Fundamentals of Immunology for Pharmacy students

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  • Difficult to purify them since they r produced locally by cells at very low conc.
  • Mother to feotus- IgG cross placenta
  • Fundamentals of Immunology for Pharmacy students

    1. 1. Miss Pradnya P Wadekar Assistant Professor ABCP, Sangli Shivaji University, Kolhapur (MS) India
    2. 2.  Definitions-pathogen, virulence, attenuation, exaltation, antigens, antibodies and antisera.  Defense mechanisms of host –  non-specific (skin and mucous membranes, phagocytosis, complement system, inflammation, host damage with exotoxins and endotoxins) .  specific defense mechanisms - cellular immunity - humoral immunity  Immunity - types of immunity (natural, naturally acquired, acquired (active and passive)  Types and Structure of immunoglobulins P P Wadekar, ABCP Sangli
    3. 3.  Pathogen: (Greek: Pathos- suffering and gen- produce) disease producing.  Pathogenecity: the capability to cause disease.  Virulence: degree of pathogenecity  Attenuation: decrease in virulence  Exaltation: increase in virulence  Antigens: any substance which when introduced in host stimulate production of antibodies and react with preformed antibodies if they are already present.  Antibodies: are the immunoglobulins produced by animal in response to introduction of antigen P P Wadekar, ABCP Sangli
    4. 4.  Antiserum: a blood serum containing antibodies  Immunity: resistance offered by the host to the harmful effects of pathogenic microbial infection.  Susceptibility: lack of power of body to resist the infection  Immunology: study of immunity  Immunological preparations: preparations used to produce immunity P P Wadekar, ABCP Sangli
    5. 5. Defence mechanism of host Natural resistance ( constitutive/ innate) defence mechanism Species racial Individual External defence Internal defence mechanism Non specific Specific P P Wadekar, ABCP Sangli
    6. 6. P P Wadekar, ABCP Sangli
    7. 7.  Non specific defence mechanism  Phagocytosis  Natural killer cells  Interferons  Inflammatory response  Fever  Complement system P P Wadekar, ABCP Sangli
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    9. 9.  Adherence is stimulated by cations (Ca++ & Mg+) and electrostatic forces  Opsonin fixed attachment  Formation of pseudopods  Pseudopods fuse to form vacule i.e. phagosome.  Lysosome granules move towards phagosome and fuse to form phagolysozome  In phagolysomes, bacteria are killed in minuts and complete degradation takes place in hours. P P Wadekar, ABCP Sangli
    10. 10.  Major method of killing bacteria is respiratory burst  It is associated with generation of highly toxic oxygen species like superoxide, singlet oxygen, hydrogen peroxide, hydroxyl radical also chloramines and aldehydes.  It also involves peroxidase ( in neutrophiles) and catalse ( in basophiles)  The lysosome granules contain 60 enzymes- lysoszymes, lipases, ribonuclease, etc.  The combined action of respiratory burst and lysosome granules kill bacteira  Gram +ve are rapidly killed, gram –ve are more persistant while some like Mycobacterium are resistant and can actually multiply inside phagocyte P P Wadekar, ABCP Sangli
    11. 11.  Also called as “Null cells” since they don’t posses certain surface antigen  They can kill cellular target without prior exposure to anigen of target cell  Thus they can kill cancer cells and virus infected cells without ingesting them.  The exact mechanism is still unknown. P P Wadekar, ABCP Sangli
    12. 12.  Are small proteins produced by eukaryotic cells in response to viral infection and double stranded RNA.  3 types- α IFN, βIFN, γIFN  Don’t react directly with virion  Induce host cell to synthesize nonspecific antiviral protein.  These are species specific.  Purified Interferons are stable at low ph and fairly heat resistant, but unstable at physiological conditions.  Resist viral infections, inhibits cell proliferation, promot cytotoxic activity of the NK P P Wadekar, ABCP Sangli
    13. 13.  Complement “C” refers to a system of factors which occur in normal serum and are activated characteristically by Ag-Ab interaction and subsequently mediate a number of bilogically significant consequences. P P Wadekar, ABCP Sangli
    14. 14.  Consists of 11 proteins- C1 to C9 ( C1 is made of 3 sunits C1q, C1r & C1s) Site of synthesis Complement protein Intestinal epithelium C1 Macrophages C2, C4 Spleen C5, C8 liver C3, C6, C9 P P Wadekar, ABCP Sangli
    15. 15. Activity Complement component Lysis of virus, virus infected cell, tumor cells, protozoa & bacteria C1-C9 Endotoxin activation C1-C5 Virus neutralization C1, C4, C2, C3 Anaphylotoxin release Opsonization, enhancement of cell mediated cytotoxicity, stimulation of production of β cell lymphocytes C3b Enhanced induction of Ab formation C3b, C3d Chemotaxis of neutrophils, eosinophils, monocytes C5a P P Wadekar, ABCP Sangli
