ESSENTIAL IMMUNOLOGY including basics to applied aspects.pptx

DETAILED PPT ABOUT ESSENTIAL IMMUNOLOGY

1. Essential immunology

2. CONTENTS: INTRODUCTION SCOPE AND HISTORY OF IMMUNOLOGY CLASSIFICATION DEVELOPMENT CELLS OF IMMUNE SYSTEM IMMUNITY AND INFECTIOUS DISEASES IMMUNIZATION CELLULAR IMMUNOLOGY MOLDECULAR IMMUNOLOGY HYPERSENSITIVITY REACTION AUTOIMMUNITY TRANSPLANTATION VACCINES AND IMMUNITY CANCER AND IMMUNE SYSTEM DIAGNOSTIC IMMUNOLOGY TRENDS IN IMMUNOLOGY CONCLUSION REFERENCES

3. INTRODUCTION The term ‘immunity’ has traditionally referred to the resistance exhibited by the host towards injury caused by microorganisms and their products. Infection and immunity involve interaction between the host and the infecting micro-organism.

4. IMMUNE SYSTEM (FUNCTIONALLY) RECOGNITION RESPONSE Local and Foreign molecule Recruits variety of cells and molecules Effector response to eliminate or to neutralize the organism LATER EXPOSURE Memory response Rapid and heightened immune reaction Eliminate the pathogen and prevent disease

5. classification

6. It is the resistance which individual possesses by birth. It is by virtue of his genetic and constitutional makeup. It does not depend on prior contact with foreign antigen. INNATE IMMUNITY:

7. Factors Influencing The Level Of Innate Immunity AGE HORMONAL INFLUENCES ENDOCRINE DISORDERS Diabetes mellitus, Hypothyroidism, Adrenal dysfunctions Diabetes - level of carbohydrates Corticosteroids - Depress host’s Resistance NUTRITION - Immune responses are reduced in malnutrition

8. MECHANISMS OF INNATE IMMUNITY : BARRIER FLUSHING ACTION CHEMICAL BIOLOGICAL

9. BARRIER FLUSHING ACTION Intact skin - Mucous membranes – Connective Tissue- Hairs - Cilia - Tear ducts Saliva- Epiglottis- Urine-

10. CHEMICAL FACTORS Gastric juice- Acid pH of skin – Unsaturated fatty acids- Lysozyme- BIOLOGICAL Interferon (IFN)- Complement – Phagocytosis- Inflammation- Feve r-

11. The resistance acquired by an individual during life is known as acquired immunity. It is of two types, active and passive. A. Active Immunity Active immunity is subdivided into two types : Natural and Artificial. ACQUIRED IMMUNITY:

12. Humoral immunity It is antibody mediated immunity. It depends on the synthesis of antibodies by plasma cells. These cells produce specific circulating antibody which combines specifically with the antigens and modify their activity. This modified activity may be in the form of lysis of antigen molecules; their toxin may be neutralised , or in the form of removal of antigen by phagocytosis. Cell mediated immunity It depends on T-lymphocytes developed against certain antigens. Antibody synthesis also occurs in response to these antigens, but their role is limited. Important in resistance to chronic bacterial infections , organisms can multiply and survive in phagolysosome i.e. intracellular parasitism (tuberculosis, leprosy) and in viral infections (Herpes simplex).

13. DEVELOPMENT OF IMMUNE SYSTEM:

14. COMPONENTS OF IMMUNE SYSTEM CELLULAR COMPONENTS SOLUBLE COMPONENTS LYMPHOCYTES B-cell T-cell Large granular lymphocyte PHAGOCYTES Mononuclear phagocyte Neutrophil Eosinophil GRANULOCYTES Basophil Mast cell Platelets Antibodies Cytokines Complement Inflammatory mediators

