Dendritic and NK Cells Overview

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Questions and Answers

What is the primary function of the VE-cadherin complex in endothelial cells?

To stabilize junctions between endothelial cells (correct)

To assist in monocyte proliferation

To promote neutrophil apoptosis

To enhance leukocyte migration

Which kinases are activated during the binding of leukocyte integrins to ICAM-1 or VCAM-1?

Reversible kinases

Cytoplasmic kinases

Phosphorylating kinases (correct)

Regulatory kinases

What is transcellular migration?

Movement of leukocytes into the bloodstream

Movement of leukocytes between endothelial cells

Movement of leukocytes through endothelial cells (correct)

Movement of leukocytes along blood vessels

What is the primary chemokine associated with neutrophil recruitment?

CXCL8 (IL-8) Signup and view all the answers

Which type of leukocyte is typically the most numerous after an initial infection or injury?

Neutrophils Signup and view all the answers

What receptor do classical monocytes predominantly express for recruitment to inflammatory sites?

CCR2 Signup and view all the answers

What determines whether neutrophils or monocytes are recruited to an inflammatory site?

Variations in expression of adhesion molecules and chemokine receptors Signup and view all the answers

After entering tissues, how do neutrophils primarily die?

Apoptosis Signup and view all the answers

What primary role do dendritic cells perform in the immune system?

Initiating inflammation and stimulating the adaptive immune response Signup and view all the answers

What is the main effector function of NK cells?

Killing infected cells and producing interferon-gamma Signup and view all the answers

Which cytokine is crucial for the maturation of NK cells?

IL-15 Signup and view all the answers

How do NK cells kill infected or stressed cells?

By releasing perforin and granzymes Signup and view all the answers

What effect does IL-10 have on NK cells?

It inactivates them after CD8 cytotoxic T-cell activation Signup and view all the answers

Which type of immune response do CD8 cytotoxic T cells provide once they are activated?

Apoptosis of infected cells Signup and view all the answers

Which of the following contributes to macrophage activation by NK cells?

IL-12 Signup and view all the answers

What specific role do perforin and granzymes serve in the activity of cytotoxic immune cells?

To induce cell death in target cells Signup and view all the answers

What is the primary difference between ILC2 and TH2 cells?

The way they get activated Signup and view all the answers

Which statement is true regarding the plasticity of ILCs?

There is flexibility between ILC1 and ILC3. Signup and view all the answers

What is a consequence of the disbalance between ILC subsets in many diseases?

It can lead to certain immune-mediated diseases. Signup and view all the answers

What role do trophoblast cells play in pregnancy?

They grow into the mother's endometrium and blood vessels. Signup and view all the answers

Why is TGF-beta significant in the context of NK cell plasticity?

It allows NK cells to differentiate into ILC1. Signup and view all the answers

What is the primary function of NK cells?

Distinguish infected and stressed cells from healthy cells Signup and view all the answers

Which cytokine is NOT mentioned as a stimulating factor for NK cell activity?

IL-10 Signup and view all the answers

How do activating receptors on NK cells function?

By recognizing ligands on infected and injured cells Signup and view all the answers

What defines KIR haplotypes in NK cells?

Their polymorphism and the groups of linked genes inherited from parents Signup and view all the answers

Which receptor is a low-affinity receptor for IgG antibodies on NK cells?

CD16 Signup and view all the answers

Which of the following statements about KIR genes is true?

KIR genes can be inherited in groups from a single parent Signup and view all the answers

Which statement correctly describes the role of type I IFNs in relation to NK cells?

They can stimulate IFN-γ secretion by NK cells despite not using activating receptors Signup and view all the answers

What is a consequence of some KIR haplotypes having fewer activating receptors?

Greater susceptibility to specific disorders Signup and view all the answers

What is the main role of ILC3s in skin inflammation?

Production of IL-17 and IL-22 Signup and view all the answers

How do ILC3 responses change in patients with asthma?

They are enhanced through NLRP3 inflammasome activation. Signup and view all the answers

What is one mechanism by which ILC3s can promote tumor growth in the intestine?

By depending on DC-derived IL-23 for IL-22 production. Signup and view all the answers

What factors induce ILC3 responses in the intestine?

DC-derived IL-1β and IL-23 after pathogen recognition. Signup and view all the answers

What is a consequence of ILC3-intrinsic MHCII activation?

Killing of CD4+ T cells specific to commensal bacteria. Signup and view all the answers

In what way do ILC3s regulate immune responses in the intestine?

By modulating myeloid cell homeostasis via GM-CSF. Signup and view all the answers

Which cytokine primarily activates ILC3s in response to inflammation mediated by macrophages?

IL-1β Signup and view all the answers

What influence does ILC3-derived LT have on B cells?

