A study of the adoptive secondary response to a protein antigen in mice

1961 ◽  
Vol 154 (956) ◽  
pp. 398-417 ◽  
Keyword(s):  
Immune Response ◽  
Cell Division ◽  
Antibody Production ◽  
Passive Immunization ◽  
Active Immunization ◽  
Lymphoid Cells ◽  
Protein Antigen ◽  
Secondary Response ◽  
Recipient Mouse ◽  
Time Control

An attempt has been made to study the cellular inheritance of the induced state of cellular differentiation associated with a secondary immune response. Lymphoid cells have been transferred from donor mice immunized against a protein antigen (bovine gamma globulin) into lethally X -irradiated recipients of the same inbred strain. Evidence is discussed which has led to the assumption that the cells capable of producing a secondary response divide in an irradiated environment. The experiments described here have been designed to show the effect of cell division on the capacity of these cells to produce antibody. The rate of anti­body production in an immune response has been measured by means of the antigen-elimina­tion technique. This technique has been calibrated in passive immunization experiments using an antiserum prepared in outbred mice. The amount of division by the transferred immunized cells before challenge was varied in two ways. First, mice were challenged at different intervals after the transfer of the same number of immunized cells into each recipient mouse. Secondly, different numbers of cells were injected into mice, and these left for a time sufficient for the smallest inoculum used to recolonize the host completely. In the first type of experiment, the results showed that the capacity to produce a secondary response steadily declined with increasing time. Control experiments showed that such a decline can occur after active immunization in non-irradiated mice. In the second type of experiment, the rate of antibody production was directly proportional to the size of the original inoculum of immunized cells. It seems that the rate of antibody production is not increased by cell division. The results are prob­ably, therefore, incompatible with those hypotheses which postulate that all of the mechan­ism responsible for antibody synthesis is capable of replication.

scholarly journals GENETIC CONTROL OF THE IMMUNE RESPONSE

1972 ◽  
Vol 136 (5) ◽  
pp. 1195-1206 ◽  
Author(s):  
John C. Ordal ◽  
F. Carl Grumet
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Genetic Control ◽  
Antibody Production ◽  
Lymphoid Cells ◽  
Antigen Challenge ◽  
Graft Versus Host ◽  
K Cells

The transfer of parental (H-2k/k) nonresponder lymphoid cells into heterozygous (H-2k/q) nonresponder recipients at the time of primary challenge with aqueous poly-L(Tyr,Glu)-poly-D,L-Ala-poly-L-Lys [(T,G)-A--L] elicited the production of both IgM and IgG anti-(T,G)-A--L antibody. Normally, the production of IgG anti-(T,G)-A--L antibody is restricted to strains possessing the responder Ir-1 allele. The timing and intensity of the graft-versus-host (GVH) reaction required for this effect were found to be critical. Injection of H-2k/k cells into H-2k/q recipients 1 wk before antigen challenge did not elicit IgG anti-(T,G)-A--L antibody production, and markedly suppressed IgM anti-(T,G)-A--L antibody production. The transfer of alloimmune (H-2q-primed) H-2k/k cells at the time of antigen challenge was also associated with no IgG and little IgM anti-(T,G)-A--L antibody production. These data are consistent with the model that nonresponder thymus-derived lymphocytes (T cells) activated in a GVH reaction can substitute for (T,G)-A--L-reactive T cells to induce a shift from IgM to IgG anti-(T,G)-A--L antibody production.

scholarly journals THE IMMUNE RESPONSE TO SHEEP ERYTHROCYTES IN THE MOUSE

1967 ◽  
Vol 126 (1) ◽  
pp. 15-33 ◽  
Author(s):  
David Eidinger ◽  
Hugh F. Pross
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Latent Period ◽  
Lymphoid Cells ◽  
Secondary Response ◽  
Lymphoid Tissues ◽  
Antibody Activity ◽  
Cellular Activity ◽  
Sheep Erythrocytes ◽  
Draining Lymph Node

