Immunology and Serology Module 6 PDF

Central Philippine University | College of Medical Laboratory Science KEY CONCEPTS MEDICAL LABORATORY SCIENCE INTERNSHIP I. IMMUNODEFICIENCY DISEASES IMMUNOLOGY AND...

Central Philippine University | College of Medical Laboratory Science KEY CONCEPTS MEDICAL LABORATORY SCIENCE INTERNSHIP I. IMMUNODEFICIENCY DISEASES IMMUNOLOGY AND SEROLOGY A. General Information MODULE 1. Group of rare disorders in which part of the body’s immune system 6 IMMUNODEFICIENCY DISEASES is missing or dysfunctional leading to incapability of the body to AND TUMOR IMMUNOLOGY defend against microorganisms and increased susceptibility to develop cancer. 2. Recurrent infection is the hallmark. 3. Inability of the body’s immune system to defend against bacterial MODULE OUTCOMES infections by opsonization and phagocytosis are attributed by the At the end of this module, the learner should have been able to: defects of phagocytic cells, complement pathways or B-cells 1. describe comprehensively primary and secondary immunodeficiency 4. There is an increased susceptibility to viral and fungal infections diseases in terms of pathophysiology and laboratory diagnosis. due to T-cell deficiencies 2. differentiate correctly the disorders associated with defects in B-cells, T- B. Classification cells, and both. 1. Primary or Congenital Immunodeficiency 3. correlate correctly tumor markers with the patient’s diagnosis. a. Affect one or more aspects of the immune system b. Parts of the lymphoid cells, phagocytic cells, regulatory INTRODUCTION molecules and complement system are may be missing or Immunodeficiency diseases are a group of disorders in which part of the dysfunctional except for IgA deficiency body’s immune system is missing or dysfunctional. People with these c. Examples: conditions have low immunity to fight infections and are even more i. B-cell deficiency disorders susceptible to acquiring certain types of cancer. Immunodeficiency may be ii. T-cell deficiency disorders classified into two, primary immunodeficiency which are inherited, and iii. Combined B and T-cells deficiency disorders secondary immunodeficiency which are caused by infections, malignancies, iv. Phagocytic Cell Defects or immunosuppressive drugs. Clinical laboratory tests play an essential role v. Complement System: C3 (opsonization) and C5 in the proper diagnosis of these diseases which will result in proper (chemotaxis) deficiencies are known to be the most severe intervention and medication. 2. Secondary or Acquired Immunodeficiency Tumor immunology is the study between the immune system and cancer a. Acquired from microorganisms and environmental factors cells. It deals with the host’s immune response against tumors, mechanisms b. Examples: on how tumors survive immune responses, and therapeutic use in an i. Acquired Immunodeficiency Syndrome caused by HIV attempt to eradicate the tumors. Tumor detection in the laboratory is ii. Protein-calorie malnutrition accomplished by microscopic examination of biopsy samples and iii. Irradiation and chemotherapy for patients with cancer serological tests. iv. Cancer metastases to bone marrow v. Splenectomy C. Laboratory Tests for Immunodeficiency Disorders 1. Patient cells need to be tested with the normal controls and if result is abnormal, repeat testing must be done for confirmation Immunology and Serology | MODULE 6 | IMMUNODEFICIENCY DISEASES AND TUMOR IMMUNOLOGY 1  2. Laboratory Tests: cells in lymph nodes a. Complete blood count d. Peyer’s patches and tonsils may be missing or hypoplastic b. Measurement of serum Ig levels e. Intact T-cells function c. CH50 assay for complement deficiencies f. Persists for >2 years of age d. Flow cytometric assay g. Recurrent bacterial infections e. Newborn screening i. Particularly sinopulmonary caused by encapsulated f. Serum protein electrophoresis bacteria g. Histologic examination of the affected organ ii. Otitis media, bronchitis, pneumonia, meningitis, and dermatitis II. PRIMARY (CONGENITAL) IMMUNODEFICIENCIES 6. IgA Deficiency A. General Information a. Most