Innate Immunity II

Question 1

As with many or most immune cells, NK cells can be stimulated for growth and activation by

Answer 1

Cytokines

Question 2

Which type of cytokine stimulates growth and activation of NK cells?

Answer 2

IL-12, Type I interferon

Question 3

What are the two important substances contained in the granules of NK cells?

Answer 3

Perforin and granzymes

Question 4

Facilitates the entry into target cells of other substances from the NK cell

Answer 4

Perforin

Question 5

Enzymes that enter the cytoplasm of target cells and initiate signaling cascades leading to cell death by apoptosis

Answer 5

Granzymes

Question 6

Thus, NK cells have several primary roles: in the early phases of a viral infection, before there are virus-specific CTLs, NK cells can

Answer 6

Kill virus-infected cells

Question 7

NK cells can also kill cells with

Answer 7

Intracellular microbes

Question 8

Released by activated NK cells activates macrophages for more efficient phagocytosis and killing of bacteria or intracellular targets such as cells carrying intracellular pathogens, such as Listeria monocytogenes

Answer 8

IFN-γ

Question 9

Form a surveillance and antigen-capture network in epithelia and subepithelial tissues and in a number of other organs

Answer 9

Dendritic Cells

Question 10

The majority of DCs are called “conventional” DCs, and these include the

Answer 10

Langerhans cells in the skin

Question 11

Their primary function is to recognize and/or capture antigen, either microbes or free antigens

Answer 11

Conventional DCs

Question 12

Have a strong array of TLRs and other pattern-recognition receptors

Answer 12

Conventional DCs

Question 13

After recognizing and capturing antigens, DCs have which 2 major effects?

Answer 13

1. ) Produce pro-inflammatory cytokines

2. ) Travel to lymph nodes to present antigen to T cells

Question 14

Set off antigen-specific T cell responses and serving as a key link to the adaptive immune response

Answer 14

Conventional DCs

Question 15

A second, more rare, but critical type of dendritic cell is the

Answer 15

Plasmactytoid dendritic cell (pDC)

Question 16

These cells specifically have high levels of TLR 3, 7 and 9 in the endosome, whereby they can respond with great sensitivity to single- and double-stranded RNA, and also to DNA, which are characteristic of viruses

Answer 16

Plasmactytoid dendritic cell (pDC)

Question 17

pDCs have high levels of TLRs

Answer 17

3, 7, and 9

Question 18

In response, the pDCs turn on very strong production of the anti-viral family of

Answer 18

Type I interfurons (especially IFN-α, and IFN-β)

Question 19

These IFNs (in contrast to gamma interferon; IFN-γ) have 2 main effects: (1) they have a direct

Answer 19

Anti-viral effects

Question 20

Also, these Type I interferons modulate a host of cellular reactions by cells of the immune system, making the Type I IFNs an important link between

Answer 20

Innate and adaptive immunity

Question 21

Primarily associated with immunity to multi-cellular parasites and to allergy and asthma, but they are also important for innate immunity

Answer 21

Mast Cells

Question 22

They are present in the skin and mucosal epithelium, where they are often found adjacent to the microvasculature and nerves

Answer 22

Mast Cells

Question 23

The mast cells have numerous cytoplasmic granules containing inflammatory mediators including

Answer 23

Histamine

Question 24

Mast cells also produce lipid mediators, such as

Answer 24

Prostaglandins and cytokines

Question 25

Mast cells contain a number of pathogen recognition receptors, including most

Answer 25

TLRs

Question 26

Mast cells contain a number of pathogen recognition receptors, including most TLRs, which can be stimulated by their ligands in vitro to induce

Answer 26

Degranulation and cytokine release

Question 27

The location of mast cells, and the presence of important PRRs suggests an important role in

Answer 27

Innate immunity

Question 28

Recognition molecules critical to innate immunity are also found in the serum and in tissues, and help

Answer 28

Tag or destroy molecules

Question 29

Recognition molecules bind to microbes, acting as

Answer 29

Opsonins

Question 30

This enhances their recognition by cellular receptors on macrophages, neutrophils and dendritic cells because these cells have receptors for these

Answer 30

Opsonins

Question 31

May initiate or promote inflammatory responses that attract phagocytes, and/or they may participate directly in killing of pathogens

Answer 31

Soluble recognition molecules

Question 32

Perhaps the best known and most important soluble recognition and effector molecules are those of the

Answer 32

Complement system

Question 33

This system is composed of roughly 20 proteins in normal human serum, most of which are produced in the liver

