CHAPTER 10: IMMUNITY EDWARD JENNER The Influenza Epidemic of 1918 – 1919 killed 22 million people in 18 months
<ul><li>10.1 IMMUNE RESPONSE </li></ul><ul><li>Describe Definition: Immunity </li></ul><ul><li>Describe Antibodies: Struct...
INTRODUCTION <ul><li>An animal must defend itself against unwelcome intruders – the many potentially dangerous viruses, ba...
<ul><li>Three cooperative lines of defense have evolved to counter this threats </li></ul><ul><li>Two of these are non-spe...
First line barriers to infection <ul><li>Intact skin is a barrier that cannot normally be penetrated by bacteria or viruse...
<ul><li>In humans, secretions from sebaceous and sweat glands give the skin a pH ranging from 3 to 5, which is acidic enou...
Second line barriers <ul><li>Microbes that penetrate the first line defense face the second line defense, which depends ma...
 
Neutrophils <ul><li>Constitute about 60 - 70% of all leukocytes </li></ul><ul><li>Cells damaged by invading microbes relea...
Monocytes <ul><li>About 5% of leukocytes </li></ul><ul><li>Provide an even more effective phagoytic defense </li></ul><ul>...
These cells extend long pseudopodia that can attach to polysaccharides on a microbe’s surface, engulfing the microbes by p...
Eosinophils <ul><li>About 1.5% of all leukocytes </li></ul><ul><li>Contribute to defense against large parasitic invaders,...
<ul><li>The blood fluke Schistosoma  infects 200 million people, leading to body pains, anemia, and dysentery. </li></ul>
THE INFLAMMATORY RESPONSE <ul><li>Damage to tissue by a physical injury or by the entry of a microorganisms triggers a loc...
<ul><li>Cells of a tissue injured by physical damage or bacteria release chemical signals such as histamine and prostaglan...
THIRD LINE OF DEFENSE ~ SPECIFIC IMMUNITY <ul><li>While microorganisms are under assault by phagocytic cells, the inflamma...
Lymphocytes <ul><li>The vertebrate body is populated by two main types of lymphocytes : </li></ul><ul><li>B lymphocytes (B...
<ul><li>Lymphocytes, like all blood cells, originate from pluripotent stem cells in the bone marrow or liver of a developi...
<ul><li>Early lymphocytes are all alike, but they later develop into T cells or B cells, depending on where they continue ...
T CELLS <ul><li>There are four main types of T cells: </li></ul><ul><li>Cytotoxic T cells (T C )  (killer cells) ~ destroy...
<ul><li>Memory T-cells  ~ have no action but multiply very fast if a second invasion of the antigen occurs, producing an e...
B CELLS <ul><li>There are three different types of B cells : </li></ul><ul><li>Plasma B cells  ~ secrete antibodies into t...
 
<ul><li>Because lymphocytes recognize and respond to particular microbes and foreign molecules, they are said to display  ...
Antigen (Immunogen) <ul><li>Definition : </li></ul><ul><li>Any substances capable of stimulating an immune response, usual...
Characteristics of antigens <ul><li>Foreign to host ~ chemical groupings (markers) must be different from those on host ce...
A single antigen such as a bacterial surface protein usually has several effective epitopes, each capable of inducing the ...
<ul><li>4. Examples   : </li></ul><ul><li>a. Soluble toxins, enzymes, venoms, plant extracts, medications, foreign serums ...
 
11.1.2 ANTIBODY <ul><li>One way that an antigen elicits an immune response is by activating B cells to secrete proteins ca...
<ul><li>Antibodies are glycoproteins which belong to a special group of blood proteins known as immunoglobulin </li></ul><...
 
 
<ul><li>Each antibody molecule has two identical  antigen binding sites </li></ul><ul><li>These are different for each kin...
<ul><li>10.1.3 </li></ul><ul><li>CLASSES OF ANTIBODIES </li></ul>
 
 
10.1.4 Humoral Response  (Antibody-Mediated Immunity) <ul><li>B cells responds to antigens by producing antibodies </li></...
10.1.5 Cell-mediated Response (Cell-mediated Immunity) <ul><li>T cells do not secrete antibodies but instead directly atta...
10.1.6 Lymphatic System <ul><li>A central location for the collection and distribution of the cells of the immune system <...
 
<ul><li>The fixed macrophages in the spleen, lymph nodes and other lymphatic tissues are particularly well located to cont...
<ul><li>Along the way, lymph must pass through numerous lymph nodes, where any pathogens present must encounter macrophage...
Structure of the lymph node
Structure of the spleen
The reaction between antibody and antigen <ul><li>The antibody becomes attached to the antigen at the antigen binding site...
 
 
 
<ul><li>It is the combined effect of antibody and complement that determines the action of antibody  </li></ul><ul><li>The...
10.1.7  Antigen-antibody Interaction <ul><li>Neutralization </li></ul><ul><li>Agglutination </li></ul><ul><li>Precipitatio...
i. Neutralization <ul><li>The antibody binds to and blocks the activity of the antigen </li></ul><ul><li>E.g.: Antibodies ...
<ul><li>Similarly, antibodies may bind to the surface of a pathogenic bacterium </li></ul><ul><li>These microbes, now coat...
 
ii. Agglutination <ul><li>Antibody-mediated agglutination (clumping) of bacteria or viruses effectively neutralizes and op...
<ul><li>These large complexes are readily phagocytosed by macrophages </li></ul>
iii. Precipitation <ul><li>In precipitation, the cross-linking of soluble antigen molecules – molecules dissolved in body ...
 
iv. Complement Fixation <ul><li>During complement fixation, the antigen-antibody system activates the complement system, a...
<ul><li>Completion results in the lysis of many types of viruses and pathogenic cells </li></ul><ul><li>Lysis can be achie...
 
i. The Classical Pathway <ul><li>Is triggered by antibodies bound to antigen and is therefore important to immune response...
<ul><li>The first complement component links two bound antibodies and is activated, initiating a cascade </li></ul><ul><li...
<ul><li>Antibody molecules attach to antigens on pathogen’s plasma membrane </li></ul><ul><li>Complement proteins link two...
ii. The Alternative Pathway <ul><li>Is triggered by substances that are naturally present on many bacteria, yeast, viruses...
<ul><li>In both the classical and alternative pathways, many activated complement proteins contribute to inflammation. </l...
<ul><li>One activated complement protein coats bacterial surfaces and stimulates phagocytosis, like antibody </li></ul><ul...
Summary of Antibody-antigen Interaction
10.2 Development of Immunity
<ul><li>Describe and explain primary and secondary immune responses to antigen. </li></ul><ul><li>Explain the concept of s...
<ul><li>Antigens interact with specific lymphocytes, inducing immune responses and immunological memory </li></ul>
<ul><li>Although it encounters a large repertoire of B and T cells, a microorganism interacts only with lymphocytes bearin...
<ul><li>One clone consists of a large number of  effector cells , short-lived cells that combat the same antigen </li></ul...
Antigen molecules bind to the antigen receptors of only one of the six B cells shown The selected B cell proliferates to g...
<ul><li>The selective proliferation and differentiation of lymphocytes that occur the first time the body is exposed to an...
<ul><li>During this period, selected B cells and T cells generate antibody-producing effector B cells, called plasma cells...
<ul><li>A second exposure to the same antigen at some later time elicits the secondary immune response </li></ul><ul><li>T...
 
 
<ul><li>The immune systems capacity to generate secondary immune response is called  immunological memory , based not only...
<ul><li>Memory cells are not active during primary response and survive in the system for long periods. </li></ul><ul><li>...
 
