Alteration in the Immune Response

7/31/2019 Alteration in the Immune Response

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DUMDUMISMs CRACKING MS


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IgE mediated mast cell degranulation Examples are:

Hay fever, asthma, anaphylaxis


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Formation of anti-bodies (IgG,IgM) againstsurface antigens. Complements usually

involved Autoimmune hemolytic anemia, hemolytic

disease of the newborn


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IgG,IgM,IgA that interact with exogenous orendogenous antigens to form antigen-

antibody complexes that cause vessel ortissue injury

Autoimmune diseases (SLE), rheumatoid

arthritis, AGN


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Synthesized T lymphocyte release cytokinesthat cause direct cell-mediated toxicity or

delayed hypersensitivity disorders Tuberculosis, contact dermatitis, transplant

rejection


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Autoimmune disorders results from thebreakdown in the integrity of immune

tolerance such that a humoral or cellularimmune response can be mounted againsthost tissue or antigens, leading to localized orsystemic injury

Immunologic tolerance is the ability of theimmune system to differentiate self fromnonself


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Mixed connective tissue disease Polymyositis dermatomyositis

Rheumatoid arthritis Scleroderma Sjogren syndrome Systemic Lupus erythematosus


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Autoimmune hemolytic anemia Autoimmune neutropenia and lymphopenia

Idiopathic Thrombocytopenic purpura


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Acute idiopathic polyneuritis Atrophic gastritis and pernicious anemia

Hashimoto thyroiditis IDDM MG Graves disease Ulcerative Colitis Primary biliary cirrhosis


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Rheumatoid arthritis systemic

inflammatory disease that attacks the jointsby producing proliferative synovitis that leadsto destruction of the articular cartilage andunderlying bone.


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Morning stiffness for at least 1 hour andpresent for at least 6 months

Simultaneous swelling of three or more jointsfor at least 6 weeks Swelling of wrist, metacarpophalangeal or

proximal interphalangeal joints for at least 6wks

Systemic joint swelling for 6 or more weeks


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Rheumatoid nodules Serum rheumatoid factor

Radiographic changes typical of rheumatoidarthritis on hand or wrist radiographs


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Reduce pain, minimize stiffness and swelling,maintain mobility

Rest (physical and emotional) Therapeutic exercise DMARD - methotrexate NSAIDS aspirn


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Degenerative joint disease Pain worsens with activity and relieved by

rest initially. In later stage, pain is experienced during rest. Arthritis of the weight bearing joints


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No cure Physical rehabilitation

Relieve pain NSAIDS


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Chronic inflammatory disease that can affectvirtually any organ system

Dominant in females Common in african americans, latin

americans, asians Idiopathic


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Systemic lupus erythematosus (SLE) is anautoimmune disease.

SLE is characterized by the production ofunusual antibodies in the blood. SLE is eight times more common in women

than men. The cause(s) of SLE is (are) unknown,

however, heredity, viruses, ultraviolet light,and drugs all may play some role.


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Up to 10% of people with lupus isolated to theskin will develop the systemic form of lupus(SLE).

Eleven criteria help doctors to diagnose SLE. Treatment of SLE is directed toward decreasing

inflammation and/or the level of autoimmuneactivity.

People with SLE can prevent "flares" of diseaseby avoiding sun exposure and not abruptlydiscontinuing medications and monitoring theircondition with their doctor.


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fatigue, low-grade fever,loss of appetite, muscleaches, hair loss (alopecia), arthritis, ulcers of themouth and nose, facial rash ("butterfly rash"),

unusual sensitivity to sunlight (photosensitivity),inflammation of the lining that surrounds thelungs (pleuritis) and the heart (pericarditis), andpoor circulation to the fingers and toes with coldexposure (Raynaud's phenomenon).Complications of organ involvement can lead tofurther symptoms that depend on the organaffected and severity of the disease.
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Skin manifestations are frequent in lupus andcan sometimes lead to scarring. In discoidlupus, only the skin is typically involved. Theskin rash in discoid lupus often is found onthe face and scalp. It usually is red and mayhave raised borders. Discoid lupus rashes are

usually painless and do not itch,but scarring can cause permanent hairloss (alopecia). Over time, 5%-10% of thosewith discoid lupus may develop SLE.
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Arthritis Thrombocytopenia Myositis Muscle pain and weakness Vasculitis Chest pain

Carditis High blood pressure Renal failure psychosis


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Malar (over the cheeks of the face) "butterfly"rash

Discoid skin rash (patchy redness withhyperpigmentation and hypopigmentationthat can cause scarring)

