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Immunology: Basic Principles of Adaptive Immunity and Immunizations 2007
Adaptive Immunity <ul><li>Recognize non self </li></ul><ul><li>Respond to a foreign invader </li></ul><ul><li>Distinguish ...
 
Antigen <ul><li>Is a substance( molecule) that the body identifies as foreign and it mounts an immune response. </li></ul>...
Proteins as antigens <ul><li>Proteins are generally more immunogenic </li></ul><ul><li>Their structure is more complex </l...
Hepatitis antigens <ul><li>Hepatitis surface antigen is a molecule attached to the exterior or the virus </li></ul><ul><li...
Haptens <ul><li>Haptens are smaller molecules that can be antigenic if they bind to a larger molecule </li></ul><ul><li>Th...
Antibody <ul><li>Antibodies are molecules that are produced as a response to foreign invaders </li></ul><ul><li>It is spec...
Titer <ul><li>Titers are the quantitiy of an antigen required to evoke an immune response </li></ul><ul><li>It is quantifi...
Antibody titer ( definition and importance) <ul><li>Quantity to bind to and neutralize a particular quantity of an antigen...
Effector Response <ul><li>Recognition of a non self presence causes a series of response reactions </li></ul><ul><li>Divid...
Development of the immune system( Immune cells) <ul><li>Differentiation of stem cells into lymphocytes is influenced by ot...
T lymphocytes and cellular immunity <ul><li>Attack and destroy  </li></ul><ul><li>Produce cytokines that enhance specific ...
T lymphocytes
T lymphocytes <ul><li>Cytotoxic T cells – destroy virally infected cells and tumor cells </li></ul><ul><li>Helper T cells ...
Natural Killer Cells ( Doc Kaiser Microbiology)
Apoptosis(  Doc Kaiser Microbology)
MHC - 1 <ul><li>Endogenous antigens, such as viral proteins, pass through proteasomes where they are degraded into a serie...
MHC I and viruses
Humoral immunity <ul><li>The result of circulating immunities </li></ul><ul><li>When stimulated by an antigenm the B lymph...
Humoral immunity <ul><li>Dependent upon the ability of white blood cells to recognize specific antigens </li></ul><ul><li>...
Antibody Response <ul><li>Each B cell carries an antibody on its outer membrane </li></ul><ul><li>It has the ability to bi...
B cells <ul><li>After the binding of the antigen to the antibody, the B cells processes the antigen, by breaking it into t...
APC( Antigen Presenting Cell)
Antigen Presentation and MHC II <ul><li>The antigen is presented on the surface of the B cell by MHC II </li></ul><ul><li>...
MHC I and II
There are five classes of Immunoglobulins - The basic form of antibodies <ul><li>IgG </li></ul><ul><li>IgA </li></ul><ul><...
Basic structure <ul><li>Basic unit is a Y shaped structure </li></ul><ul><li>They are composed of four polypeptide chains ...
IgG <ul><li>IgG-The main class of antibodies  </li></ul><ul><li>Produced as a secondary response </li></ul><ul><li>Attach ...
IgM <ul><li>Pentameric structure( secreted by Plasma cells)  </li></ul><ul><li>Monmeric on the surface of B cells </li></u...
IgA <ul><li>Occurs in bodily secretions </li></ul><ul><li>Found in breast milk </li></ul><ul><li>Attaches to the lining of...
IgD <ul><li>Found primarily on the membranes of B cells </li></ul><ul><li>It may help in immune responses </li></ul><ul><l...
IgE <ul><li>Has specially affinity for receptors on the basophils </li></ul><ul><li>In the blood or mast cells in the tiss...
Immune Disorders- SCIDS
SCIDS <ul><li>Most cases of SCID are due to mutations in the gene encoding the common gamma chain  (γc),  </li></ul><ul><l...
Genetic Diseases of the Immune System <ul><li>Severe combined immunodeficiency </li></ul><ul><li>Multiple types </li></ul>...
