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Clinical Immunology

Clinical Immunology. Dr. Khalid Farooq. Credit hours 3 (3-0). O bjectives. Major human diseases attributed to defects in immune system will be discussed I mmunological mechanism(s) that governs the onset of key human diseases T heir therapeutic potential.

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Clinical Immunology

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  1. Clinical Immunology Dr. Khalid Farooq Credit hours 3 (3-0)

  2. Objectives • Major human diseases attributed to defects in immune system will be discussed • Immunological mechanism(s) that governs the onset of key human diseases • Their therapeutic potential. • How animal models fit into the human disease experience

  3. Course Contents • 1. Etiology of autoimmune disease • Ab-mediated autoimmune disease • Autoimmune hemolytic anemia • Myasthenia gravis • Graves’ disease • Immune complex-mediated autoimmune disease • T-cell-mediated autoimmune disease • Multiple sclerosis • Insulin-dependentdiabetesmellitus • Hashimoto’sthyroiditis • Rheumatoidarthritis

  4. 4. Immunodeficiency and Other Disorders Of The Immune System • Immune deficiency syndromes • Acquired immunodeficiency syndrome (AIDS) • B-cell neoplasms • Leukemia • Lymphoma • 5. Transplantation Immunology • Immune response in allograft rejection • Histocompatibility antigens • Participation of MHC molecules in allograft rejection • Xenogeneic transplantation • Bone marrow transplantation • 6. Tumor Immunolog • Tumor Ag’s • Cytokines • Immunodiagnosis • Tumor immunoprophylaxis • Immunotherapy

  5. 7. Resistance and Immunization to Disease • Innate and adaptive immune defenses • Host defense against classes of pathogens • Immunity to viruses, bacteria, parasites and fungi • Mechanisms used by pathogens to evade the immune response • Principles of immunizations • Active immunizations • Use of vaccines in selected populations • Basic mechanisms of protection • Precautions • Passive immunization • Immunotherapy

  6. BOOKS Recommended Books: • Allergic Diseases: Diagnosis and Treatment by Phil L. Lieberman, John A. Anderson. • Essentials of Clinical Immunology by Helen Chapel, ManselHaeney, SirajMisbah, Neil Snowden. • Concise Clinical Immunology for Healthcare Professionals by Mary Keogan, Eleanor M. Wallace, Paula O'Leary. • Pocket guide to clinical immunology by James D. Folds, David E. Normansell. • Immunofluorescence in Clinical Immunology: A Primer and Atlas by WulfStorch.

  7. IMMUNOLOGY AND THE IMMUNE SYSTEM • Immunology • Study of the components and function of the immune system • Immune System • Molecules, cells, tissues and organs which provide non-specific and specific protection against • Microorganisms • Microbial toxins • Tumor cells • Crucial to human survival

  8. THE IMMUNE RESPONSE AND IMMUNITY • Immune response • Innate (non-specific) • Adaptive (specific) • Primary • Secondary • Immunity • State of non-specific and specific protection • Acquisition of Immunity • Natural • Artificial

  9. NATURALLY ACQUIRED IMMUNITY • Active • Antigens enter body naturally with response of • Innate and adaptive immune systems • Provides long term protection • Passive • Antibodies pass from mother to • Fetus across placenta • Infant in breast milk • Provides immediate short term protection

  10. ARTIFICIALLY ACQUIRED IMMUNITY • Active • Antigens enter body through vaccination with response of • Innate and adaptive immune systems • Provides long term protection • Passive • Antibodies from immune individuals injected into body • Referred to as • Immune serum globulins (ISG) • Immune globulins (IG) • Gamma globulins • Provides immediate short term protection

  11. PRINCIPAL FUNCTION OF THE IMMUNE SYSTEM • To protect humans from pathogenic microorganisms • Pathogenic microorganisms (Pathogens) • Microorganisms capable of causing infection and/or disease • Infection • Ability of pathogen to enter host, multiply and stimulate an immune response • Disease • Clinical manifestations associated with infection

  12. BACTERIA, VIRUSES, FUNGI, PARASITES… • Streptococcus pyogenes (Group A Streptococcus) • Klebsiellapneumoniae • Mycobacterium tuberculosis • Ebola virus • Human Immunodeficiency Virus (HIV) • Aspergillusfumigatus • Candida albicans • Cryptococcus neoformans • Cryptosporidium parvum • Stronglyoidesstercoralis • Ascarislumbricoides • Plasmodium falciparum • ………..

