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Pathology - Hypersensitivity Reactions
Type I: Immediate hypersensitivity mediated by IgE.
Type II: Cytotoxic hypersensitivity caused by antibodies.
Type III: Hypersensitivity mediated by immune complex.
Type IV: Delayed hypersensitivity mediated by T cells.
Type I: Vasoactive amines are released when antigen cross-links cell-bound IgE on basophils and mast cells that have been pre-sensitized. This results in tissue inflammation, vascular permeability, vasodilation, and contraction of the smooth muscle in the viscera.
Type II: In response to antigens that are bound to cells, IgG or IgM antibodies react, activating the complement cascade and destroying the antigen-bound cell.
Type III: The complement cascade is triggered when an IgG or IgM antibody combines with circulating allergens and deposits in tissue.
Type IV: T cells are exposed to allergen, which binds to endogenous protein. Memory T cells trigger an inflammatory response when they are exposed to allergens again.
Type I: Allergic rhinitis, asthma, anaphylaxis, atopy, local wheal and flare.
Type II: Goodpasture syndrome, erythroblastosis fetalis, ARF, and immune hemolytic anemia.
Serum sickness (systemic illness fever, arthralgias, proteinuria, lymphadenopathy, and dermatitis); polyarteritis nodosa; SLE; RA; Arthus reaction (localized cutaneous and subcutaneous inflammatory response to injected allergen).
Type IV: Hypersensitivity pneumonitis and Allergic Contact Dermatitis.
corticosteroids, antihistamines, and disease-specific medications.
Type I: Immediate hypersensitivity mediated by IgE.
Type II: Cytotoxic hypersensitivity caused by antibodies.
Type III: Hypersensitivity mediated by immune complex.
Type IV: Delayed hypersensitivity mediated by T cells.
Type I: Vasoactive amines are released when antigen cross-links cell-bound IgE on basophils and mast cells that have been pre-sensitized. This results in tissue inflammation, vascular permeability, vasodilation, and contraction of the smooth muscle in the viscera.
Type II: In response to antigens that are bound to cells, IgG or IgM antibodies react, activating the complement cascade and destroying the antigen-bound cell.
Type III: The complement cascade is triggered when an IgG or IgM antibody combines with circulating allergens and deposits in tissue.
Type IV: T cells are exposed to allergen, which binds to endogenous protein. Memory T cells trigger an inflammatory response when they are exposed to allergens again.
Type I: Allergic rhinitis, asthma, anaphylaxis, atopy, local wheal and flare.
Type II: Goodpasture syndrome, erythroblastosis fetalis, ARF, and immune hemolytic anemia.
Serum sickness (systemic illness fever, arthralgias, proteinuria, lymphadenopathy, and dermatitis); polyarteritis nodosa; SLE; RA; Arthus reaction (localized cutaneous and subcutaneous inflammatory response to injected allergen).
Type IV: Hypersensitivity pneumonitis and Allergic Contact Dermatitis.
corticosteroids, antihistamines, and disease-specific medications.
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Pathology - Organ Rejection
Preformed anti-donor antibodies (such as anti-blood-type antibodies) in the recipient's bloodstream are the cause of hyperacute rejection.
Class I MHC-induced cytotoxic T-cell response is the cause of acute rejection.
Rejection that is persistent: Both antibody- and cell-mediated graft deterioration might result from prolonged immunosuppressive therapy, previous acute rejection, or co-morbidities between the donor and the recipient.
Graft-versus-host disease (GVHD): In immunocompromised recipients, grafted T-cells multiply and assault recipient host cells.
Pathology
Hyperacute: fibrin-platelet thrombi, neutrophilic infiltration, and cyanosis of the graft with necrosis.
Acute: Necrotizing vasculitis with enlarged endothelial cells and thrombosis; interstitial mononuclear infiltration with edema and hemorrhage.
Chronic: Intimal fibrosis of the graft arteries and tissue, resulting in ischemia injury and graft atrophy.
GVHD: Inflammatory harm to the GI tract, skin, liver, and immune system.
Clinical Signs and Symptoms
Hyperacute: Develops minutes to hours following transplant.
Acute: Happens over the first six months following transplant.
Chronic: Begins several months to years following transplant.