The direct and indirect plaque technique for the detection of antibody-forming cells against sheep erythrocytes was utilized for the investigation of a number of biological parameters of the primary and secondary immune response on a cellular level. The sequential pattern of 19S followed by 7S antibody formation was elicited in the primary response after a latent period of at least 1–2 days and 2–3 days respectively. The secondary response initiated 140 days after primary immunization, in contrast, was characterized by the simultaneous appearance of 19S and 7S antibody-forming cells after an observed latent period of 2–3 days. The cellular dynamics of the recruitment phase of the respective immunoglobulins in the primary and secondary response was interpreted as evidence for the derivation of the two classes of immunoglobulins from separate progenitors. The 19S antibody-forming cells were derived predominantly by a process of transformation and maturation and 7S antibody formers by a process of cellular division with a doubling time of about 12 hr. The draining lymph node exhibited maximal immunological reactivity due to its capacity to retain the particulate antigen. This capacity was considerably enhanced in the sensitized draining lymph node. Minimal cellular activity was also noted in distal lymphoid tissues which included the thymus. Focal cellular activity was observed in the draining lymph node for 60 days after immunization. Subsequently, very low level plaque-forming cellular activity was observed in association with persistence of maximal antibody activity. The appearance at 120 days of a generalized peak of cellular activity in lymphoid tissues throughout the host was considered an explanation for this discrepancy. The change in distribution of cellular antibody-forming activity, from a local to a generalized lymphatic response during the late phase of the immune response, implied a fundamental alteration in homeostatic mechanisms associated with maintenance of immune reactivity. Further manifestations of such an alteration were indicated by the appearance of 2-ME-sensitive 7S antibody nearly 3 months after primary intradermal immunization, which in the ensuing 5 months was associated with, and inversely related to, two major fluctuations in 2-ME-resistant 7S antibody. Evidence for the existence of immunological memory in the 19S system was not established in the present work. 19S anamnesis, for which evidence was derived from measurements of circulating antibody levels, was interpreted from cellular studies as the result of the substantial activity of previously uncommitted 19S lymphoid cells in distal lymphoid tissue associated with previously committed 19S cells contained in the draining lymph node.

scholarly journals THE MECHANISM OF TOLERANCE PRODUCED IN RATS TO SHEEP ERYTHROCYTES

1965 ◽  
Vol 121 (5) ◽  
pp. 683-695 ◽  
Author(s):  
Donald A. Rowley ◽  
Frank W. Fitch
Keyword(s):  
Immune Response ◽  
Cell Division ◽  
Cell Response ◽  
Sheep Erythrocyte ◽  
Passive Immunization ◽  
Small Population ◽  
Antigenic Stimulation ◽  
Sheep Erythrocytes ◽  
Growing Rats ◽  
Antibody Titers

