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DR.VANDANA LAST CLASS (1).pptx
- 2. • Introduction • Examples •Immunologic tolerance (self tolerance) • Introduction • Central tolerance • Peripheral tolerance • Mechanisms of autoimmunity • Defective tolerance • Abnormal display of self antigens • Inflammation/innate immune response • Pathogenesis • Role of Susceptibility Genes • Role of Infections • General principles • Systemic lupus erythematosus • Introduction • Spectrum of autoimmune antibodies • Etiology and pathogenesis • Morphology • Clinical features • Rheumatoid arthritis • Sjogren’s syndrome • Systemic sclerosis • Inflammatory myopathies • Mixed connective tissue diseases • Polyarteritis nodosa • IgG4 related diseases
- 3. Introduction • Thepresence of an immune reaction specific for some self antigen or self tissue • Evidence that such a reaction is not secondary to tissue damage but is of primary pathogenic significance • Absence of another well-defined cause of the disease
- 5.
- 6. • The antigenreceptors of lymphocytes are generated by somatic recombination of genes in a random fashion • Hence lymphocytes with receptors capable of recognizing self antigens are generated constantly, and these cells have to be eliminated to prevent them from causing harm • This phenomenon of eliminating self reactive lymphocytes is called self tolerance
- 7.
- 8. • In thecentral (or generative) lymphoid organs (the thymus for T cells and the bone marrow for B cells), immature self-reactive T and B lymphocyte clones that recognize self antigens are killed • However, not all self antigens may be present in the thymus, and hence T cells bearing receptors for such autoantigens escape into the periphery • There is similar “slippage” in the B-cellsystem • Self-reactive lymphocytes that escape negative selection can inflict tissue injury unless they are deleted or muzzled in the peripheral tissues
- 9. • Developing Bcells strongly recognize self antigens in the bone marrow • Many of the cells reactivate the machinery of antigen receptor gene rearrangement and begin to express new antigen receptors, not specific for self antigens Negative selection (In T cells) • In developing T cells, random somatic gene rearrangements generate diverse TCRs • TCR generation produces many lymphocytes that express high- affinity receptors for self antigens • When immature lymphocytes encounter the antigens in the thymus, many of the cells die by apoptosis Receptor editing (In B cells) • If receptor editing does not occur, the self reactive cells undergo apoptosis
- 10. Anergy Suppression by regulatory T cells Deletionby apoptosis (of mature T cells)
- 11. • Lymphocytes thatrecognize self antigens are rendered functionally unresponsive by this phenomenon • Activation of antigen-specific T cells requires two signals: • Recognition of peptide antigen in association with self MHC molecules on the surface of APCs • Aset of costimulatory signals (“second signals”) provided by molecules such as CD28 • If the antigen is presented to T cells without adequate levels of costimulators, the cells become anergic • Because costimulatory molecules are not expressed on dendritic cells in normal tissues, the encounter between autoreactive T cells and their specific self antigens displayed by these dendritic cells may lead to anergy
- 12. • T cellsthat recognize self antigens receive an inhibitory signal from receptors that are structurally homologous to CD28 but serve the opposite functions • Two of these inhibitory receptors are • CTLA-4, which (like CD28) binds to B7 molecules & • PD-1 which binds to PD L1
- 13. • CTLA-4 hashigher affinity for B7 molecules than does CD28 • CTLA-4 may be preferentially engaged when the levels of B7 are low, as when APCs are presenting self antigens • Conversely, microbial products elicit innate immune reactions, during which B7 levels on APCs increase and the low-affinity receptor CD28 is engaged more
- 14. Tumor therapy and Anergy This realizationhas led to the development of antibodies that block CTLA-4 and PD-1 for tumor immunotherapy By removing the brakes on the immune response, these antibodies promote responses against tumors