The Development of Active Immunity <ul><li>1. Immunity to smallpox in Jenner’s patients occurred because their inoculation...
<ul><li>2. As a result of clonal selection, a second exposure, this time to smallpox, stimulates the immune system to prod...
10.2.1 Self and Non-self Recognition <ul><li>Lymphocytes do not react to most self antigens, but T cells do have a crucial...
<ul><li>Two main classes of MHC molecules mark body cells as self </li></ul><ul><li>Class I MHC molecules are found on alm...
<ul><li>ii.  Class II MHC  molecules are restricted to few specialized cell types, including macrophages, B cells, activat...
MHC <ul><li>It is unlikely that any two people, except identical twins, will have the same set of MHC molecules </li></ul>...
<ul><li>There are two main types of T cells, and responds to one class of MHC molecules </li></ul><ul><li>Cytotoxic T cell...
<ul><li>A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and transported to the cel...
<ul><li>ii. Helper T cells (T H ) have receptors that bind to peptides displayed by the body’s class II MHC molecules </li...
<ul><li>A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and transported to the cel...
Fig. 57.9
IMMUNE RESPONSES
The immune system can mount two types of responses depending on the antigen which stimulates the system i. Humoral respons...
<ul><li>Cell-mediated immunity  : T lymphocytes attack viruses and bacteria within infected cells and defend against fungi...
<ul><li>The humoral and cell-mediated immune responses are linked by signalling interactions, especially via the T cells <...
 
<ul><li>1. Helper T lymphocytes function in both humoral and cell-mediated immunity </li></ul>Development of Cellular Immu...
<ul><li>Both types of immune responses are initiated by interactions between antigen-presenting cells (APCs) and T H  cell...
 
<ul><li>An APC engulfs a bacterium and transport a fragment of it to the cell surface via a class II MHC molecule </li></u...
<ul><li>Activated TH cells that bind to a class II MHC-antigen complex on an APC are induced to differentiate into either ...
<ul><li>ii.  Memory T H  cells  ~ IL-1 secreted from APCs, promotes activation of the T H  cells and the subsequent secret...
<ul><li>2. In the cell-mediated response, cytotoxic T cells defend against intracellular pathogens  </li></ul>
<ul><li>Antigen-activated T C  cells, kill cancers cells and cells infected by viruses and other intracellular pathogens <...
<ul><li>An infected cell (or cancer cell) displays as an antigen fragment on its surface using a class I MHC molecule. A s...
Cytotoxic T cell
<ul><li>Destruction of the host cell not only removes the site where pathogens can reproduce, but also exposes the pathoge...
<ul><li>T C  also function to destroy cancer cells </li></ul><ul><li>Cancer cells possess distinctive markers not found on...
 
Development of Humoral Immunity <ul><li>3. In the humoral response, B cells make antibodies against extracellular pathogen...
<ul><li>The humoral response occurs when an antigen binds to B cell receptors that are specific for the antigen epitopes <...
<ul><li>A macrophage ingests a pathogen </li></ul><ul><li>Class II MHC proteins within the cell bind to fragments of the p...
<ul><li>When activated a B cell gives rise to a clone of plasma cells. </li></ul><ul><li>Each of these effector cells secr...
 
The immune system’s capacity to distinguish self from nonself limits blood transfusion and tissue transplantation
<ul><li>In addition to attacking pathogens, the immune system will also attack cells from other individuals. </li></ul><ul...
<ul><li>One source of potential problems with blood transfusions is an immune reaction from individuals with incompatible ...
<ul><li>A person with type A blood already has antibodies to the B antigen, even if the person has never been exposed to t...
 
<ul><li>However, another blood group antigen, the  Rh factor , can cause mother-fetus problems because antibodies produced...
<ul><li>To prevent this, the mother is injected with anti-Rh antibodies after delivering her first Rh positive baby.  </li...
10.3 Immune Disorder: SLE and AIDS
<ul><li>Briefly explain SLE, AIDS </li></ul><ul><li>Explain the mechanism of action of HIV Infection and Symptoms of AIDS....
<ul><li>Malfunctions of the immune system can produce effects ranging from the minor inconvenience of some allergies to th...
<ul><li>Allergies  are hypersensitive (exaggerated) responses to certain environmental antigens, called allergens. </li></...
<ul><li>The most common allergies involve antibodies of the IgE class. </li></ul><ul><ul><li>Hay fever, for example, occur...
<ul><li>This event triggers the mast cell to  degranulate  - that is, to release histamines and other inflammatory agents ...
<ul><li>High levels of histamines cause dilation and increased permeability of small blood vessels. </li></ul><ul><ul><li>...
<ul><li>Sometimes, an acute allergic response can result in  anaphylactic shock , a life threatening reaction to injected ...
Tissue grafts and organ transplantation <ul><li>The MHC is responsible for stimulating the rejection of tissue grafts and ...
<ul><li>To minimize rejection, attempts are made to match MHC of tissue donor and recipient as closely as possible. </li><...
<ul><li>In addition to MHC matching, various medicines are necessary to suppress the immune response to the transplant. </...
<ul><li>More selective drugs, which suppress helper T cell activation without crippling nonspecific defense or T-independe...
<ul><li>In bone marrow transplants, it is the graft itself, rather than the host, that is the source of potential immune r...
<ul><li>Prior marrow transplants, the  recipient is typically treated with  </li></ul><ul><li>irradiation to eliminate the...
AUTOIMMUNE DISEASES The Body Attacks Itself <ul><li>Autoimmunity arises when the ‘immune’ system fails to distinguish betw...
e.g. Autoimmune diseases <ul><li>Myasthenia gravis </li></ul><ul><li>Multiple sclerosis </li></ul><ul><li>Rheumatoid arthr...
Rheumatoid Arthritis of  the Hands Rheumatoid arthritis can result in severe deformation of the hands, wrists, feet, ankle...
Multiple sclerosis <ul><ul><ul><li>In this i ll ness the myelin sheath covering the spinal cord is destroyed, leading to d...
Myasthenia gravis Myasthenia gravis is a neuromuscular disease that causes weakness and fatigue, most commonly in the musc...
Systemic lupus erythematosus                                                                             
<ul><li>In SLE (lupus), the immune system generates antibodies against all sorts of self molecules, including histamines <...
A I D S C QUIRED MMUNO - EFICIENCY YNDROME
INTRODUCTION
<ul><li>In 1981, increased rates of two rare diseases, Kaposi’s sarcoma, a cancer of the skin and blood vessels, and pneum...
<ul><ul><li>People with AIDS are susceptible to  opportunistic diseases .   </li></ul></ul><ul><li>Opportunistic disease  ...
<ul><li>In 1983, a retrovirus, now called  human immunodeficiency virus  ( HIV ) , had been identified as the causative ag...
<ul><li>With the AIDS mortality close to 100%, HIV is the most lethal pathogen ever encountered. </li></ul><ul><ul><li>Mol...
<ul><li>There are two major strains of the virus, HIV-1 and HIV-2. </li></ul><ul><ul><li>HIV-1 is the more widely distribu...
Causative Agent  <ul><li>The viral particle includes: </li></ul><ul><ul><li>an envelope with glycoprotein  for binding to ...
Causative Agent  RNA Capsid RNA Reverse transcriptase enzyme Viral  envelope Glycoprotein
<ul><li>The entry of the virus requires not only CD4 on the surface of the susceptible cells but also a second protein mol...
The Causes
The Causes … mainly because of the  exchange of body fluid: <ul><li>Promiscuity (having many transient sexual relationship...
The Symptoms
The Symptoms  Flu or mononucleosis <ul><li>persistent or recurrent fever </li></ul><ul><li>severe dry cough </li></ul><ul>...
The Symptoms  Behavioral dementia <ul><li>(madness) due to the damage  </li></ul><ul><li>on nervous system (esp. brain  </...
The Symptoms  Pneumocystis   carinii   pneumonia (PCP) <ul><li>inflammation of lungs  </li></ul><ul><li>(alveoli filled wi...
The Symptoms  Kaposi’s sarcoma a cancer of the skin and  blood vessels (purplish spot on skin)
The mechanism of infection and HIV replication
The Mechanism of infection and the Replication of HIV <ul><li>Glycoprotein on the envelope bind to specific receptors on t...
 