An active immune response to sheep erythrocytes was demonstrated in rats made "tolerant" to sheep erythrocytes by twice-weekly antigen injections beginning on the day of birth. Groups of tolerant rats were sacrificed 4 days after they had received 5 to 42 antigen injections; spleens were sampled for plaque-forming (antibody-releasing) cells and sera were titrated for antibody to sheep erythrocytes using a sensitive "plate hemolysin" technique. During the 3rd week of life and after the 5th antigen injection, the tolerant rats had an immune response equivalent to that of rats of similar age which had received a single antigen injection, but spleens contained only about one-tenth as many plaque-forming cells as adults animals receiving similar antigen injections. Continued antigen injections produced a marked decline and stabilization of this relatively small population of antibody-forming cells; however, the number of plaque-forming cells in the tolerant rats remained considerably elevated above the numbers of plaque-forming cells present in the spleens of non-immunized animals. The sera from all but 1 tolerant rat had demonstrable antibody to sheep erythrocytes in low titer. A progressive recovery of the plaque-forming cell response and rise in antibody titers occurred in adult tolerant rats when the interval between the last 2 antigen injections was increased from 3 days to 14 or 28 days. The decline and stabilization of numbers of plaque-forming cells occurring with continued injections after the 3rd week of life paralleled a similar decline and stabilization in rats receiving similar antigen injections as adults. Also, the recovery of the plaque-forming cell and antibody response of tolerant animals paralleled the recovery observed when the interval between injections was increased in rats receiving similar antigen injections as adults. These findings suggested that the same mechanism controlled numbers of antibody-forming cells in tolerant and normally responsive adult animals. Repeated closely spaced antigen injections presumably interfered with either cell division or maturation of antibody-forming cells. As the interval between injections was increased, additional antibody-forming cells matured or were formed through cell division. Relatively constant antigenic stimulation provided a mechanism for controlling or limiting the response of antibody-forming cells. The mechanism controlling or limiting the response of antibody-forming cells would not account for the stabilization of numbers of antibody-forming cells at high levels for normal animals and at low levels for the tolerant animals. Passive immunization of growing rats with homologous anti-sheep erythrocyte serum markedly inhibited the plaque-forming cell response of growing rats. It was proposed that antibody produced by the small population of antibody-forming cells in the tolerant rats provided a feedback or homeostatic mechanism which inhibited transformation of potential antibody-forming cells to antibody-forming cells. Thus, tolerance to sheep erythrocytes was induced and maintained by two mechanisms. One mechanism, dependent on relatively constant antigenic stimulation, limited or controlled the numbers of antibody-forming cells. The other, dependent on the production of small quantities of antibody by a few antibody-forming cells, limited or controlled the transformation of potential antibody-forming cells to antibody-forming cells.

scholarly journals Maintenance of Type 2 Response by CXCR6-Deficient ILC2 in Papain-Induced Lung Inflammation

2019 ◽  
Vol 20 (21) ◽  
pp. 5493 ◽  
Author(s):  
Meunier ◽  
Chea ◽  
Garrido ◽  
Perchet ◽  
Petit ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nk Cell ◽  
Lymphoid Cells ◽  
Inflammatory Conditions ◽  
Airway Diseases ◽  
Type 2 Cytokines ◽  
Lymphoid Organogenesis ◽  
Deficient Mice

Innate lymphoid cells (ILC) are important players of early immune defenses in situations like lymphoid organogenesis or in case of immune response to inflammation, infection and cancer. Th1 and Th2 antagonism is crucial for the regulation of immune responses, however mechanisms are still unclear for ILC functions. ILC2 and NK cells were reported to be both involved in allergic airway diseases and were shown to be able to interplay in the regulation of the immune response. CXCR6 is a common chemokine receptor expressed by all ILC, and its deficiency affects ILC2 and ILC1/NK cell numbers and functions in lungs in both steady-state and inflammatory conditions. We determined that the absence of a specific ILC2 KLRG1+ST2– subset in CXCR6-deficient mice is probably dependent on CXCR6 for its recruitment to the lung under inflammation. We show that despite their decreased numbers, lung CXCR6-deficient ILC2 are even more activated cells producing large amount of type 2 cytokines that could drive eosinophilia. This is strongly associated to the decrease of the lung Th1 response in CXCR6-deficient mice.

scholarly journals Physicochemical Characterization Cascade of Nanoadjuvant–Antigen Systems for Improving Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 544
Author(s):  
Giuditta Guerrini ◽  
Antonio Vivi ◽  
Sabrina Gioria ◽  
Jessica Ponti ◽  
Davide Magrì ◽  
...  
Keyword(s):  
Immune Response ◽  
Protein Structure ◽  
Physicochemical Properties ◽  
Physicochemical Characterization ◽  
Protein Antigen ◽  
Efficacy And Safety