common congenital deficiency 1. Group of single gene disorders that result in defects in the immune b. Caused by impaired differentiation of lymphocytes to become system IgA-producing plasma cells and presence of anti-IgA antibodies 2. Genetic defect may result in: (hypogammaglobulinemia) a. Loss of an important enzyme c. Usually asymptomatic but patient may experience respiratory b. Developmental arrest in one aspect of the immune system and GIT infections, increased susceptibility to autoimmune c. Loss of a structural component diseases, allergic disorders and malignancy if symptomatic d. May create a nonfunctional protein 7. Common Variable Immunodeficiency B. B-cell Deficiency Disorders a. Low incidence but the most common primary immunodeficiency 1. Agammaglobulinemia is defined as deficiency in immunoglobulins disease with a severe clinical syndrome or antibodies b. Can be congenital or acquired, familial or sporadic and affects 2. Mechanisms of occurrence: males and females equally a. Genetic defects in B-cell maturation c. Three major types of cellular defects: b. Mutations i. T-cells suppress differentiation of B cells into plasma cells 3. Blood levels of immunoglobulins change with age ii. T cells fail to support differentiation of B cells a. IgG at birth is the same as adult level iii. Primary defect in B cells b. IgG drops after 2-3 months and reaches adult level at about 5- d. Affects 7 to 71 years of age 6 years e. Symptoms usually appear at 20s to 30s c. IgM is very low at birth and reaches adult level at about 1 year f. Patient may experience: d. IgA is very low at birth and reaches adult level until adolescence i. AIHA and thrombocytopenia (most common autoimmune 4. Transient Hypogammaglobulinemia of Infancy manifestations) a. Delayed IgG synthesis ii. Recurrent bacterial infections, shingles, and sprue-like b. IgM and IgA may or may not be depressed syndrome c. Severe pyogenic sinopulmonary (pus-forming infections) and iii. Lymphadenopathy, splenomegaly and intestinal hyperplasia skin infections 8. Acquired Hypogammaglobulinemia 5. X-linked Bruton’s Agammaglobulinemia a. Due to T-cells defects which suppress B-cell maturation a. Bruton’s tyrosine kinase deficiency which mainly affects males 9. Isolated IgG Subclass Deficiency b. Extremely low level of IgG and absence of other Ig classes a. IgG1 and IgG3 directed against protein (toxins) c. Lack of circulating CD 19+ B-cells, germinal centers and plasma b. IgG2 directed against polysaccharides (encapsulated bacteria) Immunology and Serology | MODULE 6 | IMMUNODEFICIENCY DISEASES AND TUMOR IMMUNOLOGY 2  c. IgG4 most common subclass deficiency (least clinical d. Causes: significance) i. Deficiency in adenosine deaminase which is involved in d. IgG1 least common deficiency purine metabolism 10. Selective Immunoglobulin Deficiency (Dysgammaglobulinemia) ii. Ommen’s syndrome (mutation in a RAG1 or RAG2; inability C. T-cell Deficiency Disorders of T and B cells to rearrange the DNA necessary to produce 1. Deficiencies of cellular immunity caused by abnormalities in T-cell functional immunoglobulins or T-cell receptors) development iii. Bare lymphocyte syndrome (deficiency of class II MHC on 2. Has secondary effects on humoral immunity B-cell surface) 3. More difficult to manage than defects in humoral immunity 5. Wiskott-Aldrich Syndrome (WAS) 4. Patients with severe defects may develop GVHD a. WASp important in regulation of cytoskeletal reorganization 5. DiGeorge Syndrome b. Reduced IgM and T-cell defect a. Also known as Congenital Thymic Hypoplasia c. Lethal in childhood due to infection, hemorrhage or malignancy b. Faulty development of the third and fourth pharyngeal pouches d. Three features during embryogenesis i. Thrombocytopenia present at birth (prolonged BT and low c. Patient may have mental retardation, absence of ossification of IgM levels) the hyoid bone, cardiac anomalies, abnormal facial ii. Eczema development such as fish-shaped mouth and low-set ears, and iii. Recurrent pyogenic infections (inability to produce thymic hypoplasia antibodies against polysaccharide antigens) 6. Purine Nucleoside Phosphorylase Deficiency (PNP) 6. Ataxia-Telangiectasia a. T cells progressively decreases because of the accumulation a. Defect in a gene essential to the recombination process for of deoxyguanosine triphosphate, a toxic purine metabolite genes in the immunoglobulin superfamily. 