<ul><li>Reverse transcriptase synthesizes double  </li></ul><ul><li>stranded DNA from the viral RNA </li></ul>The Mechanis...
 
The Mechanism of infection and the Replication of HIV <ul><li>The double-stranded DNA is incorporated as </li></ul><ul><li...
The Mechanism of infection and the Replication of HIV <ul><li>The  provirus  is transcribed into mRNA and went  </li></ul>...
 
The Mechanism of infection and the Replication of HIV <ul><li>mRNA are translated to viral protein forming : </li></ul><ul...
The Mechanism of infection and the Replication of HIV <ul><li>Protein coats form around viral RNA and reverse  </li></ul><...
The Mechanism of infection and the Replication of HIV <ul><li>Viruses bud from the host cell, acquiring envelopes </li></u...
 
1 2 3 4 5 6 7 8
The new HIV particles leaving the host’s cell  Mature form Budding particle
<ul><li>In spite of these challenges, the immune system engages in a prolonged battle against HIV. </li></ul><ul><ul><li>(...
 
 
THE STAGES OF HIV INFECTION <ul><li>HIV concentration increases rapidly within a 6-month of infection but is then almost e...
HIV on a lymphocyte HIV particles
Treatment of AIDS <ul><li>No cure for HIV infection is known, although research is intense in the areas of vaccine product...
<ul><li>The most promising drugs : Azidothymidine (AZT) is an effective inhibitor of HIV replication </li></ul><ul><li>A m...
The Preventive Measures <ul><li>Treat HIV infection as an illness  </li></ul><ul><li>Counseling and HIV testing for the pa...
<ul><li>Antiretroviral therapy for pregnant women  </li></ul><ul><li>to  reduce prenatal HIV transmission. </li></ul><ul><...
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Immunity

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  • Autoantibodies are often found in the blood of older people who have no disease, a phenomenon that is not properly understood.
  • Immunity

