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Immunology

Immunology. 1- decrease numbers of helper T ( CD4 positive ) lymphocytes ( leading to a decreased T- helper / T-suppressor ratio & to an absolute lymphppenia . 2- hypergammaglobulinaemia ( polyclonal rise in IgG

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Immunology

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  1. Immunology 1- decrease numbers of helper T ( CD4 positive ) lymphocytes ( leading to a decreased T- helper / T-suppressor ratio & to an absolute lymphppenia. 2- hypergammaglobulinaemia ( polyclonal rise in IgG 3- Impaired response to recall antigens on skin testing ( i.e. impaired delayed type hypersensitivity “ DTH “

  2. T-helper test Mixed lymphocyte reaction Response to soluble antigen Lymphokine production T4 T8 Specific cytotoxicity .. … T4 NK NK activity .. .. .. B Polyclonal activity Specific Ig production M Parasite killing chemotaxis

  3. T4 receptor Reverse transcriptase RNA DNA RNA RNA Diagrammatic representation of retrovirus replication.

  4. Schematic representation of genome of HIV 5’ 3’ Trs/art tat //// //// gag ior sor env pol (P55) (gp 160) (P66) gp 120 p17 p15 p51 p24 gp41 o o gp 120 ( major envelope glycoprotein gp 41 ( transmembrane glycoprotein) RNA P24 ( major core protein )

  5. Two clinical findings of HIV infection , plus two laboratory abnormalities suggestive of it Clinical findings: Lab. abnormalities - Fatigue - Decrease T helper cell - Night sweats count - Lymphadinopathy - Increase serum > 3 months globulins - Weight loss - Anergy 10% total body w. loss - Anemia - Fever > 3 months - Diarrhea

  6. Persistent generalized lymphadinopathy ( PGA ) 1- lymphadinopathy of at least three months duration involving two or extra inguinal sites 2- absence of any current illness or drug use known to cause lymphadenopathy 3- presence of reactive hyperplasia in a lymph if biopsy is performed

  7. CDC classification of HIV disease Group I Acute infection Group II Asymptomatic infection Group III progressive generalized lymphadenopathy Group IV

  8. Other diseases : a- Constitutional disease b- Neurological disease c- Secondary infectious disease i- Specified secondary infectious diseases listed in the CDC Surveillance definition for AIDS ii- Other specified secondary infectious disease. d- Secondary cancers e- Other conditions

  9. Oral cavity problems in HIV disease Oral Thrush Hairy leukoplakia Kaposi’s sarcoma Gingivitis Aphthous ulceration Dental abscess Intra oral warts

  10. Skin disease 1- Seborrheic dermatitis 2- Papuloprritic eruptions/ folliculitis 3- Shingles 4- Herpes simplex 5- Xeroderma ( dry skin ) 6- Molluscum contagiosum 7- Tineas (fungal skin and nail eruptions)

  11. ENT problems • Catarrh/postnasal drip • Sinusitis • Otitis media • Serous otitis media • Otitis external • Nerve deafness

  12. Gastrointestinal disease 1) Diarrhea • cryptosporidium • Cytomegalovirus • A typical mycobacteria • Giardiasis • Salmonella • Campylobacter

  13. 2) Oesophagitis 3) Anal herpes 4) Kaposi’s sarcoma of the gastrointestinal tract

  14. Paediatric HIV diseaseHIV infection for infants & children under 15 months 1- Virus in blood or tissue 2- HIV antibody plus evidence of both cellular & humeral immune deficiency plus one or more categories in class P2 3- Symptoms & sign meeting the CDC case definition for AIDS

  15. Precautions in the dental surgery - Gloves should always be used when touching blood , saliva , mucous membranes. They should be changed between patients & hands should be washed. - Surgical masks & protective eyewear should be worn if blood or saliva could be spattered . - Instruments which come into contact with oral tissue should be sterilized after use . Debris should be removed by scrubbing with soap & water before sterilized . Instruments should be sterilized by autoclaving for three minutes at 134C minimum. Dry takes longer ( two hours at 150 C – 160 C . Heat sensitive instruments may sterilized using glutaraldehyde

