Immune Response

IMMUNE RESPONSE: 

IMMUNE RESPONSE Dr.T.V.Rao MD Dr.T.V.Rao MD 1

Human Body is a Complex Structure: 

Human Body is a Complex Structure 2 Dr.T.V.Rao MD

Immune System Controls the Immune Responses: 

Immune System Controls the Immune Responses 3 Dr.T.V.Rao MD

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Organs of Immunity Coordinate different functions: 

Organs of Immunity Coordinate different functions 5 Dr.T.V.Rao MD

Immunity is a less Understood Puzzle: 

Immunity is a less Understood Puzzle 6 Dr.T.V.Rao MD

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Path of Immune Response: 

Path of Immune Response 9 Dr.T.V.Rao MD

Immune Response Protects: 

Immune Response Protects 10 Dr.T.V.Rao MD

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Immune Response – A complex Mechanisms : 

Immune Response – A complex Mechanisms 12 Dr.T.V.Rao MD

Several Cell Interaction compromises the Immune Response: 

Several Cell Interaction compromises the Immune Response 13 Dr.T.V.Rao MD

B Cells and T Cells work in Coordination: 

B Cells and T Cells work in Coordination 14 Dr.T.V.Rao MD

Immune response works at Cellular level: 

Immune response works at Cellular level 15 Dr.T.V.Rao MD

The Immune response: 

16 The Immune response An immune response is what the immune system does when confronted by an antigen. An immune response is an elaborate interplay between antigen, non-specific defenses, and B and T lymphocytes . The process involves direct contact (cells, molecules bind to receptors on cell surfaces) and cytokines (messenger molecules) that also bind to receptors on cell surfaces. 16 Dr.T.V.Rao MD

Results of Immune Response: 

Results of Immune Response Beneficial, Indifferent, Injurious, Reactions follow against any antigen either living or dead. May respond in Specific or No reactivity or Tolerance. 17 Dr.T.V.Rao MD

Classification of Immune Response: 

Classification of Immune Response 1 Humoral 2 Cell Mediated type May work together. May work in opposite way, One may be more active than other. 18 Dr.T.V.Rao MD

Immune Response Humoral / Cell Mediated : 

Immune Response Humoral / Cell Mediated Active against Most Extra cellular Bacterial pathogens Viruses, Participates in Type 1 , 2, 3, Hypersensitivity reactions Auto Immune Disorders. Protects against, Fungus, Viruses IC bacterial infections Rejection of Homograft ,GVH, Immunological survelliance,cancer T cell mediated Hypersensitivity Auto Immune Disorders 19 Dr.T.V.Rao MD

Structure of Immunoglobulin: 

Structure of Immunoglobulin 20 Dr.T.V.Rao MD

Humoral Immune Response: 

Humoral Immune Response Produces Antibodies B Cell – Plasma cell Antigen Presented to Immunocompetent cells Processed – Secretion of Antibodi es, Dr.T.V.Rao MD 21

Production of Antibodies: 

Production of Antibodies Immune response is brought about by three types of cells 1 APC macrophages, and dendritic cells, 2 T Cell and 3 B cells The first step is capture and processing of antigens by APC and their presentation with the association of appropriate MHC molecule to T cells However some polysaccharides and simple molecules with repeating epitopes do not require T Cell particip ation 22 Dr.T.V.Rao MD

Stages of Antibody mediated immune response: 

Stages of Antibody mediated immune response Contain three stages 1 The entry of antigen, its distribution and fate in the tissues and its contact with appropriate immunocompetent cells 2 The secretion of antigen by cells and the control of the antibody forming process 3 The secretion of antibody its distribution in tissues and body fluids and manifestations of its effects. 23 Dr.T.V.Rao MD

PowerPoint Presentation: 

Pathogens damage tissue in a variety of ways * e.g., LPS; a polyclonal B cell activator, also see next slide * 24 Dr.T.V.Rao MD

Pattern of Antibody production.: 

