LECOM-Pharmacy School Immunology 01 Overview of the Immune System Dr. Saber Hussein
Reading & Goal <ul><li>Read Chapter 1, Abbas & Lichtman:  Basic Immunology functions and Disorders of the Immune System ; ...
Why immunology for pharmacists? <ul><li>Pharmacists as healthcare providers must understand the human body and what keeps ...
Overview of the Immune System <ul><li>Innate immunity </li></ul><ul><li>Adaptive immunity:  </li></ul><ul><ul><li>Humoral ...
Learning Objectives <ul><li>1. Know the protective role of the immune system </li></ul><ul><li>2. Differentiate between th...
Protective role of the immune system <ul><li>Immune system evolved to protect us against: </li></ul><ul><ul><li>Intra- and...
Innate Immunity <ul><li>Synonyms: </li></ul><ul><ul><li>Natural  </li></ul></ul><ul><ul><li>None-adaptive </li></ul></ul><...
Exterior Innate Defenses
Adaptive (Acquired) Immunity <ul><li>Develops  in response  to microorganisms and other  foreign antigens  (Ags) </li></ul...
Antibody: A flexible adaptor <ul><li>Abs specific binding sites of the  Fab  region bind  Ag s </li></ul><ul><ul><li>As wi...
Phases of the Immune Response <ul><li>Recognition  of Ag: </li></ul><ul><ul><li>Naïve B lymphocytes recognize certain type...
 
Active & Passive Immunization <ul><li>Active  immunization   </li></ul><ul><ul><li>is acquired in response to Ag administr...
Self and Nonself <ul><li>Discrimination between self and nonself Ags is fundamental for the function and evolution of the ...
Humoral and Cell-mediated Immunity <ul><li>Acquired humoral  (soluble) immunity is based on  Abs  made by B cells </li></u...
Complement Functions <ul><li>Complement is a system of  serum proteins  that interact with one another and with other mole...
Cells of the Immune System <ul><li>Lymphocytes </li></ul><ul><ul><li>T helper cells (T H )  </li></ul></ul><ul><ul><li>Cyt...
Cells involved in the immune response Hematopoiesis
Functions of Lymphocytes NK (  )
Major histocompatibility complex (MHC) <ul><li>MHC is called  HLA  or  human lymphocytes Ag </li></ul><ul><li>Two classes:...
Cytokines <ul><li>Small peptides , synthesized by different cells involved in the immune system </li></ul><ul><li>They are...
Clonal Selection Theory <ul><li>T and B cells exist with  almost unlimited  specificities  before  any contact with foreig...
Clonal Selection Epitopes 2, 103, 821 No specialized  receptor Epitopes 2, 103, 821
Benefits of the Immune System <ul><li>Immunization and defense against infectious disease </li></ul><ul><li>Cancer detecti...
Harmful Effects of the Immune System <ul><li>Hypersensitivity or allergic reactions: </li></ul><ul><ul><li>Type I, immedia...
Genetic Recombination & Immune Response Diversity <ul><li>10 6 -10 7  of antigenic specificities might exist </li></ul><ul...
Regulation of the immune system <ul><li>Why regulation? </li></ul><ul><li>Immune response    proliferation and increased ...