  16. - Disposable gowns or washable work overalls or shirts should be worn . Gowns & work clothing should be changed daily or if they soiled with blood - Surface should be decontaminated by wiping down with sodium hypochlorite or an iodophor. Surface difficult to disinfect should be isolated with an impervious cover as plastic . - Droplet & aerosol production should be avoided where posible by use of rubber dams and high speed evacuation - Great care should be taken with hypodermic needles & sharps containers are available for use with dental syringes which enable the needle to be unscrewed from the syringe without resheathing

  17. Full definition of AIDS A case of AIDS is defined As: An illness characterized by one ore more of the following ‘ indicator ‘ diseases, depending on the status of laboratory evidence for HIV infection

  18. Without laboratory evidence regarding HIV infection: • Pneumocystis carinii pneumonia • Toxoplasmosis of the brain in patient > month of age • Cryptosporidiosis with diarrhoea persisting for> 1month • Extrapulmonary creptococcosis • Mycobacterium avium complex or M. kansasii disease at a site other than lungs or lymph nodes • Cytomegalovirus infection of an internal organ other than liver in a patient > 1 month of age

  19. Herpes simplex virus infection causing a mucocutanneous ulcer that persist for more than 1 month , or bronchitis , pneumonitis, or oesophagitis for any duration in a patient > 1 month of age • Progressive multifocal leucoencephalopathy • Primary lymphoma of the brain in patient < 60 years of age • Kaposi’s sarcoma in a patient < 60 years of age • PLH/ LIP complex ( pulmonary lymphoid hyperplasia & /or lymphoid interstitial pneumonia ) in a child < 13 years of age

  20. With laboratory evidence for HIV infection Disease diagnosed definitively • Isosporriasis with diarrhea persisting > 1 month • Extrapulmonary or disseminated histoplasmosis • Extrapulmonary or disseminated coccidioidomycosis • Extrapulmonary or disseminated tuberculosis • Any noncutaneous extrapulmonary or disseminated mycobacterial infection other than TB or leprosy

  21. - Recurrent non typhoid Salmonella septicaemia • kaposi’s sacroma at any age • Primary lymphoma of the brain at any age • Other non-Hodgkin’s lymphoma of B- cell immunologic phenotype • HIV encephalopathy ( AIDS demential complex • HIV wasting syndrome

  22. Diseases diagnosed presumptively • Pneumocystis carinii pneumonia • Toxoplasmosis of the brain in patient > 1 month of age • Oesophageal candidiasis • Extrapulmonary or disseminated mycobacterial infection • Kaposi’s sacroma • Lymphoid interstatial pneumonitis( LIP/PLH complex ) in a child < 13 years of age

  23. With evidence against HIV infection Pneumocystis carinii pneumonia diagnosed by a definitive Any other disease indicative of AIDS listed above T- helper T4 lymphocyte count <400 /mm None of the other causes of immunodeficiency listed above.

  24. Antigen / Antibody response to HIV Antigen Antigen Ab ( gp 41 ) Ab (p 24 ) Months Years

  25. Cumulative of number of HIV/AIDS by mode of transmission in Palestine 2003 Sexually Blood Drug Vertical Unknown Total Transmission Addicts Transmission Hetro Bisex Homo Hemophilia Others 30 2 1 4 6 3 1 8 55

  26. Maternal Factors • Advanced immunosuppressant • Advanced clinical disease • High viral load • Recently acquired HIV infection & placental barrier distribution ( through chronic amnionitis, placental malaria , smoking )