    1. 1. CHAPTER 10: IMMUNITY EDWARD JENNER The Influenza Epidemic of 1918 – 1919 killed 22 million people in 18 months
    2. 2. <ul><li>10.1 IMMUNE RESPONSE </li></ul><ul><li>Describe Definition: Immunity </li></ul><ul><li>Describe Antibodies: Structure and Classes </li></ul><ul><li>Explain and Compare Humoral and Cell Mediated immunity </li></ul><ul><li>Describe Lymphoid Organs Roles in Immunity </li></ul><ul><li>Describe Antigen-antibody Reactions </li></ul>
    3. 3. INTRODUCTION <ul><li>An animal must defend itself against unwelcome intruders – the many potentially dangerous viruses, bacteria and other pathogens it encounters in the air, in food and in water </li></ul><ul><li>It must also deal with abnormal body cells, in some cases , may develop into cancer </li></ul>
    4. 4. <ul><li>Three cooperative lines of defense have evolved to counter this threats </li></ul><ul><li>Two of these are non-specific – that is they do not distinguish one infectious agent from another </li></ul>
    5. 5. First line barriers to infection <ul><li>Intact skin is a barrier that cannot normally be penetrated by bacteria or viruses although even minute abrasions may allow their passage </li></ul><ul><li>Likewise, the mucous membranes that line the digestive, respiratory, and genitourinary tracts bar the entry of potentially harmful microbes </li></ul>
    6. 6. <ul><li>In humans, secretions from sebaceous and sweat glands give the skin a pH ranging from 3 to 5, which is acidic enough to prevent colonization by many microbes </li></ul><ul><li>Microbial colonization is also inhibited by the washing action of saliva, tears and mucous secretion </li></ul><ul><li>All these secretions contain antimicrobial proteins </li></ul><ul><li>One of these, the enzyme lysozyme, digests the cell walls of many bacteria, destroying them </li></ul>
    7. 7. Second line barriers <ul><li>Microbes that penetrate the first line defense face the second line defense, which depends mainly on phagocytosis , the ingestion of invading organisms by certain types of white cells. </li></ul><ul><li>Phagocyte function is intimately associated with an effective inflammatory response and also with certain antimicrobial proteins. </li></ul>
    8. 9. Neutrophils <ul><li>Constitute about 60 - 70% of all leukocytes </li></ul><ul><li>Cells damaged by invading microbes release chemical signals that attract neutrophils from the blood </li></ul><ul><li>The neutrophils enter the infected tissue, engulfing them and destroying microbes there </li></ul><ul><li>Neutrophils tend to self-destruct as they destroy foreign invaders, and their average life span is only a few days </li></ul>
    9. 10. Monocytes <ul><li>About 5% of leukocytes </li></ul><ul><li>Provide an even more effective phagoytic defense </li></ul><ul><li>After a few hours in the blood, they migrate into tissues and develop into macrophages : large, long-lived phagocytes </li></ul>
    10. 11. These cells extend long pseudopodia that can attach to polysaccharides on a microbe’s surface, engulfing the microbes by phagocytosis, and fusing the resulting vacuole with a lysosome
    11. 12. Eosinophils <ul><li>About 1.5% of all leukocytes </li></ul><ul><li>Contribute to defense against large parasitic invaders, such as the blood fluke, Schistosoma mansoni </li></ul><ul><li>Eosinophils position themselves against the external wall of a parasite and discharge destructive enzymes from the cytoplasmic granules </li></ul>
    12. 13. <ul><li>The blood fluke Schistosoma infects 200 million people, leading to body pains, anemia, and dysentery. </li></ul>
    13. 14. THE INFLAMMATORY RESPONSE <ul><li>Damage to tissue by a physical injury or by the entry of a microorganisms triggers a localized inflammatory response </li></ul><ul><li>One of the chemical signals is histamine </li></ul><ul><li>Histamine is released by circulating leukocytes called basophils and by mast cells in connective tissues </li></ul>
    14. 15. <ul><li>Cells of a tissue injured by physical damage or bacteria release chemical signals such as histamine and prostaglandin </li></ul><ul><li>In response to the signals, nearby capillaries dilate and became more permeable. Fluid and clotting elements move from the blood to the site and clotting begins. </li></ul><ul><li>Chemokines and other chemotactic factors released by various kinds of cells attract phagocytic cells from the blood </li></ul><ul><li>When the phagocytic cells arrive at the site of injury, they consume pathogens and cell debris, and the tissue heals </li></ul>
    15. 16. THIRD LINE OF DEFENSE ~ SPECIFIC IMMUNITY <ul><li>While microorganisms are under assault by phagocytic cells, the inflammatory response and antimicrobial proteins, they inevitably encounter lymphocytes, the key cells of the immune system </li></ul><ul><li>Lymphocytes generate efficient and selective immune responses that work throughout the body to eliminate particular invaders </li></ul>
    16. 17. Lymphocytes <ul><li>The vertebrate body is populated by two main types of lymphocytes : </li></ul><ul><li>B lymphocytes (B cells) </li></ul><ul><li>T lymphocytes (T cells) </li></ul><ul><li>~ Both types of lymphocytes circulate throughout the blood and lymph and are concentrated in the spleen, lymph nodes and other lymphatic tissue. </li></ul>
    17. 18. <ul><li>Lymphocytes, like all blood cells, originate from pluripotent stem cells in the bone marrow or liver of a developing fetus. </li></ul>
    18. 19. <ul><li>Early lymphocytes are all alike, but they later develop into T cells or B cells, depending on where they continue their maturation. </li></ul><ul><li>Lymphocytes that migrate from the bone marrow to thymus develop into T cells. </li></ul><ul><li>Lymphocytes that remain in the bone marrow and continue their maturation there become B cells. </li></ul>
    19. 20. T CELLS <ul><li>There are four main types of T cells: </li></ul><ul><li>Cytotoxic T cells (T C ) (killer cells) ~ destroy the antigen directly by attaching to them and releasing the chemical perforin to kill them </li></ul><ul><li>Helper T cells (T H ) ~ attract and stimulate macrophages and promote the activity of other T- and B- cells to increase antibody production </li></ul>
    20. 21. <ul><li>Memory T-cells ~ have no action but multiply very fast if a second invasion of the antigen occurs, producing an even bigger clone of T-lymphocytes and resulting in rapid destruction of antigen </li></ul><ul><li>Suppressor T-cells ~ slow down the vigorous response of the T C and T H cells, so slowing down and the stopping the immune response </li></ul>
    21. 22. B CELLS <ul><li>There are three different types of B cells : </li></ul><ul><li>Plasma B cells ~ secrete antibodies into the circulation </li></ul><ul><li>Memory B cells ~ live for a long time in the blood. They do not produce antibodies but are programmed to remember a specific antigen and respond very rapidly to any subsequent infection </li></ul><ul><li>Dividing B cells ~ produce more B lymphocyte cells </li></ul>
    22. 24. <ul><li>Because lymphocytes recognize and respond to particular microbes and foreign molecules, they are said to display specificity </li></ul><ul><li>B cells and T cells specialize in different types of antigens, and they carry out different, but complementary, defensive actions </li></ul>
    23. 25. Antigen (Immunogen) <ul><li>Definition : </li></ul><ul><li>Any substances capable of stimulating an immune response, usually a protein or a large carbohydrate that is foreign to the body </li></ul>
    24. 26. Characteristics of antigens <ul><li>Foreign to host ~ chemical groupings (markers) must be different from those on host cells (receptors) – called antigenic determinants or epitopes </li></ul><ul><li>Possesses two or more antigenic determinants ~ epitopes (2 bivalent, many multivalents) </li></ul><ul><li>May be soluble, particular, cellular </li></ul>
    25. 27. A single antigen such as a bacterial surface protein usually has several effective epitopes, each capable of inducing the production of specific antibody
    26. 28. <ul><li>4. Examples : </li></ul><ul><li>a. Soluble toxins, enzymes, venoms, plant extracts, medications, foreign serums (proteins) </li></ul><ul><li>b. Particulate ~ cell structures (cell walls, flagella, capsules, pili), viruses, mold spores, pollens, house dusts </li></ul><ul><li>c. Cellular ~ microorganism, viral infected host cells, foreign tissue cells, neoplastic cells, altered host cells </li></ul>
    27. 30. 11.1.2 ANTIBODY <ul><li>One way that an antigen elicits an immune response is by activating B cells to secrete proteins called antibodies </li></ul><ul><li>Each antigen has a particular molecular shape and stimulates certain B cells to secrete antibodies that interact specifically for it. </li></ul>
    28. 31. <ul><li>Antibodies are glycoproteins which belong to a special group of blood proteins known as immunoglobulin </li></ul><ul><li>The basic structure of an antibody consists of two pairs of polypeptide chains </li></ul><ul><li>Two of the chains are long and are referred to as heavy (H) chains </li></ul><ul><li>The other two shorter chains are referred to as light (L) chains </li></ul><ul><li>The chains are held together by disulphide (S-S) bridges to form the Y-shaped molecule </li></ul>