Photosensitivity (skin rash in reaction to

sunlight [ultraviolet light] exposure) Mucous membrane ulcers (spontaneous sores

or ulcers of the lining of the mouth, nose, orthroat)


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Arthritis (two or more swollen, tender jointsof the extremities)

Pleuritis or pericarditis (inflammation of thelining tissue around the heart or lungs,usually associated with chest pain uponbreathing or changes of body position)


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Kidney abnormalities (abnormal amounts ofurine protein or clumps of cellular elementscalled casts detectable with a urinalysis)

Brain irritation (manifested by seizures[convulsions] and/or psychosis, referred to as"lupus cerebritis")

Blood-count abnormalities: low white bloodcount (WBC) or red blood count (RBC), orplatelet count on routine complete bloodcount testing)
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Immunologic disorder (abnormal immunetests include anti-DNA or anti-Sm [Smith]

antibodies, falsely positive blood testfor syphilis, anticardiolipin antibodies, lupusanticoagulant, or positive LE prep test)

Antinuclear antibody (positive ANA antibodytesting [antinuclear antibodies in the blood])
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Corticosteroids NSAIDS

Hydroxychloroquine Immunosuppresants B cell suppresors (Rituximab)


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Infection caused by HIV Characterized by profound

immunosuppression with associatedopportunistic infections, malignancies,wasting, and CNS degeneration

AIDS is a secondary immunodeficiencydisorder that results from HIV infection and istransmitted through blood, semen, or vaginalfluids


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1 Attachment of HIV to CD4+ T cell receptors 2 Internalization and uncoating of the virus

with viral RNA and reverse transcriptase 3 Reverse transcription 4 Integration of viral DNA to host DNA

(integrase enzyme) 5 Transcription of the inserted viral DNA to

produce viral mRNA


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6 Translation of viral mRNA to create viralpolyprotein

7 cleavage of viral polyprotein into individualviral proteins that make up the new virus 8 Assembly and release of the new virus from

the host cell.


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CD4+ cell count Category 1 = >500cells/uL

Category 2 = 200-499 cells/uL

Category 3 =


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8-12 years 3 phases

Primary infection phase (2-4 weeks) Latency phase (8-10 years)

Overt or AIDS phase (2-3 years)


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Fever Fatigue Rash

Headache Lymphadenopathy Pharyngitis Arthralgia Myalgia Night sweats GI problems Aseptic meningitis Oral or genetic ulcers


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PCP and PTB CMV and MAC Esphageal candidiasis Herpes simplex virus Kaposi Sarcoma Lymphoma

Salmonella septicemia Cervical malignancies Histoplasmosis Etc.


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ELISA

Western Blot Assay Ora Quick Rapid HIV-1 Antibody test Polymerase chain reaction (PCR)


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HAART

Highly active anti-retroviral therapy


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Entry inhibitors (or fusion inhibitors) interfere withbinding, fusion and entry of HIV-1 to the host cellby blocking one of several targets.

Maraviroc and enfuvirtide are the two currentlyavailable agents in this class.


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CCR5 receptor antagonists are the firstantiretroviral drugs which do not target the virusdirectly. Instead, they bind to the CCR5 receptor

on the surface of the T-Cell and block viralattachment to the cell. Most strains of HIV attachto T-Cells using the CCR5 receptor. If HIV cannotattach to the cell, it cannot gain entry to replicate.


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Nucleoside reverse transcriptase inhibitors (NRTI)and nucleotide reverse transciptase inhibitors(NtRTI) are nucleoside and nucleotide analogues

which inhibit reverse transcription by beingincorporated into the newly synthesized viral DNAstrand as faulty nucleotides; they both act ascompetitive substrate inhibitors.


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Non-Nucleoside reverse transcriptase inhibitors(NNRTI) inhibit reverse transcriptase by binding toan allosteric site of the enzyme; NNRTIs act as

non-competitive inhibitors of reversetranscriptase.

Protease inhibitors (PIs) target viral assembly by

inhibiting the activity of protease, an enzymeused by HIV to cleave nascent proteins for thefinal assembly of new virions.


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Integrase inhibitors inhibit the enzyme integrase,which is responsible for integration of viral DNAinto the DNA of the infected cell. There are several

integrase inhibitors currently under clinical trial,and raltegravir became the first to receive FDAapproval in October 2007.


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Maturation inhibitors inhibit the last step in gagprocessing in which the viral capsid polyprotein iscleaved, thereby blocking the conversion of the

polyprotein into the mature capsid proteinBecause these viral particles have a defectivecore, the virions released consist mainly of non-infectious particles. Alpha interferon is a currentlyavailable agent in this class. Two additionalinhibitors under investigation are bevirimat andVivecon.

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Alteration in the Immune Response