Pattern of Antibody production. A Lag Phase A Log Phase raise of antibody levels, Plateau A phase of Decline . Dr.T.V.Rao MD 25

Primary and Secondary Immune Responses: 

Primary and Secondary Immune Responses A single injection of antigen helps in sensitizing or priming of immunocpompent cell producing particular antibody than in the actual elaboration of high levels of antibody. Effective levels of antibody are usually induced by only subsequent injection of antigens. 26 Dr.T.V.Rao MD

Booster Dose: 

Booster Dose The antibody response to an initial antigenic stimuli differs qualitatively and quantitatively from response to subsequent stimuli with the same antigen The former primary response and later secondary response 27 Dr.T.V.Rao MD

Primary and Secondary Response: 

Primary and Secondary Response The primary response is slow, sluggish and short lived with long lag phase and does not persist for long time The secondary response is prompt powerful and prolonged with short or negligible lag phase and with higher level of antibodies 28 Dr.T.V.Rao MD

Types of Antibody Response,: 

Types of Antibody Response , Initial Antigenic Stimulus (Primary Response Ig M Response is slow and short lived, Secondary Response Ig G Response is Prompt ,Powerful and Prolonged Higher level of Antibodies and Lasts longer, 29 Dr.T.V.Rao MD

How long a Antibody be active: 

How long a Antibody be active The duration of the lag phase and persistence of the antibody dependent on the nature of the antigen In diphtheria toxoid the lag phase in the primary response may be long as 2 -3 weeks In pneumococcal polysaccharides antigens the antibodies are detected in few hours 30 Dr.T.V.Rao MD

Priming and Booster doses: 

Priming and Booster doses The first injection is known as priming dose and subsequent injection as booster dose. With live vaccines a single dose is sufficient a single dose is sufficient as multiplication of the organisms in the body provides a continuous antigenic stimulus that acts as both the priming and booster dose 31 Dr.T.V.Rao MD

Fate of Antigens: 

Fate of Antigens Depends on the physical and chemical nature of antigens, dose and route of entry Whether induced primarily or secondarily The antigens introduced by IV are rapidly localized in the spleen, liver, bone marrow kidney and lungs Broken down by RES cells excreted in urine About 70 – 80 % eliminated in one or two days 32 Dr.T.V.Rao MD

Fate of Antigens: 

Fate of Antigens When antigens are introduced by subcutaneously are mainly localized in the draining lymph nodes only small amounts being found in the spleen The pariculate antigens are removed from circulation in two phase – the first is antigens are engulfed by phagocytic cells broken down and eliminated 33 Dr.T.V.Rao MD

Fate of Antigen: 

Fate of Antigen With the appearance of specific antibody the phase of immune elimination begins The antigen and antibody complexes are rapidly phagocytized results in disappearance of antigen from circulation Dr.T.V.Rao MD 34

Immunoglobulin controlling genes and Generation of Diversity.: 

Immunoglobulin controlling genes and Generation of Diversity. Genes control Antibody production and Diversity, V and C regions Kappa light chain / Lambda light chain Rearrangements produce enormous diversity variety of Immunoglobulin Combinations produce random selections. 35 Dr.T.V.Rao MD

Immunoglobulin Switching.: 

Immunoglobulin Switching. Ig M specific for Antigen is produced. Switch to others Ig G - Ig A -Ig E But retain the same specificity, But carry different Biological activities 36 Dr.T.V.Rao MD

Relation of Dose and Nature of Antigen to Antibody production.: 

Relation of Dose and Nature of Antigen to Antibody production. Single Dose Sensitizing. Subsequent Dose More effective. Non Living Vaccines multiple doses. Living Vaccines one Dose is productive. Fate of Antigen I V eliminate faster, in 2-3 days, in spleen. SC Lymph nodes Little in spleen Engulfed by Phagocytes Broken Down and eliminated. 37 Dr.T.V.Rao MD

Fate of Antigen in the Host: 