Answer 33

Complement proteins

Question 34

Functions in defense against pathogens, and functions in homeostasis, particularly recognizing damaged or apoptotic cells or their components and helping dispose of them without triggering inflammation

Answer 34

Complement system

Question 35

Functions to opsonize (coat) and tag microbes for phagocytosis and killing

Answer 35

Complement system

Question 36

The complement system mobilizes and recruits phagocytes to the site of

Answer 36

Infection

Question 37

In some cases, the complement system functions to directly kill

Answer 37

Pathogens

Question 38

What are the three pathways to trigger the cascade of reactions of the complement system? -Once triggered, converge to a common pathway

Answer 38

Classical, alternative, and lectin pathways

Question 39

The “classical pathway”, so-called because it was the first pathway recognized and described, is initiated by

Answer 39

Antibody binding to pathogen

Question 40

Because it involves antigen-specific antibodies, it is often considered part of adaptive immunity

Answer 40

Classical pathway

Question 41

The alternative and lectin pathways do not depend on pathogen-specific

Answer 41

Antibodies

Question 42

The 3 pathways differ primarily in their early events, but then connect through the critical protein

Answer 42

C3

Question 43

Is always going on, because it begins with the spontaneous hydrolysis of complement protein C3, which is present in high concentrations in serum (and in tissue)

Answer 43

Alternative tissue

Question 44

The C3 products are

Answer 44

C3a and C3b

Question 45

Highly reactive (and very short-lived), and can react with and covalently bind to bacterial or fungal polysaccharides or proteins

Answer 45

C3b

Question 46

If no targets of active C3b are nearby, the reactive group on C3b quickly hydrolyzes and the C3b becomes

Answer 46

Inactive

Question 47

However, C3b bound to cells binds another serum protein called

Answer 47

Factor B

Question 48

Cleaved by a plasma protease to form a “Bb” fragment, so there is now a C3bBb complex on the bacterial surface

Answer 48

Factor B

Question 49

This creates a powerful amplification of both the amount of protease activity to activate C3, and also to “decorate” or tag the bacteria or other targets with a lot of complement, particularly

Answer 49

C3b

Question 50

With multiple C3b molecules attached, the cells become targets for

Answer 50

Phagocytes

Question 51

Opsinizes pathogens

Answer 51

C3b

Question 52

Some membrane-bound C3bBb complexes can bind a 2nd molecule of C3b, changing its proteolytic specificity so it becomes a

Answer 52

C5 convertase

Question 53

Can cleave C5, producing the fragments C5b and C5a

Answer 53

C5 convertase

Question 54

The larger C5b piece can stick to the cell surface and recruit components (C6, 7, 8 and 9; this is known as the

Answer 54

Membrane attack complex (MAC)

Question 55

This forms a pore in some cells, and may be capable of lysing some cells, particularly bacteria of the

Answer 55

Neisseria genus (species of which can cause meningitis or gonorrhea)

Question 56

The cleavage of both C3 and then C5 (and C4 in the other pathways) releases the smaller, soluble protein fragments

Answer 56

C5a and C3b

Question 57

In response, many inflammatory cells chemotax toward the site of infection, and may be activated for

Answer 57

Inflammation

Question 58

The fragments can also cause degranulation of mast cells, releasing “inflammatory mediators”, including

Answer 58

Histamine and leukotrines

Question 59

Have critical effects in acute inflammation

Answer 59

Leukotrines

Question 60

If complement is extensively activated in the bloodstream, large amounts of C3a/C5a are produced, and a large number of mast cells will be stimulated

Answer 60

Degranulate

Question 61

These may release sufficient inflammatory mediators to produce systemic vasodilation, loss of blood pressure, and shock, i.e., anaphylaxis, so that these fragments are called

Answer 61

Anaphylatoxins

Question 62

Takes advantage of the fact that carbohydrates on the surface of healthy human cells may differ from those on pathogens

Answer 62

Lectin pathway

Question 63

The best known example of the initiation of the Lectin pathway is when

Answer 63

Mannan-Binding Lectin (MBL) recognizes terminal glycolipids and glycoproteins on bacteria or fungi

Question 64

After MBL binds to the bacterial (or fungal) sugar on the bacterium, it recruits specific proteases (“MBL-associated serine proteases”; MASPs) that then cleave proteins

Answer 64

C4 and C2

Question 65

This produces cell-bound

Answer 65

C4b2a, a second C3 “convertase"