- 15. • Regulatory Tcells functions to prevent immune reactions against self antigens • Develop mainly in the thymus, but they may also be induced in peripheral lymphoid tissues • Regulatory T cells are CD4+ cells that express high levels of CD25, the α chain of the IL-2 receptor, and a transcription factor of the forkhead family, called FOXP3 • Clinical significance • Foxp3 – • Prevent immune reactions against fetal antigens that are inherited from the father and therefore foreign to the mother and hence acceptance of the fetus • Possible defects in these cells are the basis for recurrent spontaneous abortions?? • Mutations in FOXP3 result systemic autoimmune disease called IPEX (an acronym for immune dysregulation, polyendocrinopathy, enteropathy, X-linked) • CD25 • polymorphisms in the CD25 gene are associated with multiple sclerosis
- 16. Deletion by apoptosis(of mature Tcells) • Two mechanisms of deletion of mature T cells which encounter self antigens have been proposed • Bim pathway • Fas-Fas ligand system • Mutations in the FAS (CD95) gene leads to autoimmune lymphoproliferativ e syndrome (ALPS) Encounter with self antigens
- 17. Immune privileged sites • Someantigens are hidden (sequestered) from the immune system, because the tissues in which these antigens are located do not communicate with the blood and lymph • As a result, self antigens in these tissues fail to elicit immune responses and are essentially ignored by the immune system • Believed to be the case for the testis, eye, and brain • If the antigens of these tissues are released, for example, as a consequence of trauma or infection, the result may be an immune response that leads to prolonged tissue inflammation and injury. This is the postulated mechanism for post- traumatic orchitis and uveitis
- 18.
- 19. • Susceptibility genes- contribute to the breakdown of self-tolerance • Environmental triggers - such as infections and tissue damage - promote the activation of self- reactive lymphocytes
- 20. Association of HLA Alleleswith Disease Association of Non-MHC Genes with Autoimmune Diseases
- 24. 1. Autoimmune diseasestend to be chronic • Epitope spreading - in which an immune response against one self antigen causes tissue damage, releasing other antigens, and resulting in the activation of lymphocytes by these newly encountered epitopes 2. Manifestations of an autoimmune disease are determined by the nature of the underlying immune response • Whether caused by antibodies or T cells
- 25. Definition Criteria Epidemiology Spectrumof autoantibodie s Etiology Pathogenesis Mechanism of tissue injury Morphology Clinica l feature s Variants
- 26. SLE is achronic remitting and relapsing autoimmune disease Involving almost any organ of the body Characterized by a vast array of autoantibodies, particularly antinuclear antibodies (ANAs) In which injury is caused mainly by deposition of immune complexes and binding of antibodies to various cells and tissues
- 27. SLE • The clinicalpresentation of SLE is so variable that the American College of Rheumatology has established a complex set of criteria for this disorder
- 28. • Arthritis -Non erosive, affecting two or more joints, characterised by tenderness/swelling/effusion • Renal disease (Persistent proteinuria >0.5 g/dL or >3 if quantitation not performed or Cellular casts—may be red blood cell, hemoglobin, granular, tubular, or mixed) • ANA (positive antinuclear antibody in the absence of drugs known to be associated with drug-induced lupus syndrome) • Serositis (pleurisy or pericarditis) • Haematological disorders (Hemolytic anemia—with reticulocytosis, or Leukopenia— <4.0 × 109 cells/L (4000 cells/mm3) total on two or more occasions, or Lymphopenia—<1.5 × 109 cells/L (1500 cells/mm3) on two or more occasions, or Thrombocytopenia—<100 × 109 cells/L (100 × 103 cells/mm3) in the absence of offending drugs • Photosensitivity (Rash as a result of unusual reaction to sunlight) • Oral ulcers (Oral or nasopharyngeal ulceration) • Immunological disorder (positive LE cell, anti-DNA, anti-Sm, false positive serological test for syphilis) • Neurological disorders (seizures or psychosis, in the absence of other causes) • Malar rash (Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds) • Discoid rash (Erythematous raised patches with adherent keratotic scaling and
- 29. • Prevalence ashigh as 1 in 2500 • Female-to-male ratio of 9 : 1 • Usually presents in the 20s and 30s
- 31. Spectrum of autoantibodies • Directedagainst • Antinuclear antibodies • Other antibodies
- 34.