15. T- LYMPHOCYTE:

16. T Helper cells; Depending upon the type of cytokines elaborated, these TH cells are further of two subclasses: TH 1 and TH 2. TH 1 cells elaborate IL-2 and interferon (IFN) [PROINFLAMMATORY] TH 2 cells elaborate IL-4, IL-5, IL-6, and IL-10.[ANTI-INFLAMMATORY] CD4+ cells are predominantly involved in cell-mediated reactions to viral infections (e.g. in HIV), tissue transplant reactions and tumour lysis. T suppressor cells ; CD8+ cells in circulation are about half the number of CD4+ cells. Compared to CD4+ cells which act by elaboration of cytokines, CD8+ cells are directly cytotoxic to the antigen. CD8+ cells are particularly involved in destroying cells infected with viruses, foreign cells and tumour cells. T CELL PROLIFERATION THUS GENERATE LARGE NO. OF ANTIGEN SPECIFIC CELLS EFFECTOR CELLS MEMORY CELLS ACTIVATED T CELLS SECRETES CYTOKINES LIKE IL-2

17. HUMAN IMMUNODEFICIENCY VIRUS: AIDS is a retroviral disease caused by the human immunodeficiency virus (HIV). It is characterized by infection and depletion of CD4+ T lymphocytes, and by profound immunosuppression leading to opportunistic infections, secondary neoplasms, and neurologic manifestations. Lab investigations: i ) Antibody tests: a) ELISA b) Western blot ii) Direct detection of HIV a) p24 antigen capture assay b) HIV RNA assay c) NA-PCR d) Culture of HIV 2. TESTS FOR DEFECTS IN IMMUNITY i ) CD4+ T cell count: Fall ii) CD8+ cell count: Increased iii) Ratio of CD4+ T cell/CD8+ T cell count: Reversed iv) Lymphopenia v) Hypergammaglobulinaemia vi) Increased -2 microglobulin level vii) Platelet count: Thrombocytopenia

18. Develop from immature precursors in the bone marrow. Constitute 10-20% of the circulating peripheral lymphocytes. Also seen in the lymph nodes (superficial cortex), spleen (white pulp), tonsils, and extra lymphatic organs ( eg. Git). Recognizes antigen via the b-cell antigen receptor complex. B LYMPHOCYTES

19. CYTOKINES: A collection of polypeptides used for communications between cells Play role similar to hormones Hormones usually act at a distance. Cytokines act locally. Differ from growth factors that are produced constitutively, while cytokine production is carefully regulated Play an important role in both innate and adaptive immunity Interleukins (1-18) Interferons ( a,b,g ) These are produced by cells as part of normal cellular activity and/or the result of environmental trigger to Bind to receptors on cells; Trigger signal transduction pathways and Initiate synthesis of new proteins.

20. CYTOKINE ACTIONS:

21. Early mediators IL-12, IL-15, 1l-18, IFN-g (from NK cells), IL-10 Proinflammatory mediators Produced by cell associated with innate immunity (macrophages, NK, etc.) Mediate direct effects Promote inflammation. Shape downstream responses LATE MEDIATORS IL-2, IL-4, IL-5, IFN-g, TNF, IL-6, IL-10 Produced by cells of the adaptive immune response (T and B cells) Direct effects More immunoregulatory functions

22. CYTOKINE CROSS-REGULATION In a given immune response, either T H 1 or T H 2 response dominates Cytokines of one response tend to down-regulate the other type of response Example: T H 1 cells secrete IFN-g, which inhibits proliferation of T H 2 subset

23. CYTOKINE-RELATED DISEASES Bacterial septic shock Blood pressure drops, clots form, hypoglycemia ensues, patient dies TNF induces IL-1 which induces IL-6 and IL-8 Bacterial toxic shock and related diseases Superantigens Lymphoid and myeloid cancers Some cancer cells secrete cytokines Chagas ’ disease Trypanosoma cruzi infection results in sever immune suppression Depression of IL-2 receptor production

24. INTERFERONS

25. Therapeutic Uses Of Cytokines Modulation of T H activation Interfere with receptor function Soluble T-cell receptor Anti-IL-2R Interleukin analogs which bind receptor, but do not trigger activation (ties up receptor) Toxins conjugated to cytokines which kill activated T-cells Administration of cytokines to enhance immunity (side effects/ short half lives) Allergies

26. The end result of b-cell activation – differentiation into antibody-secreting cells, called plasma cells. Secreted antibodies enter mucosal secretions and the blood and are able to find, neutralize, and eliminate antigens

