Lymphocyte Migration and Immune Responses (Part 2 of 2)

1975 ◽  
pp. 32-59
Author(s):  
W.L. Ford
Keyword(s):  
Immune Responses ◽  
Lymphocyte Migration

scholarly journals Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Megan M. Dunagan ◽  
Kala Hardy ◽  
Toru Takimoto
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Populations ◽  
Lymphocyte Migration ◽  
Host Immune Responses ◽  
Mhc Molecules ◽  
The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

scholarly journals Lymphocyte Homing to Bronchus-associated Lymphoid Tissue (BALT) Is Mediated by L-selectin/PNAd, α4β1 Integrin/VCAM-1, and LFA-1 Adhesion Pathways

2003 ◽  
Vol 197 (10) ◽  
pp. 1255-1267 ◽  
Author(s):  
Baohui Xu ◽  
Norbert Wagner ◽  
Linh Nguyen Pham ◽  
Vincent Magno ◽  
Zhongyan Shan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lymphoid Tissue ◽  
Lymphoid Tissues ◽  
Lymphocyte Migration ◽  
High Endothelial Venules ◽  
Level Of Involvement ◽  
Selectin Ligand ◽  
High Level ◽  
Migration Pathways ◽  
B And T Lymphocytes

Bronchus-associated lymphoid tissue (BALT) participates in airway immune responses. However, little is known about the lymphocyte–endothelial adhesion cascades that recruit lymphocytes from blood into BALT. We show that high endothelial venules (HEVs) in BALT express substantial levels of VCAM-1, in marked contrast to HEVs in other secondary lymphoid tissues. BALT HEVs also express the L-selectin ligand PNAd. Anti–L-selectin, anti-PNAd, and anti–LFA-1 mAbs almost completely block the homing of B and T lymphocytes into BALT, whereas anti–α4 integrin and anti–VCAM-1 mAbs inhibit homing by nearly 40%. α4β7 integrin and MAdCAM-1 are not involved. Importantly, we found that mAbs against α4 integrin and VCAM-1 significantly block the migration of total T cells (80% memory phenotype) but not naive T and B cells to BALT. These results suggest that an adhesion cascade, which includes L-selectin/PNAd, α4β1 integrin/VCAM-1, and LFA-1, targets specific lymphocyte subsets to BALT. This high level of involvement of α4β1 integrin/VCAM-1 is unique among secondary lymphoid tissues, and may help unify lymphocyte migration pathways and immune responses in BALT and other bronchopulmonary tissues.

scholarly journals The COMMD3/8 complex determines GRK6 specificity for chemoattractant receptors

2019 ◽  
Vol 216 (7) ◽  
pp. 1630-1647 ◽  
Author(s):  
Akiko Nakai ◽  
Jun Fujimoto ◽  
Haruhiko Miyata ◽  
Ralf Stumm ◽  
Masashi Narazaki ◽  
...  
Keyword(s):  
Immune Responses ◽  
Copper Metabolism ◽  
G Protein Coupled Receptors ◽  
Lymphocyte Migration ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cxc Chemokine Receptor 4 ◽  
Molecular Machinery ◽  
Chemokine Receptor 4 ◽  
G Protein Coupled

Lymphocyte migration is mediated by G protein–coupled receptors (GPCRs) that respond to chemoattractive molecules. After their activation, GPCRs are phosphorylated by different GPCR kinases (GRKs), which produces distinct functional outcomes through β-arrestins. However, the molecular machinery that targets individual GRKs to activated GPCRs remains elusive. Here, we identified a protein complex consisting of copper metabolism MURR1 domain–containing (COMMD) 3 and COMMD8 (COMMD3/8 complex) as an adaptor that selectively recruits a specific GRK to chemoattractant receptors and promotes lymphocyte chemotaxis. COMMD8, whose stability depended on COMMD3, was recruited to multiple chemoattractant receptors. Deficiency of COMMD8 or COMMD3 impaired B cell migration and humoral immune responses. Using CXC-chemokine receptor 4 (CXCR4) as a model, we demonstrated that the COMMD3/8 complex selectively recruited GRK6 and induced GRK6-mediated phosphorylation of the receptor and activation of β-arrestin–mediated signaling. Thus, the COMMD3/8 complex is a specificity determinant of GRK targeting to GPCRs and represents a point of regulation for immune responses.

Lymphoma dissemination: the other face of lymphocyte homing

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3102-3111 ◽  
Author(s):  
Steven T. Pals ◽  
David J. J. de Gorter ◽  
Marcel Spaargaren
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Shape Change ◽  
Lymphocyte Migration ◽  
Lymphocyte Homing ◽  
Tumor Dissemination ◽  
Cutaneous Lymphomas ◽  
Multistep Process ◽  
Physical Barriers ◽  
Tissue Compartments

Abstract The orchestration of systemic immune responses is critically dependent on coordinated lymphocyte migration and recirculation. This “homing” guides lymphocytes to the microenvironments that control their differentiation and survival, disperses the immunologic repertoire, and targets effector lymphocytes to sites of antigenic insult. Lymphocyte homing is a multistep process that requires chemotaxis and cell adhesion coupled with strategies to overcome physical barriers. At the molecular level, it is regulated by adhesion molecules and chemokines, and facilitated by intrinsic molecular programs that allow “ameboid” shape change, allowing highly effective lymphocyte traffic between different tissue compartments. In case of malignant transformation, however, the fact that lymphocytes are “licensed to move” forms a serious threat to the organism, because it permits rapid tumor dissemination irrespective of the conventional anatomic boundaries limiting early spread in most types of cancer. Thus, unlike the metastatic spread of other cancers, lymphoma dissemination generally is not a reflection of tumor progression but of conserved physiological behavior. The dissemination patterns often reflect basic rules of lymphocyte homing, explaining the strikingly tissue-specific dissemination of, for example, mucosal lymphomas, cutaneous lymphomas, and multiple myeloma. Understanding the molecular mechanisms underlying this behavior may provide novel targets for treatment of lymphoma patients.

DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1

Blood ◽  
2003 ◽  
Vol 102 (8) ◽  
pp. 2948-2950 ◽  
Author(s):  
Terukazu Sanui ◽  
Ayumi Inayoshi ◽  
Mayuko Noda ◽  
Eiko Iwata ◽  
Jens V. Stein ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Actin Polymerization ◽  
Critical Role ◽  
The Other ◽  
Hybridoma Cells ◽  
Lymphocyte Infiltration ◽  
Cytoskeletal Reorganization ◽  
Lymphocyte Migration ◽  
Endogenous Expression

Abstract Although the migratory property of lymphocytes is critical for protective immunity, tissue infiltration of lymphocytes sometimes causes harmful immune responses. DOCK2 plays a critical role in lymphocyte migration by regulating actin cytoskeleton through Rac activation, yet the mechanism by which DOCK2 activates Rac remains unknown. We found that DOCK2 associates with engulfment and cell motility (ELMO1) through its Srchomology 3 (SH3) domain. When DOCK2 was expressed in T-hybridoma cells lacking endogenous expression of DOCK2, Rac activation and actin polymerization were induced. However, such responses were not elicited by the DOCK2 mutant lacking the region required for ELMO1 binding. On the other hand, we found that the expression of ELMO1 induces Rac activation in the plasmacytoma cells expressing DOCK2 but not ELMO1. These results indicate that the association of DOCK2 with ELMO1 is critical for DOCK2-mediated Rac activation, thereby suggesting that their association might be a therapeutic target for immunologic disorders caused by lymphocyte infiltration.

scholarly journals THE DISTRIBUTION OF 51CR-LABELED LYMPHOCYTES INTO ANTIGEN-STIMULATED MICE

1971 ◽  
Vol 134 (1) ◽  
pp. 224-241 ◽  
Author(s):  
Marion M. Zatz ◽  
Eugene M. Lance
Keyword(s):  
Immune Responses ◽  
Skin Grafting ◽  
Keyhole Limpet Hemocyanin ◽  
Rat Skin ◽  
Lymphocyte Migration ◽  
Lymph Node Cells ◽  
Dose Dependent ◽  
Draining Lymph Nodes ◽  
Allograft Response

The localization of syngeneic 51Cr-labeled lymph node cells was investigated in CBA/J mice previously challenged with sheep erythrocytes, Salmonella H antigen, keyhole limpet hemocyanin, C57BL/6J skin, or rat skin. The effect of time, dose, and route of antigen administration on lymphocyte migration was studied in both primary and secondary responses. When the distribution pattern of lymphocytes was examined after 20–24 hr, it was found that increased localization of labeled cells occurred in spleen after intravenous or intraperitoneal antigen injection, and in draining lymph nodes after subcutaneous antigen injection or skin grafting. Increased localization (trapping) of lymphocytes was antigen dose dependent and could be demonstrated when 1–6 hr had elapsed between intravenous antigen administration, or when 24 hr had elapsed between subcutaneous antigen administration and intravenous cell infusion. Trapping was transient, lasting approximately 24 hr. Maximal trapping of lymphocytes in the draining nodes occurred 9 days after skin grafting in the first-set allograft response, and 3 days after grafting in the second-set allograft and first-set xenograft responses. The cell type trapped, the specificity and mechanism of action of the trap, and the role of lymphocyte trapping in the initiation of immune responses are discussed.

Lymphocyte recirculation, exercise, and immune responses

1998 ◽  
Vol 76 (5) ◽  
pp. 490-496 ◽  
Author(s):  
John B Hay ◽  
William N Andrade
Keyword(s):  
Immune Responses ◽  
Cell Tracking ◽  
Lymphocyte Subsets ◽  
Blood Pool ◽  
Exercise Stress ◽  
Lymphocyte Migration ◽  
Blood Samples ◽  
Lymphocyte Recirculation ◽  
Afferent Lymph

Alterations in leukocyte concentrations in the blood are associated with exercise, stress, and other pathophysiological perturbations. The continuous migration and redistribution of cells of the recirculating lymphocyte pool between the blood and lymphatic systems can be influenced by a variety of physiological, immunological, and pathological processes. The phenotypic distribution of lymphocyte subsets is not the same in blood, afferent lymph, and efferent lymph, and cell-tracking experiments have shown that lymphocytes vary in their migratory properties. The most comprehensive physiological studies tracking these cells in vivo have been done in sheep. It has been shown that lymph-derived cells have different migratory capacities than blood-derived lymphocytes, that antigenic challenge of a single lymph node can first reduce the output of lymphocytes from the node and then markedly increase the recruitment from the blood and subsequently the output into efferent lymph. In most mammals, the blood pool of lymphocytes represents only about 1% of the total lymphocytes and only a small fraction of the recirculating lymphocyte pool. Therefore, testing the effects of exercise on lymphocyte recirculation by examining blood samples only requires considerable deduction and inference to interpret multicompartmental effects.Key words: lymphocyte migration, blood, lymph, lymph nodes.

Specific humoral immune responses in 12 cases of food sensitization to sesame seed

1997 ◽  
Vol 27 (11) ◽  
pp. 1285-1291 ◽  
Author(s):  
M. N. KOLOPP-SARDA ◽  
D. A. MONERET-VAUTRIN ◽  
B. GOBERT ◽  
G. KANNY ◽  
M. BRODSCHII ◽  
...  
Keyword(s):  
Immune Responses ◽  
Sesame Seed ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Food Sensitization
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