- 35. Genetic HLA • Specific allelesof the HLA-DQ locus have been linked to the production of anti– double stranded DNA, anti-Sm, and antiphospholipid antibodies • Inherited deficiencies of early complement components, such as C2, C4, or C1q • Lack of complement may impair removal of circulating immune complexes by the mononuclear phagocyte system, thus favouring tissue deposition Complement system
- 36. • Failure ofself-tolerance in B and T cells • TLR engagement by nuclear DNA and RNA contained in immune complexes may activate B lymphocytes, leading to increased production of antinuclear antibodies • Type I interferons play a role in lymphocyte activation in SLE • Type I interferons are antiviral cytokines that are normally produced during innate immune responses to viruses. It may be that nucleic acids engage TLRs on dendritic cells and stimulate the production of interferons
- 37. Environmental • UV irradiationmay induce apoptosis in cells and may alter the DNA in such a way that it becomes immunogenic • Sex hormones - Gender bias of SLE is partly attributable to actions of and partly related to sex hormones and genes on the X chromosome • Drugs such as hydralazine, procainamide, and D-penicillamine can induce an SLE-like reaction
- 39. • DNA-antiDNA complexes(Type III hypersensitivity) Kidney • DNA-anti-DNA complexes can be detected in the glomeruli and small blood vessels • Antinuclear antibodies - Neutrophils and macrophages (LE cell phenomenon) • LE cell is any phagocytic leukocyte (blood neutrophil or macrophage) that has engulfed the denatured nucleus of an injured cell • Nuclei of damaged cells react with ANAs, lose their chromatin pattern, and become homogeneous, to produce so-called LE bodies or haematoxylin bodies • Readily seen when blood is agitated in vitro; was used as a test in past for SLE • Antiphospholipid antibodies - Blood vessels (Thrombosis) • Patients with antiphospholipid antibodies may develop venous and arterial thromboses, which may be associated with recurrent spontaneous miscarriages • Antibodies against clotting factors, platelets and endothelial cells have all been proposed • Neurons (antibodies that react with neurons or receptors for various neurotransmitters) • Neuropsychiatric manifestations
- 40. 1. Blood vessels 2.Kidney 1. Glomeruli 2. Tubules and interstitium 3. Skin 4. Joints 5. Central nervous system 6. CVS
- 41. • Acute necrotizingvasculitis involving capillaries, small arteries and arterioles • Characterized by fibrinoid deposits in the vessel walls
- 42. 2. Kidney (Lupus Nephritis) (Immune complex deposition) Minimal mesangiallupus nephritis (class I) Focal lupus nephritis (class III) Diffuse lupus nephritis (class IV) Membranous lupus nephritis (class V) Advanced sclerosing lupus nephritis (class VI)
- 44. • Immunoflourescence andelectron microscopy - immune complex deposition in the mesangium • Lightmicroscopy - No structural changes A. Glomerulus without mesangial or basement membrane changes by light microscopy (Jones silver stain). B. B Mesangial lupus nephritis. Mesangial deposits are present by immunofluorescence (anti-IgG)
- 45. • Mesangial cellproliferation, accompanied by accumulation of mesangial matrix, and granular mesangial deposits of immunoglobulin and complement without involvement of glomerular capillaries A glomerulus shows mild mesangial hypercellularity
- 46. • Involvement offewer than 50% of all glomeruli • The lesions may be segmental (affecting only a portion of the glomerulus) or global (involving the entire glomerulus) • Affected glomeruli may exhibit swelling and proliferation of endothelial and mesangial cells associated with leukocyte accumulation, capillary necrosis, and hyaline thrombi • Clinical presentation ranges from mild hematuria and proteinuria to acute renal insufficiency • Red cell casts in the urine are common Focal proliferative glomerulonephritis, with two focal necrotizing lesions at the 11 o’clock and 2 o’clock positions (H&E stain
- 47. Diffuselupus nephritis (class IV) • Mostcommon and severe form • Half or more of the glomeruli are affected • Lesions may be segmental (IV-S) or global (IV-G) • Involved glomeruli show proliferation of endothelial, mesangial and epithelial cells, with the latter producing cellular crescents that fill Bowman’sspace • Subendothelial immune complex deposits may create a circumferential thickening of the capillary wall, forming “wire loop” structures on light microscopy Diffuse proliferative glomerulonephritis. Note the marked increase in cellularity throughout the glomerulus (H&E stain). Lupus nephritis showing a glomerulus with several “wire loop” lesions representing extensive subendothelial deposits of immune complexes (periodic acid-Schiff stain).