27. NATURAL KILLER CELLS 10% to 15% of the peripheral blood lymphocytes do not bear T-cell receptors or cell surface immunoglobulins Morphologically, larger than small lymphocytes, and they contain abundant azurophilic granules Innate ability to kill a variety of tumor cells, virally infected cells without previous sensitization. Two cell surface molecules, CDI6 and CD56, are widely used to identify NK cells

28. MONONUCLEAR PHAGOCYTES: Monocyte Enlarge 5-15 times intracellular organelles increase in number and complexity, cells acquire increased phagocytic ability, increased secretion of many soluble factors Most powerful activator of macrophages is interferon-gamma secreted by activated TH cells. Activated macrophages Greater phagocytic activity, Inflammatory mediators secretion, Ability to activate T-cells.

29. MACROPHAGES

30. GRANULOCYTE 60% of WBC population. multilobed nucleus granular cytoplasm and are also called polymorphoneutrophils (PMN). Hematopoiesis in bone marrow. Blood stream; circulate for 7-10 hrs before migrating into tissues. Lifespan of few days. PMN are first to arrive at a site of inflammation by extravasation Neutrophils like macrophages are phagocytes and phagocytosis is almost similar to that of macrophages. NEUTROPHIL

31. EOSINOPHILS resemble neutrophils but their phagocytic activity is significantly less the defense activity is specially enhances in parasitic infestations. BASOPHILS these are non-phagocytic granulocytes function by releasing pharmacologically active substances from their cytoplasmic granule. these agents induces certain allergic responses.

32. MAST CELLS Released from the bone marrow as undifferentiated precursor cells do not differentiate until they enter the tissues (skin, connective tissue, mucosal epithelium, etc.) Morphology and function similar to circulating basophils Mast cells bear Fc receptors for IgE and contain large numbers of cytoplasmic granules(HISTAMINE) play a very important role in the allergic response.

33. DENDRITIC CELLS

34. Typical APCs express both class-I and class II MHC: Dendritic cells Macrophages B cells Tissue-specific APCs: Langerhans cells (skin) Kupffer cells (liver) Microglial cells (CNS) Antigen-Presenting Cells (APC)

35. Processing And Presentation Of Antigen

36. DETERMINANTS OF ANTIGENICITY: Large molecular size highly antigenic Low molecular size less or non-antigenic Proteins and polysaccharides highly antigenic. Lipids and nucleic acids less antigenic. Metabolized and are susceptible to the action of tissue enzymes. Only antigens that are foreign to the individual (non self) induce an immune response.

37. The same or closely related antigens present in different tissues of more than one species are known as heterophile antigens. Antibodies to these antigens produced by one species cross react with antigens of other species. Forssman antigen Paul-Bunnell test HETEROPHILE SPECIFICITY OF ANTIGENS:

38. Synthesized by Plasma cells and some extent by lymphocytes. So all the antibodies are immunoglobulins, but all immunoglobulins may not be antibodies. Glycoproteins Each molecule consists of two pairs of polypeptide chains Smaller chain – ‘Light’ chain , molecular weight 25000 Larger ones – ‘Heavy’ chain , molecular weight 50000 H chain is attached to L chain by a disulphide bond ANTIBODIES (IMMUNOGLOBULIN)

39. FUNCTIONS OF ANTIBODIES Activates B lymphocytes Antigen binds to antibody Antigen binding site Bacterial toxins Activates antibody- dependent cellular activity Acts as opsonins Causes antigen clumping and inactivation of bacterial toxins Triggers mast cell degranulation Memory cells Plasma cells NK cell or eosinophil Antibody Secrete antibodies Activates complement Enhanced phagocytosis 1 2 3 4 5 6

40. TYPES OF ANTIBODY ( Ab ) REACTIONS NEUTRALIZATION = When the antigen is a soluble toxin, the addition of an Ab against it will usually render the toxin INEFFECTIVE (nontoxic), that is it NEUTRALIZES it. Such neutralized toxins are called TOXOIDS and can be used as vaccines. PRECIPITATION = under the proper conditions a soluble antigen can be precipitated in the presence of its Ab because of the antigen-antibody net-work that forms gels large enough to form masses that SETTLE OUT (precipitate) on their own. AGGLUTINATION = When the antigen is a large PARTICLE, like a whole bacterium or a RBC, the addition of its Ab will form an Ab-antigen net work that causes the particles to CLUMP IN LARGE MASSES like milk coagulating when it spoils.