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Immuno1 overview

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  • immune - modulating therapies ( drugs which adjust the activity of the immune response to a desired level), interferon beta-1b (Betaferon)
  • Monocyte A relatively large mononuclear leukocyte (16–22 4m in diameter), that normally constitutes 3–7% of the leukocytes of the circulating blood, and is normally found in lymph nodes, spleen, bone marrow, and loose connective tissue. When treated with the usual dyes, monocytes manifest an abundant pale blue or blue-gray cytoplasm that contains numerous, fine, dustlike, red-blue granules; vacuoles are frequently present; the nucleus is usually indented, or slightly folded, and has a stringy chromatin structure that seems more condensed where the delicate strands are in contact. See Also: monocytoid cell, endothelial leukocyte. Origin [mono- + G. kytos, cell]
  • This slide shows some features of the structure and functions of the Ab
  • Apoptosis: Programmed cell death; deletion of individual cells by fragmentation into membrane-bound particles, which are phagocytosed by other cells. Whereas some cells (e.g., cardiac and skeletal muscle fibers, CNS neurons) last a lifetime, others (e.g., epithelial and glandular cells, erythrocytes) have limited life-spans, at the end of which they are genetically programmed to self-destruct, usually to be replaced by others formed by mitosis from surviving cells. Cells in tissue cultures spontaneously undergo apoptosis after about 50 cell divisions . In contrast to cell death caused by injury, infection, or circulatory impairment, apoptosis elicits no inflammatory response in adjacent cells and tissues . Features of apoptosis detectable by histological and histochemical methods include cell shrinkage , due chiefly to dehydration; increased membrane permeability , with a rise in intracellular calcium and a fall in pH ; endonucleolysis (fragmentation of nuclear DNA); and ultimately formation of apoptotic bodies , which are absorbed and removed by macrophages . Besides being due to genetic programming, apoptosis can be induced by injury to cellular DNA, as by irradiation and some cytotoxic agents used to treat cancer. It can be suppressed by naturally occurring factors (e.g., cytokines) and by some drugs (e.g., protease inhibitors). Apoptosis typically does not occur in malignant cells. Such cells therefore escape the destiny of their nonmalignant precursor cells and are said to be immortal. Immortalization can occur in various ways. The bcl-2 gene, present in many cancers, directs the production of an enzyme that blocks apoptosis and immortalizes affected cells. Injury to DNA normally triggers apoptosis by activating the p53 tumor suppressor gene, which is missing or mutated in about one-half of all human cancers. Cells that lack this gene can survive chemotherapy and irradiation intended to destroy cancer cells. Failure of apoptosis to occur is also involved in some degenerative diseases, including lupus erythematosus, and may be responsible for cellular damage caused by certain viruses, including HIV. Origin [G. a falling or dropping off, fr. apo, off, + ptosis, a falling]
  • Clonal expansion- expansion means become more or grow larger; expand your wealth from $1000 to $1 million. clonal means here a clone is expanded; a clone of B or T cells, namely the clone that recognized the Ag
  • Not based on beneficial or harmful antigen
  • These reactions may be triggered by the intrinsic ability of the complement system to recognize microbial components or by Abs bound to the microorganism Ehrlich term for the thermolabile substance, normally present in serum, that is destructive to certain bacteria and other cells sensitized by a specific complement-fixing antibody. Complement is a group of at least 20 distinct serum proteins, the activity of which is affected by a series of interactions resulting in enzymatic cleavages and which can follow one or the other of at least two pathways. In the case of immune hemolysis (classical pathway), the complex comprises nine components (designated C1 through C9) that react in a definite sequence and the activation of which is usually effected by the antigen-antibody complex; only the first seven components are involved in chemotaxis, and only the first four are involved in immune adherence or phagocytosis or are fixed by conglutinins. An alternative pathway (see properdin system) may be activated by factors other than antigen-antibody complexes and involves components other than C1, C4, and C2 in the activation of C3. See Also: component of complement. Origin [L. complementum, that which completes, fr. com-pleo, to fill up] complement pathways heparin complement