7. Chronic Mucocutaneous Candidiasis b. Rearrangement of T-cell receptor and immunoglobulin genes a. T-cells have impaired ability to produce macrophage migration- does not occur normally inhibiting factor (MIF) in response to Candida antigen c. Involves nervous, endocrine and vascular systems D. Combined B- and T-cells Deficiency Disorders d. Characterized by uncoordinated muscle movement (ataxia) 1. Also known as 𝑇 "# 𝐵 "# 𝑁𝐾 "# (+- superscript denotes whether or and by dilatation of blood vessels (telangiectasia) observable not each cell type is present in the deficiency) in the sclera of the eye 2. Disorders in both humoral (B-cell) and cell-mediated (T-cell) 7. Nezelof Syndrome immunity caused by defects in the development of both cells or a. Patients are athymic lymphocytes b. Susceptibility to viral and fungal infections (fatal) 3. Severe defect of T-cell function affects antibody levels E. Phagocytic Immunodeficiency Disorders 4. Severe Combined Immunodeficiency (SCID) 1. Quantitative Defects of Phagocytic cells a. Also known as Swiss-type agammaglobulinemia a. Neutropenia or granulocytopenia b. X-linked SCID is the most common which has an abnormal b. Caused by: gene IL2RG that codes for the common gamma chain i. Bone marrow depressant (nitrogen mustard), quinidine, and responsible for receptors of interleukins defective, thus halting oxacillin normal cell maturation ii. Reticular dysgenesis (diminish function of stem cells) c. Patients usually die within 1 to 2 years of age from iii. Fanconi syndrome (congenital pancytopenia) overwhelming microbial infection Immunology and Serology | MODULE 6 | IMMUNODEFICIENCY DISEASES AND TUMOR IMMUNOLOGY 3 2. Qualitative Defects of Phagocytic cells abnormalities, bone fragility and otitis media a. Phagocytic cells fail to engulf and kill microorganisms due to c. There is normal phagocytosis and killing activity of the defects in chemotaxis, ingestion, killing, and digestion neutrophils b. Includes CGD, G-6-PD deficiency, Myeloperoxidase 8. Leukocyte Adhesion Deficiency (LAD) deficiency, Chediak-Higashi syndrome, and Job’s syndrome a. Dysfunction in the adhesion molecules needed to facilitate 3. Chronic Granulomatous Disease (CGD) cellular interaction a. X-linked recessive disorder b. CD18 which is a component of adhesion receptors on b. Appears in the first 2 years of life neutrophils and monocytes and on T cells is defective. c. Neutrophils lack the enzyme NADH or NADPH oxidase which catalyzes the reduction of oxygen to superoxide (oxidative III. TUMOR IMMUNOLOGY burst) A. General information d. Patient suffers from excessive inflammatory reactions that 1. Tumor immunology is the study of the antigens associated with: result to gingivitis, swollen lymph nodes and nonmalignant a. Tumors granulomas b. Immune response to tumors e. Symptoms: recurrent suppurative infections, pneumonia, c. Tumor’s effect on the host’s immune status osteomyelitis, draining adenopathy, liver abscesses, dermatitis d. Use of the immune system to help eradicate the tumor and hypergammaglobulinemia 2. Mechanism of occurrence 4. Glucose-6-Phosphate Dehydrogenasen (G-6-PD) Deficiency a. Induction a. Inability to generate enough NADPH to supply reducing i. Cellular mutations could be an effect of chemical equivalents to the NADPH oxidase system causing defect in carcinogens, oncogenic viruses and radiation which are H2O2 production known to be examples of environmental factors b. Clinical picture is similar to that of CGD (but with hemolytic ii. Cells exhibit dysplasia or abnormal growth but not yet anemia present) considered as neoplasia or a consistent tumor 5. Myeloperoxidase Deficiency b. In situ: neoplastic cells have formed but are confined to the a. Myeloperoxidase enzyme is an important