ovalbumin and Granuloma

Th2-driven lung inflammation increases Arginase 1 (Arg1) expression in alternatively-activated macrophages (AAMs). AAMs modulate T cell and wound healing responses and Arg1 might contribute to asthma pathogenesis by inhibiting nitric oxide production, regulating fibrosis, modulating arginine metabolism and restricting T cell proliferation. We used mice lacking Arg1 in myeloid cells to investigate the contribution of Arg1 to lung inflammation and pathophysiology. In six model systems encompassing acute and chronic Th2-mediated lung inflammation we observed neither a pathogenic nor protective role for myeloid-expressed Arg1. The number and composition of inflammatory cells in the airways and lungs, mucus secretion, collagen deposition, airway hyper-responsiveness, and T cell cytokine production were not altered if AAMs were deficient in Arg1 or simultaneously in both Arg1 and NOS2. Our results argue that Arg1 is a general feature of alternative activation but only selectively regulates Th2 responses. Therefore, attempts to experimentally or therapeutically inhibit arginase activity in the lung should be examined with caution.

Topics: Animals; Antigens, Helminth; Arginase; Aspergillus; Gene Expression; Granuloma; Macrophage Activation; Macrophages; Mice; Mice, Knockout; Myeloid Cells; Ovalbumin; Pneumonia; Schistosoma mansoni; Th2 Cells

Parenteral injection of tolerated proteins into orally tolerant mice inhibits the initiation of immunological responses to unrelated proteins and blocks severe chronic inflammatory reactions of immunological origin, such as autoimmune reactions. This inhibitory effect which we have called "indirect effects of oral tolerance" is also known as "bystander suppression." Herein, we show that i.p. injection of OVA + Al(OH)(3) minutes before i.v. injection of Schistosoma mansoni eggs into OVA tolerant mice blocked the increase of pulmonary granulomas. In addition, the expression of ICAM-1 in lung parenchyma in areas outside the granulomas of OVA-orally tolerant mice was significantly reduced. However, at day 18 after granuloma induction there was no difference in immunofluorescency intensity to CD3, CD4, F4/80, andα-SMA per granuloma area of tolerant and control groups. Reduction of granulomas by reexposure to orally tolerated proteins was not correlated with a shift in Th-1/Th-2 cytokines in serum or lung tissue extract.

Topics: Administration, Oral; Animals; Antigens, CD; Bystander Effect; Cells, Cultured; Eggs; Granuloma; Immune Tolerance; Immunophenotyping; Inflammation; Intercellular Adhesion Molecule-1; Lung; Mice; Mice, Inbred C57BL; Ovalbumin; Schistosoma mansoni; Schistosomiasis mansoni

Brown Norway (BN) and Fischer 344 (F344) rats were exposed to aerosol of 1% ovalbumin (OVA) solution for 30 min at 1 week after the second sensitization with 1 mg of OVA at 2-week intervals. Changes in the histology and expression of cytokines and chemokines in the lung were examined for up to 96 h after the exposure. The lung weight significantly increased in BN rats but not in F344 rats. Histologically, in the lung of BN rats, multiple foci of hemorrhage in the alveolar space with infiltration of eosinophils and macrophages in the surrounding alveolar septa were first observed. Thereafter, granulomatous lesions developed in the preexisting hemorrhagic foci, finally resulting in formation of multiple eosinophilic granulomas. On the other hand, in F344 rats, infiltration of eosinophils and macrophages was observed around the vessels and bronchi. Thereafter it progressed gradually, resulting in mild thickening of alveolar septa. The levels of Th1- (interferon-gamma and interleukin 2 (IL-2)) and Th2-related cytokines (IL-4 and IL-5) and chemokines (eotaxin and monocyte chemoattractant protein-1) mRNAs measured by reverse transcription-polymerase chain reaction method were elevated in the lung of both strains, and the levels were higher in BN rats than in F344 rats. These results suggest that BN rats are more sensitive to OVA-sensitization/inhalation than F344 rats and that the difference in the severity of lung lesions between BN and F344 rats may reflect the difference in the expression levels of cytokines and chemokines between these two strains.

