02/16f Innate Immunity

Question 1

What are the three functions of the innate immune system?

Answer 1

1) Provide initial responses to microbes
2) Recognize and eliminate dead and damaged tissues and initiate repair processes
3) Stimulate the adaptive immune response

Question 2

What the three types of barriers to microorganism entry? Give an example of each

Answer 2

Anatomic/mechanical - epithelial cells, cilia
Physiologic/chemical - lysozyme, low pH
Bacteriologic - normal microbiota

Question 3

What is lysozyme?

Answer 3

Antimicrobial enzyme found in the granules of neutrophils and abundant in tears, saliva, mucous, and breastmilk
Targets Gram-positive bacteria

Question 4

What are defensins?

Answer 4

Proteins that kill bacteria by punching holes in microbial membranes
Produced by neutrophils, NK cells, and epithelial cells

Question 5

How does the innate immune system recognize threats to the host? What does it recognize?

Answer 5

By distinguishing self vs. non-self molecular patterns
Recognizes pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), sensed by pattern recognition receptors (PRRs)

Question 6

What are some general pathogen signatures?

Answer 6

Viruses - abnormal surface proteins and nucleic acids
Parasites - foreign membrane phospholipids
Fungi - foreign surface carbohydrates and glycoproteins
Bacteria - lipopolysaccharide, peptidoglycans, flagellin

Question 7

What are four specific classes of CELL-ASSOCIATED PRRs?

Answer 7

Toll-like receptors
NOD-like receptors
RIG-like receptors
C-type lectin receptors

Question 8

What are Toll-like receptors? What responses do they elicit in the cell?

Answer 8

Integral membrane glycoprotein PRRs
Activate NKkB (pro-inflammatory transcription factor) and interferon response factors

Question 9

Where in the cell are Toll-like receptors found? How does their location affect what they recognize?

Answer 9

Cell surface and endosomal
Cell surface receptors recognize molecules present on bacterial membranes, while endosomal receptors recognize molecules present within the cell

Question 10

What are NOD-like receptors? What responses do they elicit?

Answer 10

Cytosolic protein that sense cytoplasmic PAMPs and DAMPs

Recruit proteins that promote inflammation and generate active forms of the inflammatory cytokine IL-1

Question 11

What are RIG-like receptors? What responses do they elicit?

Answer 11

Cytosolic sensors of viral RNA

Induce production of antiviral interferons

Question 12

What are C-type lectin receptors? What responses do they elicit?

Answer 12

Recognize carbohydrates on the surface of various microbes

Facilitates phagocytosis of microbes and stimulates subsequent adaptive immune responses

Question 13

What are four specific classes of SOLUBLE PRRs?

Answer 13

Complement
Collectins
Pentraxins
Germline/natural antibodies

Question 14

What are collectins? What responses do they elicit?

Answer 14

Collagen lectins
Bind to oligosaccharide structures or lipids
Promote aggregation and opsonization, complement activation, and inhibition of microbial growth
Modulate inflammatory responses and adaptive immune responses

Question 15

What are pentraxins? What responses do they elicit?

Answer 15

Bind various targets, particularly lipoproteins

Promote agglutination, bacterial capsular swelling, and phagocytosis

Question 16

What is the complement system?

Answer 16

A cascade of plasma proteins that opsonize microbes, recruit phagocytes, and directly kill microbes

Question 17

What are natural/germline antibodies?

Answer 17

Antibodies (IgM) that are produced by B cells without exposure to foreign antigens
Many are specific for oxidized lipids

Question 18

What are some specific DAMPs?

Answer 18

Nuclear or cytosolic proteins that are released following cell injury
Proteins derived from the extracellular matrix that are produced following cell injury
ATP
Uric acid
Oxidized membrane lipids

Question 19

What are four of the molecules of innate immunity that “sound the alarm” by mediating inflammation?

Answer 19

Cytokines
Chemokines
Lipid inflammatory mediators
Acute phase reactants

Question 20

What are cytokines?

Answer 20

Small glyopeptides with multiple activities, that facilitate innate immune functions and assist in activating inflammation

Question 21

What are the three major proinflammatory cytokines?

Answer 21

Tumor Necrosis Factor alpha (TNFalpha)
Interleukin-1 (IL-1)
Interleukin-6 (IL-6)

Question 22

What cells produce TNFa? What does it do?

Answer 22

Produced by mast cells and macrophages
Stimulates almost all cell types by increasing expression of inflammatory mediators and inducing local and systemic inflammatory responses

Question 23

What cells produce IL-1? What does it do?

Answer 23

Produced by many cells, particularly macrophages

Increases expression of inflammatory mediators in almost all cell types

Question 24

What cells produce IL-6? What does it do?

Answer 24

Produced by macrophages, endothelial cells, and fibroblasts
Stimulates neutrophil production in the bone marrow and acute phase reactant production in the liver
Induces differentiation of T helper cell populations

Question 25

What are the systemic effects of proinflammatory cytokines?

Answer 25

Fever Production of acute phase reactants by the liver Hypotension Intravascular thrombosis Prolonged production of TNF can cause cachexia

Question 26

What are the lipid inflammatory mediators? What do they do?

Answer 26

Prostaglandins and leukotrienes | Promote vasodilation, bronchoconstriction, and chemotaxis of PMNs

Question 27

What are acute phase reactants? What do they do?