Immune Disorders
Immune disorders <ul><li>#301000 ,   WISKOTT-ALDRICH SYNDROME; WAS </li></ul><ul><li>The manifestations of Wiskott-Aldrich...
Genetics of Immunoglobulins
Generation of Immunoglobulins
Genetics of Immunoglobulins <ul><li>Genes for the constant region </li></ul><ul><li>Genes for the variable region </li></u...
Naturally Acquired Active immunity <ul><li>The immune system responds to an invader by producing antibodies and activated ...
Naturally Acquired Passive Immunity <ul><li>Antibodies transferred across the placenta to the fetus </li></ul><ul><li>Tran...
Artificially Acquired Passive Immunity <ul><li>When antibodies made by other hosts are introduced into a new host </li></u...
Venom <ul><li>Rattlesnake venom is a mixture of enzymes that possess the ability to destroy cells  </li></ul><ul><li>Can b...
Antivenin <ul><li>Antivenin is a polyvalent preparation of globulins prepared by the fractionation of horse’s serum </li><...
Artificially Acquired Active Immunity <ul><li>When an individual is exposed to a vaccine  </li></ul><ul><li>The vaccine mi...
Chicken Pox – Varicella Zoster <ul><li>Chickenpox begins as a cold </li></ul><ul><li>Sneezing, coughing, and a runny nose ...
Chicken Pox <ul><li>Infection spread by aerosolized droplets </li></ul><ul><li>It is contagious 1-2 days prior to the onse...
<ul><li>All children between 12 and 18 months of age should have one dose of chickenpox vaccine. </li></ul><ul><li>Childre...
Primary Immune Response <ul><li>In humoral immunity the primary response occurs when the antigen is first recognized by ho...
Secondary Response <ul><li>The secondary response occurs when the immune system sees an antigen for the second time </li><...
Response of B cells <ul><li>T independent antigens - This response only produces IgM and no B memory cells are formed </li...
Primary and Secondary
 
Inactivation of the antigen( microbe) <ul><li>Neutralization - IgG is the main neutralizer of these infections </li></ul><...
Neutralization Reaction  http://people.eku.edu/ritchisong/neutralization2.gif
Neutralization of a toxin
 
Agglutination reactions <ul><li>Bacteria are large particles </li></ul><ul><li>When they react with bacteria they can clum...
Ingestion by macrophages <ul><li>Both agglutination and neutralization effectively inactivate the microbe by binding to th...
COMPLEMENT <ul><li>Pathway for the elimination of microbes </li></ul><ul><li>Cascade </li></ul><ul><li>Lysis of cells </li...
Complement action <ul><li>Perforin  is a  cytolytic   protein found in the granules of CD8  T cells  and  NK . Upon degran...
Classical Complement Pathway
 
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Adaptive Immunity

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Transcript of "Adaptive Immunity"

  1. 1. Immunology: Basic Principles of Adaptive Immunity and Immunizations 2007
  2. 2. Adaptive Immunity <ul><li>Recognize non self </li></ul><ul><li>Respond to a foreign invader </li></ul><ul><li>Distinguish between invaders( potential pathogen) </li></ul>
  3. 4. Antigen <ul><li>Is a substance( molecule) that the body identifies as foreign and it mounts an immune response. </li></ul><ul><li>It is also known as an immunogen </li></ul><ul><li>Most antigens are proteins </li></ul><ul><li>Some are glycoproteins, nucleoproteins, or polysaccharides </li></ul>
  4. 5. Proteins as antigens <ul><li>Proteins are generally more immunogenic </li></ul><ul><li>Their structure is more complex </li></ul><ul><li>Large proteins may have several epitopes or antigenic determinants </li></ul>
  5. 6. Hepatitis antigens <ul><li>Hepatitis surface antigen is a molecule attached to the exterior or the virus </li></ul><ul><li>Evokes an immune response </li></ul><ul><li>First antigen detectable </li></ul>
