Lecture 5: Activation Of Innate Immunity

Question 1

____________ are the first cells to arrive at the site of tissue damage. Activation of neutrophils leads to respiratory bursts and release of granules to control bacterial growth

Answer 1

Neutrophils

Question 2

Eosinophils contain ___________ __________ proteins; fight helminthes and other multicellular parasites

Answer 2

Cationic granules

Question 3

___________ cells are large granular lymphocytes that kill infected host cells by a cytolytic mediator perforin

Answer 3

NK cells

Question 4

Neutrophils and macrophages enter the tissue through ______________ _______________ except parenchymal tissues (liver, lungs, kidney) where all blood cells enter through ____________

Answer 4

Post-capillary venules; capillaries

Question 5

What organs are considered parenchymal tissues?

Answer 5

Liver, lungs, kidney

Question 6

Inflammation-activated endothelial cells increase expression of _____-selectin and _______-selectin adhesion molecules

Answer 6

E; P

Question 7

____________ constitutively express ligands for E and P selectins on endothelial cells

Answer 7

Neutrophils

Question 8

What are the steps of neutrophil homing?

Answer 8

1) Neutrophils slow down and roll along the endothelium through interaction of selectins
2) tight binding through interaction of integrins
3) Diapedesis - transmigration through endothelium
4) Chemoattractant (IL-8) controls migration of neutrophils into inflammatory sites

Question 9

What cell type contains the integrin and which contains the integrin ligand?

Answer 9

Integrin is found on leukocyte and ligand is on endothelial cells

Question 10

What are the integrin adhesion molecules that are found on neutrophils?

Answer 10

VCAM-1 and ICAM-1

Question 11

The integrins on blood leukocytes are normally in a __________ affinity state

Answer 11

Low

Question 12

When rolling of leukocytes occurs, chemokines displayed on the endothelial surface can bind __________ receptors on the leukocyte

Answer 12

Chemokines

Question 13

Chemokines receptor signaling occurs during neutrophil rollings, which then activates the leukocyte _________, increasing their affinity for their ligands on the endothelial cells

Answer 13

Integrins

Question 14

Neutrophils contain cathepsin G, defensins, BPI, lysozyme and lactoferrin. What is cathepsin G?

Answer 14

A Ser protease that digests collagen and proteoglycans

Question 15

Neutrophils contain cathepsin G, defensins, BPI, lysozyme and lactoferrin. What are defensins?

Answer 15

Cationic (rich in Arg) antibiotic peptides

• Insert into microbial membranes and destabilize ion channels
• Effective against all gram + and - bacteria, fungi, and enveloped viruses

Question 16

Neutrophils contain cathepsin G, defensins, BPI, lysozyme and lactoferrin. What is BPI?

Answer 16

Increases permeability of bacterial membrane

Question 17

Neutrophils contain cathepsin G, defensins, BPI, lysozyme and lactoferrin. What is lysozyme and lactoferrin ?

Answer 17

Bactericidal or bacteriostatic proteins

Question 18

Chemoattractants (in addition to MCP-1) for monocytes are ________ and ________

Answer 18

MIP-1alpha and beta

Question 19

Which macrophage type is proinflammatory versus antiinflammatory?

Answer 19

Proinflammatory = classical (M1)
Antiinflammatory = alternative (M2)

Question 20

Classical macrophage activation is induced by ________ and by the cytokine ________

Answer 20

TLRs; IFN-gamma

Question 21

Alternative macrophage activation is induced by what 2 cytokines?

Answer 21

IL-4 and 13

Question 22

Alternatively activated macrophages are important for what?

Answer 22

Tissue repair and to control inflammation

Question 23

How are NK cells directly involved in an immune response?

Answer 23

They recognize infected or stressed cells and release granules that kill the cell

Question 24

How are NK cells indirectly involved in the immune response?

Answer 24

They are activated by IL-12 produced by macrophage Andre in return secrete IFN-gamma that activates phagocytosis and killing of pathogens by macrophages

Question 25

How are NK cells activated?

Answer 25

Not by detection of foreign Ags, but by failure to detect a common Ag expressed on all healthy cells -> MHC class 1

Question 26

NK cells use 2 surface receptors, activating and inhibitory receptors, which recognize Ags normally expressed on host cells. The activating receptor is always on. What is the inhibitory receptor and when is it engaged?