- 48. • Diffuse thickeningof the capillary walls due to deposition of subepithelial immune complexes, similar to idiopathic membranous nephropathy • The immune complexes are usually accompanied by increased production of basement membrane- like material • This lesion is usually accompanied by severe proteinuria or nephrotic syndrome, and may occur concurrently with focal or diffuse lupus nephritis
- 49. • Sclerosis ofmore than 90% of the glomeruli • Represents end-stage renal disease
- 50. Discrete immune complexes similarto those in glomeruli are present in the tubular or peritubular capillary basement membranes There are well organized B- cell follicles in the interstitium, with plasma cells that may be sources of autoantibodies
- 51. • Characteristic erythemaaffects the face along the bridge of the nose and cheeks (the “butterfly” rash) • Exposure to sunlight incites or accentuates the erythema • Histologically the involved areas show vacuolar degeneration of the basal layer of the epidermis. In the dermis, there is variable edema and perivascular inflammation. Vasculitis with fibrinoid necrosis may be prominent. • Immunofluorescence microscopy shows deposition of immunoglobulin and complement along the dermoepidermal junction
- 52. 4. Joints • Nonerosive synovitis • The changes are usually reversible since they are due to tendon involvement rather than synovial damage and so the patient does not usually require or benefit from joint surgery X-ray of hands of lupus patient showing non-erosive arthropathy including Z thumbs
- 53. • Neuropsychiatric symptomsof SLE have been attributed to noninflammatory occlusion of small vessels by intimal proliferation is sometimes
- 54. • Pericardium • Themesothelial surfaces are sometimes covered with fibrinous exudate • Later they become thickened, opaque, and coated with a shaggy fibrous tissue • Endocardium and valves • Primarily the mitral and aortic valves are affected • Manifest as stenosis or regurgitation • Libman-Sacks endocarditis was more common prior to the widespread use of steroids. This nonbacterial verrucous endocarditis takes the form of single or multiple 1- to3-mm warty deposits on any heart valve, distinctively on either surface of the leaflets • Coronary artery disease • increasing number of patients have clinical evidence of coronary artery disease (angina, myocardial infarction) owing to coronary atherosclerosis. This complication is particularly notable in young patients with long-standing disease, and especially in those who have been treated with corticosteroids.
- 56. • Diagnosis isbased on criteria as discussed earlier • Typically SLE presents as • A young woman with some, but not necessarily all, of the following features: • Butterfly rash over the face • Fever • Pain but no deformity in one or more peripheral joints (feet, ankles, knees, hips, fingers, wrists, elbows, shoulders) • Pleuritic chest pain • Photosensitivity.