Topics: Animals; Chemokines; Disease Models, Animal; Granuloma; Hemorrhage; Hypersensitivity; Inhalation Exposure; Lung; Lung Diseases; Male; Organ Size; Ovalbumin; Rats; Rats, Inbred BN; Rats, Inbred F344; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Species Specificity; Trachea

The objective of the present study was to investigate whether the injection of a tolerated protein (indirect effects) affects the formation of granulomas around Schistosoma mansoni eggs trapped in the lungs after intravenous (iv) injection into normal (noninfected) C57BL/6 mice (6 animals per group). To induce oral tolerance to chicken egg ovalbumin a 1/5 dilution of egg white in water was offered ad libitum in a drinking bottle for 3 days. Control mice received water. After 7 days, control and experimental animals were injected iv with 2,000 S. mansoni eggs through a tail vein. In some mice of both groups the iv injection of eggs was immediately followed by intraperitoneal (ip) immunization with 10 micro g of dinitrophenylated conjugates of ovalbumin (DNP-Ova) emulsified in complete Freund's adjuvant (CFA) or only CFA; 18 days later, mice were bled and killed by ether inhalation. The lungs were fixed in formalin and embedded in paraffin. Serial sections of 5 m were stained with Giemsa, Gomori's silver reticulin and Sirius red (pH 10.2). Granuloma diameters were measured in histological sections previously stained with Gomori's reticulin. Anti-DNP and anti-soluble egg antigen (SEA) antibodies were analyzed by ELISA. In mice orally tolerant to ovalbumin the concomitant ip injection of DNP-Ova resulted in significantly lower anti-SEA antibodies (ELISA*: 1395 +/- 352 in non-tolerant and 462 +/- 146 in tolerant mice) and affected granuloma formation around eggs, significantly decreasing granuloma size (area: 22,260 +/- 2478 to 12,993 +/- 3242 m ). Active mechanisms triggered by injection of tolerated antigen (ovalbumin) reduce granuloma formation.

Topics: Administration, Oral; Animals; Antigens, Helminth; Dinitrophenols; Enzyme-Linked Immunosorbent Assay; Granuloma; Haptens; Immune Tolerance; Lung Diseases, Parasitic; Mice; Mice, Inbred BALB C; Ovalbumin; Schistosoma mansoni

Chemokine receptors transduce signals important for the function and trafficking of leukocytes. Recently, it has been shown that CC chemokine receptor (CCR)8 is selectively expressed by Th2 subsets, but its functional relevance is unclear. To address the biological role of CCR8, we generated CCR8 deficient (-/-) mice. Here we report defective T helper type 2 (Th2) immune responses in vivo in CCR8(-/)- mice in models of Schistosoma mansoni soluble egg antigen (SEA)-induced granuloma formation as well as ovalbumin (OVA)- and cockroach antigen (CRA)-induced allergic airway inflammation. In these mice, the response to SEA, OVA, and CRA showed impaired Th2 cytokine production that was associated with aberrant type 2 inflammation displaying a 50 to 80% reduction in eosinophils. In contrast, a prototypical Th1 immune response, elicited by Mycobacteria bovis purified protein derivative (PPD) was unaffected by CCR8 deficiency. Mechanistic analyses indicated that Th2 cells developed normally and that the reduction in eosinophil recruitment was likely due to systemic reduction in interleukin 5. These results indicate an important role for CCR8 in Th2 functional responses in vivo.

Topics: Administration, Inhalation; Animals; Antigens; Cockroaches; Cytokines; Dose-Response Relationship, Immunologic; Eosinophils; Granuloma; Hypersensitivity; Immunity, Cellular; Injections, Subcutaneous; Interleukin-5; Lung; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Ovum; Receptors, CCR8; Receptors, Chemokine; RNA, Messenger; Schistosoma mansoni; Th1 Cells; Th2 Cells