41. Discovered at the end of the 19th century as a heat-labile component of serum that augmented (or ‘complemented’) its bactericidal properties. Now known to comprise some 16 plasma proteins, together constituting nearly 10% of the total serum proteins, and forming one of the major immune defence systems of the body. Functions: the triggering and amplification of inflammatory reactions; attraction of phagocytes by chemotaxis clearance of immune complexes cellular activation direct microbial killing; and an important role in the development of antibody responses THE COMPLEMENT SYSTEM

42. ACTIVATORS OF COMPLEMENT PATHWAYS

43. MEMBRANE ATTACK PHASE CLASSCAL COMPLEMENT ACTIVATION PATHWAY

44. COMPLEMENT SYSTEM AND INFLAMMATION Efficient, rapid , and occurring in synchrony with the initiation of an inflammatory reaction, the activation of complement is a prerequisite for its involvement in regulation of inflammatory processes.  soluble components of complement are present not only in the circulation but also in body fluids and tissues, ready to engage in defense reactions triggered by exogenous ( eg , infectious agents) or endogenous ( eg , ischemia, autoimmunity) stimuli that could cause cell injury For example, in infection induced by  Leishmania , approximately 90% of promastigotes are lysed by complement in just 2.5 minutes after contact with human blood.  Therefore, complement effectors generated as a result of this activation can participate in the earliest events of an inflammatory reaction.   C5a activates the lipoxygenase pathway of arachidonic acid metabolism in neutrophils and monocytes, leading to an acceleration of eicosanoid production by these cells. Mast cells and neutrophils that are activated by complement anaphylatoxins release mediators that cause vasodilation and extravasation of fluid. C5a and  C3a stimulate the production of cytokines. The interactions between the complement system and proinflammatory cytokines are reciprocal. Several reports have suggested that proinflammatory cytokines enhance the expression of anaphylatoxin receptors in inflammatory cells.

45. HEREDITARY ANGIOEDEMA Hereditary angioedema (HAE) is a rare disorder, characterized by intermittent attacks of swelling in any part of the body, without the presence of hives. Presents in the first 2 decades of life. Commonly associated with a deficiency in functional C1 esterase inhibitor (C1-INH) activity. C1-INH levels may be decreased or normal, with an accompanied decrease in functionality. Early diagnosis of the disease can lead to the development of an individualized treatment plan to assist with prevention and management of angiodema attacks.

46. PHAGOCYTOSIS

47. Macrophages Ingest and digest whole antigen molecule, pathogens, insoluble particles, cellular debris, and activated clotting factors PHAGOCYTOSIS

48. O 2 dependent Activated Macrophages reactive O 2 intermediators (ROIs), and reactive N 2 intermediators (RNIs). Respiratory burst of cell Activation of membrane bound oxidases Oxygen Superoxide ion catalyses Hydroxyl radicals H 2 O 2 Toxic to pathogens Secrete Cytokines, Activate T H cells, RNIs NO synthatase PHAGOCYTOSIS

49. Activated macrophages lysosomes and various other hydrolyzing enzymes defensins which are cytotoxic enzymes, can kill a variety of bacteria including staphylococci, streptococci, E. coli, Psuedomonas species etc The tumor necrosis factor is also secreted by the activated macrophages which has a variety of effects including cytotoxic to tumor cells . Kill pathogens O 2 independent PHAGOCYTOSIS

50. Activated macrophages receptors for certain classes of antibodies Antigen coated with ANTIBODY Process of phagocytosis is enhanced. opsonin OPSONIZATION

