1 Cells of the Immune system in the human body

Overview of Immune System Cells
The immune system is a complex network of cells, tissues, and organs that work together to defend the body against harmful invaders like bacteria, viruses, and other pathogens. Here are the main types of cells involved:

1. White Blood Cells (Leukocytes)
White blood cells are the primary cells of the immune system. They circulate in the blood and lymphatic system, constantly searching for pathogens. There are several types of white blood cells, each with a specific role:

Neutrophils: These are the most abundant type of white blood cells and are the first responders to infection. They engulf and destroy pathogens through a process called phagocytosis.
Lymphocytes: These include B cells, T cells, and natural killer (NK) cells.
B Cells: Responsible for producing antibodies that bind to specific antigens on pathogens, marking them for destruction.
T Cells: There are several types of T cells, including helper T cells, which activate other immune cells, and cytotoxic T cells, which kill infected cells.
NK Cells: These cells can recognize and destroy infected or cancerous cells without the need for prior activation.
Monocytes: These cells circulate in the blood and migrate into tissues, where they differentiate into macrophages and dendritic cells.
Eosinophils: These cells are involved in combating multicellular parasites and certain infections. They also play a role in allergic reactions.
Basophils: These cells release histamine and other chemicals during allergic reactions and help defend against parasites.
2. Macrophages
Macrophages are large phagocytic cells that are derived from monocytes. They reside in tissues throughout the body and are essential for detecting, engulfing, and destroying pathogens. They also play a crucial role in activating other immune cells by presenting antigens on their surface.

3. Dendritic Cells
Dendritic cells are antigen-presenting cells that capture antigens from pathogens and present them to T cells, initiating an adaptive immune response. They are found in tissues that are in contact with the external environment, such as the skin and mucous membranes.

4. Mast Cells
Mast cells are found in tissues throughout the body and play a key role in allergic reactions. They release histamine and other chemicals that cause inflammation and recruit other immune cells to the site of infection or injury.

Functions of Immune Cells
Each type of immune cell has a specific function in the immune response:

Phagocytosis: Neutrophils and macrophages engulf and digest pathogens.
Antibody Production: B cells produce antibodies that neutralize pathogens or mark them for destruction.
Cell-Mediated Immunity: T cells destroy infected cells and coordinate the immune response.
Allergic Reactions: Eosinophils, basophils, and mast cells release chemicals that cause inflammation and recruit other immune cells.
Coordination and Communication
The immune system relies on a complex network of signals to coordinate it

1. 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

2. 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

3. Neutrophils Major phagocytic granulocyte Contain multilobed nucleus Neutrophilic granules Respond to chemotactic stimuli Activated by macrophage and endothelial derived cytokines Major cell of acute inflammation Primary effector cells in IR to pyogens

4. Neutrophils Have Fc receptors for IgG and c’ Bind and phagocytose opsonised antigens Link between 2 arms of immune system Regulates activation and recruitment of macrophages by cytokines

5. Phagocytosis Principal mechanism of pathogens Enter site of infection Opsonins produced to allow phagocytosis Taken into vacuole Killing by aerobic or anaerobic mechanisms Cytokine induction

6. Eosinophil

7. Eosinophils Contain eosinophilic granules Express Fc receptors for IgE IgE prevalent in parasitic infections IgE mediates activation of eosinophil killing mechanisms Role in immediate hypersensitivity to allergens Cause tissue injury and inflammation

8. Basophils In circulation –basophils In tissue- Mast cells Express Fc receptors for IgE Release chemical mediators of immediate hypersensitivity

9. 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

10. Monocyte

11. Macrophages Main cells of chronic IR Regulators of specific acquired response Fewer numbers than neutrophils Peaks in hours to days Participate in both acute and chronic inflammation Phagocytose apoptotic PMN’s

12. Tissue macrophages Second major class of phagocytic cells Provide innate immunity and initiate host defenses Release inflammatory cytokines Act as APC Link between innate immunity and acquired humoral and cellular immunity

13. Cells of monocyte macrophage system

14. 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

15. 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

16. 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 1 st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA)

17. 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-

18. Lymphocytes Mediate adaptive immune response Recognize antigen specifically Each clone has antigen specificity Arrange V, J and D elements if Ig and T cell receptor genes to form different clones B lymphocytes recognize native Ag T lymphocytes recognize processed Ag

19. Lymphocytes Ag binds to receptor Lymphoid activation and Clonal expansion Effector cells or products all have same specificity as parent cell Inactivation of self reactive clones

20. Lymphocytes Ag independent maturation occurs in primary lymphoid organs Ag dependent occurs in secondary lymphoid organs Cells are indistinguishable morphologically Phenotypically and functionally different

21. B lymphocyte development

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 – MARCH OF 2009 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 – MARCH OF 2009 Laboratory studies Blood CBC with differential Basic metabolic panel (BMP) C-reactive protein (CRP) Culture Sputum Culture Radiology studies