We investigated the contribution of mast cell chymase in mast cell-dependent angiogenesis using the hamster sponge-implant model, where angiogenesis in the granulation tissue surrounding the subcutaneously implanted sponge was evaluated by measuring the hemoglobin content. Daily local injection of compound 48/80 (3-100 microg/site/day), a potent mast cell activator, induced formation of granulomas and angiogenesis in time- and dose-dependent manners. This angiogenic response was inhibited by chymase inhibitors including chymostatin (> or = 1 nmol/site/day), soybean trypsin inhibitor (SBTI; > or = 1.4 nmol/site/day) and lima bean trypsin inhibitor (LBTI; > or = 3.3 nmol/site/day), but not by a tryptase inhibitor like leupeptin (> or = 700 nmol/site/day). Although pyrilamine (> or = 2,580 nmol/site/day), a histamine H1 receptor antagonist, and protamine (300 microg/site/day) also inhibited angiogenesis, these effects were much less pronounced than those by chymase inhibitors. Furthermore, antigen-induced angiogenesis in hamsters pre-sensitized with ovalbumin was also inhibited by the chymase inhibitors by 60-70%. Our results suggest that chymase is a major mediator in mast cell-mediated angiogenesis.

Topics: Animals; Chymases; Cricetinae; Granuloma; Hemoglobins; Heparin; Histamine; Hypersensitivity; Male; Mast Cells; Mesocricetus; Neovascularization, Pathologic; Oligopeptides; Ovalbumin; p-Methoxy-N-methylphenethylamine; Serine Endopeptidases; Serine Proteinase Inhibitors; Trypsin Inhibitors

Using a single vector targeting strategy, we have generated mice with a combined deficiency of interleukin (IL)-4 and IL-13 to clarify their roles in T helper type 2 (Th2) cell responses. Using immunological challenges normally characterized by a Th2-like response, we have compared the responses of the double-deficient mice with those generated by wild-type, IL-4-deficient, and IL-13-deficient mice. Using a pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that although eosinophil infiltration, immunoglobulin E, and IL-5 production are reduced in the IL-4-deficient mice and IL-13-deficient mice, they are abolished only in the combined absence of both cytokines. Furthermore, IL-4/13-deficient animals are severely impaired in their ability to expel the gastrointestinal nematode Nippostrongylus brasiliensis. Unexpectedly, N. brasiliensis-infected IL-4/13-deficient mice developed elevated IL-5 and eosinophilia, indicating that compensatory mechanisms exist for the expression of IL-5, although serum IgE remained undetectable. IL-4/13-deficient mice default to a Th1-like phenotype characterized by the expression of interferon gamma and the production of IgG2a and IgG2b. We conclude that IL-4 and IL-13 cooperate to initiate rapid Th2 cell-driven responses, and that although their functions overlap, they perform additive roles.

Topics: Animals; Eosinophilia; Granuloma; Immunoglobulin E; Immunoglobulin G; Interferon-gamma; Interleukin-13; Interleukin-4; Interleukin-5; Lung Diseases; Mice; Mice, Knockout; Nippostrongylus; Ovalbumin; Schistosoma mansoni; Strongylida Infections; Th2 Cells

An experimental system involving injections of ovalbumin (OVA) and ferritin (FER) in Freund's incomplete adjuvant (FIA) into the right and left flank skin folds of sheep was used to study the influence of the FIA/antigen depot and the draining lymph node in maintaining an antibody response. Excision of the injection granuloma and draining lymph node from one side 2-3 months after injections resulted in a profound decrease in serum antibody titres. This response was observed in all eight sheep in the experimental group. In five of eight animals in another experiment, excision of the injection sites had no appreciable effect on antigen-specific antibody titres when compared with antibody specific for antigen on the intact side of the sheep. In the remaining three animals, excision of the injection site did cause some fall in titre. Radiotracer studies revealed that about one-third of the original [125I]OVA/FIA injected was present in the granuloma 20 weeks after injection. Lymphatic cannulation approaches were used to study the responsiveness of the lymph node draining an FIA/antigen granuloma established 12 weeks earlier and showed that increments of 1-2 mg OVA in saline administered adjacent to the granuloma at 6-7 day intervals gave rise to strong anti-OVA containing cell (AOCC) responses in lymph. There were 2-6-fold increases in serum antibody titre in response to 3-5 doses of OVA or FER (1-2 mg) in saline injected adjacent to the FIA/antigen injection site (which had been administered 14-16 weeks previously). It is concluded that the release rate of antigen from a FIA/antigen depot is insufficient to sustain maximal antibody levels in blood serum.