    29. 34. <ul><li>Each antibody molecule has two identical antigen binding sites </li></ul><ul><li>These are different for each kind of antibody, which allows the antibody to recognize and attach specifically to a particular antigen </li></ul><ul><li>The antigen attachment site is known as variable region and specific to each antigen </li></ul><ul><li>The rest of each polypeptide chain is termed the constant region. </li></ul>
    30. 35. <ul><li>10.1.3 </li></ul><ul><li>CLASSES OF ANTIBODIES </li></ul>
    31. 38. 10.1.4 Humoral Response (Antibody-Mediated Immunity) <ul><li>B cells responds to antigens by producing antibodies </li></ul><ul><li>Antibodies are secreted into the blood and other body fluids and thus provide humoral immunity </li></ul><ul><li>(Humor = body fluid) </li></ul>
    32. 39. 10.1.5 Cell-mediated Response (Cell-mediated Immunity) <ul><li>T cells do not secrete antibodies but instead directly attack the cells that carry the specific antigens </li></ul><ul><li>These cells are described as producing cell-mediated immunity </li></ul>
    33. 40. 10.1.6 Lymphatic System <ul><li>A central location for the collection and distribution of the cells of the immune system </li></ul><ul><li>Consists of a network of lymphatic capillaries, ducts, nodes and lymphatic organs </li></ul>
    34. 42. <ul><li>The fixed macrophages in the spleen, lymph nodes and other lymphatic tissues are particularly well located to contact infectious agent </li></ul><ul><li>Interstitial fluid, perhaps containing pathogen, is taken up by lymphatic capillaries, and flows as lymph, eventually returning to the blood circulatory system </li></ul>
    35. 43. <ul><li>Along the way, lymph must pass through numerous lymph nodes, where any pathogens present must encounter macrophages and lymphocytes </li></ul><ul><li>Microorganisms, microbial fragments and foreign molecules that enter the blood encounter macrophages when they become trapped in the netlike architecture of the spleen </li></ul>
    36. 44. Structure of the lymph node
    37. 45. Structure of the spleen
    38. 46. The reaction between antibody and antigen <ul><li>The antibody becomes attached to the antigen at the antigen binding site like a key in a lock </li></ul><ul><li>This causes the antibody to change from a T shape to a Y shape </li></ul><ul><li>This exposes part of the antibody to substances in the plasma that are together known as complement </li></ul>
    39. 50. <ul><li>It is the combined effect of antibody and complement that determines the action of antibody </li></ul><ul><li>The binding of antibodies to antigens to form antigen-antibody complexes is the basis of several antigen disposal mechanisms </li></ul>
    40. 51. 10.1.7 Antigen-antibody Interaction <ul><li>Neutralization </li></ul><ul><li>Agglutination </li></ul><ul><li>Precipitation </li></ul><ul><li>Complement-fixation </li></ul>
    41. 52. i. Neutralization <ul><li>The antibody binds to and blocks the activity of the antigen </li></ul><ul><li>E.g.: Antibodies neutralize a virus by attaching to molecules that the virus uses to infect its host cell. </li></ul>
    42. 53. <ul><li>Similarly, antibodies may bind to the surface of a pathogenic bacterium </li></ul><ul><li>These microbes, now coated by antibodies, are readily eliminated by phagocytosis </li></ul><ul><li>In a process called opsonization (coating) , the bound antibodies enhance macrophage to, and thus phagocytosis of, the microbes </li></ul>
    43. 55. ii. Agglutination <ul><li>Antibody-mediated agglutination (clumping) of bacteria or viruses effectively neutralizes and opsonizes the microbes </li></ul><ul><li>Agglutination is possible because each antibody has at least two antigen-binding sites (IgG) </li></ul><ul><li>IgM can link together five or more viruses or bacteria </li></ul>
    44. 56. <ul><li>These large complexes are readily phagocytosed by macrophages </li></ul>
    45. 57. iii. Precipitation <ul><li>In precipitation, the cross-linking of soluble antigen molecules – molecules dissolved in body fluids – forms immobile precipitates that are disposed of by phagocytosis </li></ul>
    46. 59. iv. Complement Fixation <ul><li>During complement fixation, the antigen-antibody system activates the complement system, a complex of 20 different serum proteins </li></ul><ul><li>In an infection, the first in a series of complement proteins is activated, triggering a cascade of activation steps, each component activating the next in series </li></ul>
    47. 60. <ul><li>Completion results in the lysis of many types of viruses and pathogenic cells </li></ul><ul><li>Lysis can be achieved in two ways: </li></ul><ul><li>The classical pathway </li></ul><ul><li>The alternative pathway </li></ul>
    48. 62. i. The Classical Pathway <ul><li>Is triggered by antibodies bound to antigen and is therefore important to immune response </li></ul><ul><li>Begins when IgM or IgG antibodies bind to a pathogen </li></ul>
    49. 63. <ul><li>The first complement component links two bound antibodies and is activated, initiating a cascade </li></ul><ul><li>Ultimately, complement proteins generate a membrane attack complex (MAC), which forms a pore in the bacterial membrane, resulting in cell lysis. </li></ul>
    50. 64. <ul><li>Antibody molecules attach to antigens on pathogen’s plasma membrane </li></ul><ul><li>Complement proteins link two antibody molecules </li></ul><ul><li>Activated complement proteins attach to pathogen’s membrane in step-by step sequence, forming a membrane attack complex (MAC) </li></ul><ul><li>MAC pores in the membrane causes cell lysis. </li></ul>
    51. 65. ii. The Alternative Pathway <ul><li>Is triggered by substances that are naturally present on many bacteria, yeast, viruses and protozoan parasites </li></ul><ul><li>It does not involved antibodies and thus is an important non specific defense. </li></ul>
    52. 66. <ul><li>In both the classical and alternative pathways, many activated complement proteins contribute to inflammation. </li></ul><ul><li>Some triggers the release of histamine by binding the basophils and mast cells </li></ul><ul><li>Several active complement proteins also attract phagocytes to the site. </li></ul>
    53. 67. <ul><li>One activated complement protein coats bacterial surfaces and stimulates phagocytosis, like antibody </li></ul><ul><li>During immune adherence, microbes coated with antibodies and complement adhere to blood vessels walls, making the pathogens easier prey for phagocytic cells circulating in the blood </li></ul>
    54. 68. Summary of Antibody-antigen Interaction
    55. 69. 10.2 Development of Immunity
    56. 70. <ul><li>Describe and explain primary and secondary immune responses to antigen. </li></ul><ul><li>Explain the concept of self and non-self recognition and its application in organ transplant, grafting and blood transfusion. </li></ul>
    57. 71. <ul><li>Antigens interact with specific lymphocytes, inducing immune responses and immunological memory </li></ul>
    58. 72. <ul><li>Although it encounters a large repertoire of B and T cells, a microorganism interacts only with lymphocytes bearing receptors specific for its various antigenic molecules </li></ul><ul><li>The selection of a lymphocytes by one of the microbe’s antigens activate the lymphocyte, stimulating it to divide and differentiate and eventually, producing two clones of cells </li></ul>CLONAL SELECTION
    59. 73. <ul><li>One clone consists of a large number of effector cells , short-lived cells that combat the same antigen </li></ul><ul><li>Effector cells are populations of cells resulting from divisions of lymphocytes that were activated by the binding of antigens to their antigen receptors </li></ul><ul><li>The other clone consists of memory cells bearing the receptors for the same antigen </li></ul>
    60. 74. Antigen molecules bind to the antigen receptors of only one of the six B cells shown The selected B cell proliferates to give rise to a clone of identical cells bearing receptors for the selecting antigen Some proliferating cells develop into long-lived memory cells that can respond rapidly upon subsequent exposure to the same antigen Some proliferating cells develop into short-lived plasma cells that secrete antibody specific for the antigen
    61. 75. <ul><li>The selective proliferation and differentiation of lymphocytes that occur the first time the body is exposed to an antigen is the primary immune response </li></ul><ul><li>About 10 – 17 days lag period between initial exposure and production of effector cells </li></ul>PRIMARY IMMUNE RESPONSE
    62. 76. <ul><li>During this period, selected B cells and T cells generate antibody-producing effector B cells, called plasma cells, and effector T cells respectively </li></ul><ul><li>While this response is developing, a stricken individual may become ill, but symptoms of the illness diminish and disappear as antibodies and effector T cells clear the antigen from the body </li></ul>
    63. 77. <ul><li>A second exposure to the same antigen at some later time elicits the secondary immune response </li></ul><ul><li>This response is faster (only 2 to 7 days), of greater magnitude and more prolonged </li></ul><ul><li>The antibodies produced in the secondary response tend to have greater affinity for the antigen than those secreted in the primary response </li></ul>SECONDARY IMMUNE RESPONSE
    64. 80. <ul><li>The immune systems capacity to generate secondary immune response is called immunological memory , based not only on effector cells, but also clones of long-lived T and B memory cells </li></ul>IMMUNOLOGICAL MEMORY