Fate of Antigen in the Host Ag+Ab from complexes and Phagocytes will engulf and Disappear -- Immune Elimination. Immune Complexes can cause damage. Proteins eliminated in 1-2 weeks, Polysaccharides months to years. Pneumococcal polysaccharides up to 20 years. 38 Dr.T.V.Rao MD

Production of Antibodies.: 

Production of Antibodies . Immune Responses to Antigen, Antigen Presenting Cells APC Macrophages Dendritic Cells T and B Lymphocytes, Capture by APC ( Proteins RBC ) T Cell take active part. T Cell Independent - Polysaccharides. 39 Dr.T.V.Rao MD

Production of Antibodies needs help and coordination with other structures : 

Production of Antibodies needs help and coordination with other structures CD4 Helper cells MHC II CD8 Cytotoxic cells MHC TH cells require two signals IL1 Next produce IL2 Produce cytokines IL4 IL5 IL6 B cells stimulated Produce antibody producing plasma cells produced 40 Dr.T.V.Rao MD

Factors Influencing Antibody production: 

Factors Influencing Antibody production 41 Dr.T.V.Rao MD

Factors Influencing Antibody Production: 

Factors Influencing Antibody Production Under genetic control, May be responder or Non responder.- defines the capacity of the individual to respond or not respond Ir (Immune response genes) control this property. Age The embryos is immunologic ally immature During the embryonic life the developing lymphoid cells come into contact with all the tissue antigens of the body released by cellular breakdown – lead to elimination of self antigens 42 Dr.T.V.Rao MD

Immunity in Neonates: 

Immunity in Neonates Early mechanisms of self tolerance. -> 3-6 months Maternal antibodies , Ig G 5-7 years Ig A 10-15 years B cell responses to most proteins and other T cells dependent develop early. The responses to Polysaccharide and other T cell independent antigens develop later. 43 Dr.T.V.Rao MD

Humoral Immunity in vivo uses: 

Humoral Immunity in vivo uses Immunoglobulin IgA can stop colonization of mucosal surface. It interferes with the attachment molecular adhesions present on the bacterial surface. Bacterial exotoxins are inhibited – as the antibodies can prevent interaction of enzymes with substrate. 44 Dr.T.V.Rao MD

Humoral immunity in vivo uses: 

Humoral immunity in vivo uses Antibodies can kill bacteria. Antibodies can affect the specific transport systems and deprive the energy needs of the bacteria. Affect the motility Reduces the invasion Antibodies can cause agglutination Stimulate the phagocytosis, and complement activity. 45 Dr.T.V.Rao MD

Other Factors influencing the Antibody production: 

Other Factors influencing the Antibody production Nutrition Malnutrition Humoral reduced, CMI reduced Route of administration Large particles – increased. Application to skin CMI Deltoid more effective 46 Dr.T.V.Rao MD

Other factors,: 

Other factors, Size and Dose has relation Massive Dose paralysis. Anamnestic reaction Administration of Multiple antigens Triple antigen, Freund’s Adjuvant. Increases with Tubercle Bacilli 47 Dr.T.V.Rao MD

Uses of Administration of Antibodies: 

Uses of Administration of Antibodies Passive administration of Antibodies eg Hyper immune globulins, Sensitization issues in Rh negative mothers. The effect occurs due to feedback mechanism The antibody may also combine with antigen and prevent its availability for the immunocompetent cells. Rh –ve mother + Rh+ ve fetus Administration of Anti-Rh globulin immediately following delivery 48 Dr.T.V.Rao MD

Administration of Immunoglobulin's: 

Administration of Immunoglobulin 's IV administration has immunomodulation effect Administered in Thrombocytopenia's, and autoimmune hemolytic anemia. Dr.T.V.Rao MD 49

Adjuvants : 

Adjuvants Defined as substance that enhances the immunogenicity of an antigen. Eg Aluminum hydroxide or phosphate Freund’s incomplete adjuvant – Incorporation of protein antigen in water phase of water in oil emulsion, it causes delay of release of antigen from the site of injection and prolong the antigenic stimulus. Freund’s complete adjuvant – contains also the suspension of killed tubercle bacilli. The effect is due to MDP ( muramyl dipeptide ) 50 Dr.T.V.Rao MD