Question 66

Cleaves C3 to C3b and C3a

Answer 66

C4b2a

Question 67

Some of the C3b can join bind to the C4b2a to form a C5 convertase, analogous to that of the alternative pathway, leading to the same outcomes as from the

Answer 67

Alternative pathway

Question 68

As mentioned above, the “classical pathway” relies on an antigen-specific antibody that recognizes and binds to an antigen of the pathogen. The bound antibody is then recognized by

Answer 68

Complement C1

Question 69

Subunits of complement C1 cleave C4 and C2, creating

Answer 69

C3 convertase

Question 70

Some of cleaved C3b binds to C4bC2a to form the

Answer 70

C5 convertase

Question 71

An example of extending the older complement system of innate immunity and coupling it to antibodies, produced by the B cells of adaptive responses

Answer 71

Classical pathway

Question 72

Because of the requirement for pathogen-specific antibodies, this pathway is generally engaged only on repeated or prolonged encounter with a pathogen, when specific antibodies have been produced

Answer 72

Classical Pathway

Question 73

Can produce increased susceptibility to bacterial infections, particularly early in life

Answer 73

C3 deficiency

Question 74

Variable from asymptomatic to increased susceptibility to bacterial infection. Can be associated with systemic lupus erythematosus

Answer 74

C2 and C4 deficiency

Question 75

Increased susceptibility to Neisseria

Answer 75

C9 deficiency

Question 76

Increased complement activation → Reduced levels of C3 (“depletion”) → increased infection.

Answer 76

Factor I or Factor H deficiency

Question 77

Complement also serves an important role in helping to clear complexes of

Answer 77

Antigen and antibody

Question 78

Have complement receptors and bind circulating immune complexes

Answer 78

Erythrocytes

Question 79

The complexes bound to red cells are phagocytosed and destroyed by macrophages in the

Answer 79

Liver and spleen

Question 80

Alternatively, if the complexes reach lymph nodes and are trapped by dendritic cells, this is a potent stimulus to an

Answer 80

Immune response

Question 81

Persons genetically defective in early components of complement (C1 through C3) have an elevated frequency of

Answer 81

Autoimmune disease

Question 82

Antibody-antigen complexes (“immune complexes”) lodged in tissue create damage by

Answer 82

Complement activation

Question 83

A major target of such damage, since it filters these complexes from blood

Answer 83

The kidney

Question 84

In autoimmune disease, because a component of the body is the antigen, immune complexes are

Answer 84

Continuously formed

Question 85

Ongoing or very high level deposition of an antigen-antibody complex, can lead to high levels of complement recognition and activation, leading to cellular damage, thereby contributing to life-threatening

Answer 85

Kidney Damage

Question 86

There are other soluble recognition and effector molecules. One important family is the

Answer 86

Pentraxins

Question 87

Include some of the proteins that are produced during inflammation, called acute-phase proteins, or acute-phase reactants

Answer 87

Pentraxins

Question 88

What are two examples of pentraxins?

Answer 88

C-reactive protein (CRP) and serum amyloid protein (SAP)

Question 89

These can activate complement C1, feeding into the complement pathway

Answer 89

CRP and SAP

Question 90

In addition, these proteins, particular CRP sometimes serve diagnostically as important “biomarkers” for

Answer 90

Inflammation

Question 91

Proteins that act as signals with the immune system (and some also during development and other processes)

Answer 91

Cytokines

Question 92

In the pro-inflammatory pathways, the major cytokines are

Answer 92

TNF-α, IL-1, and IL-6

Question 93

During viral infections, the main signal released are

Answer 93

Type I and Type III interferons

Question 94

The major outcomes of activating the components of innate immunity are either an

Answer 94

Inflammatory response or an immune response

Question 95

Includes the recruitment of leukocytes, and the phagocytosis and killing of microbes by activated phagocytes, as well as stimulating elements of adaptive immunity to both produce a stronger response and initiate immunological memory

Answer 95

Inflammatory Response

Question 96

Depends on the production of Type I and Type III interferons (primarily IFN-αs and IFN-β) by cells infected by virus

Answer 96

Antiviral response

Question 97

Is NOT a Type I IFN, does not have a major role in the antiviral response, is produced under different conditions and has distinct biological activities

Answer 97

Gamma interferon, IFN-γ

Question 98

Can activate almost all nucleated cells

Answer 98

Type I IFNs

Question 99

Primarily promote antiviral responses on epithelial cells of mucosal tissue, which are a common sites of virus invasion

Answer 99

Type III IFNs

Question 100

All nucleated mammalian cells can respond to viruses through their various

Answer 100

PRRs