  13. DEFENSE MECHANISMS OF THE HUMAN HOST • Innate Mechanisms (Innate immunity) • First line of defense • Non-specific • Adaptive Mechanisms (Adaptive immunity) • Second line of defense • Highly specific with memory • Cooperation between mechanisms

  14. ORIGIN OF CELLS OF THE IMMUNE SYSTEM • Derived from common progenitor cell in bone marrow • Pluripotent hematopoietic stem cell • Progenitor Stem Cells • Erythroid lineage • Erythrocytes and Megakaryocytes • Myeloid lineage • Monocyte/macrophage, dendritic cells, PMN’s, mast cells • Lymphoid lineage • Small and large lymphocytes

  15. ORIGIN OF CELLS OF THE IMMUNE SYSTEM

  16. CELLS OF INNATE AND ADAPTIVE IMMUNITY • Myeloid Lineage • Neutrophil • Principal phagocytic cell of innate immunity • Eosinophil • Principal defender against parasites • Basophil • Functions similar to eosinophils and mast cells • Referred to as • Polymorphonuclear leukocytes (PMN’s) • Nuclei are multilobed (2 to 5) • Granulocytes • Cytoplasmic granules

  17. CELLS OF INNATE AND ADAPTIVE IMMUNITY • Myeloid lineage • Monocytes • Leukocytes with bean shaped or brain-like convoluted nuclei • Circulate in blood with half life of 8 hours • Precursors of tissue macrophages • Macrophages • Mononuclear phagocytic cells in tissue • Derive from blood monocytes • Participate in innate and adaptive immunity

  18. CELLS OF INNATE AND ADAPTIVE IMMUNITY • Myeloid lineage • Dendritic cells • Cells with dendriform (star shaped) morphology • Interdigitating reticular cells (synonym) • Capture and present antigens to T lymphocytes • Mast cells • Located in mucous membrane and connective tissue throughout body • Major effector cell in allergy • Modulation of initial immune response

  19. CELLS OF INNATE AND ADAPTIVE IMMUNITY • Lymphoid Lineage • Large lymphocytes (large granular lymphocytes) • Natural killer (NK) cells (CD16, CD56) • Innate immunity to viruses and other intracellular pathogens • Participate in antibody-dependent cell-mediated cytotoxicity (ADCC) • Small lymphocytes • B cells (CD19) • T cells (CD3, CD4 or CD8) • Adaptive immunity • Lymphocytes refers to small lymphocytes

  20. THE CLUSTER OF DIFFERENTIATION (CD) • A protocol for identification and investigation of cell surface molecules • CD number assigned on basis of 1 cell surface molecule recognized by 2 specific monoclonal antibodies • CD nomenclature established in 1982 • 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA)

  21. THE CLUSTER OF DIFFERENTIATION (CD) • CD markers on leukocytes Granulocyte CD45+, CD15+ Monocyte CD45+, CD14+ T lymphocyte CD45+, CD3+ T helper lymphocyte CD45+, CD3+, CD4+ T cytotoxic lymphocyte CD45+, CD3+, CD8+ B lymphocyte CD45+, CD19+ Natural killer cell CD45+, CD16+, CD56+, CD3-

  22. COMPLETE BLOOD COUNT WITH DIFFERENTIAL (CBC WITH DIFF) References Ranges Erythrocytes (RBC) 4.0 to 5.4 M/uL Thrombocytes (Platelets) 145 to 400 K/uL Leukocytes (WBC) 4.8 to 10.8 K/uL Neutrophils 40 to 74 % Band neutrophils 0 to 9 Eosinophils 0 to 6 Basophils 0 to 1 Lymphocytes 15 to 47 Monocytes 0 to 12

  23. CASE STUDY • 47 year old female presents to ER with 24 hour history • Fever (101.3 F) • Rigors (shaking chills) • Headache • Chest pain • Cough • Shortness of breath • Admitting diagnosis (?) • Diagnostic studies • Radiology and laboratory

  24. CASE STUDY • Laboratory studies • Blood • CBC with differential • Basic metabolic panel (BMP) • C-reactive protein (CRP) • Culture • Sputum • Culture • Radiology studies

  25. CASE STUDY • Laboratory studies • CBC with diff P RR • WBC 40.7 K/uL 4.8 to 10.8 • Neutrophils 44 % 40 to 74 • Bands 46 % 0 to 9 • Monocytes 1 % 0 to 12 • Lymphocytes 8 % 15 to 47 • BMP mild elevation of BUN and creatinine • CRP 24 mg/dL > 1.0 mg/dL