Super antigens,: 

Super antigens, Protein Molecules, eg Staphylococcal Enterotoxin, Activate large number of T cells, Irrespective of Antigenic specificity, Usually few cells are stimulated ( 0.001%) Massive stimulation leads to Massive out porins of T cell cytokines, Multi organ Dysfunction Staphylococcal Shock syndrome 51 Dr.T.V.Rao MD

Super antigens,: 

Super antigens, Protein Molecules, Eg Staphylococcal Enterotoxin, Activate large number of T cells, Irrespective of Antigenic specificity, Usually few cells are stimulated ( 0.001%) Massive stimulation leads to Massive out pouring of T cell cytokines, Multi organ Dysfunction Staphylococcal Shock syndrome 52 Dr.T.V.Rao MD

Immunosuppressive Agents: 

Immunosuppressive Agents X rays, Corticosteroids Anti metabolites. Cytotoxic Chemical s Dr.T.V.Rao MD 53

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Superatigens stimulates several lymphocytes: 

Superatigens stimulates several lymphocytes 55 Dr.T.V.Rao MD

Monoclonal Antibodies: 

Monoclonal Antibodies Kohler and Milstein ( Nobel Prize 1984 ) A single antibody forming cell or clone produces Antibodies against single antigen, Antibodies are usually polyclonal, Clone of Lymphocytes – Monoclonal antibodies. Useful in Diagnostic / Research work. 56 Dr.T.V.Rao MD

How Hybridoma Created.: 

How Hybridoma Created . Immunize Mice with Antigen, Obtain spleen cells Fuse with Mouse Myeloma cells Grow then in HPRT medium Hypoxanthine,Phosphoribosyl transfeerase Transfer to HAT Medium ) Hypoxanthine, Aminoptren and Thymidine Medium } Lead to formation of Hybridoma. 57 Dr.T.V.Rao MD

Hybridoma Technology Produce Monoclonal Antibodies: 

Hybridoma Technology Produce Monoclonal Antibodies What is Hybridoma Fusion of Spleen cells + Myeloma Cells, Attains the capacity to produce 1. Antibody producing capacity. 2. Multiply indefinitely, 58 Dr.T.V.Rao MD

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Contents of Hybridoma: 

Contents of Hybridoma Splenic cells + Myeloma cells Produce Monoclonal Antibodies, Propagated by injecting intraperitoneally In Mice - Frozen Monoclonal are similar in Ig class and other characters. 61 Dr.T.V.Rao MD

Uses of Monoclonal Antibodies: 

Uses of Monoclonal Antibodies 1 Research applications, 2. Diagnostic. 3.Theraputic, Mice Monoclonal are suitable for Humans, Chimeras antibodies are created. Grafting of Murine Monoclonal on CDR loops. Antibodies can be used with Bacteriophages Advances in Immunotherapy. 62 Dr.T.V.Rao MD

Immune Response in Cell mediated Immunity CMI: 

Immune Response in Cell mediated Immunity CMI T Lymphocytes play the major role 63 Dr.T.V.Rao MD

CMI helps in : 

CMI helps in Delayed hypersensitivity Immunity in infections caused by Obligate and facultative intracellular parasites Eg – Tuberculosis, Leprosy Listeriosis, Brucellosis, Fungi – Histoplasmosis, Cocccidiomysosis,Blastomycosis, Parasites – Trypanosomiasis In transplantation immunity, Immunologioly in Transplantation, malignancy, Pathogenesis of Autoimmune diseases 64 Dr.T.V.Rao MD

Induction of Cell Mediated Immunity: 

Induction of Cell Mediated Immunity Depends on Nature of Antigenic stimulus Best developed after following infection with intracellular parasites Live vaccines highly stimulating Killed vaccine not very effective But effective if contains Freund type adju vant. 65 Dr.T.V.Rao MD