- 57. • Skin plaqueson face and scalp • Systemic manifestations are rare • ANA is positive but antibodies to double-stranded DNA are rarely present • Immunofluorescence studies of skin biopsy specimens show deposition of immunoglobulin and C3 at the dermoepidermal junction similar to that in SLE
- 58. • Also presentswith predominant skin involvement and can be distinguished from chronic discoid lupus erythematosus by • Skin rash in this disease tends to be widespread, superficial, and nonscarring • Mild systemic symptoms consistent with SLE • Strong association with antibodies to the SS-A antigen and with the HLA-DR3 genotype
- 59. • Lupus erythematosus-likesyndrome may develop in patients receiving a variety of drugs, including hydralazine, procainamide, isoniazid, D- penicillamine and anti TNF therapy for RA • Associated with the development of ANAs • Multiple organ systems are involved but renal and central nervous system involvement is distinctly uncommon • High frequency of antibodies specific for histones • The disease remits after withdrawal of the offending drug
- 60. Majority of manifestationsof this autoimmune disease are in joints
- 62. Definition • Chronic diseasecharacterized by • dry eyes (keratoconjunctiviti s sicca) and • dry mouth (xerostomia) • resulting from immunologically mediated destruction of the lacrimal and salivary glands • Types • Primary form - Sicca syndrome • Secondary form – associated with other disorders like • Rheumatoid arthritis • SLE • Polymyositis • Scleroderma, • Vasculitis • Mixed connective tissue disease • Thyroiditis
- 63. Viral infection ofthe salivary glands Local cell death and release of tissue self antigens (cytoskeletal protein called α-fodrin is a candidate autoantigen) Aberrant T-cell and B-cell activation Antibodies directed against two ribonucleoprotein antigens, SS-A (Ro) and SS-B (La) can be detected in as many as 90% of patients Tissue damage, and, eventually, fibrosis
- 64. Women between the ages of50 and 60 Keratoconjunctivitis - blurring of vision, burning, and itching; thick secretions accumulate in the conjunctival sac Xerostomia - difficulty in swallowing solid foods, a decrease in the ability to taste, cracks and fissures in the mouth, and dryness of the buccal mucosa Glandula r disease Diffuse pulmonary fibrosis Peripheral neuropathy Tubulointerstitial nephritis Extraglandul ar disease
- 65. Labdiagnosis andprognosis • Biopsy ofthe lip (to examine minor salivary glands) is essential for the diagnosis of Sjögren syndrome • In early stages of the disease, this immune infiltrate consists of a mixture of polyclonal T and B cells • However, if the reaction continues unabated there is a strong tendency over time for individual clones within the population of B cells to gain a growth advantage, presumably because of the acquisition of somatic mutations. • Emergence of a dominant B-cell clone is usually indicative of the development of a marginal zone lymphoma (also a feature of other autoimmune disorders like Hashimoto’s)
- 66. Morphology • Lacrimal andsalivary (both major and minor) glands • Periductal and perivascular lymphocytic infiltration • Lymphoid follicles with germinal centers • Atrophy of the acini, fibrosis, and hyalinization • Replacement of parenchyma with fat
- 67. • Definition • Pathogenesis •Clinical features • Lab Diagnosis • Morphology
- 68. Definition and Types • Chronicinflammation thought to be the result of autoimmunity • Widespread damage to small blood vessels • Progressive interstitial and perivascular fibrosis in the skin and organs like gastrointestinal tract, kidneys, heart, muscles, and lungs Type s • Diffuse scleroderma • widespread skin involvement at onset • rapid progression • Early visceral involvement (renal failure, cardiac failure, pulmonary insufficiency, or intestinal malabsorption) • Limited scleroderma • skin involvement is often confined to fingers, forearms, and face • Slow progression • Visceral involvement occurs late
- 69. • Some patentswith the limited disease also develop a combination of • Calcinosis • Raynaud phenomenon • Esophageal dysmotility • Sclerodactyly • Telangiectasia
- 71. Clinical Features • Female;50-60 years • Striking cutaneous changes, notably skin thickening • Raynaud phenomenon - episodic vasoconstriction of the arteries and arterioles of the extremities • Dysphagia attributable to esophageal fibrosis and its resultant hypomotility • Abdominal pain, intestinal obstruction, or malabsorption syndrome with weight loss and anemia reflect involvement of the small intestine • Respiratory difficulties caused by the pulmonary fibrosis may result in right-sided cardiac dysfunction, and myocardial fibrosis may cause either arrhythmias or cardiac failure • Proteinuria or nephrotic syndrome • Malignant hypertension
