigens or pathogens previously encountered

Answer 8

Innate immunity

Question 9

The molecules of innate immunity that recognize foreign or unusual molecules are generically referred to as

Answer 9

Pattern Recognition Receptors (PRRs)

Question 10

The molecules on the pathogen, or produced by the pathogen, that are recognized by PRRs are referred to as

Answer 10

“Pathogen-Associated Molecular Patterns (“PAMPS”)

Question 11

If these recognized patterns arise from “unmasked” or unusual host components, they are called

Answer 11

“Damage-Associated Molecular Patterns” (“DAMPS”)

Question 12

PRRs may be located in the

Answer 12

Serum or Tissues

Question 13

Cellular PRRs can be located on the cell membrane to sense

Answer 13

PAMPS outside of the cell

Question 14

Cellular PRRs can be located on the endosomal membrane, to sense PAMPs that have been brought into the cell by

Answer 14

Endocytosis

Question 15

Cellular PRRs can be located in the cytoplasm, where they sense

Answer 15

PAMPs

Question 16

Can have several outcomes: (1) it may directly affect the pathogen; (2) it can trigger a cascade of molecular, cellular and global responses by the host

Answer 16

Binding of PRRs to pathogen

Question 17

The two major global responses against pathogens are

Answer 17

Acute inflammation and the antiviral response

Question 18

Can also arise in response to damaged or dead cells, or to the accumulation of abnormal substances in cells or tissues

Answer 18

Inflammatory response

Question 19

However, while it’s useful to consider innate immune responses separately, a 3rd outcome of the innate response in many cases is the initiation of a longer-term, more specific

Answer 19

Adaptive Immune response

Question 20

The initiation of a longer-term, more specific “adaptive immune response” causes the generation of

Answer 20

T and B cells and antibodies

Question 21

Was first recognized in the late 1890s, and a number of other recognition molecules were discovered throughout the ensuing 100 years

Answer 21

Complement

Question 22

A major landmark for our understanding of how the body recognizes pathogens came in the med-1990’s with the discovery of

Answer 22

Toll-like receptors

Question 23

Bacteria, viruses and fungi have a number of unique molecules that serve as

Answer 23

Pathogen-Associated Molecular Patterns (PAMPs)

Question 24

Damaged and dead cells, or cellular inclusions, may also be recognized by the immune system, and these are referred to as

Answer 24

“Damage-Associated Molecular Patterns” (DAMPS)

Question 25

An important property of PAMPs is that these molecules are often essential for

Answer 25

Microbial survival

Question 26

Produced by host cell damage from infection, injury, trauma, ischemia, etc

Answer 26

DAMPs

Question 27

Note that these are cell debris resulting from apoptosis is efficiently cleared, so that inflammation does not result). Defects in the mechanisms of debris clearance from apoptotic cells can contribute to

Answer 27

Autoimmune disease

Question 28

Found on a wide variety of cells

Answer 28

Cell-associated Pathogen Recognition Receptors (Cell-associated PRRs)

Question 29

Express the greatest variety and amount of PRRs -have direct and immediate roles in defense

Answer 29

Phagocytes (macrophages and neutrophils) and dendritic cells

Question 30

However, other cell types, such as epithelial and endothelial cells that can play important but less direct roles in the immune response and regulation, may also express

Answer 30

PRRs

Question 31

In both instances, binding to cell-associated PRRs most often activates signal transduction pathways that lead to

Answer 31

Anti-microbial and pro-inflammatory responses

Question 32

A family of PRRs that are conserved through evolution, are expressed on many cell types, and are capable of recognizing a wide variety of PAMPs from different classes of pathogens

Answer 32

Toll-like Receptors (TLRs)

Question 33

TLRs on the cell surface can recognize various structures from

Answer 33

Bacteria or Fungi

Question 34

May be part of the intact pathogen, shed by the pathogen, or released following phagocytosis of pathogens by macrophages or killing by neutrophils

Answer 34

The PAMPs for TLRs

Question 35

Pathogens that are endocytosed into endosomes, such as many viruses, may have components such as single- or double-stranded RNA, or bacterial DNA that are recognized by

Answer 35

Endosomal TLRs

Question 36

A characteristic molecule of Gram-negative bacteria that is a ligand for TLRs

Answer 36

Lipopolysaccharide (LPS)

Question 37

Once the PAMP binds to its cognate TLR, a series of molecules are recruited and activated in a

