Lecture 5: Activation Of Innate Immunity Flashcards Preview

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Flashcards in Lecture 5: Activation Of Innate Immunity Deck (60):

____________ 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



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

Cationic granules


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

NK cells


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

Post-capillary venules; capillaries


What organs are considered parenchymal tissues?

Liver, lungs, kidney


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

E; P


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



What are the steps of neutrophil homing?

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


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

Integrin is found on leukocyte and ligand is on endothelial cells


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

VCAM-1 and ICAM-1


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



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



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



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

A Ser protease that digests collagen and proteoglycans


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

Cationic (rich in Arg) antibiotic peptides

- Insert into microbial membranes and destabilize ion channels

- Effective against all gram + and - bacteria, fungi, and enveloped viruses


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

Increases permeability of bacterial membrane


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

Bactericidal or bacteriostatic proteins


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

MIP-1alpha and beta


Which macrophage type is proinflammatory versus antiinflammatory?

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


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

TLRs; IFN-gamma


Alternative macrophage activation is induced by what 2 cytokines?

IL-4 and 13


Alternatively activated macrophages are important for what?

Tissue repair and to control inflammation


How are NK cells directly involved in an immune response?

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


How are NK cells indirectly involved in the immune response?

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


How are NK cells activated?

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


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?

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


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

PK (protein tyrosine kinase)


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

PTP (protein tyrosine phosphatase)


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

class I MHC


All complement pathways lead to the production of C___



C3b initiates activation of ______



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

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


What is the role of C3a?

Inflammation and chemotaxis


What is the role of C3b?

Formation of C5 convertase


How is C5 convertase made?

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)


Surface-bound C3b serves as an ___________ and increases ____________

Opsonin; phagocytosis


Explain the steps of MAC formation

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


What is the MAC complex responsible for?

Creating the transmembrane channels that lead to cell lysis


What produces APPs?



What cytokine is the main regulator of APP production?



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

Fixes complement and opsonizes


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

Fixes complement and opsonizes


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


- Causes activation and maturation of APCs


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

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


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

B) Complement C5a and IL-8


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

D) NK cell killing is extracellular


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

E) None of these

- All of these functions are mediated by complement components that come after C3 and in its absence cant be activated


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

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


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

C) Phagocytosis

- C3b opsonin enhances phagocytosis of the opsonized bacteria by phagocytes


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

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.


Which of the following can activate the alternative pathway of complement?
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

E) all of the above

- Alternative pathway is activated by microbial-cell walls


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
D) Lipoarabinomannan
E) Phosphatidylinositol dimannoside

A) Lippoteichoic acid


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

E) Mast cell degranulation


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

C) Lysozyme


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

A) Pyrogens

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


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

D) NK cell activation


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

Inflammation and antiviral defense


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

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


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

Natural killer cells

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


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.


- 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.