BL4640 Clinical Immunology and Serology Syllabus

Fall / Fourth Year2 credits, (2-0-0)

BL 4640 Clinical Immunology SerologyIntegrates basic and clinical immunological principles as well as outlines the diagnosis and evaluation of immune disorders and selected infectious diseases. Credits: 2.0 Lec-Rec-Lab (2-0-0) Semesters Offered: Fall Restrictions: Must be enrolled in one of the following Class(es): Junior Senior Prerequisites: BL 1710 and BL 2410 and BL 3640 or permission of instructor.

Lecturer

Alice Soldan, M.S., MT(ASCP), CLS(NCA)Director, Clinical Laboratory Science ProgramOffice: Dow 735Office Phone: 487-2547Email address: afsold@mtu.edu

Textbooks

Title: Clinical Immunology and Serology, 2nd ed. The Immune System

Author: C. D. Stevens P. Parham

Publisher: F. A. Davis Company, 2003 Garland Publishing, 2000

Fundamental Concepts: Integration of Basic and Clinical Immunology

Lecture Topics and Reading Assignments

Lecture 1 The Scope of Clinical Immunology and Serology

no reading assignmentSafety and Specimen Preparation (review)Stevens: 114-123

Lecture 2 Immunity and ImmunizationStevens: 2-4, 9-18 Parham: 1-9, 26-27, 233-235, 328-338

Lecture 3 Primary and Secondary Lymphoid OrgansStevens: 24-28 Parham: 10-18

Lecture 4 T Cells, B Cells, Third Population – Natural Killer CellsStevens: 28-40 Parham: 182, 221-223

Lecture 5 Antigens and HaptensStevens: 45-49 Parham: 19, G-2

Lecture 6 The Major Histocompatibility (Gene) Complex and AntigensStevens: 49-55 Parham: 22-23, 61-81

Lecture 7 Antibodies (Immunoglobulins)Stevens: 59-73 Parham: 19-23, 31-40

Lecture 8 Cellular Activities and InteractionsStevens: 77-88 Parham: 145-147

Lecture 9 ComplementStevens: 92-108 Parham: 183-197

Exam I

Lecture 10 Immunological Precipitation

Stevens: 128-134Electrophoretic Precipitation TechniquesStevens: 134-137

Lecture 11 Immunological AgglutinationStevens: 142-151

Lecture 12 Labeled Immunoassays (radio-, enzyme, fluorescent)Stevens: 156-168

Lecture 13 Automated Procedures - Instrumentationno text assignment

Lecture 14 Molecular Biology TechniquesStevens: 173-185

Diagnosis / Evaluation of Immune Disorders and Infectious Diseases

Lecture 15 Hypersensitivity

Stevens: 192-207Lecture 16 Autoimmunity

Stevens: 212-213, 227-228Systemic Lupus Erythematosus Stevens: 214-218Rheumatoid ArthritisStevens: 218-220

Lecture 17 Hashimoto’s ThyroiditisStevens: 221Graves’ DiseaseStevens: 222Type I Diabetes Mellitus (Insulin-Dependent Diabetes)Stevens: 223-224

Lecture 18 Multiple SclerosisStevens: 224-225Myasthenia GravisStevens: 225-226Goodpasture’s SyndromeStevens: 226

Exam II

Lecture 19 Immunoproliferative DisordersStevens: 235-245

Lecture 20 Immunodeficiency Diseases

Stevens: 212-219, 280-293Lecture 21 Transplantation Immunology

Stevens: 262-273Lecture 22 Tumor Immunology

Stevens: 278-287Lecture 23 Spirochete Diseases

Stevens: 294-307SyphilisLyme Disease

Lecture 24 Streptococcal Infections/SerologyStevens: 313-318

Lecture 25 Serology of Non-HIV Viral InfectionsStevens: 324-325, 337-339

HepatitisStevens: 325-330Herpesvirus GroupStevens: 330-334

Herpes Simplex Virus Parham: 246Epstein-Barr VirusCytomegalovirusVaricella-Zoster Virus