Topics: Animals; Antibody Formation; Antigens; Female; Ferritins; Freund's Adjuvant; Granuloma; Immunization; Lymph Nodes; Male; Ovalbumin; Sheep; Time Factors

Egg-induced granuloma formation in murine schistosomiasis mansoni results from vigorous anti-parasite reaction by activated T cells, macrophages, eosinophils, and fibroblasts. The present study suggests that strain-specific, autoimmune T-cell reactivity directed against host matrix proteins might also contribute to granulomatous hypersensitivity. T cells from infected C57B1/6, but not from CBA or BALB/c mice, proliferative in vitro in response to denatured collagen. T cells from uninfected mice, previously immunized with soluble egg antigen (SEA), did not respond in vitro to collagen. Spleen cells from acutely infected mice, but not chronically infected or uninfected animals, formed granulomas around collagen-coupled polyacrylamide beads in vitro. This response was blocked by anti-collagen antibodies that had no inhibitory effect on in vitro granuloma formation around SEA-coupled beads. In related in vivo studies, granuloma formation was quantitated after iv injection of SEA-, collagen-, or uncoated beads into normal or infected recipients. The mean diameter of lung granulomas induced by collagen-coupled beads in infected mice was significantly greater than the diameter of granulomas around either collagen beads in uninfected mice or uncoated beads in infected mice. these observations indicate that anti-collagen responses develop spontaneously in Schistosoma-infected mice and suggest that such reactivity might play a secondary role in granuloma formation and the pathogenesis of hepatic fibrosis.

Topics: Animals; Autoimmune Diseases; Collagen; Female; Granuloma; Lymph Nodes; Lymphocyte Activation; Mice; Ovalbumin; Peritoneal Cavity; Schistosomiasis mansoni; T-Lymphocytes

An experimental model to investigate orbital granuloma formation in inbred rats was established. Animals sensitized to trinitrophenyl ovalbumin (TNP-OA) and challenged retro-orbitally with TNP-OA covalently linked o Sepharose 4B beads specifically developed a granulomatous response. This granulomatous reactivity was passively transferred into normal animals by lymph node cells, but not by serum antibody from sensitized donors. Lymphocytes which transfer granuloma formation in normal recipients were characterized by cell fractionation and membrane marker analysis. These experiments show that the effector cells capable of transferring granulomatous hypersensitivity are enriched in the lower density fractions on discontinuous Percoll gradients. These cells are lymphoblasts and express the W3/25 helper T lymphocyte marker. It was also demonstrated that lymphoid cells from sensitized donors in the higher density Percoll fraction appear to be incapable of adoptively transferring granulomatous responsiveness directly to normal recipients. However, incubation of these high density lymphocytes with specific antigen resulted in marked enhancement of their ability to transfer the disease. Antigen-induced activation also resulted in an increase in both lymphoblasts and the W3/25 marker. The authors conclude, therefore, that a subset of T cells which are lymphoblasts and express the helper-cell marker is responsible for granuloma formation in sensitized animals and is capable of transferring orbital granuloma formation to non-sensitized normal recipients.

Topics: Animals; Cell Count; Drug Hypersensitivity; Female; Granuloma; Intradermal Tests; Lymphocyte Activation; Orbital Diseases; Ovalbumin; Rats; Rats, Inbred Lew; T-Lymphocytes

Rats (BN X Wistar) and mice (CBA/Ca) were immunized by exposure in 10-day periods to an aerosol of ovalbumin (OA). In rats this immunization resulted in IgE antibodies detectable at very low levels in bronchial washings, whereas IgG, IgA and IgM antibodies were recorded both in serum and in bronchial washings. In mice, exposure to aerosolized antigen resulted in specific IgE and IgG antibodies in serum. The levels of IgM antibodies were low and no IgA antibodies could be recorded with the enzyme-linked immunosorbent assay (ELISA). Histological examination of lung tissue from immunized rats and mice revealed increased numbers of cells with characteristics of both immature and mature mast cells. In addition, in the rats these cells were more closely located to the bronchi in immunized than in control animals. In the latter animals the mast cells were located around the blood vessels. Immature mast cells were located in the bronchiole-associated lymphatic tissue (BALT) which showed a marked proliferation in immunized animals. The findings indicate that sensitization via the airways provides possibilities to develop a model in rodents for studies of IgE-mediated allergy in the lung.