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Functions of T cells: 

Functions of T cells Only T cell dependent antigens lead to development of CMI Certain chemicals which come in contact with skin induces Delayed hypersensitivity T Cell contain the specific receptor ( TCR ) One epitope ( Antigen ) on contact with receptor undergoes blast transformation Leads to Clonal proliferation 67 Dr.T.V.Rao MD

Functions of T cells: 

Functions of T cells Cytotoxic T cells recognize antigen on surface of virus infected cells, tumor cells, allograft cells with MHC I and sectored Lymhokines and destroy target cells Dr.T.V.Rao MD 68

Functions of T cells: 

Functions of T cells The stimulated cells undergoes blast transformation, Clonal proliferation Leads to Effectors cells and Memory cells T cell react on presentation with MHC Helper T cells when presented on surface of macrophages or other cells complexes with MHC II molecule – leads to release of Biological Mediators Lymhokines – activate Macrophages and kills intracellular parasites 69 Dr.T.V.Rao MD

Broad view on Cytokines: 

Broad view on Cytokines Cytokines are a category of signalling proteins and glycoproteins that, like hormones and neurotransmitters, are used extensively in cellular communication 70 Dr.T.V.Rao MD

Cytokines: 

Cytokines Cytokines have been classed as Lymhokines, interleukins, and chemokine's, based on their presumed function, cell of secretion, or target of action. Because cytokines are characterised by considerable redundancy and pleiotropism, such distinctions, allowing for exceptions, are obsolete. 71 Dr.T.V.Rao MD

Definitions: 

Definitions Lymhokines Biologically active substance released by activated T Lymphocytes Monokines – Substances secreted by Monocytes and Macrophages Interleukins – Produces by lymphocytes which exert a regulatory effect on other cells All above grouped under cytokines 72 Dr.T.V.Rao MD

Definitions: 

Definitions Autocrine , if the cytokine acts on the cell that secretes it. Paracrine, if the target is restricted to the immediate vicinity of a cytokine's secretion. Endocrine , if the cytokine diffuses to distant regions of the body (carried by blood or plasma). It seems to be a paradox that cytokines binding to antibodies have a stronger immune effect than the cytokine alone. This may lead to lower therapeutic doses. 73 Dr.T.V.Rao MD

What are Cytokines: 

What are Cytokines They are peptide mediators, intracellular messengers, which regulate immunological, inflammatory and reparative host cell responses They are potent hormones Active even at Fetomolar concentrations produced by widely distributed cells ( Lymphocytes, Macrophages, Platelets, and Fibroblasts. 74 Dr.T.V.Rao MD

Cytokines: 

Cytokines Cytokines may act on the cells that secrete them ( Autocrine action ), on nearby cells ( paracrine action ), or in some instances on distant cells ( endocrine action) Dr.T.V.Rao MD 75

Cytokines have: 

Cytokines have Paracrine effect – acts locally – near the producing cells Having pleotrophic effects – Multiple effects on growth and differentiation of various cell types. Dr.T.V.Rao MD 76

Important Cytokines: 

Important Cytokines Interleukin I 1979 Interleukin I divided into Alpha and Beta IL1 is secreted by Macrophages, Monocytes other nucleated cells. Stimulated by Antigens, Toxins, Injury, Inflammation, Inhibited by Cyclosporins,Corticosteiods,Prostaglandins 77 Dr.T.V.Rao MD

Functions of Interleukin 1: 

Functions of Interleukin 1 IL1 stimulates T cells and Produces IL2 and other Lymhokines Helps B cell proliferation Synthesizes Antibodies Helps Neutrophils in Chemo taxis Promotes Phagocytosis Promotes Metabolic Physiological and inflammatory responses by action on Bone marrow 78 Dr.T.V.Rao MD

IL1 initiates Fever: 

IL1 initiates Fever IL1 is crucial in promoting fever and called as Pyrogens. With the help of Tumor Necrosis factor causes hematological changes in Septicemias, Shock and bacterial meningitis Dr.T.V.Rao MD 79