GVHD symptoms include diarrhea, liver damage, and maculopapular rash.
Handling
Both chronic and hyperacute: irreversible.
Acute: Reversible with immunosuppressive medication (cyclosporine, for example).
GVHD: Use monoclonal grafts or antithymocyte globulin on donor tissue, as well as immunosuppressive medications (such as tacrolimus and cyclosporine).
Preformed anti-donor antibodies (such as anti-blood-type antibodies) in the recipient's bloodstream are the cause of hyperacute rejection.
Class I MHC-induced cytotoxic T-cell response is the cause of acute rejection.
Rejection that is persistent: Both antibody- and cell-mediated graft deterioration might result from prolonged immunosuppressive therapy, previous acute rejection, or co-morbidities between the donor and the recipient.
Graft-versus-host disease (GVHD): In immunocompromised recipients, grafted T-cells multiply and assault recipient host cells.
Pathology
Hyperacute: fibrin-platelet thrombi, neutrophilic infiltration, and cyanosis of the graft with necrosis.
Acute: Necrotizing vasculitis with enlarged endothelial cells and thrombosis; interstitial mononuclear infiltration with edema and hemorrhage.
Chronic: Intimal fibrosis of the graft arteries and tissue, resulting in ischemia injury and graft atrophy.
GVHD: Inflammatory harm to the GI tract, skin, liver, and immune system.
Clinical Signs and Symptoms
Hyperacute: Develops minutes to hours following transplant.
Acute: Happens over the first six months following transplant.
Chronic: Begins several months to years following transplant.
GVHD symptoms include diarrhea, liver damage, and maculopapular rash.
Handling
Both chronic and hyperacute: irreversible.
Acute: Reversible with immunosuppressive medication (cyclosporine, for example).
GVHD: Use monoclonal grafts or antithymocyte globulin on donor tissue, as well as immunosuppressive medications (such as tacrolimus and cyclosporine).
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Pathology - Bruton Agammaglobulinemia
Bruton Agammaglobulinemia is a recessive X-linked tyrosine kinase gene deficiency that prevents B-cell precursors from developing into B cells.
most frequently observed in newborn boys.
Germinal centers are absent or ill-defined in lymphoid tissue.
occurs after six months of age, when levels of maternal IgG start to decrease, and manifests as recurrent pyogenic bacterial infections in boys (otitis media, sinusitis, pneumonia); cell-mediated immune function is normal.
Lab results: Absence of serum B cells and low levels of all immunoglobulin types.
routine IVIG treatment; infection management.
An X-linked recessive abnormality in the capacity to mount an IgM response to encapsulated bacteria, such as Pneumococcus, is known as Wiskott-Aldrich syndrome. Elevated IgA, low IgM, and normal IgG and total immunoglobulin levels are its defining characteristics. The patients exhibit a combination of eczema, petechiae, and bleeding due to thrombocytopenia, as well as recurring pyogenic infections. Splenectomy and bone marrow transplant are alternate supportive treatment options.
Bruton Agammaglobulinemia is a recessive X-linked tyrosine kinase gene deficiency that prevents B-cell precursors from developing into B cells.
most frequently observed in newborn boys.
Germinal centers are absent or ill-defined in lymphoid tissue.
occurs after six months of age, when levels of maternal IgG start to decrease, and manifests as recurrent pyogenic bacterial infections in boys (otitis media, sinusitis, pneumonia); cell-mediated immune function is normal.
Lab results: Absence of serum B cells and low levels of all immunoglobulin types.
routine IVIG treatment; infection management.
An X-linked recessive abnormality in the capacity to mount an IgM response to encapsulated bacteria, such as Pneumococcus, is known as Wiskott-Aldrich syndrome. Elevated IgA, low IgM, and normal IgG and total immunoglobulin levels are its defining characteristics. The patients exhibit a combination of eczema, petechiae, and bleeding due to thrombocytopenia, as well as recurring pyogenic infections. Splenectomy and bone marrow transplant are alternate supportive treatment options.
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Pathology - Common Variable Immunodeficiency
Caused by a deficiency in intrinsic B cells that stops them from maturing into plasma cells that release antibodies, which leads to insufficient secreted antibody production.