Childhood Viral InfectionsStevens: 334-337

Rubella RubeolaMumps

Human T Cell Lymphotropic VirusStevens: 336-337Other Important VirusesStevens: 338

Lecture 26 HIV SerologyStevens: 346-363

Lecture 27 Parasitic ImmunologyStevens: 370-376

Toxoplasma gondii (toxoplasmosis)Giardia lamblia (backpacker's diarrhea)Entamoeba histolytica/dispar (amebic dysentery)Trichinella spiralis (trichinosis)

Fungal ImmunologyStevens: 376-381

Aspergillosis

CandidiasisCoccidioidomycosisCryptococcosis

Grading Policy Grading ScaleParticipation & Presentations 100 points

Exam I 100 points 90% - 100% A

Exam II 100 points 86% - 89% ABFinal Exam 100 points 80% - 85% B

76% - 79% BCTOTAL 400 points 70% - 75% C

66% - 69% CD60% - 65% D59% or less F

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BL4640 Clinical Immunology and SerologyLecture Objectives

Fundamental Concepts: Integration of Basic and Clinical Immunology(first third of the course - Exam I information)After completing these lecture-discussion sessions, each student should be able to:

Correlate the basic information learned in BL3640 General Immunology with howThat information is used in the clinical laboratory.

Diagnosis and Evaluation of Immune disorders and Infectious diseases(second third of the course - Exam II information)

After completing these 'student taught' lecture-discussion sessions each student should be able to:

1. gather technical information from scientifically reputable sources.

2. cite their information sources.

3. present information in a concise, organized fashion using appropriate technical terminology.

4. field questions and lead a discussion dealing with advanced topics in immunology.

The following are specific objectives for the last third of the course (final exam information).

Transplantation and Tumor Immunology

After completing the lecture-discussion session on transplantation and tumor immunology, each student should be able to:

a. summarize the role played by the major histocompatibility complex in acceptance/rejection of transplanted tissue.

b. define and state an example of each of the following.

autograftsyngraftallograft (homograft)xenograft (heterograft)

c. describe each of the following forms of graft rejection.

hyperacuteacceleratedacutechronic

d. explain how and why the following tests are done prior to transplantation.

ABO grouping on donor and recipientLymphocytotoxicity Test (for HLA typing)Lymphocytotoxicity Test (selected donor-recipient)Mixed Lymphocyte Reaction Test

e. recognize the following as types of tissues/organs that may be transplanted

cornea heart-lungbone liverkidney pancreasheart bone marrow

f. state the organ most commonly transplanted in the U.S.

g. briefly describe graft-vs- host disease.

h. compare and contrast the following terms.

tumor specific antigen tumor-associated antigen

i. name the malignancy associated with each of the following.

carcinoembryonic antigen (CEA)alpha-fetoprotein (AFP)human chorionic gonadotropin (hCG)prostate-specific antigen (PSA)prostatic acid phosphatase (PAP)CA-125

CA-15-3

Immunodeficiency Diseases

After completing the lecture-discussion session on primary and secondary immunodeficiency, each student should be able to:

a. state the difference between

specific and non-specific immunodeficiency diseases.primary and secondary immunodeficiency diseases.

b. explain which types of deficiencies result in increased susceptibility to

pyogenic infections.opportunistic infections.

c. recognize the following as primary B-cell deficiencies and briefly describe each.

transient hypogammaglobulinemia of infancyIgA deficiencyX-linked agammaglobulinemiacommon variable immunodeficiencyisolated IgG subclass deficiencyimmunodeficiency with hyper IgM

d. recognize the following as primary T-cell deficiencies and briefly describe each.