Answer 37

Signal Transduction Cascade

Question 38

This signal transduction cascade results in the activation of

Answer 38

Transcription factors in the nucleus

Question 39

For an inflammatory response, a very important transcription factor is

Answer 39

NF-kB (“NK-kappaB”)

Question 40

Antiviral responses particularly work through transcription factors of the

Answer 40

Interferon Response Factor (IRF) family

Question 41

These and other activated transcription factors turn on or off a host of genes that then feed into two main responses, the

Answer 41

Inflammatory Response and Antiviral Response

Question 42

Of particular interest, the activation of NF-kB helps turn on pro-inflammatory responses through the production and secretion of the “pro-inflammatory cytokines”

Answer 42

Tumor necrosis factor (TNF) α, interleukin 1 (IL-1) β, and interleukin 6

Question 43

Similarly, during viral infections, activation of IRF-family transcription factors lead, among other outcomes, to the production and secretion of

Answer 43

Type I and Type III interferons

Question 44

The most common forms of Type I and Type III interferons are the

Answer 44

Alpha interferons (IFN-α) and interferon beta (IFN-β)

Question 45

The Type I and Type III IFNs are crucial to early

Answer 45

Antiviral Defense

Question 46

Interferons are protein signals called

Answer 46

Cytokines

Question 47

Thus, the molecular events triggered through the TLRs (and other PRRs) begin to determine whether the host mounts an

Answer 47

Appropriate Response

Question 48

In addition to these membrane-associated PRRs, there are also receptors and recognition molecules for PAMPs and DAMPs in the

Answer 48

Cytoplasm

Question 49

These are important because some pathogens, including many viruses, have parts of their life-cycle in the

Answer 49

Cytoplasm

Question 50

One major family of cytoplasmic PRRs is called the

Answer 50

NOD-like receptors (NLRs)

Question 51

Occur in a variety of cell types, including immune, inflammatory and epithelial barrier cells

Answer 51

NLRs

Question 52

The binding of NLRs to their PAMPs or DAMPs initiates an intracellular signaling cascade. As with the TLRs, one important outcome is the activation of the key transcription factor for the

Answer 52

Inflammatory genes, NF-kB, and the activation of the pro-inflammatory cytokine IL-1

Question 53

Genetic evidence suggests that mis-regulation of some NLRs may be involved in the pathogenesis of gut diseases, particularly

Answer 53

Inflammatory Bowel Disease (IBD)

Question 54

Other inflammatory diseases, such as gout, pseudo-gout or lung disease related to silica or asbestos exposure may be related to the activation of NLRs and inflammatory cytokines such as

Answer 54

IL-1

Question 55

In addition to the NLRs in the cytoplasm, there are important cytoplasmic sensors for both

Answer 55

RNA and DNA

Question 56

As an example of how an RNA sensor can distinguish between cellular and viral RNA, requires that there be a triphosphate on the 5-prime end of the RNA

Answer 56

RIG-I RNA sensor

Question 57

Cellular mRNAs have the specially modified “cap” (modified guanine residue) at their 5-prime end, and do not bind to

Answer 57

RIG-I

Question 58

Some cell membrane receptors recognize bacterial carbohydrates that do not have equivalents on host cells. These carbohydrate receptors are in the

Answer 58

C-lectin Family

Question 59

Proteins that bind carbohydrates

Answer 59

Lectins

Question 60

For their binding, C-lectins depend on

Answer 60

Calcium

Question 61

Can aid in the phagocytosis of microbes and some can also stimulate signaling pathways

Answer 61

C-Lectins

Question 62

One example of a C-lectin receptor is the

Answer 62

Mannose receptor

Question 63

A diverse collection of cell surface receptors. Some have very broad specificity, including the recognition or oxidized lipoproteins

Answer 63

Scavenger receptors

Question 64

May mediate phagocytosis of microorganisms

Answer 64

Scavenger receptors

Question 65

Responds to the N-terminus of bacterial proteins

Answer 65

FMLP (f-Met-Leu-Phe) receptor

Question 66

Recall that the first amino acid at the N-terminus of most bacterial proteins is

Answer 66

f-Met

Question 67

Some mammalian cells, including macrophages and neutrophils, have a specific receptor that recognizes peptides with a terminal

Answer 67

f-Met

Question 68

Unlike other receptors we’ve discussed, these are in the family of

Answer 68

G-protein coupled receptors (GPCRs)

Question 69

What are the four main cells involved in innate immunity?