    16. 16.  Normally is in inactivated state but enzyme cascade- preceeding component acts as enzyme on proceding components cleaving them into dissimilar fragments.  Larger framgents join the cascade while the small ones contribute the defence mechanism by initiating the inflammatory response, increasing vascular permiability, inducing smooth muscle contraction , causing destruction of parasite, virus neutralization and detoxification of endotoxins P P Wadekar, ABCP Sangli
    17. 17.  Properties of complement-  Present in sera of animals, birds, fish  Non specific serological agent  Doesn’t increase the immunization  Does’nt bind to free Ag/Ab  Destroyed at 56C in 30 min  IgM, IgG1, IgG2, IgG3 react with complent  Classical pathway- 9 proteins  Alternate ptahway- 13 proteins  Activation of Ag-Ab complex P P Wadekar, ABCP Sangli
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    22. 22.  Biological effects of complement-  Causes bacteriolysis and cytolysis  Complement fragments released during cascade reaction amplifies inflammatory response.  Participates in type II & type III hypersensitivity reaction  Lowered complement concentration on autoimmune diseases  C3 &C6 help in coagulation  C bound to Ag-Ab complex adhere to erythrocyte phagocytosis P P Wadekar, ABCP Sangli
    23. 23.  Is due to tissue injury, irritation initiated by entry of mos or of other irritants  Arteriols at the site constrict first and then dialate increased blood flow at the site.  Blood flow slows down increased amount of leucocytes neutrophils get attracted by chemotactic substances released at the site escape into tissue phagocytosis. Inflammatory response P P Wadekar, ABCP Sangli
    24. 24.  Rise in temperature following infection if natural defense mechanism  Kills/ inhibits mos  Also stimulate production of INFs P P Wadekar, ABCP Sangli
    25. 25.  The immunity developed by the individual during his life time is known as acquired immunity  It is by virtue of production of specific proteins i.e. Ab against Ag P P Wadekar, ABCP Sangli
    26. 26. P P Wadekar, ABCP Sangli
    27. 27. Activity immunity Passive imnunity Ag containing preparation stimulates activity Ab containing preparation gives passive immunity Patient produces Ab Patient receives Ab Immunity develops slowly Immunity develops quickly Long lasting Temporary effect Used for prevention of disease (prophylaxis) Used for short term prophylaxis and therapeutically Not applicable in immunodeficient host Appplicable in immunodeficient host Negative phase may occur No negative phase Immunological memory present No immunological memory Cell mediated and humoral immunity is involved Exclusive humoral immunity is involved No inheritance of immunity May be acquired from motherP P Wadekar, ABCP Sangli
    28. 28.  Local immunity: has importance in infections which are either localised or where it is operative in combating infection at the site of primary entry of the pathogen.  Eg- poliomyelitis, parentral vaccine systemic immunity (Ab neutralise virus when it is in blood); but cant prevent proliferation of virus at entry ie gut mucosa. Hence live oral vaccine local immunity.  Eg- live influenza virus administered intranasally provides local immunity  Herd immunity: over all level of immunity in country.  It is relevant to control epidemic disease. P P Wadekar, ABCP Sangli
    29. 29.  Is due to lymphocytes.  Are found in high concentration in lymph nodes, spleen, and at the site where they are processed and manufactured i.e. bone marrow and thymus. P P Wadekar, ABCP Sangli
    30. 30. Lymphoid organs Primary/ central organs Thymus & bone marrow Secondary/ peripheral organs Lymph nodes, spleen, adenoids, tonsils, appendix, etcP P Wadekar, ABCP Sangli
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    35. 35.  Resistance against most extracellular bacterial pathogen and viruses that attack respiratory and intestinal tract.  B cells have Ab receptors which they are capable of producing  B cell is destined to produce only one Ab though it can produce more than one class of Ab.  B cell must receive a signal form interacting cell (T cell/ macrophage)in order to stimulate proliferation and differentiation.  A plasma cell secrets Ab and die after the function has been served by it.  A mature plasma cell can produce an unique class and subclass Ig. P P Wadekar, ABCP Sangli
    36. 36.  Ab response to stimulation by Ag can be described as Primary response and secondary response 5-10 days P P Wadekar, ABCP Sangli
    37. 37.  Negative phase is seen  Memory/ booster/ anamnestic response  Fisrt does is called priming dose, subsequent dose is called booster dose P P Wadekar, ABCP Sangli
    38. 38. Priming dose Booster dose •Priming dose and booster dose are imp in case of killed vaccines •For live vaccines, single dose is sufficient as proliferation of mos inside body provide continous stimulus that acts as both priming and booster dose P P Wadekar, ABCP Sangli