  6. 7. Haptens <ul><li>Haptens are smaller molecules that can be antigenic if they bind to a larger molecule </li></ul><ul><li>The antigen is the result of the combination. Neither is antigenic by itself </li></ul>
  7. 8. Antibody <ul><li>Antibodies are molecules that are produced as a response to foreign invaders </li></ul><ul><li>It is specific for an antigen </li></ul><ul><li>It has the capacity to bind to the antigen </li></ul>
  8. 9. Titer <ul><li>Titers are the quantitiy of an antigen required to evoke an immune response </li></ul><ul><li>It is quantifiable </li></ul><ul><li>Measured in clinical situations to determine immunity,the presence of disease,the course of an infection </li></ul>
  9. 10. Antibody titer ( definition and importance) <ul><li>Quantity to bind to and neutralize a particular quantity of an antigen </li></ul><ul><li>Rubella is a virus that produces teratogenic effects in a fetus </li></ul><ul><li>Rubella titers are diagnostically significant in young women planning on pregnancy </li></ul>
  10. 11. Effector Response <ul><li>Recognition of a non self presence causes a series of response reactions </li></ul><ul><li>Divided into </li></ul><ul><li>a. Humoral response – Based upon the presence to antibodies </li></ul><ul><li>b.Cellular response – based upon the activity of special cells such as T lymphocytes </li></ul>
  11. 12. Development of the immune system( Immune cells) <ul><li>Differentiation of stem cells into lymphocytes is influenced by other tissues </li></ul><ul><li>B cells are differentiated in the bone marrow </li></ul><ul><li>Found in the lymph nodes, spleen, gut associated lymphoid tissues( GALT) </li></ul><ul><li>B CELLS </li></ul><ul><li>T cells are are differentiated in the thymus </li></ul><ul><li>They are located in lymph nodes </li></ul><ul><li>They are the majority of circulating lymphocytes </li></ul><ul><li>T CELLS </li></ul>
  12. 13. T lymphocytes and cellular immunity <ul><li>Attack and destroy </li></ul><ul><li>Produce cytokines that enhance specific immunity and non specific mechanisms of defense </li></ul>
  13. 14. T lymphocytes
  14. 15. T lymphocytes <ul><li>Cytotoxic T cells – destroy virally infected cells and tumor cells </li></ul><ul><li>Helper T cells – they divide rapidly and secrete cytokines </li></ul><ul><li>Memory T cells – They are antigen specific cells </li></ul><ul><li>Regulatory T cells( suppressor T cells) – Cell mediated immunity </li></ul><ul><li>Natural Killer Cells – Connects the innate and the adaptive immune system </li></ul><ul><li>Other subsets of cells </li></ul>
  15. 16. Natural Killer Cells ( Doc Kaiser Microbiology)
  16. 17. Apoptosis( Doc Kaiser Microbology)
  17. 18. MHC - 1 <ul><li>Endogenous antigens, such as viral proteins, pass through proteasomes where they are degraded into a series of peptides. 2. The peptides are transported into the rough endoplasmic reticulum (ER) by a transporter protein called TAP. 3. The peptides then bind to the grooves of newly synthesized MHC-I molecules. 4. The endoplasmic reticulum transports the MHC-I molecules with bound peptides to the Golgi complex. 5. The Golgi complex, in turn, transports the MHC-I/peptide complexes by way of an exocytic vesicle to the cytoplasmic membrane where they become anchored. Here, the peptide and MHC-I/peptide complexes can be recognized by CTLs by way of TCRs and CD8 molecules having a complementary shape. </li></ul>
  18. 19. MHC I and viruses
  19. 20. Humoral immunity <ul><li>The result of circulating immunities </li></ul><ul><li>When stimulated by an antigenm the B lymphocytes initate a process that leads to the release of antibodies </li></ul><ul><li>Most effective at defending the body against viruses and bacteria </li></ul><ul><li>Works on the basis of </li></ul><ul><li>Specificity </li></ul><ul><li>Diversity </li></ul><ul><li>Memory </li></ul><ul><li>Self vs. Non self </li></ul>