Answer 69

Phagocytes. dendritic cells, Natural Killer (NK) cells, and mast cells

Question 70

Once thought to be inert barrier cells, contain a large complement of diverse PRRs, including many of the TLRs and some NOD-like receptors, and thus are important outer sentinels

Answer 70

Keratinocytes

Question 71

Among the more important anti-microbial molecules of the epithelial barrier are a class of small peptides called

Answer 71

Defensins

Question 72

The skin and mucosa of the respiratory, gastrointestinal, and genitourinary tracts are referred to as the

Answer 72

Epithelial Barriers

Question 73

Have direct antimicrobial toxicity, and can activate cells involved in the inflammatory response

Answer 73

Defensins

Question 74

A second class of molecules that also have microbicidal activity and immune activation functions is the

Answer 74

“cathelicidins”

Question 75

Among the important immune cells in the skin and mucosal epithelia are

Answer 75

Intrepithelial T-lymphocytes

Question 76

Although we generally consider T lymphocytes as element s of adaptive immunity, at least some intraepithelial T lymphocytes seem to be pre-programmed with a fixed and limited antigen specificity to recognized common

Answer 76

PAMPs

Question 77

Cells with the ability to engulf, kill and otherwise process microbes, and represent a powerful cellular defense against microbes that breach the physical barriers

Answer 77

Phagocytes

Question 78

The two primary types of phagocytes are

Answer 78

Macrophages and Neutrophils

Question 79

Arise from circulating blood monocytes that migrate into tissues and undergo differentiation

Answer 79

Macrophages

Question 80

Macrophages arise from circulating blood monocytes that migrate into tissues and undergo differentiation into macrophages, where they are generically known as

Answer 80

Resident Macrophages

Question 81

The first function of these macrophages is

Answer 81

Surveillance

Question 82

Can be activated by several mechanisms such as binding of microbes to Toll-like receptors (TLRs), or to other cell-surface PRRs on the macrophages, such as a receptor for complement

Answer 82

Resident Macrophages

Question 83

Can be activated by signaling from other activated immune cells, such as the cytokine gamma interferon (IFN-γ), which can be released from natural killer (NK) cells

Answer 83

Resident Macrophages

Question 84

“Activation” has many facets: phagocytosis is made more efficient, for instance by expression of additional cell-surface

Answer 84

PRRs

Question 85

Included in these mechanisms are the up-regulation of enzymes that produce

Answer 85

ROS and Nitric Oxide

Question 86

In addition, activated macrophages produce a number of “pro-inflammatory cytokines”, including

Answer 86

Tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin 6 (IL-6)

Question 87

Help activate and mobilize other immune cells, change the vascular permeability properties of nearby vasculature, and other functions related to initiating or propagating an inflammatory response

Answer 87

TNF, IL-1, and IL-6

Question 88

During infection, monocytes can be attracted to sites of infection in increase and replenish the

Answer 88

Macrophage population

Question 89

About 60% of the white cells in blood, and their abundance can increase during infections

Answer 89

Neutrophils

Question 90

The first cells to infiltrate areas of bacterial and fungal infection, and are the dominant cells in tissue with acute inflammation

Answer 90

Neutrophils

Question 91

Basically, they are killing machines with a short half life (several hours) in tissues, so they do not provide long-lasting defense

Answer 91

Neutrophils

Question 92

Neutrophils also are used for clearance of cell debris at sites of tissue damage not related to

Answer 92

Infection

Question 93

Low neutrophil counts, such as in patients undergoing chemotherapy, is a cause of high rate of

Answer 93

Bacterial and Fungal infections

Question 94

Can sense and kill infected cells, with a second function of producing the cytokine interferon-γ (IFN-γ) to activate macrophages

Answer 94

NK Cells

Question 95

Unlike most cells of innate immunity, NK cells are in the lymphocyte lineage that includes

Answer 95

B and T cells

Question 96

Large lymphocytes with numerous cytoplasmic granules, whose contents are primarily used for killing target cells

Answer 96

NK Cells

Question 97

How do NK cells distinguish infected or damaged host cells from healthy host cells? NK cells have both

Answer 97

Inhibitory and Activatory receptors

Question 98

Most inhibitory receptors recognize

Answer 98

Class I MHCs

Question 99

However, many viruses and other causes of cell stress lead to down-regulation of MHC surface molecules that are involved in

Answer 99

Antigen presentation

Question 100

In such cases, the inhibitory receptors are not efficiently engaged, and the balance of signals will favor cellular

Answer 100

Activation and killing