Peak onset typically occurs in late adolescence, after the ages of 1 and 5.
Pathology
Histiocytes encircle noncaseating granulomas in the skin, lungs, liver, and spleen.
increased frequency of autoimmune disorders, sprue-like GI condition, and recurring pyogenic infections, which typically impact the respiratory system.
Skin cancer, stomach carcinomas, and B-cell neoplasms are among the complications that may arise.
The results of the lab analysis show that there is a decline in IgG levels over time, affecting all antibody classes; functional antibody responses to protein antigen vaccinations are either missing or reduced; and the total number of B cells in peripheral blood is normal.
routine IVIG treatment; infection management.
The most prevalent primary immunodeficiency disease, selective lgA deficiency, is characterized by a lack of serum IgA, maybe as a result of an isotype switching problem. It manifests as lung and sinus infections, GI tract infections leading to chronic diarrhea, food allergies and other allergy illnesses (such as rhinitis or atopic dermatitis), and anaphylaxis following blood transfusions.
Caused by a deficiency in intrinsic B cells that stops them from maturing into plasma cells that release antibodies, which leads to insufficient secreted antibody production.
Peak onset typically occurs in late adolescence, after the ages of 1 and 5.
Pathology
Histiocytes encircle noncaseating granulomas in the skin, lungs, liver, and spleen.
increased frequency of autoimmune disorders, sprue-like GI condition, and recurring pyogenic infections, which typically impact the respiratory system.
Skin cancer, stomach carcinomas, and B-cell neoplasms are among the complications that may arise.
The results of the lab analysis show that there is a decline in IgG levels over time, affecting all antibody classes; functional antibody responses to protein antigen vaccinations are either missing or reduced; and the total number of B cells in peripheral blood is normal.
routine IVIG treatment; infection management.
The most prevalent primary immunodeficiency disease, selective lgA deficiency, is characterized by a lack of serum IgA, maybe as a result of an isotype switching problem. It manifests as lung and sinus infections, GI tract infections leading to chronic diarrhea, food allergies and other allergy illnesses (such as rhinitis or atopic dermatitis), and anaphylaxis following blood transfusions.
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Pathology -DiGeorge Syndrome
Caused by microdeletion on chr 22q11, which results in the failure of formation of third and fourth pharyngeal pouches.
Thyroid and parathyroid: Hypoplasia of tissue.
Pathophysiology: Thymic hypoplasia resulting in T-cell insufficiency; parathyroid hypoplasia results in hypocalcernia.
Recurrent viral, fungal, and protozoa infections; tetany (owing to hypocalcemia); congenital cardiovascular malformations (including Tetralogy of Fallot or truncus arteriosus); facial deformities including cleft palate; developmental delay.
Treatments
Fetal thymus transplanted to restore T-cell immunity in situations of severe immunodeficiency; treatment of heart abnormalities; calcium supplementation.
Chronic mucocutaneous candidiasis is a T-cell failure primarily against Candida a lbicans that manifests with Candida skin and mucous membrane infections.
Caused by microdeletion on chr 22q11, which results in the failure of formation of third and fourth pharyngeal pouches.
Thyroid and parathyroid: Hypoplasia of tissue.
Pathophysiology: Thymic hypoplasia resulting in T-cell insufficiency; parathyroid hypoplasia results in hypocalcernia.
Recurrent viral, fungal, and protozoa infections; tetany (owing to hypocalcemia); congenital cardiovascular malformations (including Tetralogy of Fallot or truncus arteriosus); facial deformities including cleft palate; developmental delay.
Treatments
Fetal thymus transplanted to restore T-cell immunity in situations of severe immunodeficiency; treatment of heart abnormalities; calcium supplementation.
Chronic mucocutaneous candidiasis is a T-cell failure primarily against Candida a lbicans that manifests with Candida skin and mucous membrane infections.
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Pathology -Severe Combined Immunodeficiency Disease (SCID)
Adenosine deaminase deficiency, tyrosine kinase deficiency, failure to synthesize class II MHC antigens, or a defective recombinase-activating gene mutation account for the remaining cases of autosomal recessive disorders, which cause other mutations. Fifty-five percent of cases are caused by X-Iinked recessive disorders, which result in defective IL-2 receptors on T cells.