51. MHC or HLA complex –located on short arm of chromosome 6 They code for 3 different classes of proteins: 1 class I protein that determines histocompatibility and the acceptance and rejection of allografts 2 class II protein regulate immune response 3 class III protein that include some component of immune system Antigen The Major Histocompatibility Complex (MHC) HLA class I antigens found on all nucleated cells. Principle antigens involved in graft rejection and cell mediated cytolysis HLA class II antigens Found only in cells of immune system Macrophages, dendritic cells, Activated T cells HLA class III antigens Heterogenous Take part in formation of C3 convertase and tumor necrosis factor

52. GRAFT VERSUS HOST DISEASE: Multisystem Disorders due to immune reaction caused by transplanted cells from a non-identical donor ( the graft ) that recognize recipient cells ( the host ) as foreign, thus disease is caused in the recipient organs. PATHOPHYSIOLOGY OF GVHD: CLASSIFICATION: Classic acute GVHD Persistent, recurrent, late onset acute GVHD Classic chronic GVHD Overlap syndrome “Acute on Chronic GVHD” CLINICAL MANIFESTATIONS: Diarrhea skin lesions Jaundice spleen enlargement, and death. Epithelial cells of the skin and gastrointestinal tract often become necrotic, causing the skin and intestinal lining to be sloughed.

53. T he afferent phase: activation of APC ( antigen presenting cells ) The efferent phase: activation, proliferation, differentiation and migration of effector cells The effector phase: target tissue destruction PATHOPHYSIOLOGY:

54. MANAGEMENT: Grade 1 GVHD Management A. Topical steroids are the most commonly used skin-directed therapy for acute GVHD. B. Antihistamines may be used as supportive therapy for patients with pruritus . C. In Resistant grade 1 aGVHD , Topical Tacrolimus may be useful. D. Optimizing prophylactic agents When acute GVHD of any grade develops, to ensure a therapeutic level. For those no longer receiving prophylaxis, the prior prophylactic agent should be restarted again. GRADE 2-4 GVHD A. First Line of Treatment: Corticosteroids Second Line of Treatment: Given in Patients who fail to respond To steroids 1. Mycophenolate mofetil (MMF) 2. Etanercept “ Anti TNF Antibodies” 3. Pentostatin 4. Sirolimus 5. Basiliximab 6. Extracorporeal Photopheresis .

55. HYPERSENSITIVITY Hypersensitivity is defined as an exaggerated or inappropriate state of normal immune response with onset of adverse effects on the body. These lesions are termed as hyper sensitivity reactions or immunologic tissue injury, of which 4 types are described: type I, II, III and IV. Depending upon the rapidity , duration and type hypersensitivity reactions are grouped into: Immediate type of hypersensitivity reactions include type I, II and III. Delayed type includes Type IV reaction.

56. TYPE I HYPERSENSITIVITY ( IgE MEDIATED):

57. ANAPHYLAXIS: A llergic reactions may be triggered by a variety of factors including drugs (e.g. penicillin), foods (e.g. shellfish), insect stings and chemicals. Wide spectrum of severity ranging from a harmless skin rash (urticaria), to potentially fatal airway obstruction (laryngeal oedema) and full-blown anaphylaxis (hypotension, bronchospasm).

58. Pathophysiology: The clinical manifestations of allergy result from an antigen-antibody reaction. Such reactions are a part of the body’s defense mechanisms (i.e., immune system), described in the following section to provide a better understanding of the processes involved in allergy. For acute, immediate allergy or for anaphylaxis to occur, three conditions must be met: An antigen-induced stimulation of the immune system with specific immunoglobulin E ( IgE ) antibody formation A latent period after the initial antigenic exposure for sensitization of mast cells and basophils Subsequent reexposure to that specific antigen

59. EITIOLOGY FOR PERIOPERATIVE ANAPHYLAXIS: M uscle relaxants Latex Antibiotics: Penicillin, cephalosporins, and other‑lactam antibiotics Plasma volume expanders (colloids) Intravenous drugs used for anesthetic induction Benzodiazepines Povidone‑iodine Chlorhexidine Nonsteroidal anti‑inflammatory drugs Local Anaesthesia

60. Ring J, Messmer K. Incidence and severity of anaphylactoid reactions to colloid volume substitutes. Lancet 1977;1(8009):466–9.