microbicidal agent tissue of origin present in neutrophils c. Invasion: occurs if cells are malignant b. Patient susceptible to C. albicans and S. aureus d. Dissemination: usually via blood and lymphatics 6. Chediak-Higashi Syndrome B. Neoplasms a. Autosomal recessive disease 1. Result from new growth of cells that proliferate in uncontrolled b. Neutrophils contain abnormally giant lysosomes which are manner impaired to release digestive enzymes against microorganisms 2. May be: c. Characterized by recurrent bacterial infections, partial a. Benign oculocutaneous albinism, aggressive but non-malignant i. Slow growth and restricted anatomic location, and infiltration of organs by the lymphoid cells ii. Do not cause death 7. Job’s Syndrome or Hyper-IgE Syndrome b. Malignant a. Defective chemotaxis i. Often referred as cancer or tumor b. Autosomal dominant multi system disorder characterized by ii. Characterized by anaplasia (cells lose their differentiating skin abscesses (“cold” staphylococcal abscesses), eosinophilia features), invasion of the body, and metastatic spread which recurrent pneumonia, eczema and increased IgE with facial can cause death Immunology and Serology | MODULE 6 | IMMUNODEFICIENCY DISEASES AND TUMOR IMMUNOLOGY 4 C. Tumor-Associated Antigens c. Used to follow a patient for therapy and/or after surgical removal 1. Develop at the cell surface and the host recognizes malignant cells of the cancer of the colon as non-self E. Virus-induced Tumor Associated Antigens 2. Highly-specific since cells of tumor will have different TAA 1. Proteins or enzymes that are induced in the cell to aid in the 3. Increases proportionally with the tumor growth and decreases with replication of the virus therapeutic response 2. Viral “finger prints” used as an evidence that links viruses with Tumor-Associated Antigen Cancer human malignancy Beta-Human chorionic Choriocarcinoma, Virus-induced TAAs Cancer gonadotropin nonseminatous testicular Epstein-Barr virus Burkitt’s lymphoma, cancer nasopharyngeal carcinoma CA -125 Ovarian cancer Hepatitis B Primary hepatoma Adenocorticotropic hormone Increased in lung cancer Human Papilloma virus 16 Cervical carcinoma CA-19-9 Pancreatic cancer and 18 Bence Jones Protein Multiple myeloma Human T-cell leukemia virus Adult T-cell Leukemia CA-15-3 Breast cancer/ Lung cancer F. Tumor-Specific Transplantation Antigens Common Acute Lymphoblastic Increased in leukemia 1. Antigens that can induce a protective immune response in the host Leukemia Antigen (CALLA) if they occur in the membrane of the malignant cell Human Placental Lactogen Trophoblastic neoplasm G. Tumor Marker Screening and Diagnostic Tests Prostate-specific antigen (PSA) Prostate cancer 1. Fecal Occult Blood Test (FOBT) – colon cancer Acid Kinase Stomach cancer 2. Pap’s smear – cervical cancer Prostatic Acid Phosphatase Prostate cancer 3. Gross and microscopic morphology of the organ Alkaline Phosphatase Bone Cancer 4. Detection of antigen/ protein tumor markers S-100 calcium-binding protein Melanoma 5. DNA/RNA molecular diagnostics Calcitonin Thyroid Medullary carcinoma 6. Cytogenetic studies 7. Nucleic Acid Amplification test such as PCR D. Oncofetal Antigens 8. Fluorescent In Situ Hybridization 1. Present during normal fetal development but lost during differentiation of fetal tissue and are not synthesized by adults 2. May reappear with the development of malignancy 3. Alpha Feto Protein (AFP) FURTHER READING a. Synthesized by fetal liver cells Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: b. Presence in serum is suggestive of primary hepatoma A Laboratory Perspetive. FA Davis. (screening) McPherson, R. A., Msc, M. D., & Pincus, M. R. (2021). Henry's clinical c. Seen also in nonseminomatous testicular cancer diagnosis and management by laboratory methods E-book. Elsevier 4. Carcinoembryonic antigen (CEA) Health Sciences. a. A glycoprotein found in the glycocalyx of cells derived from endoderm b. Present in gastro- intestinal carcinoma (colon cancer) Immunology and Serology | MODULE 6 | IMMUNODEFICIENCY DISEASES AND TUMOR IMMUNOLOGY 5