  26. CASE STUDY • Sputum • Gram stained smear • 50 WBC’s per high power field • Numerous gram-positive cocci in pairs and short chains • Culture • Heavy Streptococcus pneumoniae • Blood cultures • Gram stained smear • Gram-positive cocci in pairs and short chains • Culture • Streptococcus pneumoniae

  27. CASE STUDY • 22 year old male presents to ED with 36 hour history of • Fever (100.4 F) • Headache • Nausea • Vomiting • AMS (Irritability) • Anorexia • Nuchal rigidity • Photophobia • Admitting and differential diagnosis (?)

  28. CASE STUDY • Diagnostic studies • Radiology • Laboratory • Blood • CBC with diff, BMP and CRP • Cerebrospinal fluid (CSF) • Glucose, protein and cells (number and type) • Culture • Polymerase chain reaction (PCR)

  29. CASE STUDY Laboratory studies Cerebrospinal fluid (CSF) Patient Reference Range Cell # 465 / uL 0 - 8 / uL Cell type Lymphocytes (97%) Protein 117 mg/dL 15 – 45 mg/dL Glucose 43 mg/dL 40 – 70 mg/dL

  30. CASE STUDY • 50 year old female presents to ER with 15 to18 hour history • Fever (103.1 F) • Headache • AMS (Irritability and confusion) • Nausea • Vomiting • Nuchal rigidity • Sore throat • Photophobia • Admitting and differential diagnosis (?)

  31. CASE STUDY • Diagnostic studies • Radiology • Laboratory • Blood • CBC with diff, BMP and CRP • Cerebrospinal fluid • Protein, glucose and cells (number and type) • Culture • Bacterial antigens (latex agglutination)

  32. CASE STUDY • Blood • CBC with diff • Leukocytes 30.2 4.8-10.8 K/uL • Neutrophils 88 40-74 % • BMP (normal) • CRP 12 mg/dL >1 mg/dL • Cerebrospinal fluid • Gram stain • 50 WBC’s per high power field • Numerous gram-positive cocci in pairs and chains • Culture • Heavy Streptococcus pneumoniae

  33. CASE STUDY Laboratory diagnosis Cerebrospinal Fluid (CSF) Patient Reference Range Cell # 2,100 / uL 0 – 8 uL Cell type Neutrophils (98%) Protein 325 mg/dL 15 – 45 mg/dL Glucose 10 mg/dL 40 – 70 mg/dL

  34. LYMPHOCYTES, LYMPHOID TISSUES AND ORGANS • Lymphocytes originate in bone marrow • Lymphoid tissues and organs • Primary • Development and maturation of lymphocytes • Bone Marrow (B cells) and thymus gland (T cells) • Secondary • Mature lymphocytes meet pathogens • Spleen, adenoids, tonsils, appendix, lymph nodes, Peyer’s patches, mucosa-associated lymphoid tissue (MALT)

  35. THE LYMPHATIC SYSTEM • Lymph • Fluid and cells in lymphatic vessels • Lymphatic vessels • Collect and return interstitial fluid to blood • Transport immune cells throughout body • Transport lipid from intestine to blood • Lymph nodes • Kidney shaped organs at intervals along lymphatic vessels • Other secondary lymphatic tissues and organs

  36. LYMPHOCYTES AND THE LYMPH NODES • Naïve lymphocytes circulate between blood, lymph and secondary lymph nodes • Pathogens from infected tissue sites are picked up by lymphatic vessels and arrive at closest lymph node • T and B cells congregate at specific regions of nodes • Architecture and size of nodes change in response to activation of lymphocytes

  37. LYMPHOCYTES AND THE SPLEEN • Spleen • Lymphoid organ in upper left abdomen • Functions • Remove damaged or old erythrocytes • Activation of lymphocytes from blood borne pathogens • Architecture of Spleen • Red pulp • Erythrocytes removed • White pulp • Lymphocytes stimulated

  38. SECONDARY LYMPHOID TISSUES ASSOCIATED WITH MUCOUS MEMBRANES • Primary portals of entry for pathogens • Respiratory tract • Gastrointestinal tract • Secondary lymphoid tissues • Bronchial-associated lymphoid tissue (BALT) • Gut-associated lymphoid tissues (GALT) • Tonsils, adenoids, appendix, Payer's patches • Pathogens are directly transferred across mucosa by mucosal cells

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