61. TYPE II: ANTIBODY-MEDIATED (CYTOTOXIC) REACTION Type II or cytotoxic reaction is defined as reaction by humoral antibodies that attack cell surface antigens on the specific cells and tissues and cause lysis of target cells.

62. TRANSFUSION REACTIONS DUE TO ABO INCOMPATIBILITY Transfusion reactions are the adverse reactions in the body, which occur due to transfusion error that involves transfusion of incompatible (mismatched) blood. In mismatched transfusion, the transfusion reactions occur between donor’s RBC and recipient’s plasma. So, if the donor’s plasma contains agglutinins against recipient’s RBC, agglutination does not occur because these antibodies are diluted in the recipient’s blood. But, if recipient’s plasma contains agglutinins against donor’s RBCs, the immune system launches a response against the new blood cells. Donor RBCs are agglutinated resulting in transfusion reactions.

63. TRANSFUSION REACTIONS DUE TO Rh INCOMPATIBILITY When a Rh negative person receives Rh positive blood for the first time, he is not affected much, since the reactions do not occur immediately. But, the Rh antibodies develop within one month. The transfused RBCs, which are still present in the recipient’s blood, are agglutinated. These agglutinated cells are lysed by macrophages. So, a delayed transfusion reaction occurs. But, it is usually mild and does not affect the recipient. However, antibodies developed in the recipient remain in the body forever. So, when this person receives Rh positive blood for the second time, the donor RBCs are agglutinated and severe transfusion reactions occur immediately

64. HEMOLYTIC DISEASE OF FETUS AND NEWBORN – ERYTHROBLASTOSIS FETALIS Œ Haemolytic disease of newborn results from the passageof IgG antibodies from the maternal circulation across the placenta into the circulation of the foetal red cells. It c ould be due to incompatibility of Rh or ABO groups. ŒUltimately due to excessive hemolysis severe complica tions develop, viz. 1. Severe anemia 2. Hydrops fetalis 3. Kernicterus. Prevention or treatment for erythroblastosis fetalis If mother is found to be Rh negative and fetus is Rh positive, anti D (antibody against D antigen) should be administered to the mother at 28 th and 34th weeks of gestation, as prophylactic measure. If the baby is born with erythroblastosis fetalis, the treatment is given by means of exchange transfusion. Rh negative blood is transfused into the infant, replacing infant’s own Rh positive blood.

65. TYPE III: IMMUNE COMPLEX MEDIATED (ARTHUS) REACTION Type III reactions result from deposition of antigen-antibody complexes on tissues, which is followed by activation of the complement system and inflammatory reaction, resulting in cell injury. The onset of type III reaction takes place about 6 hours after exposure to the antigen.

66. RHEUMATOID ARTHRITIS Rheumatoid arthritis is a chronic disease of unknown aetiology . But there is evidence to indicate that it may be a hypersensitivity reaction to bacterial toxins, specifically streptococci. Involvement of the TMJ may occur concomitantly with the other joint lesions or may arise subsequently. Radiographically, joints may be irregular, articular surfaces become flat, and subcortical pseudocysts and osteophytes may be present

67. TYPE IV: DELAYED HYPERSENSITIVITY(T CELL-MEDIATED) REACTION: Type IV or delayed hypersensitivity reaction is tissue injury by T cell-mediated immune response without formation of antibodies (contrary to type I, II and III) but is instead a slow and prolonged response. The reaction occurs about 24 hours after exposure to antigen and the effect is prolonged which may last up to 14 days.

68. STEVEN JOHNSON SYNDROME SJS is a  type IV hypersensitivity  reaction in which a drug or its metabolite stimulates  cytotoxic T cells  (i.e. CD8 +  T cells) and  T helper cells  (i.e. CD4 +  T cells) to initiate  autoimmune reactions  that attack self tissues The immune reaction can be triggered by drugs or infections Individuals may have variations in their efficiency to  absorb ,  distribute to tissues ,  metabolize , or  excrete  (this combination is termed  ADME ) a drug.