Topics: Aerosols; Animals; Antibody Formation; Antigens; Bronchi; Bronchial Diseases; Disease Models, Animal; Female; Granuloma; Immunoglobulin E; Immunoglobulins; Lung; Male; Mast Cells; Mice; Mice, Inbred CBA; Ovalbumin; Rats; Rats, Inbred Strains

Topics: Animals; Anti-Inflammatory Agents; Capillary Permeability; Carrageenan; Dextrans; Dose-Response Relationship, Drug; Edema; Granuloma; Histamine Antagonists; Hyaluronoglucosaminidase; Male; ortho-Aminobenzoates; Ovalbumin; Rats; Time Factors

Topics: Animals; Cattle; Cattle Diseases; Granuloma; Hypersensitivity, Immediate; Male; Nose Diseases; Ovalbumin; Passive Cutaneous Anaphylaxis

Topics: Animals; Arthritis; Aspirin; Carrageenan; Croton Oil; Edema; Foot; Granuloma; Hindlimb; Hydrocortisone; Inflammation; Male; Methods; Mycobacterium; Ovalbumin; Phenylbutazone; Prostaglandins; Rats; Serotonin

Rabbits sensitized intravenously with heat-killed Mycobacterium tuberculosis (strain H37Ra) suspended in mineral oil developed a strong pulmonary granulomatous response which reached its peak about 3 to 4 weeks after injection. Alveolar cells (4 x 10(6) cells/ml of tissue culture medium 199) procured 6 weeks after sensitization showed extensive development of multinucleated giant cells after 12 hr of incubation in tissue culture flasks containing heat-killed H37Ra (5 mug/ml). Giant cells measured 80 mum to 2.5 mm in length and contained between 30 and 700 nuclei. In contrast, no giant cells were observed when similar samples of the same cell populations were incubated in flasks containing: (i) no mycobacteria; (ii) heat-killed Escherichia coli; (iii) heat-killed Bacillus subtilis; (iv) latex particles; (v) ovalbumin; or (vi) phytohemagglutinin. The addition of immune (anti-H37Ra) sera potentiated the phenomenon of giant cell formation. In addition, supernatant fluids obtained from sensitive alveolar cells incubated with H37Ra were capable of inducing giant cell formation when incubated with nonsensitized alveolar cells. The results suggest that fusion of alveolar macrophages is mediated by an immunological mechanism.

Topics: Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacillus subtilis; Body Weight; Cell Fusion; Cell Migration Inhibition; Cells, Cultured; Escherichia coli; Granuloma; Hot Temperature; Immune Sera; Immunity, Cellular; Injections, Intravenous; Latex Fixation Tests; Lectins; Lung; Lung Diseases; Macrophages; Mycobacterium tuberculosis; Organ Size; Ovalbumin; Pulmonary Alveoli; Rabbits; Time Factors

Topics: Adrenocorticotropic Hormone; Aminopyrine; Animals; Anti-Inflammatory Agents; Aspirin; Carrageenan; Dextrans; Dimethyl Sulfoxide; Disease Models, Animal; Edema; Flufenamic Acid; Formaldehyde; Granuloma; Indomethacin; Inflammation; Kaolin; Male; Mefenamic Acid; Ovalbumin; Oxyphenbutazone; Phenylbutazone; Prednisolone; Rats; Sodium Salicylate; Trypsin

Topics: Adrenalectomy; Animals; Anti-Inflammatory Agents; Arthritis; Calcium; Capillary Permeability; Carrageenan; Depression, Chemical; Dextrans; Edema; Erythema; Granuloma; Hemolysis; Hyaluronoglucosaminidase; Indicators and Reagents; Male; Malonates; Mice; Ovalbumin; Phenylbutazone; Phenylhydrazines; Prednisolone; Protein Denaturation; Radiation Injuries, Experimental; Rats; Serotonin; Ultraviolet Rays; Wound Healing

Topics: Animals; Arthritis; Arthus Reaction; Bradykinin; Capillary Permeability; Carrageenan; Depression, Chemical; Dextrans; Disease Models, Animal; Dogs; Edema; Exudates and Transudates; Female; Formaldehyde; Granuloma; Guinea Pigs; Histamine; Hyaluronoglucosaminidase; Kaolin; Lymph; Male; Mice; Mycobacterium Infections; Ovalbumin; p-Methoxy-N-methylphenethylamine; Phytotherapy; Plants, Medicinal; Rabbits; Rats; Serotonin; Species Specificity; Swine