  20. 21. Humoral immunity <ul><li>Dependent upon the ability of white blood cells to recognize specific antigens </li></ul><ul><li>Antigens are generally exposed on the outer surface of a pathogen or are toxins </li></ul>
  21. 22. Antibody Response <ul><li>Each B cell carries an antibody on its outer membrane </li></ul><ul><li>It has the ability to bind to a specific antigen </li></ul><ul><li>The binding of an antigen sensitizes or activates the B cells </li></ul><ul><li>This causes the cells to divide may times </li></ul><ul><li>The B cell divides to produce </li></ul><ul><li>Plasma cells that actively produce antibodies at a rapid rate </li></ul><ul><li>They also produce a memory cell that retains the information necessary to produce the antibody </li></ul>
  22. 23. B cells <ul><li>After the binding of the antigen to the antibody, the B cells processes the antigen, by breaking it into tiny fragments </li></ul><ul><li>The fragments bind to molecules on the surface of the B cell MHCII </li></ul>
  23. 24. APC( Antigen Presenting Cell)
  24. 25. Antigen Presentation and MHC II <ul><li>The antigen is presented on the surface of the B cell by MHC II </li></ul><ul><li>The T cells are activated to produce interleukin 2 </li></ul><ul><li>The activation further stimulates the production of more B cells - memory cells </li></ul>
  25. 26. MHC I and II
  26. 27. There are five classes of Immunoglobulins - The basic form of antibodies <ul><li>IgG </li></ul><ul><li>IgA </li></ul><ul><li>IgM </li></ul><ul><li>IgD </li></ul><ul><li>IgE </li></ul>
  27. 28. Basic structure <ul><li>Basic unit is a Y shaped structure </li></ul><ul><li>They are composed of four polypeptide chains </li></ul><ul><li>The chains are held together by disulfide bonds </li></ul><ul><li>They possess both variable and constant regions </li></ul>
  28. 29. IgG <ul><li>IgG-The main class of antibodies </li></ul><ul><li>Produced as a secondary response </li></ul><ul><li>Attach to antigens on microorganisms and their receptors attach to phagocytic cells </li></ul><ul><li>They work effectively with phagocytic cells </li></ul><ul><li>The tails section also activates complement </li></ul><ul><li>Crosses the placenta </li></ul>
  29. 30. IgM <ul><li>Pentameric structure( secreted by Plasma cells) </li></ul><ul><li>Monmeric on the surface of B cells </li></ul><ul><li>It is the first antibody made in response to an infection </li></ul><ul><li>It has ten antigen binding regions </li></ul><ul><li>Activates complement and causes clumping of microbes </li></ul>
  30. 31. IgA <ul><li>Occurs in bodily secretions </li></ul><ul><li>Found in breast milk </li></ul><ul><li>Attaches to the lining of the digestive, respiratory, and gastrointestinal tract </li></ul><ul><li>Transported through epithelial cells </li></ul><ul><li>Attaches to microbes before they invade tissues </li></ul><ul><li>Activates complement </li></ul><ul><li>Exists as a dimer </li></ul>
  31. 32. IgD <ul><li>Found primarily on the membranes of B cells </li></ul><ul><li>It may help in immune responses </li></ul><ul><li>It also may be active in allergic responses </li></ul>
  32. 33. IgE <ul><li>Has specially affinity for receptors on the basophils </li></ul><ul><li>In the blood or mast cells in the tissues </li></ul><ul><li>When IgE binds to antigens, the associated B cells secrete specific molecules that are related to allergic responses </li></ul><ul><li>Histamine is one of these molecules </li></ul><ul><li>IgE is found primarily in tissues and bodily fluids </li></ul>
  33. 34. Immune Disorders- SCIDS