DiGeorge anomalyPNP deficiencysevere combined immunodeficiency (SCID)

Wiskott-Aldrich syndromeataxia telangiectasiareticular dysgenesis

e. recognize that genetic deficiencies of almost all human complement components have been documented.

f. recognize the following as primary defects influencing phagocyte function and briefly describe each one.

chronic granulomatous diseaseleucocyte adhesion molecule deficiency

g. recognize the following as factors which can cause secondary (acquired) immunodeficiency.

drugssteroidsantineoplastic agentsimmunosuppressives used to facilitate organ transplantation

malnutritionprotein-energy malnutrition (PEM)individual nutrients such as:

zinc vitamin Airon vitamin B6selenium folatecopper

human immunodeficiency virus (HIV)

h. list the screening, and confirmatory tests performed in the clinical laboratory when trying to detect and diagnose immunodeficiency diseases of the following classes.

all immunodeficiencies (screening test only)humoral immunity deficiencycell-mediated immunity deficiencyphagocyte defectcomplement system defect

Immunoproliferative Diseases

After completing the lecture-discussion session on immunoproliferative disorders, each student should be able to:

a. define immunoproliferative.

b. state the fundamental difference between leukemias and lymphomas.

c. explain the concept termed 'monoclonality of malignancy'.

d. define the following terms:

dyscrasiamonoclonal gammopathypara-proteincryoglobulin

e. briefly describe each of the following plasma cell malignancies.

multiple myelomaWaldenstrom's macroglobulinemia

f. explain how each of the following laboratory procedures is used in the detection and diagnosis of monoclonal gammopathies.

serum immunoglobulin levelsserum protein electrophoresisimmunoelectrophoresisimmunofixation electrophoresis

Non-HIV Viral Infections

After completing the lecture-discussion session on non-HIV viral infections, each student should be able to: re: Hepatitisa. define hepatitis.

b. recognize that hepatitis may be caused by:

autoimmune processes.exposure to chemicals.exposure to radiation.viral infections.

c. list the five hepatitis viruses.

d. describe each of the five hepatitis viruses with attention to the followingcharacteristics. (See Stevens text, Table 17-1, p. 265.)

type (DNA or RNA)route of transmission

form of disease (acute, chronic, or both)disease complications

e. associate the antibody and/or antigen marker(s) listed with the diagnosis and monitoring of each of the following kinds of hepatitis.

hepatitis A - poor sanitation and/or contaminated food and waterIgM anti-HAV - acute infectionIgG anti HAV - convalescence

hepatitis B - blood and/or body fluids (three marker systems)

HBsAg (surface antigen) - seen first, current or recent infectionanti-HBs - end of 'core window', late convalescence, Hep B vaccine

HBcAg (core antigen) IgM anti-HBc - 'core window'IgG anti-HBc - convalescence, past infection

HBeAg (capsid antigen) - acute and chronic infectionanti-HBe -conclusion of infection

hepatitis C - blood and/or body fluidsimilar to HBV, but more commonly leads to chronichepatitis, cirrhosis, and hepatocellular carcinoma

marker system under study currently no characteristic antigens

anti-HCV - most common diagnostic test (high risk populations)RIBA (low risk populations) - uses recombinant HCV proteins /blotHCV RNA - major confirmatory test for disease persistence

hepatitis D - found only in conjunction with hepatitis B infectionHDAg - very early infection (measurement of questionable value)IgM anti-HDAg - acute infectiontotal (IgM and IgG) anti-HDAg - acute infection, chronic infection

hepatitis E - poor sanitation and/or contaminated food and water

marker system under studycurrently no characteristic antigens

f. name the laboratory technique most commonly used to detect/measurehepatitis markers.

g. recognize that hepatitis D is associated with a biphasic (i.e. HBV, then HDV) alanine aminotransferase (ALT) pattern.

re: Herpesvirus Groupa. recognize that the following viruses are categorized as herpesviruses.