Answer 26

The KIR (killer-cell immunoglobulin-like receptor) and is engaged and activated only if there is no change in expression of class I MHC (if cell is normal) - In virus-infected cells, the level of class I MHC is decreased that truncated the inhibitory signal and allows activating receptor to dominate activating NK cells to destroy the target cell

Question 27

In healthy cells, the activating receptors of NK cells recognize ligands on target cells and activate _________

Answer 27

PK (protein tyrosine kinase)

Question 28

In healthy cells, PTK is inhibited by inhibitory receptors on NK cells that recognize class I MHC molecules and activate _______

Answer 28

PTP (protein tyrosine phosphatase)

Question 29

In a virus-infected cell, the virus inhibits ___________ expression on infected cells, the NK cell inhibitory receptor is not engaged

Answer 29

class I MHC

Question 30

All complement pathways lead to the production of C___

Answer 30

C3b

Question 31

C3b initiates activation of ______

Answer 31

C5

Question 32

What is the general classical complement pathway up to the formation of C3 convertase?

Answer 32

1) C1 protein complex binds IgM or IgG 2) C1 cleaves C2 and C4 3) C4b can attach covalently to microbial surfaces 4) C2a binds to the surface attached C4b and the C3 convertase formed

Question 33

What is the role of C3a?

Answer 33

Inflammation and chemotaxis

Question 34

What is the role of C3b?

Answer 34

Formation of C5 convertase

Question 35

How is C5 convertase made?

Answer 35

1) C3 convertase cleaves off C3a from C3 2) C3b fragment can be deposited on surface of bacteria 4) C3b can form a complex with the C3 convertase to give rise to C5 convertase (C4b, 2a, 3b)

Question 36

Surface-bound C3b serves as an ___________ and increases ____________

Answer 36

Opsonin; phagocytosis

Question 37

Explain the steps of MAC formation

Answer 37

1) C5 convertase cleaves C5 into active C3a and C5b fragments 2) C5b fragment initiates self-assembly of the MAC 3) C5a anaphylatoxin is a potent mediator of inflammatory responses 4) MAC is a supramolecular organization of molecules that contains C5b, C6, C7, C8, together with numerous molecules of C9

Question 38

What is the MAC complex responsible for?

Answer 38

Creating the transmembrane channels that lead to cell lysis

Question 39

What produces APPs?

Answer 39

Hepatocytes

Question 40

What cytokine is the main regulator of APP production?

Answer 40

IL-6

Question 41

C-reactive protein is an APP, what is its role?

Answer 41

Fixes complement and opsonizes

Question 42

Mannose binding protein is an APP, what is its role?

Answer 42

Fixes complement and opsonizes

Question 43

Pathogen recognition through _________ is an important bridge between innate and adaptive immunity

Answer 43

PRRs - Causes activation and maturation of APCs

Question 44

Cells of the innate immune system are triggered by the binding of surface receptors. In general, the action taken is determined by A) A single receptor per cell B) A single type of receptor found on all cells C) The integration of signals generated by multiple receptors on single cells D) Multiple receptors that bind soluble ligands only E) Nonspecific Receptors capable of binding a wide array of ligands

Answer 44

C) The integration of signals generated by multiple receptors on single cells - Cells bear many types of receptors, each capable of specifically binding a different ligand. The signals generated by the binding of various combinations of receptors on the surface of a given cell are integrated by that cell and used to determine the action to be taken