Adjuvants have been used for decades to enhance the immune response to vaccines, in particular for the subunit-based adjuvants. Physicochemical properties of the adjuvant-protein antigen complexes, such as size, morphology, protein structure and binding, influence the overall efficacy and safety of the vaccine. Here we show how to perform an accurate physicochemical characterization of the nanoaluminum–ovalbumin complex. Using a combination of existing techniques, we developed a multi-staged characterization strategy based on measurements of increased complexity. This characterization cascade has the advantage of being very flexible and easily adaptable to any adjuvant-protein antigen combinations. It will contribute to control the quality of antigen–adjuvant complexes and immunological outcomes, ultimately leading to improved vaccines.

scholarly journals DNA epitope vaccine containing complement component C3d enhances anti-amyloid-β antibody production and polarizes the immune response towards a Th2 phenotype

2008 ◽  
Vol 205 (1-2) ◽  
pp. 57-63 ◽  
Author(s):  
Nina Movsesyan ◽  
Mikayel Mkrtichyan ◽  
Irina Petrushina ◽  
Ted M. Ross ◽  
David H. Cribbs ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Production ◽  
Amyloid Β ◽  
Complement Component ◽  
Epitope Vaccine

Respiratory Syncytial Virus (RSV) Diseases

2022 ◽  
Author(s):  
Heinz-Josef Schmitt ◽  
Khrystyna Hrynkevych
Keyword(s):  
Respiratory Syncytial Virus ◽  
Rna Virus ◽  
Passive Immunization ◽  
Active Immunization ◽  
F Protein ◽  
Hospitalization Rates ◽  
Syncytial Virus ◽  
Repeated Infections ◽  
Long Acting ◽  
Underlying Diseases

The respiratory syncytial virus (RSV) is an RNA virus that causes annual ARI outbreaks during winter with mild URTI in the general population, but with severe LRTI particularly among young children (bronchiolitis), patients with underlying diseases and people >65 years of age. RSV does not induce a long-lasting protective immunity and repeated infections throughout life are the norm. Basically, all children have been infected by 2 years of age and of those hospitalized, >50% are <3 months and 75% are <6 months of age. The overall CFR is 1/500. For adults ≥65 years, RSV hospitalization rates are 90–250/105. There is no specific therapy, general preventive measures include general hygiene and isolation/separation of patients. A monoclonal anti-F-protein antibody is available for passive immunization of selected high-risk children. It requires monthly injections, comes at a high cost and has limited efficacy (50% against RSV hospitalization). Active immunization failed in the past, probably as the post-fusion conformation of the F-protein was used. Long-acting monoclonal antibodies (for infants) as well as stabilized pre-fusion F-protein vaccines (for immunization of pregnant women, children, older adults) produced on various platforms are in late stages of clinical development.

Remembering As We Look Ahead: The Three E's and Firearm Injuries

PEDIATRICS ◽  
1991 ◽  
Vol 88 (2) ◽  
pp. 379-383
Author(s):  
MARK D. WIDOME
Keyword(s):  
Young Child ◽  
American Academy ◽  
Passive Immunization ◽  
Active Immunization ◽  
Accident Prevention ◽  
Safety Education ◽  
Childhood Injury ◽  
Firearm Injuries ◽  
American Academy Of Pediatrics ◽  
Look Ahead

There was a little man, and he had a little gun, And his bullets were made of lead, lead, lead; He went to the brook, and he saw a little duck, And he shot it through the head, head, head. —Mother Goose Four decades ago, Harry Dietrich,1 a member of the American Academy of Pediatrics' newly established Accident Prevention Committee, described a developmentally based approach to the prevention of childhood injury. Dietrich stressed the great need for protection ("passive immunization") for the young child and for safety education ("active immunization") as the child matures. It was also in the early 1950s that George Wheatley, the first chairman of the Accident Prevention Committee, popularized the "three E's"2—education, enforcement, and engineering—as a framework for developing and categorizing strategies to prevent injuries.

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