  • Fig 2-1 Cells involved in the immune response
  • LGL =large granulocyte
  • Uncommitted cells have no specialized receptor Committed B cells possess a specific receptor that recognizes one and only one EPITOPE of an antigen
  • Immuno1 overview

    1. 1. LECOM-Pharmacy School Immunology 01 Overview of the Immune System Dr. Saber Hussein
    2. 2. Reading & Goal <ul><li>Read Chapter 1, Abbas & Lichtman: Basic Immunology functions and Disorders of the Immune System ; Saunders, 2 nd Editions 2004 </li></ul><ul><ul><li>If you have1 st Edition 2001 that is o.k. </li></ul></ul><ul><li>Or Chapter 1, Immunology A Short Course, Benjamini et al </li></ul><ul><li>The goal of this lecture is to introduce to you some of the subjects studied under the umbrella of Immunology. It is not meant to teach you the whole Immunology in one hour </li></ul>
    3. 3. Why immunology for pharmacists? <ul><li>Pharmacists as healthcare providers must understand the human body and what keeps it healthy and what causes its disease </li></ul><ul><li>Pharmacists might provide vaccines. Therefore you must know how immunization works </li></ul><ul><li>Immunology helps understand mechanisms of action of some drugs such as: </li></ul><ul><ul><li>monoclonal antibodies </li></ul></ul><ul><ul><li>cytokine analogs or antagonists </li></ul></ul><ul><ul><li>immunosuppressants </li></ul></ul><ul><ul><li>immune modulating drugs </li></ul></ul>
    4. 4. Overview of the Immune System <ul><li>Innate immunity </li></ul><ul><li>Adaptive immunity: </li></ul><ul><ul><li>Humoral and </li></ul></ul><ul><ul><li>cell-mediated immunity </li></ul></ul><ul><li>Properties of adaptive immunity: </li></ul><ul><ul><li>Specificity and </li></ul></ul><ul><ul><li>memory </li></ul></ul><ul><li>Phases of the immune response </li></ul><ul><li>Cells of the immune system: Lymphocytes, antigen-presenting cells, effector cells </li></ul><ul><li>Tissues and organs of the immune system: Peripheral lymphoid organs, lymphocyte circulation </li></ul>
    5. 5. Learning Objectives <ul><li>1. Know the protective role of the immune system </li></ul><ul><li>2. Differentiate between the adaptive (acquired) and the innate immunity </li></ul><ul><li>3. Know the fundamental role of the discrimination between self and nonself in the work of the immune system </li></ul><ul><li>4. Know the major branches of the immune system: the humoral and the cell-mediated immune response </li></ul><ul><li>5. Have an idea about the benefits and the harmful effects of the immune system </li></ul><ul><li>6. Recognize genetic recombination as a basis of the diversity of the immune response </li></ul><ul><li>7. Know that the immune system is usually regulated up and down </li></ul>
    6. 6. Protective role of the immune system <ul><li>Immune system evolved to protect us against: </li></ul><ul><ul><li>Intra- and extracellular bacterial infections </li></ul></ul><ul><ul><li>Viral infections : Always intracellular </li></ul></ul><ul><ul><li>Fungal infections : Extracellular </li></ul></ul><ul><ul><li>Parasitic infestation : Some unicellular protozoa such as malarial parasites, Plasmodium species, are intracellular but most are large, extracellular and even lumen dweller </li></ul></ul><ul><ul><li>Malignant cells </li></ul></ul><ul><li>Intracellular pathogens live inside host’s (patient’s) cells </li></ul><ul><li>Extracellular pathogens live outside host’s cells </li></ul>
    7. 7. Innate Immunity <ul><li>Synonyms: </li></ul><ul><ul><li>Natural </li></ul></ul><ul><ul><li>None-adaptive </li></ul></ul><ul><ul><li>Nonspecific </li></ul></ul><ul><li>Cells involved: </li></ul><ul><ul><li>All white blood cells except B and T lymphocytes </li></ul></ul><ul><ul><li>Phagocytes </li></ul></ul><ul><ul><ul><li>Monocytes (mono[ nuclear leuko ]cytes)/macrophages </li></ul></ul></ul><ul><ul><ul><li>PMN (polymorphonuclear) neutrophils </li></ul></ul></ul><ul><ul><li>Natural killer (NK) cells </li></ul></ul><ul><li>Humoral or soluble components </li></ul><ul><ul><li>Complement system </li></ul></ul><ul><li>Exterior defenses </li></ul><ul><ul><li>Skin, Stomach acidity, Mucus, Cilia, Microflora, Lysozyme in tears, Flushing of urinary tract by urination </li></ul></ul>