Other Interleukins: 

Other Interleukins Interleukins 2 Modulates the immune response Major activator of T and B Lymphocytes Stimulates cytotoxic T cells and Natural Killer cells. Interleukin 3 Stimulates multilineage cells of the Hematopoietic system. 80 Dr.T.V.Rao MD

Other Interleukins: 

Other Interleukins Interleukin 4 Acts as a Growth factor for T Lymphocytes Interleukin 5 Causes the proliferation of activated B Lymphocytes Interleukin 6 Produced by Stimulated B and T Lymphocytes Induces the production of Immunoglobulin synthesis Stimulates the Hepatocytes, nerve cells,Hematopoetic cells 81 Dr.T.V.Rao MD

Theraputic Uses of Cytokines: 

Theraputic Uses of Cytokines IL1,2,3 and colony stimulating factors are used in Inflammatory diseases, Infections, Autoimmune diseases. Neoplastic diseases and cancers 82 Dr.T.V.Rao MD

Mechanisms in Inflammatory Response: 

Mechanisms in Inflammatory Response 83 Dr.T.V.Rao MD

Mechanisms in Inflammatory Response: 

Mechanisms in Inflammatory Response 84 Dr.T.V.Rao MD

Functions of Cytokines: 

Functions of Cytokines Autocrine, if the cytokine acts on the cell that secretes it. Paracrine, if the target is restricted to the immediate vicinity of a cytokine's secretion. Endocrine, if the cytokine diffuses to distant regions of the body (carried by blood or plasma). It seems to be a paradox that cytokines binding to antibodies have a stronger immune effect than the cytokine alone. This may lead to lower therapeutic doses. 85 Dr.T.V.Rao MD

Properties of Cytokines : 

Properties of Cytokines Cytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis. They must be produced de novo in response to an immune stimulus. They generally (although not always) act over short distances and short time spans and at very low concentration. 86 Dr.T.V.Rao MD

Properties of Cytokines : 

Properties of Cytokines They act by binding to specific membrane receptors, which then signal the cell via second messengers , often tyrosine kinases, to alter its behaviour ( gene expression ). Responses to cytokines include increasing or decreasing expression of membrane proteins (including cytokine receptors), proliferation, and secretion of effector molecules. 87 Dr.T.V.Rao MD

Properties of Cytokines : 

Properties of Cytokines Cytokine is a general name; other names include lymphokine (cytokines made by lymphocytes), monokine (cytokines made by monocytes), chemokine (cytokines with chemotactic activities), and interleukin (cytokines made by one leukocyte and acting on other leukocytes). 88 Dr.T.V.Rao MD

Properties of Cytokines : 

Properties of Cytokines 89 Dr.T.V.Rao MD

Other Cytokines: 

Other Cytokines Other groups of cytokines include interferons and chemokine's. Interferons IFNa and IFNb inhibit virus replication in infected cells, while IFNg also stimulates antigen-presenting cell MHC expression. Chemokine's attract leukocytes to infection sites. Chemokine's have conserved cysteine residues that allow them to be assigned to four groups. 90 Dr.T.V.Rao MD

Inhibitory Cytokines: 

Inhibitory Cytokines Some cytokines are predominantly inhibitory. For example, IL-10 and IL-13 inhibit inflammatory cytokine production by macrophages. Dr.T.V.Rao MD 91

INTERFERONS: 

INTERFERONS 92 Dr.T.V.Rao MD

Interferons: 

Interferons Primarily identified as Antiviral agents Now classified as Cytokines Interferons play an important role in the first line of defence against viral infections. They are part of the non-specific immune system and are induced at an early stage in viral infection – before the specific immune system has had time to respond.. 93 Dr.T.V.Rao MD

Dynamics of Interferons: 

Dynamics of Interferons Interferons are made by cells in response to an appropriate stimulus, and are released into the surrounding medium; they then bind to receptors on target cells and induce transcription of  approximately 20-30 genes in the target cells, and this results in an anti-viral state in the target cells. 94 Dr.T.V.Rao MD