Modulates stromal cell responses resulting in IgA production. Signup and view all the answers

Study Notes

Dendritic Cells (DCs)

Bridge the innate and adaptive immune systems by activating T cells
Respond to microbes by producing cytokines
Cytokines initiate inflammation and stimulate the adaptive immune response

Natural Killer (NK) cells

Exhibit cytotoxic activity similar to CD8+ T cells
Circulate in blood and reside in lymphoid tissues
Kill infected cells and produce IFN-γ, which activates macrophages to destroy phagocytosed microbes
Recognize infected and stressed cells, killing them and secreting macrophage-activating cytokine IFN-γ
NK cells release the contents of their cytoplasmic granules into the extracellular space
NK cell-activating cytokines include IL-15 (NK cell maturation), type I interferons, and IL-12 (enhancing killing functions)
Deactivated by IL-10 produced by CD8 T cells
Kill infected cells using proteins like perforin and granzymes, similar to CD8 cells
Activate macrophages through IFN-γ
Macrophages produce IL-12
Perforin forms channels in the membrane of the target cell
Granzymes enter the cell and activate caspase enzymes leading to apoptosis

Leukocyte Migration

Leukocytes migrate through endothelial cells using a process called diapedesis
Diapedesis requires temporary disruption of adherens junction proteins, primarily the VE-cadherin complex, holding endothelial cells together
Kinase activation, triggered by leukocyte integrins binding ICAM-1 or VCAM-1, disrupts the VE-cadherin complex
Kinases phosphorylate the cytoplasmic tail of VE-cadherin, leading to reversible disruption of the adherens complex
In rare cases, leukocytes migrate through endothelial cells via a process called transcellular migration

Neutrophil and Monocyte Recruitment

Neutrophils are the most abundant leukocytes in tissues within 24-48 hours after infection or injury, followed by monocytes
Neutrophils respond rapidly to chemokines compared to monocytes or other leukocytes
Neutrophils have short lifespans in tissues and die by apoptosis, while monocytes survive longer and may proliferate
Variations in expression of adhesion molecules and chemokine receptors determine whether neutrophils or monocytes are recruited to inflammatory sites
Neutrophils express CXCR1 and CXCR2, binding CXCL1 and CXCL8 (IL-8), chemokines with ELR motifs supporting their migration into tissues
Early neutrophil recruitment is driven by early CXCL8 production by tissue-resident macrophages and other cells
Classical monocytes, primarily recruited to inflammatory sites, express CCR2
CCR2 binds CCL2 (MCP-1), crucial for monocyte recruitment
Monocyte recruitment occurs when resident tissue cells produce CCL2 in response to infection

ILC3 Functions

Involved in chronic inflammation and cancer in the skin, lung, and intestine
Increased ILC3 responses contribute to skin inflammation in psoriasis and mouse models through IL-22 and IL-17 production
Elevated ILC3s in bronchoalveolar lavage fluid of asthma patients and mouse models of obesity-induced asthma
Activation of the NLRP3 inflammasome and macrophage production of IL-1β trigger ILC3 production of IL-17, which directly promotes airway inflammation and hyper-responsiveness
ILC3s in the intestine can promote IL-22-dependent tumor growth
ILC3-derived LTα1β2 or LTα3 promote IgA production by B cells indirectly by influencing stromal cell or DC responses
ILC3-derived GM-CSF modulates myeloid cell homeostasis to promote Treg cell responses and tolerance to food antigens
ILC3-intrinsic MHCII can directly kill commensal bacteria-specific CD4+ T cells, potentially causing intestinal inflammation
ILC3s can limit chronic inflammation by regulating innate and adaptive immune responses in the intestine
ILC3 responses are triggered by myeloid cell and DC-derived IL-1β and IL-23 after recognition of microbes

NK Cell Function

Distinguish infected and stressed cells from healthy cells
Function regulated by a balance of signals generated by activating and inhibitory receptors
Activating receptors recognize ligands on infected and injured cells
Inhibitory receptors recognize ligands on healthy normal cells

NK Cell Stimulating Cytokines

IL-12, IL-15, IL-18, and type I IFNs enhance the cytotoxic activity of NK cells
These cytokines stimulate IFN-γ secretion by NK cells
IL-15 is a growth factor for NK cells

NK Cell Activating Receptors

Killer cell Ig-like receptors (KIRs)
- KIR genes exhibit polymorphism, with different allelic variants in the population
- Individuals express various KIR receptors
- Groups of KIR alleles are often inherited together as KIR haplotypes
- Haplotypes differ in the number of receptors encoded
- Some haplotypes are associated with increased susceptibility to disorders like spontaneous abortion and uveitis
Lectin-like NK cell receptor (NKG2D) binds class 1 MHC proteins
CD16 (FcγRIIIA) is a low-affinity receptor for IgG antibodies, binding to the Fc region of IgG1 and IgG3, producing IFN-γ

Functional Plasticity of NK Cells and ILCs

Flexibility exists between different ILC types
True NK cells cannot become ILC3s but can become ILC1s with sufficient TGF-beta
ILC1 and ILC3 exhibit flexibility, crucial for proper tissue responses
Disbalance between ILC subsets can contribute to certain immune-mediated diseases

NK/ILC in Pregnancy

Proper placenta development requires trophoblast cells from the fetus to invade the maternal uterine layer
Trophoblast cells grow into maternal blood vessels, allowing nutrient exchange between fetus and mother
These blood vessels dilate to increase blood flow, primarily driven by NK cell modulation
NK cells secrete factors that adjust blood vessel tone
This ensures adequate blood flow to support fetal growth

ILC2 and TH2 Cells

ILC2s are analogous to TH2 cells
The difference lies in their activation mechanisms
ILC2s are activated through innate mechanisms, while TH2 cells are activated through antigen-specific T cell activation

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Description

Explore the roles of dendritic cells and natural killer cells in the immune system. This quiz covers their activation, functions, and the cytokines involved in their processes. Understand how these cells bridge innate and adaptive immunity and their cytotoxic activities.