    65. 81. <ul><li>Memory cells are not active during primary response and survive in the system for long periods. </li></ul><ul><li>When the same antigen that caused a primary immune response again enters the body, the memory cells are activated and rapidly proliferate to form a new clone of effector cells and memory cells </li></ul><ul><li>These new clones of effector and memory cells are the secondary immune response </li></ul>
    66. 83. The Development of Active Immunity <ul><li>1. Immunity to smallpox in Jenner’s patients occurred because their inoculation with cowpox stimulated the development of lymphocyte clones with receptors that could bind not only to cowpox but also to smallpox antigens. </li></ul>
    67. 84. <ul><li>2. As a result of clonal selection, a second exposure, this time to smallpox, stimulates the immune system to produce large amounts of the antibody more rapidly than before. </li></ul>
    68. 85. 10.2.1 Self and Non-self Recognition <ul><li>Lymphocytes do not react to most self antigens, but T cells do have a crucial interaction with one important group of native molecules </li></ul><ul><li>These are a collection of cell surface glycoproteins encoded by a family of genes called the major histocompatibility complex (MHC) or specifically in humans, human leukocyte antigens (HLA) </li></ul>
    69. 86. <ul><li>Two main classes of MHC molecules mark body cells as self </li></ul><ul><li>Class I MHC molecules are found on almost all nucleated cells – that is on almost every cells </li></ul><ul><li>~ the interaction between the antigen-presenting infected cell is greatly enhanced by a T cell surface protein called CD8 </li></ul>
    70. 87. <ul><li>ii. Class II MHC molecules are restricted to few specialized cell types, including macrophages, B cells, activated T cells and those inside the thymus </li></ul><ul><li>~ The interaction between antigen-presenting cell and a T H cell is greatly enhanced by CD4 </li></ul>
    71. 88. MHC <ul><li>It is unlikely that any two people, except identical twins, will have the same set of MHC molecules </li></ul><ul><li>The MHC provides a biochemical fingerprint virtually unique to each individual </li></ul><ul><li>MHC molecules vary from person to person because of their central role in the immune system </li></ul>
    72. 89. <ul><li>There are two main types of T cells, and responds to one class of MHC molecules </li></ul><ul><li>Cytotoxic T cells (T C ) have antigen receptors that bind to protein fragments displayed by the body’s class I MHC molecules </li></ul><ul><li>~ Tc responds by killing the infected cells </li></ul>
    73. 90. <ul><li>A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and transported to the cell surface. </li></ul><ul><li>The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. </li></ul>(CD8 protein)
    74. 91. <ul><li>ii. Helper T cells (T H ) have receptors that bind to peptides displayed by the body’s class II MHC molecules </li></ul><ul><li>~ Macrophages and B cells (antigen - presenting cells, APCs), ingest bacteria and viruses and then destroy them </li></ul>
    75. 92. <ul><li>A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and transported to the cell surface. </li></ul><ul><li>The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. </li></ul>(CD4 protein)
    76. 93. Fig. 57.9
    77. 94. IMMUNE RESPONSES
    78. 95. The immune system can mount two types of responses depending on the antigen which stimulates the system i. Humoral response ii. Cell-mediated response <ul><li>Humoral immunity : involves B cell activation and results from the production of antibodies that circulate in the blood plasma and lymph </li></ul><ul><li>Circulating antibodies defend mainly against free bacteria, toxins and viruses in the body fluid </li></ul>
    79. 96. <ul><li>Cell-mediated immunity : T lymphocytes attack viruses and bacteria within infected cells and defend against fungi, protozoa and parasitic worms </li></ul><ul><li>They also attack “non-self” cancer and transplant cells </li></ul>
    80. 97. <ul><li>The humoral and cell-mediated immune responses are linked by signalling interactions, especially via the T cells </li></ul>
    81. 99. <ul><li>1. Helper T lymphocytes function in both humoral and cell-mediated immunity </li></ul>Development of Cellular Immunity
    82. 100. <ul><li>Both types of immune responses are initiated by interactions between antigen-presenting cells (APCs) and T H cells </li></ul><ul><li>The APCs, including macrophages and some B cells, tell the immune system, via T H cells, that a foreign antigen is in the body </li></ul><ul><li>At the heart of the interactions between APCs and T H cells are class II MHC molecules produced by the APCs, which bind to foreign antigens </li></ul>
    83. 102. <ul><li>An APC engulfs a bacterium and transport a fragment of it to the cell surface via a class II MHC molecule </li></ul><ul><li>A specific T H cell is activated by binding to the MHC-antigen complex. The CD4 protein of the T H cells enhances the activation, as does interleukin-1 (IL-1) secreted by the APC </li></ul><ul><li>The activated T H cell proliferates, giving rise to a clone of identical clones (not shown), all with receptors keyed to the same MHC-antigen combination. These cells secrete cytokines (e.g. : Interleukin-2) </li></ul><ul><li>The cytokines further stimulate the T H cells and also help activates B cells and T C cells </li></ul>
    84. 103. <ul><li>Activated TH cells that bind to a class II MHC-antigen complex on an APC are induced to differentiate into either of two clones of cells : </li></ul><ul><li>i. Activated T H cells ~ secrete cytokines, factors that stimulate other lymphocytes (e.g. : IL-2 stimulates differentiation of B cells into antibody-secreting plasma cells and induces T C cells to become active killers) </li></ul>
    85. 104. <ul><li>ii. Memory T H cells ~ IL-1 secreted from APCs, promotes activation of the T H cells and the subsequent secretion of IL-2 from the activated T H cell. </li></ul><ul><li>~ T H cells themselves are regulated by cytokines </li></ul>
    86. 105. <ul><li>2. In the cell-mediated response, cytotoxic T cells defend against intracellular pathogens </li></ul>
    87. 106. <ul><li>Antigen-activated T C cells, kill cancers cells and cells infected by viruses and other intracellular pathogens </li></ul><ul><li>This is mediated through class 1 MHC molecules </li></ul><ul><li>All nucleated cells continuously produce class 1 MHC molecules, which capture a small fragment of one of the other proteins synthesized by that cell and carries it to the surface </li></ul>
    88. 107. <ul><li>An infected cell (or cancer cell) displays as an antigen fragment on its surface using a class I MHC molecule. A specific T C cell is activated by binding to the MHC-antigen complex. The CD8 protein of the T C cell enhances the activation, along with IL-2 from T H cells (not shown) </li></ul><ul><li>The activated T C cell discharges perforin molecules, which create pores in the membrane of the infected cell. </li></ul><ul><li>Water and ions flow into the infected cell, and the cell lyses. </li></ul>
    89. 108. Cytotoxic T cell
    90. 109. <ul><li>Destruction of the host cell not only removes the site where pathogens can reproduce, but also exposes the pathogens to circulating antibodies from humoral response. </li></ul><ul><li>T C continue to live after destroying the infected cell and may kill many others displaying the same antigen-class I MHC marker </li></ul>
    91. 110. <ul><li>T C also function to destroy cancer cells </li></ul><ul><li>Cancer cells possess distinctive markers not found on normal cells, known as tumor antigen </li></ul><ul><li>T cells recognize these markers as non-self and attach and lyse the cancer cells </li></ul><ul><li>Certain types of cancers and viruses have diminish the amounts of class I MHC proteins on affected cells, thereby reducing the ability of T C to recognize and destroy them </li></ul>
    92. 112. Development of Humoral Immunity <ul><li>3. In the humoral response, B cells make antibodies against extracellular pathogens </li></ul>
    93. 113. <ul><li>The humoral response occurs when an antigen binds to B cell receptors that are specific for the antigen epitopes </li></ul><ul><li>The B cells differentiate into a clone of plasma cells which begin to secrete antibodies that are most effective against pathogens circulating in the blood and lymph </li></ul><ul><li>Memory cells are also produced and form the basis for secondary immune responses </li></ul>
    94. 114. <ul><li>A macrophage ingests a pathogen </li></ul><ul><li>Class II MHC proteins within the cell bind to fragments of the pathogen and transport them to the cell surface </li></ul><ul><li>A T H cell with a receptor specific for the presented antigen contacts the macrophage and is induced to proliferate and secrete cytokines </li></ul><ul><li>The activated T H cell binds with a B cell that has previously taken up antigen. As an APC, the B cell’s class II MHC molecules present fragments of the antigen. Cytokines help activate the B cell. </li></ul><ul><li>The B cell proliferates and differentiates into memory cells and plasma cells that secrete antibody molecules specific for the bacterium. </li></ul>
