Arthritis is what type of hypersensitivity

Article Google Scholar. Fernandes, E. Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner. Download references. You can also search for this author in PubMed Google Scholar. Reprints and Permissions. Duarte, J. A chilling link to joint pain and hypersensitivity.

Nat Rev Rheumatol 12, Download citation. Published : 29 January Type II hypersensitivity reactions are referred to as cytotoxic, as they involve antibodies that are specific to particular tissues within the body and cause destruction of cells in these tissues e.

Type III hypersensitivity reactions are immune complex-mediated , with tissue damage caused by antigen - antibody complex deposition e. Type IV hypersensitivity reactions e. Unlike true hypersensitivity reactions, which occur after sensitization , nonallergic hypersensitivity reactions e. Type IV : delayed T-cell mediated. Drugs can cause all four types of hypersensitivity reactions. Type I is Fast and Furious. Contact prevention and avoidance of offending agents is the best treatment for allergies.

IgM and IgG mistakenly bind to surface antigens of the cells in the body , which results in:. Type II is cytoxic and consists of 2 components antigen and antibody. Type IV hypersensitivity reactions involve two major steps:. Contact dermatitis due to poison oak , poison ivy , or poison sumac is the most likely cause in a patient presenting with itching, burning, red skin lesions arranged in a linear pattern appearing 24 hours after a camping trip.

Expand all sections Register Log in. Trusted medical expertise in seconds. Find answers fast with the high-powered search feature and clinical tools. Try free for 5 days Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer. Hypersensitivity reactions. Summary Hypersensitivity reactions occur when the normally protective immune system responds abnormally, potentially harming the body.

All animal experiments have been conducted according to Danish legislation and have been approved by the Danish Animal Inspectorate and the local ethical review board.

Paw swelling was measured by using a dial thickness gage Mitutoyo, Kanagawa, Japan and was calculated as right paw thickness minus left paw thickness.

Clinical score results are displayed as the median. The results are representative of at least five experiments. Hind paws were sampled and processed by standard histopathological procedures. For detection of osteoclasts, a histochemical stain for the osteoclast enzyme tartrate-resistant acid phosphatase TRAP was performed. Deparaffinized sections were stained in a TRAP staining solution containing 1. Cell nuclei appeared blue, and the osteoclast cytoplasm appeared red. For evaluation of cartilage destruction, the Safranin O staining protocol, which stains cartilage proteoglycan red, was used.

Briefly, the deparaffinized sections were first counterstained with hematoxylin before staining in 0. To visualize the target, sections were treated with '-diamino-benzidine-tetrahydrochloride Sigma-Aldrich for 5 minutes. The extra-articular infiltration of inflammatory cells assessed on a scale of 0 to 3 and arthritic changes were assessed separately.

Arthritic changes were assessed on metatarsal and tarsal joints, where synovitis, cartilage destruction, and bone erosion were scored separately on a scale of 0 to 3. For each of the three parameters of arthritic changes, an average between the two joint areas was calculated.

In addition, new bone formation overall in the paw was scored on a scale of 0 to 3. The histology sum score was calculated by adding the five scores extra-articular infiltration, synovitis, cartilage destruction, bone erosion, and bone formation , whereas the extra-articular infiltration score is left out in the arthritis score.

Lymph nodes draining the PBS-challenged side were pooled. The experiment was performed once. Depletion was confirmed by flow cytometry analysis of whole-blood samples taken 24 hours after the first depletion treatment day -7 and on day 9 after DTH-arthritis induction. Samples were analyzed as described above. Hind paws from mice with DTH arthritis were sampled at selected times after DTH-arthritis induction and each was placed in 1.

The paws were homogenized by using a T25 Ultraturrax homogeniser IKA, Staufen, Germany followed by centrifugation at 10, g for 15 minutes. The supernatants were decanted and centrifuged once more at 10, g for 15 minutes. Results are displayed as the median, and difference from the control value was tested. In the analysis of cytokine production in untreated animals, left PBS-challenged hind paws removed on day 14 after DTH-arthritis induction were used as controls, and the results are representative of two experiments.

Any values below the detection limit were set to the detection limit for the analyte in question, and any values above the detection limit were set to the upper detection limit for the analyte in question. Control groups received no treatment. Statistical analyses were conducted by using GraphPad Prism software version 5. Non-parametric data or non-normal parametric data were analyzed by using the Mann-Whitney U test, and parametric data were analyzed by using a two-sided unpaired t test.

For statistical analysis of the histological sum scores, an unpaired Student t test with Welch's correction was used.

Differences between groups were considered significant when P values were not more than 0. The control group receiving isotype control mAb cocktail developed a transient response consistent with a DTH response, whereas the unchallenged control group failed to develop a response. The unimmunized control group developed a very slight response on day 1 after the challenge because of the local irritant effect of mBSA data not shown. A titration study was undertaken to determine the optimal sub-arthritogenic dose of anti-CII for elicitation of a robust and sustained paw inflammation without any signs of arthritis unrelated to challenge with mBSA, such as swelling in any paw other than the mBSA-challenged one or any paw swelling before the time of mBSA challenge.