  27. Delivery factors - Vaginal delivery or caesarian section - Invasive procedures - Prolonged rupture of membrane

  28. Factors after delivery - Breast-feeding Cracked nipple Oral lesion in the infant

  29. Diagnosis • Elisa 2) Western Blot ( W.B ) 3) P.C.R. Elisa Test Negative Positive Repeat Negative Positive Repeat W.B Negative Indeterminate Positive Repeat Indeterminate P.C.R

  30. Causes of false- Negative ELISA reactions to HIV:- • Incubation period or acute disease before seroconversion (widow-period) • Malignancy • Intensive or long-term immunosuppressive therapy • Replacement transfusion • Bone-marrow transplantation • Kits that detect antibody to p24 primarily • B-cell dysfunction

  31. Cause of false positive ELISA Reactions to HIV:- Antibody against smooth muscle ,parietal cell, mitochondria, nuclear , leukocyte, and T-cell antigen ; anti-HAV-IgM and anti HBc- IgM Antibodies against class II leukocyte antigen( HLA-DR4,-DQw3) present on H-9 cell (more frequently observed in multiply transfused patients) Several alcoholic liver disease , primary biliary cirrhosis, sclerosing cholangitis

  32. Heat inactivation or RPR positively of serum tested ( abott EIA only ) • Hematologic malignangies, lymphoma • Acute DNA viral infections, HIV-2 infection • Renal transplants, chronic renal failure • Stevens-johnson syndrom • Passively acquired HIV-1 antibody ( hepatitis B immunoglobulin)

  33. Causes of false-positive W.B. reactions to HIV-1 antigen ( gag, env, and pol proteins ):- Cross reactions with Normal human ribonucleoproteins Other human retroviruses Antibody to mitochondrial, nuclear ,T-cell , and leukocyte antigen Antibodies to HLA antigens (classes I and II) Globulins produced during polyclonal gammopathy

  34. Recommendations for when to initiate treatment Symptomatic HIV disease* Therapy recommended for all patients * Include symptoms as recurrent mucosal candidacies , oral hairy leukoplakia, chronic or other wise unexplained fatigue, night sweats or weight loss

  35. Asymptomatic CD4 cell count <500/uL :therapy recommended+ CD4 cell count <500/uL : therapy recommended for patients with > 30,000-50,000 HIV RNA copies/ mL or rapidly declining CD4 cell counts consider therapy for patients > 5000- 10000 HIV RNA copies. + some would defer therapy in subset of patients with stable CD4 cell count between 350-500/uL And plasma HIV RNA consistently below 5000-10000 copies/ mL

  36. LTR : long terminal report .promoter/enhancer for the HIV genes ( it interacts with the cell proteins that undulate viral replication) Pole gene: codes for construction of reverse transcriptase ,protease & integrase enzyme nef gene : contributions to the virulence of HIV rev. gene : the rev protein swiches the replication cycle to the production of whole virus particles tat gene : accelerate viral replication. vif gene : determines the infectivity of cell –free virus vpr gene : facilitate the transport of HIV DNA into the cell nucleus & regulates the cell cycle itself

  37. Transcriptase enzyme

  38. Entry to the cell & HIV replication: • HIV bind to the CD4 protein on the cell membrane • After binding , the looped segment V3 of the gp 120 molecule interacts with chemokine receptor CKR5, CKR3, CKR2b, CXCR4 , to allow fusion of the cell & viral membrane • After penetration , the virus loses its envelope • The reverse transcriptase enzyme of DNA copies of viral RNA • Viral RNA is conveyed to the nucleus & inserted into cellular DNA . This integrated DNA copy of the HIV genome is called provirus

  39. 6- The HIV DNA provirus is transcribed into RNA copies, which are either incorporated into new virus particles as the genome or function as messenger RNA and are translated into core, envelope or accessory proteins. 7- The core proteins and genomic RNA are assembled into viral cores in the cytoplasm beneath patches of the cell membrane containing the envelope proteins. 8- The virus particle buds out through the altered cell membrane into infect other cells.

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