Epstein-Barr virus (EBV)cytomegalovirus (CMV)herpes simplex viruses (HSV-1, HSV-2)varicells-zoster virus (VSV)

b. recognize that the viruses listed in a. above are DNA viruses

re: EBVa. list four diseases caused by the EBV.

b. define the following terms.

heterophil(e) antibodiesForssman antibodiesIM heterophil(e)antibodies (= Paul-Bunnell, or non-Forssman antibodies)

c. name the EBV antigens associated with each of the following phases of the viral replication cycle.

early acute late latent

d. explain the conditions under which EBV-specific antibody testing is performed.

e. name the EBV-specific antibody most useful in early diagnosis of IM.

re: CMVa. explain how CMV is transmitted.

b. describe CMV infections as seen in:

healthy adultsnewbornsimmunosuppressed patients

c. recognize the following as laboratory methods used to diagnose CMV.

latex agglutination screening tests (most practical for routine use)other serological tests

ELISA, RIA, IHAmonoclonal IFA for CMV antigensviral culture (fibroblast cells)

microscopy (urine, blood, biopsy)

cytomegalic cell with 'owl's eye' due to central intranuclear inclusionPCR and DNA probes

re: HSV-1 and HSV-2a. describe the typical infections caused by HSV-1 and HSV-2.

b. explain how the following laboratory methods are used in the diagnosis of HSV infections.

Tzanck smeardirect immunofluorescent or immunoperoxidase staining of cells from lesionviral culture plus labeled HSV antibodiesviral culture plus ELISAPCR and DNA probes

re: VZVa. state the common name for each of the following infections.

varicellazoster

b. describe the symptoms associated with the primary and latent stages of VZVinfections.

c. name the other viral disease that has symptoms which are often confused withthose of VZV.

d. recognize that laboratory methods used in the diagnosis of VZV infections are comparable to those used for HSV infections, and serological methods are generally preferred over culture methods.

re: Rubella Virus a. list two 'common name' synonyms for rubella infection.

b. recognize that the rubella virus is an RNA virus.

c. describe rubella infection as it typically appears in:

a fetus.a child or young adult.

d. state two reasons for performing rubella testing.

e. name the analyte most commonly measured to detect acute rubella infection.

f. recognize that serological test procedures are generally preferred over viral culture methods for detection of rubella infection.

g. list five criteria used to determine which of the many available serological procedures for detecting rubella infection is appropriate for a particular laboratory.

h. recognize that the rubella test procedure currently used most often is theELISA.

Spirochete Diseases

After completing the lecture-discussion session on spirochete diseases, each student should be able to:

a. give a general description of spirochetes with respect to the following.

morphologyGram reactionoxygen requirementmotility

b. list three characteristics that spirochete diseases have in common.

c. state the two most important human spirochete diseases.

d. explain why serological testing is generally used to diagnose spirochetediseases.

re: Syphilisa. recognize that syphilis is a sexually transmitted disease (STD), and is usually

transmitted by direct contact.

b. name, to subspecies, the organism that causes syphilis.

c. describe each of the following conditions.

primary (initial) syphilissecondary syphilislatent syphilistertiary syphiliscongenital syphilis

d. define reagin and cardiolipin.

e. name and briefly describe the tests in each of the following categories of lab procedures used to diagnose syphilis. See Stevens, Table 15-1, p. 234.

direct microscopyserological tests

nontreponemaltreponemal

re: Lyme diseasea. explain the connection between Lyme, Connecticut and Lyme disease.

b. recognize that Lyme disease is the most common vector-borne diseasein the U.S.

c. name the Lyme disease:

causative agent (genus and specific epithet).vector (genus and specific epithet, common name). reservoir host (genus, common name).

d. describe each of the following stages of Lyme disease.

erythema chronicum migransinitial spread to various organ systemschronic disseminated diseasespontaneous remission

e. recognize that although it is possible to culture the causative agent of Lyme disease, until recently it has been very hard to isolate from patient specimens.New growth media are now available for culture of skin samples.

f. state the source of the antigen and/or antibody used in each of the followingtests used to diagnose Lyme disease.

IFAELISAWestern BlotDNA probe

g. define seronegative and seroconversion.