Presents by three months of age on average.
Lymphoid tissues: Hypoplastic with depleted T-cell regions; small, undifferentiated thymus with low lymphocyte counts; other lymphoid tissues.
Pathophysiology: Mutations lead to abnormal lymphocyte growth and function, which impairs T cell and, occasionally, B cell differentiation. Consequently, there is a reduction in the generation of antibodies.
Clinical Signs and Symptoms
severe, recurring infections caused by bacteria, fungi, viruses, and protozoa (particularly susceptible to C. albicans, Pneumocystis carinii, Pseudomonas, CMV, and VZV); may also manifest as severe diarrhea, thrush, and failure to thrive.
Results from the lab: severe lymphopenia; reduced levels of total immunoglobulin.
Treatments include bone marrow transplantation, infection control, routine IVIG delivery, and experimental adenosine deaminase gene transplantation have all been examined.
Adenosine deaminase deficiency, tyrosine kinase deficiency, failure to synthesize class II MHC antigens, or a defective recombinase-activating gene mutation account for the remaining cases of autosomal recessive disorders, which cause other mutations. Fifty-five percent of cases are caused by X-Iinked recessive disorders, which result in defective IL-2 receptors on T cells.
Presents by three months of age on average.
Lymphoid tissues: Hypoplastic with depleted T-cell regions; small, undifferentiated thymus with low lymphocyte counts; other lymphoid tissues.
Pathophysiology: Mutations lead to abnormal lymphocyte growth and function, which impairs T cell and, occasionally, B cell differentiation. Consequently, there is a reduction in the generation of antibodies.
Clinical Signs and Symptoms
severe, recurring infections caused by bacteria, fungi, viruses, and protozoa (particularly susceptible to C. albicans, Pneumocystis carinii, Pseudomonas, CMV, and VZV); may also manifest as severe diarrhea, thrush, and failure to thrive.
Results from the lab: severe lymphopenia; reduced levels of total immunoglobulin.
Treatments include bone marrow transplantation, infection control, routine IVIG delivery, and experimental adenosine deaminase gene transplantation have all been examined.
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Pathology - Chronic Granulomatous Disease of Childhood
Caused by hereditary recessive or X-linked abnormalities in genes that code for parts of the superoxide-producing enzyme NADPH oxidase.
Ninety percent of patients are men, and most of them show up in the first year of life.
The myeloperoxidase-halide system is how neutrophils fight off germs. H2O2 is necessary for the myeloperoxidase halide system to work. NADPH oxidase and bacterial metabolism both produce H202. Bacterial metabolism produces H202, which can be destroyed by species that generate catalase, such as Staphylococcus. The myeloperoxidase-halide system cannot destroy catalase-positive bacteria in the absence of NADPH oxidase activity, which also eliminates the source of H202.
shows a clear predisposition to opportunistic infections caused by catalase-positive bacteria and fungi, such as Aspergillus, S aureus, E coli, and Serratia. Subcutaneous abscesses, infectious dermatitis, and recurrent pneumonia are common presentations for patients.
Results from the lab: Nitroblue tetrazolium dye reduction test results are negative due to the lack of reactive H202 intermediates.
Treatment options include stem cell transplantation, interferon-gamma therapy for infection prophylaxis, antibiotics for infections, and donor granulocyte transfusions.
Microtubules and phagocyte lysosomal emptying are both impacted by the autosomal recessive leukocyte function abnormality known as Chediak-Higashi syndrome. Neutropenia, albinism, hemorrhage, neuropathy, and recurrent Staphylococcus and Streptococcus infections are some of the symptoms that are seen.
LFA-1 adhesion proteins on the surface of phagocytes have a malfunction that results in leukocyte adhesion deficit syndrome. It first manifests as severe pyogenic infections and poor wound healing in infancy.
Caused by hereditary recessive or X-linked abnormalities in genes that code for parts of the superoxide-producing enzyme NADPH oxidase.
Ninety percent of patients are men, and most of them show up in the first year of life.