  34. 35. SCIDS <ul><li>Most cases of SCID are due to mutations in the gene encoding the common gamma chain (γc), </li></ul><ul><li>A protein that is shared by the receptors for InterleukinsIL-2, IL-4, IL-7, IL-9 and IL-15. </li></ul><ul><li>These interleukins and their receptors are involved in the development and differentiation of T and B </li></ul><ul><li>Another well-known form of SCID is caused by a defective enzyme, adenosine deaminase (ADA), </li></ul><ul><li>Necessary for the breakdown of purines. Lack of ADA causes accumulation of dATP. </li></ul><ul><li>This metabolite will inhibit the activity of ribonucleotide diphosphate reductase, the enzyme that reduces ribonucleotides to generate deoxyribonucleotides </li></ul>
  35. 36. Genetic Diseases of the Immune System <ul><li>Severe combined immunodeficiency </li></ul><ul><li>Multiple types </li></ul><ul><li>X linked and autosomal </li></ul><ul><li>Affect both cellular and humoral aspects of the immune system </li></ul><ul><li>T cell-negative (T-), B cell-negative (B-), natural killer cell-positive (NK+) </li></ul><ul><li>Gene map locus 11p13, 11p13 </li></ul><ul><li>SCIDS </li></ul>
  36. 37. Immune Disorders
  37. 38. Immune disorders <ul><li>#301000 , WISKOTT-ALDRICH SYNDROME; WAS </li></ul><ul><li>The manifestations of Wiskott-Aldrich syndrome are eczema, thrombocytopenia, proneness to infection, and bloody diarrhea. </li></ul><ul><li>Death usually occurs before age 10 years . </li></ul><ul><li>Bone Marrow transplants are a treatment possibility </li></ul>
  38. 39. Genetics of Immunoglobulins
  39. 40. Generation of Immunoglobulins
  40. 41. Genetics of Immunoglobulins <ul><li>Genes for the constant region </li></ul><ul><li>Genes for the variable region </li></ul><ul><li>Light and heavy chained molecules are synthesized separately </li></ul><ul><li>The diversity of antibody-binding sites comes from the random combinations of variable gene segments that join with constant gene segments </li></ul>
  41. 42. Naturally Acquired Active immunity <ul><li>The immune system responds to an invader by producing antibodies and activated lymphocytes </li></ul><ul><li>This can produce a life long immunity </li></ul>
  42. 43. Naturally Acquired Passive Immunity <ul><li>Antibodies transferred across the placenta to the fetus </li></ul><ul><li>Transfer of antibodies through the colostrum in the breast milk </li></ul><ul><li>Both of these provide temporary immunity to an infant </li></ul>
  43. 44. Artificially Acquired Passive Immunity <ul><li>When antibodies made by other hosts are introduced into a new host </li></ul><ul><li>An example of this is rattlesnake antivenin injection </li></ul><ul><li>Antivenins are antibodies produced by other animals such as horses or cows </li></ul><ul><li>The host does not make new antibodies - the antibodies supplied circulate for as long as a month and are eventually destroyed in the host </li></ul>
  44. 45. Venom <ul><li>Rattlesnake venom is a mixture of enzymes that possess the ability to destroy cells </li></ul><ul><li>Can be a neurotoxin as well </li></ul><ul><li>Injected like a hypodermic </li></ul>
  45. 46. Antivenin <ul><li>Antivenin is a polyvalent preparation of globulins prepared by the fractionation of horse’s serum </li></ul><ul><li>It is a mixture of globulins from different types of rattlesnakes </li></ul>One of antigens in rattlesnake venom
  46. 47. Artificially Acquired Active Immunity <ul><li>When an individual is exposed to a vaccine </li></ul><ul><li>The vaccine might include attenuated </li></ul><ul><li>( weakened) organism, portions of the organism, toxins, subunits of antigenic portions of the organism </li></ul>
  47. 48. Chicken Pox – Varicella Zoster <ul><li>Chickenpox begins as a cold </li></ul><ul><li>Sneezing, coughing, and a runny nose </li></ul><ul><li>Two days later a rash begins </li></ul><ul><li>Usually begins on the chest and face </li></ul><ul><li>It may spread all over the body </li></ul>