25. CASE STUDY – MARCH OF 2009 Laboratory studies Blood CBC with differential Basic metabolic panel (BMP) C-reactive protein (CRP) Culture Sputum Culture Radiology studies

26. CASE STUDY – MARCH OF 2009 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

27. CASE STUDY – MARCH OF 2009 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

28. 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)

29. 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

30. 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

31. 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

32. 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, Peyer’s patches Pathogens are directly transferred across mucosa by “M” cells

33. 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, Peyer’s patches Pathogens are directly transferred across mucosa by “M” cells

34. THE INNATE IMMUNE RESPONSE Mediated (initiated) by phagocytes, NK cells and soluble proteins Phagocytes Cells specialized in the process of phagocytosis Macrophages Reside in tissues Neutrophils Enter infected tissues in large numbers Recognize common molecules of bacterial cell surface using a few surface receptors Phagocytosis Capture, engulfment and breakdown of bacterial pathogen

35. THE INNATE IMMUNE RESPONSE Inflammatory response enhances phagocytosis through acute phase proteins Mannose-binding lectin (MBL) Binds to bacterial surface with particular spatial arrangement of mannose or fucose C-reactive protein (CRP) Binds to phosphorylcholine on bacterial surface Complement Set of proteins which bind to bacterial surface Inflammatory response Accumulation of fluid and cells at infection site (swelling, redness, heat and pain)

36. THE ADAPTIVE IMMUNE RESPONSE Creates millions of different B and T cells for specific antibody-mediated and cell-mediated immunity Antibody-Mediated Immunity (AMI) Involves B lymphocytes, plasma cells and antibodies Humoral immunity Name derives from antibodies found in body fluids (humors - old medical term) Cell-Mediated Immunity (CMI) Involves T lymphocytes, antigen-presenting cells and MHC (major histocompatibility complex) molecules Cellular immunity

37. ANTIBODY-MEDIATED (HUMORAL) IMMUNITY Directed against extracellular microorganisms and toxins B-lymphocytes (B cells) Differentiate into plasma cells which produce antibodies Function as antigen-presenting cells (APC’s) Classification of Antibodies (Immunoglobulins) Immunoglobulin M (IgM) Immunoglobulin G (IgG) Immunoglobulin A (IgA) Immunoglobulin D (IgD) Immunoglobulin E (IgE)

38. CELL-MEDIATED IMMUNITY (CMI ) Directed against intracellular microorganisms Non-phagocytic cells and phagocytic cells T-lymphocytes (T cells) Differentiate into effector cells following antigen presentation by antigen presenting cells (APC’s) Functional types of T cells Helper (CD4 T cells) TH1 and TH2 cells Cytotoxic (CD8 T cells) Regulatory CD4 and CD8 Tregs

39. THE NATURE OF ANTIGENS Historically named as anti body gen erators Molecule which stimulates production of and binds specifically to an antibody Contemporary view distinguishes between Antigen Molecule which can bind to specific antibody but cannot elicit adaptive immune response Immunogen Molecule which can stimulate adaptive immune response Best immunogens are proteins with MW > 10,000

40. THE NATURE OF ANTIGENS Carbohydrates, nucleic acids and lipids are also potential antigens / immunogens Hapten Small (low MW) molecule unable to elicit immune response Combines with larger carrier molecule which together function as immunogen Antibody may react independently with hapten following hapten/carrier adaptive immune response Example Penicillin G (MW of 372) Albumin (MW of 66,000)

41. THE NATURE OF ANTIBODIES Antibodies are glycoproteins Exist as monomers, dimers or pentamers of basic structure Basic antibody structure has 4 polypeptide chains 2 identical light chains 2 identical heavy chains Regions of heavy and light chains Variable Constant

42. THE NATURE OF ANTIBODIES Also referred to as Immune globulins / Immunoglobulins (IG) Immune serum globulins (ISG) Gamma globulins Contemporary immunology Antibody Secreted form of IG made by plasma cells Immunoglobulin Antigen binding molecules of B cells (B cell antigen receptors)

43. CLASSIFICATION OF ANTIBODIES (IMMUNOGLOBULINS) Five (5) classes (isotypes) Immunoglobulin A (IgA) Immunoglobulin G (IgG) Immunoglobulin M (IgM) Immunoglobulin D (IgD) Immunoglobulin E (IgE) Based on structural differences in constant regions of heavy chains Classes have specialized effector functions

44. B LYMPHOCYTES AND HUMORAL IMMUNITY Originate from stem cells in bone marrow Maturation in bone marrow followed by migration to secondary lymphoid tissue Antigen exposure in secondary lymphoid tissue Following exposure to antigen, differentiation into plasma cells and memory cells Plasma cells produce antibodies of all IG classes