The myeloperoxidase-halide system is how neutrophils fight off germs. H2O2 is necessary for the myeloperoxidase halide system to work. NADPH oxidase and bacterial metabolism both produce H202. Bacterial metabolism produces H202, which can be destroyed by species that generate catalase, such as Staphylococcus. The myeloperoxidase-halide system cannot destroy catalase-positive bacteria in the absence of NADPH oxidase activity, which also eliminates the source of H202.
shows a clear predisposition to opportunistic infections caused by catalase-positive bacteria and fungi, such as Aspergillus, S aureus, E coli, and Serratia. Subcutaneous abscesses, infectious dermatitis, and recurrent pneumonia are common presentations for patients.
Results from the lab: Nitroblue tetrazolium dye reduction test results are negative due to the lack of reactive H202 intermediates.
Treatment options include stem cell transplantation, interferon-gamma therapy for infection prophylaxis, antibiotics for infections, and donor granulocyte transfusions.
Microtubules and phagocyte lysosomal emptying are both impacted by the autosomal recessive leukocyte function abnormality known as Chediak-Higashi syndrome. Neutropenia, albinism, hemorrhage, neuropathy, and recurrent Staphylococcus and Streptococcus infections are some of the symptoms that are seen.
LFA-1 adhesion proteins on the surface of phagocytes have a malfunction that results in leukocyte adhesion deficit syndrome. It first manifests as severe pyogenic infections and poor wound healing in infancy.
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Pathology - Job Syndrome
caused by a mutation on chromosome 7q21 in the STAT3 gene.
The pathophysiological understanding A family of transcription factors known as STAT3 proteins is involved in signaling and the synthesis of cytokines. Decreased IL-6 and IL-23 signaling impairs the ability of a subset of helper T cells (Th 17) to differentiate. These cells are essential for the production of cytokines (IL-17 and IL-22) that are required to destroy bacteria and fungus. Decreased production of IL-10 and IL-4, which control the release of pro-inflammatory cytokines, raises interferon-gamma or tumor necrosis factor levels, which can then raise IgE levels.
Pathology
presents with eczema, recurrent infections (such as pneumonia, sinusitis, and otitis), and non-inflamed, cold staphylococcal abscesses; patients may also have skeletal anomalies, such as coarse facial features, scoliosis, and retained primary teeth.
results from the lab: increased levels of lgE and eosinophilia.
Treatment: Antibiotics for both infection prevention and treatment.
Remarks A malfunction in the CD40 ligand on CD4 T helper cells causes the inability to class switch from lgM to other classes, which is the cause of hyper-IgM syndrome. Early in life, it exhibits severe pyogenic infections.
caused by a mutation on chromosome 7q21 in the STAT3 gene.
The pathophysiological understanding A family of transcription factors known as STAT3 proteins is involved in signaling and the synthesis of cytokines. Decreased IL-6 and IL-23 signaling impairs the ability of a subset of helper T cells (Th 17) to differentiate. These cells are essential for the production of cytokines (IL-17 and IL-22) that are required to destroy bacteria and fungus. Decreased production of IL-10 and IL-4, which control the release of pro-inflammatory cytokines, raises interferon-gamma or tumor necrosis factor levels, which can then raise IgE levels.
Pathology
presents with eczema, recurrent infections (such as pneumonia, sinusitis, and otitis), and non-inflamed, cold staphylococcal abscesses; patients may also have skeletal anomalies, such as coarse facial features, scoliosis, and retained primary teeth.
results from the lab: increased levels of lgE and eosinophilia.
Treatment: Antibiotics for both infection prevention and treatment.
Remarks A malfunction in the CD40 ligand on CD4 T helper cells causes the inability to class switch from lgM to other classes, which is the cause of hyper-IgM syndrome. Early in life, it exhibits severe pyogenic infections.
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Pathology - Langerhans Cell Histiocytosis
Caused by aberrant proliferation of dendritic tumor cells, which are in charge of presenting antigens to T and B cells and express HLA-DR and CD1a.
Pathology Gross: Lesions affect the skin, bones, lungs, and stomach, among other organ systems.
Under the microscope: eosinophils in lesions associated with eosinophilic granuloma; proliferation of neoplastic histiocytic cells resembling epidermal Langerhans cells; Birbeck granules, cytoplasmic aggregates shaped like tennis rackets, within neoplastic cells.