Answer 27

Molecules produced in the liver in response to circulating cytokines Promote opsonization, complement activation, and degradation of extracellular matrix Also bind iron to sequester it from microbes

Question 28

What are the four types of resident innate immune cells?

Answer 28

Mast cells Macrophages and other mononuclear phagocytes Dendritic cells Innate-like lymphocytes

Question 29

What are mast cells?

Answer 29

Granular cells that are resident in tissues | Rapidly release TNFa, histamine, prostaglandins, leukotrienes, IL-4, and other factors

Question 30

What are the effects of mast cell activation and granule release?

Answer 30

Activation of endothelial cells and dendritic cells Vasodilation and increased vascular permeability Lymph node response Mucosal edema and mucous secretion Smooth muscle contraction

Question 31

What are macrophages? What are their functions?

Answer 31

Large phagocytic cells covered in PRRs and cytokine receptors Ingest and destroy microbes and dead host cells Produce cytokines Present antigen to and activate memory T cells Promote repair of damaged tissue

Question 32

How do macrophages kill microbes?

Answer 32

Activated by Toll-like receptors to produce reactive oxygen species, nitric oxide, and proteolytic enzymes

Question 33

What are dendritic cells? What are their functions?

Answer 33

Antigen-presenting cells Activate naive T cells in secondary lymphoid organs Produce cytokines and chemokines

Question 34

What are plasmacytoid dendritic cells?

Answer 34

Atypical dendritic cells that are specialized for viral infections Major source of type 1 interferon

Question 35

What are innate-like lymphoctyes?

Answer 35

Atypical lymphocytes that perform innate functions

Question 36

What are the six types of innate-like lymphocytes?

Answer 36

``` Natural killer cells Natural killer T cells Gamma-delta T cells Intraepithelial T cells B-1 cells Marginal zone B cells ```

Question 37

What are intraepithelial T cells? What are their functions?

Answer 37

Innate lymphocytes found in the epidermis and mucosal epithelia Recognize molecules associated with infected epithelial cells Secrete cytokines, activate phagocytes, and kill infected cells

Question 38

What are natural killer T cells?

Answer 38

Innate lymphocytes that share properties of both T cells and natural killer cells, and are specialized to recognize lipids and glycolipids

Question 39

What are B-1 cells? What are their functions?

Answer 39

Innate lymphocytes found in the peritoneum and mucosal sites | Secrete IgM against microbial polysaccharides and lipids, independent of T cells

Question 40

What are the endothelial cell responses to inflammation?

Answer 40

Vasodilation and increased permeability cause warmth and swelling Expression of cell adhesion molecules and chemokines lead to increased cell adhesion and migration

Question 41

What are the five types of cells that are recruited during an inflammatory response?

Answer 41

``` Neutrophils Monocytes (become macrophages) Natural killer cells Eosinophils Basophils ```

Question 42

What are neutrophils? What are their functions?

Answer 42

Highly phagocytic granular cells that destroy microorganisms Granules are filled with enzyme and other microbicidal substances Possess a robust phagocyte oxidase system to produce ROS

Question 43

What are monocytes? What are their functions?

Answer 43

Precursors to macrophages and some dendritic cell types Become resident macrophages and tissue specific phagocytes Recruited to sites of inflammation to become highly active "exudate" macrophages during inflammatory responses

Question 44

What are natural killer cells?

Answer 44

Lymphocytes that play an important role against intracellular viruses and bacteria, and distinguish infected/stressed cells from healthy cells

Question 45

What are KIRs? What do they do?

Answer 45

``` Killer cell Ig-like receptors - inhibit NK cells (allow them to recognize self) Bind a variety of class I MHC molecules and block the signaling pathways of activating receptors ```

Question 46

How do NK cells destroy infected cells?

Answer 46

Make perforin - punches holes in target cell membranes Express destructive enzymes Express cytokines to activate other cells

Question 47

What are basophils? What are their functions?

Answer 47

Circulating granulocytes similar to mast cells Synthesize many of the same substances as mast cells (histamine, prostaglandins, TNFa, etc.) Triggered by antigen binding to IgE

Question 48

What are eosinophils? What are their functions?

Answer 48

Eosinophilic blood granulocytes that contain enzymes that destroy the cells walls of parasites Active in fighting parasite infections and in allergic responses

Question 49

How to neutrophils respond to infection?

Answer 49

Arrive first to site of infection, but don't last long Phagocytose bacteria and produce destructive enzymes, ROS, and defensins Most active in extracellular bacterial infections

Question 50

How do monocytes and macrophages respond to infection?

Answer 50

Arrive after neutrophils to the site of infection, and are longer-lasting Eat dead and dying cells, produce proinflammatory cytokines and chemokines, and mediate tissue repair Most active against intracellular bacteria and viruses

Question 51

How do natural killer cells respond to infection?

Answer 51

Recognize abnormal cells through a combination of inhibitory and activating signals and receptors Kill cells that fail to respond properly, and produce cytokines to alert and activate other cells Most active in viral infections and against neoplastic cells

Question 52

What are the characteristics of the innate antiviral response?

Answer 52

Immediate response - production of Type I Interferons, which induce an antiviral state in adjacent cells to limit the spread of virus NK cells are also activated to kill virally-infected cells

Question 53

What are Type I Interferons? What are their effects?

Answer 53

Cytokines that are released in response to a viral infection Confer cell resistance to viral infection by inhibiting viral protein synthesis and nucleic acid replication Increase the destructive power of NK cells and cytotoxic T cells