69. AUTOIMMUNE DISORDERS CLASSIFICATION: ORGAN NON-SPECIFIC (SYSTEMIC) Systemic lupus erythematosus* Rheumatoid arthritis Scleroderma (Systemic sclerosis)* Inflammatory myopathies (polymyositis, dermatomyositis, inclusion body myositis)* Polyarteritis nodosa (PAN) Sjögren’s syndrome* Wegener’s granulomatos IS ORGAN SPECIFIC (LOCALISED) 1. ENDOCRINE GLANDS ( i ) Hashimoto’s (autoimmune) thyroiditis (ii) Graves’ disease (iii) Type 1 diabetes mellitus (iv) Idiopathic Addison’s disease 2. ALIMENTARY TRACT ( i ) Autoimmune atrophic gastritis in pernicious anaemia (ii) Ulcerative colitis (iii) Crohn’s disease 3. BLOOD CELLS ( i ) Autoimmune haemolytic anaemia (ii) Autoimmune thrombocytopenia (iii) Pernicious anaemia 4. OTHERS ( i ) Myasthenia gravis (ii) Autoimmune orchitis (iii) Autoimmune encephalomyelitis (iv) Goodpasture’s syndrome (v) Primary biliary cirrhosis (vi) Lupoid hepatitis (vii) Membranous glomerulonephritis (viii) Autoimmune skin diseases

70. LICHEN PLANUS Oral lichen planus (OLP) is a common mucocutaneous disease. The condition can affect either the skin or mucosa or both. O ral lichen planus is a T cell-mediated autoimmune disease in which cytotoxic CDS+ T-cells trigger the apoptosis of oral epithelial cells. It can cause bilateral white striations, papules, or plaques on the buccal mucosa, tongue, and gingivae. The involvement of the oral mucous membrane is so frequent and accompanies or precedes the appearance of lesions on the skin and genital mucous membrane. TREATMENT: symptomatic relief, topical corticosteroids.

71. MIKULICZ SYNDROME Mikulicz disease is a chronic condition characterized by the abnormal enlargement of salivary and lacrimal glands. The tonsils and other glands in the soft tissue of the face and neck may also be involved. The exact cause of Mikulicz disease is not known, although it is suspected to be an autoimmune disorder. The symptoms of Mikulicz disease may occur due to the excessive accumulation of lymphocytes into involved glands.

72. SJOGREN’S SYNDROME Sjogren syndrome is a condition, consisting of a triad of keratoconjunctivitis sicca, xerostomia and rheumatoid arthritis. Sjogren syndrome have been found to be associated with the HLA system, specifically HLA-DR3 and HLA-B8, which are associated with the primary form of the disease, and HLA-DRw52

73. SYSTEMIC LUPUS ERYTHEMATOSUS: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies, immune complex formation, and immune dysregulation resulting in damage to essentially any organ, including kidney, skin, blood cells, and CNS. Patients with SLE produce autoantibodies against DNA, other nuclear antigens, ribosomes, platelets, erythrocytes, leukocytes, and other tissue-specific antigens. Thus, the resulting immune complexes result in widespread tissue damage. FEATURES: butterfly malar rash, photosensitivity, fibrinoid thickening of glomerular capillaries, localized telangiectasis

74. VACCINES A state of immunity can be induced by passive or active immunization a) Short-term passive immunization is induced by transfer of preformed antibodies. b) Infection or inoculation achieves long-term active immunization. ■ Three types of vaccines are currently used in humans: attenuated ( avirulent ) microorganisms, inactivated (killed) microorganisms,or purified macromolecules.

75. Human papillomavirus vaccine for cancer cervix prevention

76. IMMUNOMODULATORS: These are natural or synthetic substances that help regulate or normalize the immune system. T hey correct immune systems out of balance, Immunomodulators may be further classified into immunostimulants and immunosuppressants .