The doses tested were To determine whether the response was truly restricted to the mBSA-challenged side of the animal, we performed a 3 H-thymidine incorporation assay. This allowed us to quantify cell proliferation in response to mBSA re-stimulation on cells isolated from the popliteal lymph nodes excised from the antigen-challenged and PBS-challenged sides of the animals.

The results Figure 1e clearly demonstrate that the proliferative response to mBSA was restricted to the lymph node draining the mBSA-challenged footpad in animals receiving either anti-CII or isotype control antibody cocktails.

To have a secondary readout parameter and to determine whether DTH arthritis has a systemic disease component, serum levels of the acute-phase protein SAP and the cytokine IL-6 were measured. After that, the levels of SAP remained elevated above baseline until day 9 after arthritis induction. IL-6 levels had returned to baseline levels by day 4 after arthritis induction.

The biphasic response corresponds to the two interventions: immunization and challenge; the use of CFA in the immunization step probably had an effect on the first observed peak in SAP and IL-6 levels. Establishment and assessment of the delayed-type hypersensitivity DTH -arthritis model. For the other two groups, paw swelling until day 14 after arthritis induction is shown. For the other two groups, area under the curve AUC of the paw swelling until day 14 after arthritis induction is shown.

Histopathological analyses were performed to evaluate the arthritic pathology in the DTH-arthritis model, and a scoring system was applied see Materials and methods for details. The evaluation revealed that, in the mBSA-challenged paw, the mice developed a severe arthritis and peri-articular inflammation characterized by influx of inflammatory cells, hyperplasia of the synovial membrane and pannus formation with the presence of fibroblast-like cells, increased compared with unchallenged control animals osteoclast activity assessed by the increase in number of TRAP-positive cells, stained red, Figure 2a and bone erosion, and cartilage destruction evidenced by loss of Safranin O staining Figure 2b.

The arthritis was localized in the ankle, tarsus, and metatarsophalangeal joints of the mBSA-challenged paw. Bone erosion was evident on day 4 after DTH-arthritis induction and afterwards, and cartilage destruction assessed by loss of Safranin O staining of articular cartilage was evident on day 2 after DTH-arthritis induction and afterwards.

Osteoclast number was reduced by day 14 after DTH-arthritis induction compared with days 4, 7, and 9, but no repair of the damage to bone integrity was apparent. However, new bone formation was observed and was most prevalent as osteophytes adjacent to the affected joints of the paw Figure 2c. The histology sum score reached a peak on day 7 after arthritis induction Figure 2d , and the extra-articular inflammation peaked on day 4 after arthritis induction Figure 2e.

The sum score for arthritic changes calculated as the total sum score minus the score for extra-articular inflammation reached its peak on days 7 to 9 after arthritis induction Figure 2f. Neutrophils comprised a large proportion of the infiltrating inflammatory cells, in both the synovial tissue and intra-articular space on days 1 and 2 after the challenge. The infiltration persisted on day 7 but was reduced by day 14 Figure 3a. Macrophages were observed in great number in the soft tissue and to a lesser degree in the intra-articular space Figure 3a.

Fibroblast-like cells were also observable within the hyperplastic synovial lining and pannus tissue Figures 2a and 3a, b , where they most likely also contribute to the inflammatory process. Development of severe arthritis in mice with delayed-type hypersensitivity DTH arthritis. Osteoclasts appear red. Arrows indicate areas with increased osteoclast numbers and bone erosion. Cartilage proteoglycan is stained red, and the intensity of the red color is proportional to the proteoglycan content of cartilage.

Arrows indicate areas displaying cartilage loss, which is most prominent in the uncalcified cartilage. Mice with DTH arthritis developed severe arthritis characterized by increased cartilage degradation as assessed by loss of Safranin O staining and osteoclast activity as assessed by the increase in TRAP-positive cells and bone erosion; synovitis and pannus formation is also observed.

The sections shown in a and b are representative of mice with DTH arthritis immunization, anti-type II collagen antibody cocktail anti-CII , and antigen challenge and of mice receiving immunization, anti-CII, and no challenge control. Samples were taken on days 2, 4, 7, 9, and Hematoxylin and eosin staining was used. B, bone; BM, bone marrow; O, osteophyte. Maximum possible score is Maximum possible score is 3.

Details of the histopathological scoring system can be found in the Materials and methods section. Composition of the inflammatory infiltrate in delayed-type hypersensitivity DTH arthritis.

Unchallenged control samples are from mice receiving immunization, anti-CII, and no challenge. Severe hyperplasia of the synovial membrane and pannus formation were also observed.

These data, taken together, demonstrated that mice with DTH arthritis developed a semi-chronic arthritic disease limited to the mBSA-challenged paw and draining lymph node while still displaying a systemic component. The arthritis pathology observed included synovitis, hyperplasia of the synovial membrane and pannus formation, increased osteoclast activity, bone erosion and remodeling, and cartilage destruction.

We next wanted to characterize the cell subsets involved in the inflammatory response. The same picture was seen in the absolute cell counts; however, there was no observable increase in macrophage numbers. The involvement of effector T-cell subsets was investigated by treating mice with depleting mAbs against CD4 or CD8 24 hours prior to immunization and again 24 hours prior to induction of arthritis. The control group received PBS injections.

Together, these data demonstrated that neutrophils were involved in the acute stage of DTH arthritis, and the major increase in macrophage numbers occurred after a few days.