    95. 115. <ul><li>When activated a B cell gives rise to a clone of plasma cells. </li></ul><ul><li>Each of these effector cells secretes up to 2000 antibodies per second into body fluids for its 4 – 5 day lifespan </li></ul><ul><li>The specific antibodies help eliminate the foreign invader from the body </li></ul>
    96. 117. The immune system’s capacity to distinguish self from nonself limits blood transfusion and tissue transplantation
    97. 118. <ul><li>In addition to attacking pathogens, the immune system will also attack cells from other individuals. </li></ul><ul><ul><li>For example, a skin graft from one person to a nonidentical individual will look healthy for a day or two, but it will then be destroyed by immune responses. </li></ul></ul><ul><ul><li>Interestingly, a pregnant woman does not reject the fetus as a foreign body, as apparently, the structure of the placenta is the key to this acceptance. </li></ul></ul>
    98. 119. <ul><li>One source of potential problems with blood transfusions is an immune reaction from individuals with incompatible blood types. </li></ul><ul><ul><li>In the ABO blood groups , an individual with type A blood has A antigens on the surface of red blood cells. </li></ul></ul><ul><ul><ul><li>This is not recognized as an antigen by the “owner,” but it can be identified as foreign if placed in the body of another individual. </li></ul></ul></ul><ul><ul><li>B antigens are found on type B red blood cells. </li></ul></ul><ul><ul><li>Both A and B antigens are found on type AB red blood cells. </li></ul></ul><ul><ul><li>Neither antigen is found on type O red blood cells. </li></ul></ul>
    99. 120. <ul><li>A person with type A blood already has antibodies to the B antigen, even if the person has never been exposed to type B blood. </li></ul><ul><ul><li>These antibodies arise in response to bacteria (normal flora) that have epitopes very similar to blood group antigens. </li></ul></ul><ul><ul><li>Thus, an individual with type A blood does make antibodies to A-like bacterial epitopes - these are considered self - but that person does make antibodies to B-like bacterial epitopes. </li></ul></ul><ul><ul><li>If a person with type A blood receives a transfusion of type B blood, the preexisting anti-B antibodies will induce an immediate and devastating transfusion reaction. </li></ul></ul>
    100. 122. <ul><li>However, another blood group antigen, the Rh factor , can cause mother-fetus problems because antibodies produced to it are IgG. </li></ul><ul><ul><li>This situation arises when a mother that is Rh-negative (lacks the Rh factor) has a fetus that is Rh-positive, having inherited the factor from the father. </li></ul></ul><ul><ul><li>If small amounts of fetal blood cross the placenta as may happen late in pregnancy or during delivery, the mother mounts a T-dependent humoral response against the Rh factor. </li></ul></ul><ul><ul><li>The danger occurs in subsequent Rh-positive pregnancies, when the mother’s Rh-specific memory B cells produce IgG antibodies that can cross the placenta and destroy the red blood cells of the fetus. </li></ul></ul>
    101. 123. <ul><li>To prevent this, the mother is injected with anti-Rh antibodies after delivering her first Rh positive baby. </li></ul><ul><ul><li>She is, in effect, passively immunized (artificially) to eliminate the Rh antigen before her own immune system responds and generates immunological memory against the Rh factor, endangering her future Rh-positive babies. </li></ul></ul>
    102. 124. 10.3 Immune Disorder: SLE and AIDS
    103. 125. <ul><li>Briefly explain SLE, AIDS </li></ul><ul><li>Explain the mechanism of action of HIV Infection and Symptoms of AIDS. </li></ul><ul><li>List the possible causes and prevention of HIV Infection. </li></ul>
    104. 126. <ul><li>Malfunctions of the immune system can produce effects ranging from the minor inconvenience of some allergies to the serious and often fatal consequences of certain autoimmune and immunodeficiency diseases. </li></ul>
    105. 127. <ul><li>Allergies are hypersensitive (exaggerated) responses to certain environmental antigens, called allergens. </li></ul><ul><ul><li>One hypothesis to explain the origin of allergies is that they are evolutionary remnants of the immune system’s response to parasitic worms. </li></ul></ul><ul><ul><li>The humoral mechanism that combats worms is similar to the allergic response that causes such disorders as hay fever and allergic asthma. </li></ul></ul>
    106. 128. <ul><li>The most common allergies involve antibodies of the IgE class. </li></ul><ul><ul><li>Hay fever, for example, occurs when plasma cells secrete IgE specific for pollen allergens. </li></ul></ul><ul><ul><li>Some IgE antibodies attach by their tails to mast cells present in connective tissue, without binding to the pollen. </li></ul></ul><ul><ul><li>Later, when pollen grains enter the body, they attach to the antigen-binding sites of mast cell-associated IgE, cross-linking adjacent antibody molecules. </li></ul></ul>
    107. 129. <ul><li>This event triggers the mast cell to degranulate - that is, to release histamines and other inflammatory agents from vesicles called granules. </li></ul>
    108. 130. <ul><li>High levels of histamines cause dilation and increased permeability of small blood vessels. </li></ul><ul><ul><li>These inflammatory events lead to typical allergy symptoms: sneezing, runny nose, tearing eyes, and smooth muscle contractions that can result in breathing difficulty. </li></ul></ul><ul><ul><li>Antihistamines diminish allergy symptoms by blocking receptors for histamine. </li></ul></ul>
    109. 131. <ul><li>Sometimes, an acute allergic response can result in anaphylactic shock , a life threatening reaction to injected or ingested allergens. </li></ul><ul><ul><li>Anaphylactic shock results when widespread mast cell degranulation triggers abrupt dilation of peripheral blood vessels, causing a sudden drop in blood pressure. </li></ul></ul><ul><ul><ul><li>Death may occur within minutes. </li></ul></ul></ul><ul><ul><li>Triggers of anaphylactic shock in susceptible individuals include bee venom, penicillin, or foods such as peanuts or fish. </li></ul></ul><ul><ul><li>Some hypersensitive individuals carry syringes with epinephrine, which counteracts this allergic response. </li></ul></ul>
    110. 132. Tissue grafts and organ transplantation <ul><li>The MHC is responsible for stimulating the rejection of tissue grafts and organ transplants. </li></ul><ul><li>Because MHC creates a unique protein </li></ul><ul><li> fingerprint for each individual, foreign </li></ul><ul><li>MHC molecules are antigenic, inducing </li></ul><ul><li>immune responses against the donated </li></ul><ul><li>tissue or organ. </li></ul>
    111. 133. <ul><li>To minimize rejection, attempts are made to match MHC of tissue donor and recipient as closely as possible. </li></ul><ul><li>In the absence of identical twins, </li></ul><ul><li>siblings usually provide the closest </li></ul><ul><li> tissue-type match. </li></ul>
    112. 134. <ul><li>In addition to MHC matching, various medicines are necessary to suppress the immune response to the transplant. </li></ul><ul><li>However, this strategy leaves the </li></ul><ul><li>recipient more susceptible to </li></ul><ul><li>infection and cancer during the </li></ul><ul><li>course of treatment. </li></ul>
    113. 135. <ul><li>More selective drugs, which suppress helper T cell activation without crippling nonspecific defense or T-independent humoral responses, have greatly improved the success of organ transplant. </li></ul>
    114. 136. <ul><li>In bone marrow transplants, it is the graft itself, rather than the host, that is the source of potential immune rejection. </li></ul><ul><li>Bone marrow transplants are used to treat leukemia and other cancers as well as various hematological diseases. </li></ul>
    115. 137. <ul><li>Prior marrow transplants, the recipient is typically treated with </li></ul><ul><li>irradiation to eliminate the </li></ul><ul><li>recipient’s immune system, leaving </li></ul><ul><li>little chance of graft rejection. </li></ul><ul><li>However, the donated marrow, </li></ul><ul><li>containing lymphocytes, may react </li></ul><ul><li>against the recipient, producing graft </li></ul><ul><li>versus host reaction, unless well </li></ul><ul><li>matched. </li></ul>
    116. 138. AUTOIMMUNE DISEASES The Body Attacks Itself <ul><li>Autoimmunity arises when the ‘immune’ system fails to distinguish between ‘self’ and ‘non-self’ (foreign) cells, and attacks ‘self’, or body tissues. </li></ul><ul><li>Causes generally not known, but may involve genetic, viral and environmental factors or after recovery from infection. </li></ul>
    117. 139. e.g. Autoimmune diseases <ul><li>Myasthenia gravis </li></ul><ul><li>Multiple sclerosis </li></ul><ul><li>Rheumatoid arthritis </li></ul><ul><li>Systemic lupus erythematosus </li></ul><ul><li>Heart damage following rheumatic fever & Type I diabetes. </li></ul>
    118. 140. Rheumatoid Arthritis of the Hands Rheumatoid arthritis can result in severe deformation of the hands, wrists, feet, ankles, hips, and shoulders. The characteristic swelling, pain, and restricted movement Rheumatoid arthritis can result in severe deformation of the hands, wrists, feet, ankles, hips and shoulders. The characteristic swelling, pain and restricted movement