77. CANCER AND THE IMMUNE SYSTEM CANCER INDUCTION Proto-oncogenes-encode proteins involved in control of normal cellular growth. proto- oncongenes oncogenes Tumor suppressors - inhibit cell proliferation. Inactivation of these results in unregulated proliferation. Regulators of apoptosis- bcl-2, an anti-apoptosis gene Chromosome translocation-Defects in any of these can lead to uncontrolled cell growth

78. IMMUNE RESPONSE TO TUMORS: - Cell-mediated response appears to play the major role: - Tumors reduce MHC Class I expression The recognition of tumor cells by NK cells is not MHC restricted. Activated macrophages ~ regression (lytic enzymes, ROI, RNI, TNF-alpha) Tumors can evade immune response Anti-tumor antibody can block T cell responses (enhance tumor growth) The antibody binds to tumor-specific antigens and masks the antigens from cytotoxic T cells. Tumors can modulate antigens – “Ag modulation”

79. 5. Monoclonal antibodies are useful in treating some tumors Immunomodulators 4. Cytokine therapy Augment Immune Responses to Tumors Interferons (INF- alpha , beta, gamma), -(increase. MHC I, MHC II expression on tumour cells). Tumor necrosis factors (TNF-alpha, beta,)- inhibits tumour induced vascularization 3. Adjuvants Any substance which enhances the immunogenicity of an antigen is called adjuvant The attenuated strains of Mycobacterium bovis called bacillus calmette-guerin (BCG) and corynebacterium parvuum These adjuvants activate macrophages, increasing their expression of various cytokines, class II MHC molecules, and the B7 co-stimulatory molecule. These activated macrophages are better activators of TH cells, resulting in generalized increases in both humoral and cell-mediated responses. 2. Enhancement of Antigen Presenting Cells Activity Can Modulate Tumor Immunity 1. Manipulation of Co-Stimulatory Signals Can Enhance Immunity CANCER IMMUNOTHERAPY

80. ELISA The  enzyme-linked immunosorbent assay  ( ELISA ) is a commonly used analytical  biochemistry   assay . The assay uses a solid-phase type of  enzyme immunoassay  (EIA) to detect the presence of a  ligand  (commonly a protein) in a liquid sample using antibodies directed against the protein to be measured. The sample with an unknown amount of antigen is immobilized on a solid support either non-specifically or specifically. After the antigen is immobilized, the detection antibody is added, forming a complex with the antigen. The detection antibody can be covalently linked to an  enzyme  or can itself be detected by a  secondary antibody  that is linked to an enzyme through  bioconjugation .

81. POLYMERASE CHAIN REACTION: Principle: it is a DNA amplification system that produces a large amount of DNA in vitro from small amounts of starting material. It amplifies a specific DNA sequence or gene of interest. It is used in the early stages of processing DNA for  sequencing ? , for detecting the presence or absence of a gene to help identify  pathogens  ? during infection, and when generating forensic DNA profiles from tiny samples of DNA. Procedure: it involves 4 main stages: Denaturation Primer annealing DNA synthesis Detection of amplified product .

82. APPLICATIONS OF PCR:

83. Roth Karin, Hadrick Werner-Animal and human bite wounds-nature (2015) Incidence of animal or human bites 200/100000/year Most commonly by dogs and cats , affecting children more than adults . Classification of bite wound by Lackman superficial not involving muscle deep injury with muscle deep injury with muscle and tissue loss above+ nerves and vessels the above with bone involvement Wounds with high risk of infection Deep contaminated wounds with poor perfusion , wounds on hands ,feet and face involving bones , joints and tendons.

84. The knowledge of essential immunology is essential to understand the ability of an individual to cope-up to the disease situation and also to modify the immune mechanisms to be effective in cases of immunocompromised statuses. I t can be applied for the benefit of patients either in terms of immune enhancement or immune suppression whichever is beneficial to the patients. CONCLUSION

85. REFERENCES: Essential Immunology, Ivon Roitt . Basic immunology and its medical approaches (2 nd edit). Barette Oral microbiology with basic microbiology and immunology. - William A. Nolte Immunology – Weir Oral microbiology and basic immunology – Newman and Nisergaurd . Immune Defects In Specific Diseases: Oral Maxillofacial Surg Clin N Am 15 (2003) 103–110 Immunology and immunohistochemistry-Williams a Curtis Microbiology in dentistry – Frank J. Orland. Immunology – Zamtito Immunology and infectious diseases of head and neck- zambito and clevi . Textbook of microbiology – Ananthanarayan and Paniker .

86. THANK YOU