- 72. LabDiagnosis • Two ANAsstrongly associated with systemic sclerosis • DNA topoisomerase I (anti-Scl 70) • More likely to have pulmonary fibrosis and peripheral vascular disease • Anticentromere antibody • Found in 20% to 30% of patients, who tend to have the CREST syndrome • Have relatively limited involvement of skin, often confined to fingers, forearms, and face
- 73. Morphology • Begins inthe fingers and distal regions of the upper extremities and extends proximally to involve the upper arms, shoulders, neck, and face • Edema and perivascular infiltrates containing CD4+ T cells, together with swelling and degeneration of collagen fibres, which become eosinophilic • Extensive deposition of dense collagen in the dermis with virtual absence of appendages (e.g., hair follicles) and foci of inflammation
- 74. 2)In appropriate immuneresponse 1. Transplant rejection, organs transplantation used to treat irreversible diseases of kidney, liver, heart, lung and bone marrow. The action of immune system destroy the transplanted tissue by HI and CMI directed against the MHC Ag (HLA) of donor graft endothelial cells are rich with MHC (HLA) Ag and blood group Ag. Types of transplant rejection: 1-Hyper acute rejection: Occur within minutes to few hours. There is wide spread thrombosis, focal necrosis, it formed due to reaction of preformed Abs against graft Ags. TheseAbs developed either by: 1. Previous rejection of previous graft. 2. Women who develop anti HLA Abs against paternal Ags. 3. Prior blood transfusion. 2-Acute rejection: Occur within days or weeks, when stop immunosuppressive drugs also occurred by HI and CMI against donor graft Ag. Particularity MHC class II Ag. So renal failure with infiltration of CD4+,CD8+vasculitis endothelial necrosis, neutrophils infiltration, damage of B.V. 3-Chronic rejection: Occur slowly during months and years of graft transplant. It is slowly breakdown of self-tolerance to graft due to inadequate immune suppression. So increase creatinine level (renal dysfunction). Antimal fibrosis lead to ischemic damage hyalinization, loss of glomeruli, tubular necrosis, atrophy and interstitialfibrosis. Transplantation of other organ liver, heart, lungs, pancreas unlike of kidney it can preformed with: 1. ABO blood grouping. 2. Absence of preformed Abs. 3. Body habitus example child not receive heart of adult.
- 75. 1)In adequate immuneresponse: Result from immunodeficiency states there are 2classes of immunodeficiency syndrome: 1.Primary immunodeficiency at birth due to genetic disorders. 2.Secondary immunodeficiency during the life (acquired).
- 76. 1-Transient hypogammaglobinemia thisoccur in infants during 3-6month of birth, in which breakdown of maternal IgG it is considered physiological hypogammaglobinemia, and occur when infants unable to synthesize IgG level so child become susceptible to recurrent pyogenic infection. 2-X-linked a gammaglobulinemia (Bruton disease) it is a genetic disorder in which failure of B cells maturation result in absence of antibodies, the disease mostly occur in males so suffering from recurrent bacterial infection. 3 Isolated IgA deficiency: There is reduction in IgA level but other antibodies are normal level. 4 Hyper IgM syndrome: In normal condition IgM and IgD produced first against protein antigen (Ag), followed by IgG, IgA and IgE antibodies (Ab). Patient with this syndrome have normal level of IgM or abnormal level of IgM Abs but fail to produce other Abs suchas IgG, IgA, IgE, although IgM important for the fixation of complement for activation and opsonizationbacteria.
- 77. 5 IgG subclassesdeficiency: Selective of IgG (IgG1, 2,3,4)are easily missed because IgG1 contribute 70-of total IgG-IgG2 predispose the individuals to respiratory infections and meningitis. IgG2 deficiency occur together with IgG4 and IgA. Similarly IgG1 and IgG3 are commonly seen deficiency together. 6 Thymic hypoplasia (diGoeorge syndrome) Affective Tcells due to hypoplasia of thymus glands occur together with hypoplasia of parathyroid gland so hypocalcemia, tetany, cardiac malformation, facial abnormalities. 7-Severe combined immunodeficiency: This inherited either autosomal or x-linked occur due to failure of development of Band T cells, therefore thymus is small and body lymphoid tissue are also small so children are susceptible to candida thrush, pneumonia, diarrhea. 8-Defects in neutrophils and complementsystem. Continued
- 78. More common thanprimary, it occur during life, caused by: 1 Protein loss (nephrotic syndrome). 2 Impaired protein synthesis, malnutrition. 3Lymph proliferative disease: lymphoma, leukemia. 4- Multiple myeloma. 5 Immunosuppressive drugs. 6 Spleenectomy, tonsillectomy. 7Infections suchas cytomegalovirus. Measles, rubella, infectious mononucleosis, viral hepatitis.