  48. 49. Chicken Pox <ul><li>Infection spread by aerosolized droplets </li></ul><ul><li>It is contagious 1-2 days prior to the onset of symptoms </li></ul><ul><li>It takes 20 days to develop symptoms </li></ul><ul><li>It takes 5-10 days for the immune system to defeat the virus </li></ul>
  49. 50. <ul><li>All children between 12 and 18 months of age should have one dose of chickenpox vaccine. </li></ul><ul><li>Children who have had chickenpox do not need the vaccine. </li></ul><ul><li>No tests need to be administered to determine immune status - a parent's recollection of the disease is considered a reliable measure of previous infection and therefore immunity. ・ </li></ul><ul><li>Children between 19 months and their 13 th birthday who have not had chickenpox should be vaccinated with a single dose. ・ People 13 and older who have not had chickenpox should get two doses of the vaccine 4 to 8 weeks apart. </li></ul>
  50. 51. Primary Immune Response <ul><li>In humoral immunity the primary response occurs when the antigen is first recognized by host B cells </li></ul><ul><li>B cells divide to form plasma cells </li></ul><ul><li>Antibodies begin to appear - IgM </li></ul><ul><li>Cytokines trigger the proliferation of B cells </li></ul><ul><li>IgG synthesis accelerates </li></ul><ul><li>Memory cells are formed </li></ul>
  51. 52. Secondary Response <ul><li>The secondary response occurs when the immune system sees an antigen for the second time </li></ul><ul><li>Memory cells divide more rapidly than B cells </li></ul><ul><li>IgM is still produced first, but in smaller quantities than the secondary response </li></ul><ul><li>IgG is produced second, but in greater amounts </li></ul>
  52. 53. Response of B cells <ul><li>T independent antigens - This response only produces IgM and no B memory cells are formed </li></ul><ul><li>T- dependent antigens - B cell becomes the antigen presenting cell, makes contact with the T helper cell and the T helper then produces lymphokines that stimulate thethe B cell to differentiate </li></ul>
  53. 54. Primary and Secondary
  54. 56. Inactivation of the antigen( microbe) <ul><li>Neutralization - IgG is the main neutralizer of these infections </li></ul><ul><li>Prevents the toxin from doing further damage </li></ul><ul><li>Antibiotics are required to kill the microbe causing the infection </li></ul><ul><li>Viruses can be inactivated by neutralization </li></ul><ul><li>Viruses with envelopes can be removed by complement </li></ul>
  55. 57. Neutralization Reaction http://people.eku.edu/ritchisong/neutralization2.gif
  56. 58. Neutralization of a toxin
  57. 60. Agglutination reactions <ul><li>Bacteria are large particles </li></ul><ul><li>When they react with bacteria they can clump </li></ul><ul><li>IgM causes strong agglutination reactions </li></ul><ul><li>IgG also causes agglutination </li></ul>
  58. 61. Ingestion by macrophages <ul><li>Both agglutination and neutralization effectively inactivate the microbe by binding to the antigenic site </li></ul><ul><li>Macrophages can then ingest the pathogen </li></ul>
  59. 62. COMPLEMENT <ul><li>Pathway for the elimination of microbes </li></ul><ul><li>Cascade </li></ul><ul><li>Lysis of cells </li></ul><ul><li>Augmentation of immune response </li></ul><ul><li>Disposal of waste by products </li></ul>
  60. 63. Complement action <ul><li>Perforin is a cytolytic protein found in the granules of CD8 T cells and NK . Upon degranulation, perforin inserts itself into the target cell's plasma membrane forming a pore </li></ul><ul><li>This finally results in the lysis of a cell </li></ul>
  61. 64. Classical Complement Pathway
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