    8. 8. Exterior Innate Defenses
    9. 9. Adaptive (Acquired) Immunity <ul><li>Develops in response to microorganisms and other foreign antigens (Ags) </li></ul><ul><li>Anamnesis </li></ul><ul><ul><li>Improves after each encounter with the Ag  has a memory </li></ul></ul><ul><li>Antibodies (Abs) = Immunoglobulins (Ig): </li></ul><ul><ul><li>IgA, IgG, IgM, IgE, IgD </li></ul></ul><ul><li>Lymphocytes : </li></ul><ul><ul><li>B cells </li></ul></ul><ul><ul><li>T cells </li></ul></ul>
    10. 10. Antibody: A flexible adaptor <ul><li>Abs specific binding sites of the Fab region bind Ag s </li></ul><ul><ul><li>As with microbe 1 </li></ul></ul><ul><li>No specific Ag  No binding </li></ul><ul><ul><li>As with microbe 2 </li></ul></ul><ul><li>The Fc region of the Ab binds Fc receptors on some cells such as phagocytes </li></ul><ul><li>The Ag-Ab complex can activate the complement system via the Fc of the Ab </li></ul>L chain H chain Papain V C Ag
    11. 11. Phases of the Immune Response <ul><li>Recognition of Ag: </li></ul><ul><ul><li>Naïve B lymphocytes recognize certain types of Ags </li></ul></ul><ul><ul><li>Naïve T lymphocytes recognize peptides presented by Ag presenting cells (APC) </li></ul></ul><ul><ul><li>Clonal expansion </li></ul></ul><ul><li>Activation phase </li></ul><ul><ul><li>Differentiation: </li></ul></ul><ul><ul><ul><li>B cell  Ab producing cell </li></ul></ul></ul><ul><ul><ul><li>T cell  Effector T cell </li></ul></ul></ul><ul><li>Effector phase </li></ul><ul><ul><li>Elimination of Ags by: </li></ul></ul><ul><ul><ul><li>Humoral immunity </li></ul></ul></ul><ul><ul><ul><li>Cell-mediated immunity </li></ul></ul></ul><ul><li>Decline (homeostasis)  Apoptosis </li></ul><ul><li>Memory  Surviving memory cells </li></ul>
    12. 13. Active & Passive Immunization <ul><li>Active immunization </li></ul><ul><ul><li>is acquired in response to Ag administration </li></ul></ul><ul><ul><ul><li>All vaccinations </li></ul></ul></ul><ul><li>Passive immunization </li></ul><ul><ul><li>acquired through administration of Ab from immunized individual </li></ul></ul><ul><ul><ul><li>Hepatitis A </li></ul></ul></ul><ul><ul><ul><li>Anti-rabies treatment </li></ul></ul></ul><ul><ul><ul><li>Anti-tetanus </li></ul></ul></ul><ul><li>Adoptive transfer : </li></ul><ul><ul><li>Transfer of immunity by transplantation of immunocompetent cells </li></ul></ul><ul><ul><ul><li>E.g. bone marrow transplant </li></ul></ul></ul>
    13. 14. Self and Nonself <ul><li>Discrimination between self and nonself Ags is fundamental for the function and evolution of the immune system </li></ul><ul><li>This is the basis of immune response against pathogens and transplant rejection </li></ul><ul><li>Self fanaticism </li></ul><ul><ul><li>Reacting against foreign Ag because it is foreign </li></ul></ul><ul><ul><li>Not based on beneficial or harmful Ag </li></ul></ul>
    14. 15. Humoral and Cell-mediated Immunity <ul><li>Acquired humoral (soluble) immunity is based on Abs made by B cells </li></ul><ul><li>Complement and cytokines may be considered part of the humoral immunity </li></ul><ul><li>Acquired cell-mediated immunity depends on T helper cells (T H ) and cytotoxic T cells (Tc), or cytolytic T lymphocytes (CTLs) </li></ul><ul><li>Other leukocytes are part of the cellular immunity, including: </li></ul><ul><ul><li>Phagocytes, </li></ul></ul><ul><ul><li>macrophages, </li></ul></ul><ul><ul><li>natural killer cells (NK) </li></ul></ul>
    15. 16. Complement Functions <ul><li>Complement is a system of serum proteins that interact with one another and with other molecules to generate important effects </li></ul><ul><li>Lysis </li></ul><ul><ul><li>The complement system has an intrinsic ability to lyse the cell membranes of many bacterial species </li></ul></ul><ul><li>Chemotaxis </li></ul><ul><ul><li>Complement products released in this reaction attract phagocytes to the site of the reaction </li></ul></ul><ul><li>Opsonization </li></ul><ul><ul><li>Complement components coat the bacterial surface allowing the phagocytes to recognize the bacteria and engulf them </li></ul></ul>