Classification of Interferons: 

Classification of Interferons There are three classes of Interferons: Alpha, Beta and Gamma. Interferon Alpha and Beta are produced by many cell t ypes Dr.T.V.Rao MD 95

Types of Interferons: 

Types of Interferons Interferon-alpha (leukocyte interferon) is produced by virus-infected leukocytes, etc Interferon-beta (fibroblast interferon) is produced by virus-infected fibroblasts, or virus-infected epithelial cells, etc Interferon-gamma  (immune interferon) is produced by certain activated T-cells and NK cells. Interferon-gamma is made in response to antigen (including viral antigens) or mitogen stimulation of lymphocytes. 96 Dr.T.V.Rao MD

Functions of Interferons: 

Functions of Interferons Interferons are within the cytokine family of proteins. Interferons are especially important because they enhance the immune system’s ability to recognize foreign invaders, enabling the system as a whole to function more effectively 97 Dr.T.V.Rao MD

Interferons Gama: 

Interferons Gama Interferon-Gamma is involved in the regulation of immune response throughout the body. Interferon-Gamma is the signalling protein that gets the immune system as a whole ready for attack and fine tunes it to quickly and effectively get rid of foreign and unwanted intruders 98 Dr.T.V.Rao MD

Uses of Interferons: 

Uses of Interferons Interferons-alpha and -beta have been used to treat various viral infections. One currently approved use for various types of interferon-a is in the treatment of certain cases of acute and chronic hepatitis C and chronic hepatitis B. 99 Dr.T.V.Rao MD

Uses of Interferons: 

Uses of Interferons Interferon-gamma has been used to treat a variety of disease in which macrophage activation might play an important role in recovery, eg. lepromatous leprosy, leishmaniasis, toxoplasmosis. Since interferons have anti-proliferative effects, they have also been used to treat certain tumours such as melanoma and Kaposi’s sarcoma. 100 Dr.T.V.Rao MD

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Detection of CMI: 

Detection of CMI The basic and earlier test was skin test for delayed hypersensitivity Now other tests are available Lymphocyte transformation test Migration inhibiting factor test. Dr.T.V.Rao MD 103

Theories of Immune Response: 

Theories of Immune Response Several theories are considered 1 Direct template theory 2 Indirect template theory 3 Natural selection theory 4 Clonal selection theory 104 Dr.T.V.Rao MD

What is Clonal Selection Theory: 

What is Clonal Selection Theory Burnet proposed the theory 1957 The theory emphasizes the immunological specificity to cellular level In this theory the cell are formed by somatic mutation, the cells that react with self antigens are eliminated and called as Forbidden clones. Their persistence in later life leads to Autoimmune process 105 Dr.T.V.Rao MD

Jerne’s network hypothesis: 

Jerne’s network hypothesis It explains the mechanism of antibody response The variable region of an immunoglobulin molecule carrying the antigen combining site is different in different antibodies The distinct Aminoacid sequence at antigen combing site and the adjacent parts of the variable regions are termed as idiotype Produce antiidotypic antibodies Which in turn produce antibodies to them 106 Dr.T.V.Rao MD

Nobel Prize winning theory: 

Nobel Prize winning theory Which in turn produce antibodies to them Forms a idiotype network The above process controls the amount of antibodies The above theory by Niels K.Jerne was awarded Nobel Prize for Medicine in 1984 Dr.T.V.Rao MD 107

Recent Theories: 

Recent Theories Now genetic basis of antibody diversity is identified. The recent theory of Split genes explains many unknown mechanisms The theory says the information occurs in discontinuous stretches of DNA, each coding for separate regions of the antibody molecule 108 Dr.T.V.Rao MD

PowerPoint Presentation: 

Programme created by Dr.T.V.Rao MD for Medical students in the Developing World Email doctortvrao@gmail.com Dr.T.V.Rao MD 109