    39. 39.  Involves T lymphocytes and macrophages  Protects against fungi, viruses and intracellular bacterial pathogens, intracellular parasites, rejecction of foreign tissues grafts, delayed hypersensitivity and resistance to some cancers  Response starts with sensitization/ activation of T cells against Ag activated T cells undergo prliferation release lymphokines cytotoxicity and trigger phagocytosis by macrophages. P P Wadekar, ABCP Sangli
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    42. 42.  It is Y shaped, comprising of 4 polypeptide chains  2 light chains (20000-25000 D & 213/214 amino acid residues) and 2 heavy chains(50000-70000 D & 446 amino acid residues)  Upon reduction and acidification Ab can yield 2 identical fragments each with Ag binding fragment ie Fab & one fragment which lacks ability of binding with Ag ie crystallizable fragment ie Fc which has other properties like complement fixation, placental tranfer, skin fixaton and secretion of body fluids. P P Wadekar, ABCP Sangli
    43. 43.  Ag binding site is at its amino terminus while Fc fragment of H chain has carboxy terminus  Fd piece= protion of H chain present in Fab  Variable (V) region and constant (C) region  Amino acid sequence of varible differs from that of C region  Structure is flexible because of hinge region, so might be T shaped when not binding to Ab  Polypeptide chains are folded and held together by disulphide bonds P P Wadekar, ABCP Sangli
    44. 44.  Compact globular regions formed due to folding are called domains  L chain has only 2 domains- VL and CL  H chain has 4 domians- VH and 3 Ch (CH1, CH2, CH3)  The portion between Ch1 and CH2 is hinge region P P Wadekar, ABCP Sangli
    45. 45.  5 classes- IgG, IgM, IgA, IgD and IgE P P Wadekar, ABCP Sangli
    46. 46.  Major serum Ig constituting about 80% of total Ig  Is the only Ig traported across placenta  Participates in most of the immunological reactions like complement fixation, precipitation and neutralization of toxins and viruses  4 subclasses- Subclass % IgG1 70 IgG2 19 IgG3 8 IgG4 3 P P Wadekar, ABCP Sangli
    47. 47.  Second most aboundant class, 10-13% of total serum Ig  Major Ig present in tears, saliva, seminal fliud, urine and colostrum  IgA is subclassified as IgA1 and IgA2 P P Wadekar, ABCP Sangli
    48. 48.  Is monomeric molecule but in mucosal surface and secretions is dimer formed by 2 monomers joined together by J (joining) chain.  This called secretary IgA (SIgA)  SIgA contains glycerin rich polypeptide called secretary component or secretary piece  secretary piece is believed to protect IgA from denaturation by bacterial protease  SIgA is relatively resistant to digestive enzymes and reducing agents P P Wadekar, ABCP Sangli
    49. 49.  Molecular wieght-9,00,000 D  Pentameric Ig protein  5 monomeric units are held together by disulphide bonds anf J chian that connects H chains  It is synthesized in early immune response  It has short half life  It binds to complement, is acitve in agglutination and opsonization P P Wadekar, ABCP Sangli
    50. 50.  Molecular wieght1,80,000 constitute 1% of tatal serum Ig  It is present on surface of B lymphocyte which differentiate in to Ab secreting plasma cells  It is chiefly produced in lining of respirator and intestinaly tracts  It is present in extreamly low concentratioon in serum  It mediates Prausnitz-Kustner reaction  In involved in protection against pathogen by mast cell degranulation and release of inflammatory mediators P P Wadekar, ABCP Sangli
    51. 51.  Ag-Ab reaction in vitro are known as serological reaction  characteristics of Ag-Ab reactions:  Reaction is highly specific, cross reaction may occur due to similarity in Ag  No denaturation during reaction  Combination occurs at surface and hence surface antigens are immunologically relevant  Combination is firm but reversible  Entire molecule reacts not the fragment  Both Ag and Ab participates in formation of ppt/agglutinate and they may combine in varying proportion P P Wadekar, ABCP Sangli
    52. 52.  Ag-Ab react form lattice that eventually results into ppt  Flocculation  Prozone, zone of equivalence and post zone P P Wadekar, ABCP Sangli
    53. 53.  Similar to pptn  Agglutination= visible clumping  Occurs when Ag and Ab react in equivalent proportion  False negative agglutination may occur P P Wadekar, ABCP Sangli
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    55. 55. P P Wadekar, ABCP Sangli
    56. 56.  Anathanarayan and Panikar’s Textbook of Microbiology, Seventh edition, Orient Longman Publication  Microbiology, Pelzar, Chan, Krieg, Fifth edition, Tata McGaw Hill publication  Pharmaceutical Microbiology- Principal applications, Dr. Chandrakant Kokare, Nirali ppublication  www.google.com P P Wadekar, ABCP Sangli

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