45. ACTIVATION OF ANTIBODY PRODUCING CELLS BY CLONAL SELECTION B lymphocytes recognize intact pathogenic microorganisms and toxins B lymphocytes possess specific surface receptors for recognition of specific antigen IgM and IgD Binding of specific antigen results in proliferation of a clonal population of cells Antigen determines clonal proliferation

46. ACTIVATION OF ANTIBODY PROCDUCING CELLS BY CLONAL SELECTION Proliferation of activated cells is followed by differentiation into Plasma cells Life span of 4 to 5 days 1 to 2 months Produce 2,000 antibody molecules / second Memory cells Life span of years to decades Differentiate into plasma cells following stimulation by same antigen

47. PRIMARY AND SECONDARY ANTIBODY RESPONSE Primary Response Following exposure to an antigen, there is a slow rise in IgM followed by a slow rise in IgG Secondary Response Following exposure to previously encountered antigen, there is a rapid rise in IgG and slow or no rise in IgM Memory or anamnestic response

48. T LYMPHOCYTES AND CELL-MEDIATED IMMUNITY Originate from stem cells in bone marrow followed by migration to thymus gland Maturation takes place in thymus gland followed by migration to secondary lymphoid tissue Respond to antigens on the surface of antigen presenting cells (APC’s) Antigen presenting cells (APC’s) Macrophages Dendritic cells B lymphocytes

49. T LYMPHOCYTES AND CELL-MEDIATED IMMUNITY Antigen presenting cells (APC’s) Ingest and process antigens then display fragments (short peptides) on their surface in association with molecules of major histocompatibility complex (MHC) Major histocompatibility (MHC) molecules MHC class I molecules Present antigens to CD8 T cells MHC class II molecules Present antigens to CD4 T cells T cells which encounter antigen differentiate into effector T cells

50. ROLES OF EFFECTOR T CELLS IN IMMUNE RESPONSE CD8 cytotoxic T cells Enter bloodstream and travel to infection site Kill cells infected with viruses and other intracellular microorganisms CD4 TH1 helper T cells Enter blood stream and travel to infection site Help activate macrophages CD4 TH2 helper T cells Work within secondary lymphoid tissues Help activate B cells

51. DISORDERS OF THE IMMUNE SYSTEM Hypersensitivity Reactions Over-reaction of adaptive immune response to harmless antigens Four Types of reactions (I- IV) Autoimmunity Misdirected adaptive immune response Results from a loss of self-tolerance Three Types (II, III, IV) of reactions Immunodeficiencies Components of immune system either absent or defective Genetic or acquired etiology

52. IMMUNOLOGY FOR DIAGNOSIS OF DISEASES Analytical methods using either antibody or antigen with an indicator system for detecting specific Antibodies Detected using antigens or antibody Antigens Detected using antibody Indicator systems Latex particles (colored) Microspheres (colored) conjugated with antibody Enzymes conjugated to antibody Fluorochromes conjugated to antibody Nitrocellulose membranes fixed with antigen or antibody

53. METHODS IN DIAGNOSTIC IMMUNOLOGY Latex agglutination (LA) Latex particles (dyed) coated with antigen, antibody or? Read visually for clumping of latex particles Staphyloslide (Becton Dickinson) Identification of Staphylococcus aureus Staphylococcus aureus produces Coagulase (bound and free) Protein A Blue latex particles coated and not coated with Fibrinogen IgG

54. METHODS IN DIAGNOSTIC IMMUNOLOGY Immunochromatographic assay (ICA) Antibody or antigen immobilized (Test line) Antibody immobilized (Control line) Membranes Nitrocellulose, cellulose acetate Read visually for colored test and control lines Examples Group A Streptococcus (GAS) antigen Influenza A and B antigens Respiratory syncytial virus (RSV) antigen Rotavirus antigen HIV-1/2 antibody

55. PRINCIPLES OF OraQuick RAPID HIV-1/2 ICA ANTIBODY TEST Antigens and antibody immobilized onto nitrocellulose membrane in T and C zones Test (T) Zone Synthetic peptides from HIV envelope region Control (C) Zone Goat anti-human IgG Developer solution Facilitates flow of specimen onto test strip Rehydrates protein-A gold colorimetric reagent

56. IMMUNOLOGY FOR PREVENTION OF DISEASE Hepatitis B Pre-exposure prophylaxis Vaccination with hepatitis B surface antigen (HBsAg) Post-exposure prophylaxis Administration of Hepatitis B Immune Globulin (HBIG) Human Purified IgG antibody from plasma of donors with high titer of antibody to the hepatitis B surface antigen (anti-HBs)

57. IMMUNOLOGY FOR TREATMENT OF DISEASE Rheumatoid Arthritis Remicade (Infliximab) IgG kappa monoclonal antibody against tumor necrosis factor – alpha (TNF-alpha) Breast Cancer Herceptin (Trastuzumab) IgG kappa monoclonal antibody against human epidermal growth factor receptor 2 (HER2)