    16. 17. Cells of the Immune System <ul><li>Lymphocytes </li></ul><ul><ul><li>T helper cells (T H ) </li></ul></ul><ul><ul><li>Cytotoxic T cells (Tc) </li></ul></ul><ul><ul><li>B cells </li></ul></ul><ul><ul><li>NK </li></ul></ul><ul><li>PMNs </li></ul><ul><ul><li>Neutrophil </li></ul></ul><ul><ul><li>Basophil & Mast cells </li></ul></ul><ul><ul><li>Eosinophil </li></ul></ul><ul><li>Monocytes </li></ul><ul><ul><li>Dendritic cells </li></ul></ul><ul><ul><li>Macrophages </li></ul></ul>
    17. 18. Cells involved in the immune response Hematopoiesis
    18. 19. Functions of Lymphocytes NK ( )
    19. 20. Major histocompatibility complex (MHC) <ul><li>MHC is called HLA or human lymphocytes Ag </li></ul><ul><li>Two classes: I & II </li></ul><ul><li>Important in presenting Ags to the T H and T C cells </li></ul><ul><ul><li>MHC I presents Ag peptides to T C </li></ul></ul><ul><ul><li>MHC II presents Ag peptides to T H </li></ul></ul>
    20. 21. Cytokines <ul><li>Small peptides , synthesized by different cells involved in the immune system </li></ul><ul><li>They are regulators : activate cells or inhibit cell functions </li></ul><ul><li>Major means of communication among cells of the immune system and between them and others </li></ul><ul><li>Examples: </li></ul><ul><ul><li>Interleukins </li></ul></ul><ul><ul><ul><li>IL-2 </li></ul></ul></ul><ul><ul><ul><li>IL-4 </li></ul></ul></ul><ul><ul><li>Interferons </li></ul></ul><ul><ul><ul><li>IFN α </li></ul></ul></ul><ul><ul><ul><li>IFN γ </li></ul></ul></ul>
    21. 22. Clonal Selection Theory <ul><li>T and B cells exist with almost unlimited specificities before any contact with foreign Ags </li></ul><ul><li>Ag-specific receptors that recognize foreign Ags: </li></ul><ul><ul><li>Abs are the B cell receptors on the surface of B cell & </li></ul></ul><ul><ul><li>T-cell receptor ( TCR ) on T cell </li></ul></ul><ul><li>Each lymphocyte has a single specificity </li></ul><ul><li>The antigenic determinant ( epitope ) on the Ag binds with lymphocyte (B or T) and triggers their differentiation and proliferation </li></ul><ul><li>Negative selection by self Ags  shut off cells that recognize them during maturation </li></ul>
    22. 23. Clonal Selection Epitopes 2, 103, 821 No specialized receptor Epitopes 2, 103, 821
    23. 24. Benefits of the Immune System <ul><li>Immunization and defense against infectious disease </li></ul><ul><li>Cancer detection and management </li></ul><ul><li>A benefit of immunology (application): </li></ul><ul><ul><li>Organ transplantation and blood transfusion </li></ul></ul>
    24. 25. Harmful Effects of the Immune System <ul><li>Hypersensitivity or allergic reactions: </li></ul><ul><ul><li>Type I, immediate hypersensitivity </li></ul></ul><ul><ul><li>Type II, cytotoxic Ab-mediated reactions </li></ul></ul><ul><ul><li>Type III,immune complex Ab-mediated </li></ul></ul><ul><ul><li>Type IV, delayed-type cell-mediated </li></ul></ul><ul><li>Autoimmune diseases </li></ul><ul><ul><li>The immune system attacks body’s own Ags causing diseases like rheumatoid arthritis, diabetes mellitus and systemic lupus erythematosus </li></ul></ul><ul><li>Immunodeficiencies </li></ul><ul><ul><li>Occur when one or more components of the immune system fail to function properly </li></ul></ul><ul><ul><li>This can be result of genetic defect (SCID) or acquired (AIDS) </li></ul></ul><ul><li>Graft rejection </li></ul><ul><ul><li>Occurs because of immune response against transplant’s Ags </li></ul></ul>
    25. 26. Genetic Recombination & Immune Response Diversity <ul><li>10 6 -10 7 of antigenic specificities might exist </li></ul><ul><li>If 1 gene = 1 response, are 10 7 genes needed? </li></ul><ul><ul><li>No </li></ul></ul><ul><li>Genetic recombination “within “ a gene that encodes the Ig proteins is the answer </li></ul><ul><li>So, the basic Ab is composed of 2 types of polypeptides : H-chain , L-chain and each chain has a variable domain </li></ul><ul><li>This mechanism generates Ab & T cell receptor (TCR) specificity </li></ul>
    26. 27. Regulation of the immune system <ul><li>Why regulation? </li></ul><ul><li>Immune response  proliferation and increased synthesis of specific molecules that will not be useful after their job is finished (infection  response  cure) </li></ul><ul><li>Homeostasis or equilibrium must be established by shutting down the system </li></ul><ul><li>Deregulation of the immune system has severe consequences </li></ul><ul><li>Immune response to self Ags  Autoimmunity </li></ul>

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