- 79. It is retrovirusdisease caused by human immunodeficiency virus (HIV) characterized by: 1- Immunosuppression leading to opportunistic infections. 2- Secondary tumors. 3- Neurological manifestations The diseases is worldwide, about 20years ago discovered and more than 22 million people died. Three major routes for the transmission of virus: 1 Sexual contact. 2Parenteral inoculation drugs, hemophilia, blood transfusion. 3- Infected mother to newborn. Cause: retrovirus belong to lenti virus family (HIV 2types) HIV-1 in USA, Europe, central Africa where HIV-2 in West Africa.
- 80. Two major targetsfor HIV immune system and central nervous system: *In immune system: Aids lead to impair cell mediated immunity. It distruct CD4+lymphocytes and decrease helper suppressor Tcells ratio. Virus has selective tropism for CD4+and macrophages and dendritic cells. Whereas viral envelope bind to other cells to enhance cell entry. The virus core enter the cytoplasm have genes undergoes for reverse transcriptase in which complementary DNA making and enter nucleus of cells as a latent provirus DNA transcribed to from complete virus, bud from the cell membrane and death of the cells. HIV colonizes the spleen, lymph node, tonsils. The Tcells, macrophages and dendritic cells represent reservoir of infection. *In central nervous system: Virus carried into brain by infected monocytes in brain microglia (equivalent macrophages) is the target for HIV. In brain the neurological deficit is caused by indirect viral products, cytokines produced by macrophage/ microglia.
- 81. 1 Primary infection: Atthe beginning when viral replication in body organs, an immune response developed with increase virus infected CD8+to replace dying Tcells, followed by decrease CD4+/ CD8+ratio, resulted in influenza, skin rash, lymphadenopathy. 2 Asymptomatic phase (incubation period): In this phase the immune system is intact but viral replication continued, this stage may still for years, patients have AbS and transmit the disease.
- 82. Copyrights © 2017 l Aliraqia University l Dentistry l Pathology l Prof.Dr. Khalil Hassan Zenad Aljeboori. 3 Aids relatedcomplex: In this CD4+infected cells increased, their function impaired, their number in blood fall to 400cell/ ULSo malaise, fever, night sweating weight loss, diarrhea and lymphadenopathy. Impaired CMI and CD4+so fungal infection, salmonella and hemophilus are sever. 4 Aids (crisis phase): In which fully developed immune deficiency so fatigue, fever, weight loss, lymphadenopathy and diarrhea, CD4+cells is below 200/UL.So most of opportunistic infection, secondary tumors and neurological manifestations occurred and death.
- 83. Responsible for 80%ofaids patients death it include: 1- Pneumocystis carinii pneumonia. 2- Recurrent candidiasis. 3 Cytomegalovirus infection mainly retinitis, enteritis. 4Herpes simplex infection in mouth, perianal infection. 5- Mycobacterium infection. 6 Toxoplasmosis. 7 Cryptococcus meningitis. 8 Cryptosporidium- enteritis. Patients with aids have high incidence of Neoplasms (Tumors): due to defects in Tcells so; 1 Kaposi sarcoma occur in association with human herpes virus (KS) infect skin, lung, lymph node, GIT. 2 Non-Hodgkin's lymphoma occur in association with (EBV)Epstein bar virus. It affect brain, lymphoid tissue. 3 Cervix-uterus carcinoma tissue it occur with papilloma virus.
- 84.