Skin involvement with a maculopapular erythematous rash, usually on the torso, scalp, or in the creases of the elbow or knee; endocrinologic abnormalities (including diabetes insipidus, hypothalamus deficiency, or delayed puberty); otitis media; involvement of the bones with lesions or fractures presenting in the skull or long bones; infiltrative pulmonary disease; lymphadenopathy; liver dysfunction.
Therapy: chemotherapy (cyclosporine, for example); bone marrow transplantation may be an option.
Caused by aberrant proliferation of dendritic tumor cells, which are in charge of presenting antigens to T and B cells and express HLA-DR and CD1a.
Pathology Gross: Lesions affect the skin, bones, lungs, and stomach, among other organ systems.
Under the microscope: eosinophils in lesions associated with eosinophilic granuloma; proliferation of neoplastic histiocytic cells resembling epidermal Langerhans cells; Birbeck granules, cytoplasmic aggregates shaped like tennis rackets, within neoplastic cells.
Skin involvement with a maculopapular erythematous rash, usually on the torso, scalp, or in the creases of the elbow or knee; endocrinologic abnormalities (including diabetes insipidus, hypothalamus deficiency, or delayed puberty); otitis media; involvement of the bones with lesions or fractures presenting in the skull or long bones; infiltrative pulmonary disease; lymphadenopathy; liver dysfunction.
Therapy: chemotherapy (cyclosporine, for example); bone marrow transplantation may be an option.
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Pathology - Amyloidosis
Primary: Linked to dyscrasias of the plasma cell.
Secondary: Develops as a side effect of underlying long-term inflammatory conditions (RA, IBD) or long-term infections (TB, osteomyelitis).
Primary: Monoclonal immunoglobulin light chains (AL protein) are deposited in the heart, gastrointestinal tract, muscles, brain, and kidneys, typically.
Secondary: The skin, GI tract, and kidneys are typically affected by the deposition of AA protein, which is produced from apolipoprotein precursors.
Histopathology: The amyloid protein exhibits apple-green birefringence when stained with Congo red.
Pathophysiology: Insoluble protein fibrils infiltrate tissues, resulting in impaired organ function.
The symptoms (such as nephrotic syndrome, renal failure, restrictive cardiomyopathy, arthritis, neuropathy, intestinal malabsorption, and respiratory failure) are associated with the malfunction of the implicated organ.
Management
First: prednisone and melphalan; organ transplant, then bone marrow transplant.
Secondary: Treating predisposed diseases aggressively.
Other conditions involving amyloid deposition include diabetes (islet amyloid polypeptide), Alzheimer's disease (amyloid beta protein), Portuguese type polyneuropathy (transthyretin), nephropathic hereditary amyloidosis (AA protein), medullary thyroid cancer (amyloid formed from calcitonin precursors), and dialysis amyloidosis (beta-microglobulin).
Primary: Linked to dyscrasias of the plasma cell.
Secondary: Develops as a side effect of underlying long-term inflammatory conditions (RA, IBD) or long-term infections (TB, osteomyelitis).
Primary: Monoclonal immunoglobulin light chains (AL protein) are deposited in the heart, gastrointestinal tract, muscles, brain, and kidneys, typically.
Secondary: The skin, GI tract, and kidneys are typically affected by the deposition of AA protein, which is produced from apolipoprotein precursors.
Histopathology: The amyloid protein exhibits apple-green birefringence when stained with Congo red.
Pathophysiology: Insoluble protein fibrils infiltrate tissues, resulting in impaired organ function.
The symptoms (such as nephrotic syndrome, renal failure, restrictive cardiomyopathy, arthritis, neuropathy, intestinal malabsorption, and respiratory failure) are associated with the malfunction of the implicated organ.
Management
First: prednisone and melphalan; organ transplant, then bone marrow transplant.
Secondary: Treating predisposed diseases aggressively.
Other conditions involving amyloid deposition include diabetes (islet amyloid polypeptide), Alzheimer's disease (amyloid beta protein), Portuguese type polyneuropathy (transthyretin), nephropathic hereditary amyloidosis (AA protein), medullary thyroid cancer (amyloid formed from calcitonin precursors), and dialysis amyloidosis (beta-microglobulin).