Topics: Acetylcholine; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Atropine; Croton Oil; Depression, Chemical; Edema; Exudates and Transudates; Female; Formaldehyde; Glycosides; Granuloma; Guinea Pigs; Histamine H1 Antagonists; In Vitro Techniques; Intestines; Male; Ovalbumin; Papaverine; Parasympatholytics; Phenylbutazone; Plant Extracts; Plants, Medicinal; Rabbits; Rats

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Croton Oil; Edema; Exudates and Transudates; Female; Foreign Bodies; Formaldehyde; Glycosides; Gossypium; Granuloma; Hydrocortisone; Ovalbumin; Phenylbutazone; Rats

Topics: Animals; Culture Techniques; Glycolipids; Granuloma; Guinea Pigs; Hypersensitivity, Delayed; Immune Sera; Mycobacterium; Ovalbumin; Waxes

Topics: Amino Acids; Animals; Antibody Formation; Carbon Isotopes; Chromatography; Chromatography, Gel; Granuloma; Guinea Pigs; Immunoglobulin G; Immunoglobulin M; Lymphoid Tissue; Ovalbumin; Spectrophotometry; Spleen

Topics: Aluminum Silicates; Animals; Antibody Formation; Fluorescent Antibody Technique; gamma-Globulins; Granuloma; Guinea Pigs; Hypersensitivity, Delayed; Immunoelectrophoresis; Lymph Nodes; Mycobacterium tuberculosis; Ovalbumin; Precipitin Tests; Spleen

Topics: Adrenal Glands; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Body Weight; Formaldehyde; Granuloma; Hydrocortisone; Hypothalamo-Hypophyseal System; Inflammation; Ovalbumin; Phenylbutazone; Rats; Thymus Gland

Topics: Amino Acids; Animals; Antibody Formation; Bone Marrow; Electrophoresis; Granuloma; Guinea Pigs; Immunoglobulin G; In Vitro Techniques; Lymph Nodes; Ovalbumin; Spleen

Topics: Adjuvants, Immunologic; Aluminum Silicates; Animals; Antibody Formation; Freund's Adjuvant; Granuloma; Guinea Pigs; Hypersensitivity, Delayed; Immunoglobulin G; Injections, Intradermal; Injections, Intraperitoneal; Ovalbumin

Topics: Adjuvants, Immunologic; Amino Acids; Amino Sugars; Antigen-Antibody Reactions; Biological Assay; Chemical Phenomena; Chemistry; Cornea; Encephalomyelitis; Glycolipids; Granuloma; Hypersensitivity; Mycobacterium; Mycobacterium bovis; Mycobacterium tuberculosis; Ovalbumin; Precipitin Tests; Research; Waxes

Topics: Anaphylaxis; Animals; Diabetes Mellitus, Experimental; Dietary Carbohydrates; Glucose; Granulation Tissue; Granuloma; Insulin; Mice; Ovalbumin; Pharmacology; Research

After subcutaneous injection of hen's ovalbumin or diphtheria toxoid precipitated with aluminum phosphate, the production of antibody, as judged by the presence in the tissues of antibody-containing cells, proceeds partly within the regional lymphatic glands and partly in the granulation tissue surrounding the nodule which develops at the site of injection. The first production of antibody takes place in the regional lymphatic gland and antibody production in the local granuloma becomes apparent only from 14 days onwards (rabbit). Antibody-containing plasma cells were demonstrated in the local granuloma up to 7 weeks. Antibody-containing cells in the regional lymphatic glands reach maximum numbers at 2 weeks following injection and decrease thereafter to few cells at 5 weeks. The adjuvant effect of the aluminum phosphate is interpreted as due partly to the delay in absorption of antigen from the local site of its injection which results in prolongation of stimulation of cells within the regional lymphatic glands, and partly to the production of a local granuloma which contains antibody-producing plasma cells.

Topics: Adjuvants, Immunologic; Alum Compounds; Animals; Antibodies; Antibody Formation; Antigens; Granuloma; Lymph Nodes; Ovalbumin; Rabbits