    119. 141. Multiple sclerosis <ul><ul><ul><li>In this i ll ness the myelin sheath covering the spinal cord is destroyed, leading to difficulty in walking and other movements. The damage in multiple sclerosis is not produced by an auto antibody but by a lymphocyte that reacts directly with the protective sheath. </li></ul></ul></ul>
    120. 142. Myasthenia gravis Myasthenia gravis is a neuromuscular disease that causes weakness and fatigue, most commonly in the muscles of the eyes, face, throat and limbs. MG is an acquired disease, meaning it isn't inherited as a genetic disease. The word &quot;myasthenia&quot; means muscle weakness.
    121. 143. Systemic lupus erythematosus                                                                             
    122. 144. <ul><li>In SLE (lupus), the immune system generates antibodies against all sorts of self molecules, including histamines </li></ul><ul><li>Lupus is characterized by skin rashes, fever, arthritis and kidney dysfunction </li></ul>
    123. 145. A I D S C QUIRED MMUNO - EFICIENCY YNDROME
    124. 146. INTRODUCTION
    125. 147. <ul><li>In 1981, increased rates of two rare diseases, Kaposi’s sarcoma, a cancer of the skin and blood vessels, and pneumonia caused by the protozoan Pneumocystis carinii , were the first signals to the medical community of a new threat to humans, later known as acquired immunodeficiency syndrome , or AIDS . </li></ul><ul><ul><li>Both conditions were previously known to occur mainly in severely immunosuppressed individuals. </li></ul></ul>
    126. 148. <ul><ul><li>People with AIDS are susceptible to opportunistic diseases . </li></ul></ul><ul><li>Opportunistic disease : infection rarely observed in humans with normal immune response </li></ul><ul><li>Eg : The Pneumocystis protozoan is an ubiquitous organism, yet it does not cause pneumonia in a person with a healthy immune system </li></ul><ul><li>In people with AIDS, opportunistic diseases, neurologic damage and physiological wasting, lead to death </li></ul>
    127. 149. <ul><li>In 1983, a retrovirus, now called human immunodeficiency virus ( HIV ) , had been identified as the causative agent of AIDS. </li></ul>A T cell infected with HIV. The virus (blue) bud continuously from the surface of the T cell (orange). The cell will die, but only after it produces many copies of its viral killers
    128. 150. <ul><li>With the AIDS mortality close to 100%, HIV is the most lethal pathogen ever encountered. </li></ul><ul><ul><li>Molecular studies reveal that the virus probably evolved from another HIV-like virus in chimpanzees in central Africa and appeared in humans sometimes between 1915 and 1940. </li></ul></ul><ul><ul><ul><li>These first rare cases of infection and AIDS went unrecognized. </li></ul></ul></ul>
    129. 151. <ul><li>There are two major strains of the virus, HIV-1 and HIV-2. </li></ul><ul><ul><li>HIV-1 is the more widely distributed and more virulent. </li></ul></ul><ul><li>Both strains infect cells that bear CD4 molecules, especially helper T cells and class II MHC-bearing antigen-presenting cells, but also macrophages, some lymphocytes and some brain cells. </li></ul><ul><ul><li>CD4 functions as the major receptor for the virus. </li></ul></ul>
    130. 152. Causative Agent <ul><li>The viral particle includes: </li></ul><ul><ul><li>an envelope with glycoprotein for binding to receptor molecule on T H surface </li></ul></ul><ul><ul><li>a capsid containing: </li></ul></ul><ul><li>1. two identical RNA strands as its genome </li></ul><ul><li>2. two copies of reverse transcriptase. </li></ul>
    131. 153. Causative Agent RNA Capsid RNA Reverse transcriptase enzyme Viral envelope Glycoprotein
    132. 154. <ul><li>The entry of the virus requires not only CD4 on the surface of the susceptible cells but also a second protein molecule, a coreceptor . </li></ul><ul><ul><li>Two of the coreceptors that have been identified normally function as receptors for chemokines. </li></ul></ul><ul><ul><li>Some people who are innately resistant to HIV-1 owe their resistance to defective chemokine receptors which prevents HIV from binding and infecting cells. </li></ul></ul>
    133. 155. The Causes
    134. 156. The Causes … mainly because of the exchange of body fluid: <ul><li>Promiscuity (having many transient sexual relationship) </li></ul><ul><li>Through injection drug use </li></ul><ul><li>Prenatal infection or in infancy </li></ul><ul><li>Blood transfusion. </li></ul>
    135. 157. The Symptoms
    136. 158. The Symptoms Flu or mononucleosis <ul><li>persistent or recurrent fever </li></ul><ul><li>severe dry cough </li></ul><ul><li>sore throat </li></ul><ul><li>night sweat </li></ul><ul><li>chronic fatigue </li></ul><ul><li>decreased appetite (rapid </li></ul><ul><li>weight loss) blood/mucus in </li></ul><ul><li>feces </li></ul><ul><li>upper-body rash </li></ul>
    137. 159. The Symptoms Behavioral dementia <ul><li>(madness) due to the damage </li></ul><ul><li>on nervous system (esp. brain </li></ul><ul><li>and myelin sheath) </li></ul>
    138. 160. The Symptoms Pneumocystis carinii pneumonia (PCP) <ul><li>inflammation of lungs </li></ul><ul><li>(alveoli filled with fluid) </li></ul>
    139. 161. The Symptoms Kaposi’s sarcoma a cancer of the skin and blood vessels (purplish spot on skin)
    140. 162. The mechanism of infection and HIV replication
    141. 163. The Mechanism of infection and the Replication of HIV <ul><li>Glycoprotein on the envelope bind to specific receptors on the host’s membrane (T H cell) </li></ul><ul><li>The envelope fuses with the host’s membrane, </li></ul><ul><li>transporting the capsid and viral genome inside </li></ul>
    142. 165. <ul><li>Reverse transcriptase synthesizes double </li></ul><ul><li>stranded DNA from the viral RNA </li></ul>The Mechanism of infection and the Replication of HIV
    143. 167. The Mechanism of infection and the Replication of HIV <ul><li>The double-stranded DNA is incorporated as </li></ul><ul><li>a provirus into the host cell's chromosomal </li></ul><ul><li>DNA, where it may lie dormant for years. </li></ul>
    144. 168. The Mechanism of infection and the Replication of HIV <ul><li>The provirus is transcribed into mRNA and went </li></ul><ul><li>out from the host’s nucleus into its cytoplasm </li></ul>
    145. 170. The Mechanism of infection and the Replication of HIV <ul><li>mRNA are translated to viral protein forming : </li></ul><ul><ul><ul><ul><li>protein for capsid </li></ul></ul></ul></ul><ul><ul><ul><ul><li>viral RNA </li></ul></ul></ul></ul><ul><ul><ul><ul><li>reverse transcriptase enzyme </li></ul></ul></ul></ul>
    146. 171. The Mechanism of infection and the Replication of HIV <ul><li>Protein coats form around viral RNA and reverse </li></ul><ul><li>transcriptase molecules and move towards host’s </li></ul><ul><li>membrane cell. </li></ul>
    147. 172. The Mechanism of infection and the Replication of HIV <ul><li>Viruses bud from the host cell, acquiring envelopes </li></ul><ul><li>as they leave. </li></ul>
    148. 174. 1 2 3 4 5 6 7 8
    149. 175. The new HIV particles leaving the host’s cell Mature form Budding particle
    150. 176. <ul><li>In spite of these challenges, the immune system engages in a prolonged battle against HIV. </li></ul><ul><ul><li>(1) The immune response diminishes the initial viral load, but HIV continues to replicate in lymphatic tissue. </li></ul></ul><ul><ul><li>(2) Viral load gradually rises as HIV is released from lymphatic tissue and helper T cell levels decrease. </li></ul></ul><ul><ul><li>(3) This results in extensive loss of humoral and cell-mediated immunity. </li></ul></ul>
    151. 179. THE STAGES OF HIV INFECTION <ul><li>HIV concentration increases rapidly within a 6-month of infection but is then almost eliminated by the immune response. </li></ul><ul><li>However, in 1 to 3 years of infection, some of the viruses survive and slowly increase the number of the viruses. </li></ul><ul><li>In 9 to 10 years of infection, the body almost total loss of cellular immunity. </li></ul><ul><li>While the T helper cell concentration decreases, AIDS is the last stage of the process. </li></ul>
    152. 180. HIV on a lymphocyte HIV particles
    153. 181. Treatment of AIDS <ul><li>No cure for HIV infection is known, although research is intense in the areas of vaccine production and chemotherapy </li></ul><ul><li>Several drugs have been identified as helpful in delaying symptoms of AIDS and in some cases in prolonging the life of those infected with HIV </li></ul>
    154. 182. <ul><li>The most promising drugs : Azidothymidine (AZT) is an effective inhibitor of HIV replication </li></ul><ul><li>A major problem observed with many AIDS drugs is that the compounds are frequently toxic when used on a long term basis </li></ul>
    155. 183. The Preventive Measures <ul><li>Treat HIV infection as an illness </li></ul><ul><li>Counseling and HIV testing for the patient </li></ul><ul><li>Education for children and adults </li></ul><ul><li>Health care programme providing antiretroviral therapy to extend life and to reduce HIV transmission rate . </li></ul>
    156. 184. <ul><li>Antiretroviral therapy for pregnant women </li></ul><ul><li>to reduce prenatal HIV transmission. </li></ul><ul><li>Promote sexual barrier precautions </li></ul><ul><li>(use of condoms) </li></ul><ul><li>War on drug abuse. </li></ul>The Preventive Measures

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