Question 45

``` Neutrophils are attracted to the sites of Extracellular bacterial infections by which 2 important chemotactic substances? A) Bacterial mannose and LPS B) Complement C5a and IL-8 C) Histamine and complement C3b D) IL-7 and IL-16 E) Leukotriene B4 and G-CSF ```

Answer 45

B) Complement C5a and IL-8

Question 46

Which of the following about NK cells is correct? A) NK cells proliferate in response to Ag B) NK cells kill their target cells by phagocytosis and intracellular digestion C) NK cells are a subset of polymorphonuclear cells D) NK cell killing is extracellular E) NK cells are particularly effective against certain bacteria

Answer 46

D) NK cell killing is extracellular

Question 47

A pt is admitted to your hospital with multiple bacterial infections. He is found to have a complete absence of C3 component of complement. Which complement-mediated function would remain intact in such a patient? A) Lysis of bacteria B) Opsonization of bacteria C) Generation of anaphylatoxins D) Generation of neutrophil chemotactic factors E) None of these

Answer 47

E) None of these - All of these functions are mediated by complement components that come after C3 and in its absence cant be activated

Question 48

Which of the following screening tests would be most useful for confirming a presumptive diagnosis of a complement immunodeficiency? A) Quantification of serum opsonic activity B) Quantification of serum hemolytic activity C) Quantification of C3 content of serum D) Quantification of C1 content of serum E) Electrophoretic analysis of patient's serum

Answer 48

B) Quantification of serum hemolytic activity - Hemolytic assay would reveal a defect in any one of the complement components since all are required to induce hemolysis

Question 49

``` Complement is required for which of the following processes? A) lysis of erythrocytes by lecithinase B) NK-mediated lysis of tumor cells C) Phagocytosis D) Enhancement of APP responses E) All of the above ```

Answer 49

C) Phagocytosis - C3b opsonin enhances phagocytosis of the opsonized bacteria by phagocytes

Question 50

Active fragments of C5 can lead to the following, except: A) contraction of smooth muscle B) vasodilation C) attraction of leukocytes D) attachment of lymphocytes to macrophages

Answer 50

D) Attachment of lymphocytes to macrophages - C5a induces degranulation of mast cells, resulting in the release of histamine which causes vasodilation and contraction of smooth muscles. C5a also attracts leukocytes to the area of its release where the complement is activated.

Question 51

Which of the following can activate the alternative pathway of complement? A) LPS B) Some viruses and virus-infected cells C) Fungal and yeast cell walls (zymosan) D) Many strains of gram-positive bacteria E) All of the above

Answer 51

E) all of the above - Alternative pathway is activated by microbial-cell walls

Question 52

``` Which of the following pathogen-associated molecular patterns is important for activating of the innate immune system against an infection caused by gram-positive bacteria? A) Lipoteichoic acid B) dsRNA C) LPS D) Lipoarabinomannan E) Phosphatidylinositol dimannoside ```

Answer 52

A) Lippoteichoic acid

Question 53

``` Which of the following actions does the complement protein perform? A) They cause Ab release B) T cell development C) The release of histamine D) Promotes tissue repair E) Mast cell degranulation ```

Answer 53

E) Mast cell degranulation

Question 54

``` Which of the following is an additional chemical defense found in tears and saliva? A) T lymphocytes B) Saline C) Lysozyme D) EFC ```

Answer 54

C) Lysozyme

Question 55

``` Which substance induces fever? A) Pyrogens B) Pus C) Monocytes D) Edema E) Interferon ```

Answer 55

A) Pyrogens - The definition of a pyrogen: a substance, typically produced by a bacterium, that produces fever when introduced or released into the blood

Question 56

Which of the following is not part of the innate immune response to extracellular bacteria? A) Complement activation by lipopolysaccharide B) Complement activation by mannose C) Activation of phagocytes by TLRs D) NK cell activation E) Inflammation

Answer 56

D) NK cell activation

Question 57

What are the 2 principal types of reactions of the innate immune system?

Answer 57

Inflammation and antiviral defense

Question 58

Inflammation and antiviral defense are the 2 principal types of reactions of the innate immune system. What does inflammation consist of?

Answer 58

The accumulation and activation of leukocytes and plasma proteins at sites of infection or tissue injury. - These cells and proteins act together to kill mainly extracellular microbes and to eliminate damaged tissues

Question 59

What cell type mediates the innate immune defense against intracellular viruses?

Answer 59

Natural killer cells - Type I interferons also work to block viral replication within host cells

Question 60

PRRs of the innate immune system are ____________ distributed, that is, identical receptors are expressed on all the cells of a particular types, such as macrophages.

Answer 60

Nonclonally - THis is in contrast to the Ag receptors of the adaptive immune system which a re encoded by genes formed by somatic rearrangement of gene segments during lymphocyte development, resulting in unique receptors in each clone of B and T lymphocytes.