Streptococcal Infections

After completing the lecture-discussion session on streptococcal infections, each student should be able to:

a. give a general description of streptococci.

b. compare and contrast streptococcal serotypes and Lancefield groups.

c. explain, using the following terms, why infection with one strain of Streptococcuspyogenes doesn't confer immunity to other strains.

M proteinphagocytesC3serotype

d. name the two most common sites of strep infections and the major disease/s associated with each one.

e. recognize that strep infection may result in the following.

tonsillitis otitis mediascarlet fever erysipelascellulitis puerperal sepsisabscess septic arthritisbacterial endocarditis meningitis

f. define nephritogenic streptococcal strain.

g. name and describe two nonsuppurative complications that may follow a strep infection.

h. state the two methods commonly used to rapidly diagnose acute strep pharyngitis,and explain the value of each.

i. explain why serological procedures, rather than culture procedures, are used todiagnose rheumatic fever and poststreptococcal glomerulonephritis.

j. list the five antibodies measured in diagnostic tests for strep infections.

Febrile Diseases

After completing the lecture-discussion session on febrile diseases, each student should be able to:

a. recognize the following as organisms that cause febrile diseases in humans.

Brucella abortusFrancisella tularensisSalmonella spp.

b. name the febrile disease that may be diagnosed by testing patient serum

with each of the following antigens in a Widal Test. See Stevens, Table 9-3,p. 139.

Brucella abortusSalmonella HSalmonella OSalmonella H (paratyphi A)Salmonella H (paratyphi B)

c. define the following.

Rickettsiarickettsiarickettsiae

d. name the test procedure used to test patient serum for antibodies to rickettsialdiseases.

e. list the three bacterial antigens that are used to diagnose rickettsial febrile diseasesdue to cross-reactivity with rickettsial antibodies. See Stevens, Table 9-2, p. 138.

f. name the disease caused by each of the following rickettsial organisms. SeeStevens, Table 9-2, p. 138.

R. prowazekiiR. typhiR. rickettsiiR. tsutsugamushiCoxiella burnetii

g. explain the significance of performing febrile agglutinin tests on paired sera.

Fungal Infections

After completing the lecture-discussion session on fungal infections, each student should be able to:

a. recognize that fungal diseases are rapidly rising worldwide due to the following.

use of broad-spectrum antibioticsuse of immunosuppressant drugsthe AIDS epidemic

b. name the two basic morphological forms of fungi.

c. define the following terms.

hyphaemycelium septaaseptateconidiamonomorphicthermal dimorphismmycoses

d. recognize that diagnosis of fungal diseases may include the following procedures.

ID of fungal organisms in patient specimens (w/o culturing)fungal cultureantigen detection via serologyantibody detection via serology

e. name the causative agent for each of the following.

aspergillosis (Genus only.)candidiasiscoccidioidomycosiscryptococcosis

f. recognize that there commercial serodiagnostic tests are currently available for each of the diseases listed in e. above, as well as some other fungal conditions

(i.e., blastomycosis, histoplasmosis, sporotrichosis, paracoccidioidomycosis).

g. name the organism that is the single most common cause of serious fungal infections.

h. describe the India Ink preparation used to diagnose cryptococcal meningitis.

Parasitic Infections

After completing the lecture-discussion session on parasitic infections, each student should be able to:

a. explain why most parasitic infections are diagnosed by morphologic (macroscopic or microscopic) identification, rather than serological procedures, including the following issues. See Stevens, p. 315.

cost effectiveness technologist timeproficiency testingFDA regulationlife cycles

antigen switchingantibody classcross-reactions

b. name the two parasitic infections most commonly diagnosed by serological procedures.

c. list two reasons why serological procedures are performed to aid in the diagnosis of toxoplasmosis, cysticercosis, echinococcosis, and trichinosis.

d. state the similarity in serologic test procedures available for the following parasites.

Entamoeba histolytica (not in our text)Cryptosporidium parvum

Giardia lambliaPneumocystis cariniiTrichomonas vaginalis

e. explain the purpose of a ToRCH panel.

f. list the organisms included in a ToRCH panel.