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Immune Function & HIV. dr shabeel pn. Inflammation. Response of vascular tissues to harmful stimuli i.e. pathogens, damaged cells, or irritants Protective attempt by the organism to remove injurious stimuli and initiate the healing process May be acute or chronic

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immune function hiv
Immune Function&HIV

dr shabeel pn

inflammation
Inflammation
  • Response of vascular tissues to harmful stimuli
    • i.e. pathogens, damaged cells, or irritants
  • Protective attempt by the organism to remove injurious stimuli and initiate the healing process
  • May be acute or chronic
  • Inflammatory response includes :
    • Vascular response
    • Cellular response
    • Formation of exudate
    • healing
acute inflammation
Acute Inflammation
  • Short term process characterized by the classic signs of inflammation
    • Swelling
    • Redness
    • Pain
    • Heat
  • Predominant celltype: neutrophils
chronic inflammation
Chronic Inflammation
  • Lasts for weeks – years
  • Injurious agent persistent
  • Predominant cell type: lymphocytes and macrophages
  • Examples:
    • Autoimmune reactions
      • Rheumatoid arthritis
    • Prolonged exposure to chemical agents
      • silica
immune system structures
Immune system structures
  • The immune system protects the body from potentially harmful substances. The inflammatory response (inflammation) is part of innate immunity. It occurs when tissues are injured by bacteria, trauma, toxins, heat or any other cause.
lymphoid organs
Lymphoid Organs
  • Central lymphoid organs
    • Thymus
    • Bone marrow
  • Peripheral lymphoid organs
    • Tonsils
    • Gut-, genital-, bronchial-, & skin-associated lymphoid tissue
    • Lymph nodes
    • spleen
normal immune response
Normal Immune Response
  • Immunity
    • State of responsiveness to foreign substances such as microorganisms and tumor proteins
  • Types of Immunity
    • Active Acquired Immunity
    • Passive Acquired Immunity
slide8
Antigen
    • Large molecules (usually proteins) on the surface of cells, viruses, fungi or bacteria
  • Antibody
    • Protein produced by the immune system in response to the presence of an antigen
antibodies
Antibodies
  • Attach to specific antigen
  • Make it easier for phagocytes to destroy antigen
acquired immunity
Acquired Immunity
  • Is when the body is exposed to various antigens and builds a defense that is specific to that antigen
passive immunity
Passive Immunity
  • Antibodies that are produced in someone else\'s body
    • Infants have passive immunity because antibodies are transferred through the placenta from the mother
      • Last 6-12 months
    • Gamma globulin
      • Given IV, IM
      • Temporary protection
aging and the immune system
Aging and the Immune System
  • Decline in the immune system with aging
  • Characterized by higher incidence of tumors in elderly
  • Also seen with greater susceptibility to infections such as influenza and pneumonia
altered immune response
Altered Immune Response
  • Immunocompetence
  •  immunity
    • Immunodeficiency diseases
    • Severe infections
    • Malignancies
  •  immunity
    • Hypersensitivity disorders
      • Allergies
      • Autoimmune diseases
hypersensitivity reactions
Hypersensitivity Reactions
  • Autoimmune Diseases
  • Four Types
    • Type 1, II, III are immediate and humoral
    • Type IV is a delayed hypersensitivity and cell-mediated
type i hypersensitivity immediate anaphylactic reactions
Type I Hypersensitivity Immediate/Anaphylactic Reactions
  • Occur in in susceptible people who are highly sensitized to specific allergens
  • Mediated by IgE antibodies
  • Release histamine and others by mast cells and basophils
  • Result in systemic inflammatory response (seconds to minutes)
  • Reaction can be local or systemic
    • Runny nose anaphylaxis
    • Mild irritation  sudden death
type i hypersensitivity reactions
Type I Hypersensitivity Reactions
  • Anaphylaxis
    • Immediate release of mediators
      • Injection
      • Bee sting
    • Reaction is within minutes
    • Can be life threatening
      • Bronchial constriction  airway obstruction
      • Vascular collapse
    • Initial symptoms
      • Edema, itching at site of exposure
      • Can rapidly escalate into shock
        • Rapid weak pulse
        • Hypotension
        • Dyspnea
        • cyanosis
      • See Table 12-12
anaphylactic shock
Anaphylactic Shock
  • Most severe type of anaphylaxis
  • From quick release of mast cells
  • Estimated 1.3-16.8% of population are “at risk” for having anaphylactic reaction especially to insect stings and penicillin (see table 13-11)
  • Results in ~1,000 deaths per year
    • Usually related to sudden cardiovascular collapse
anaphylaxis
Anaphylaxis
  • IgE acts to release histamine from mast cells
  • Histamine causes vasodilation of arterioles and constriction of bronchioles in lungs (bronchospasm)
  • Symptoms:

Respiratory distress Unconsciousness

Hypotension Urticaria (hives)

Flushed appearance Angioedema (swelling of lips, face, throat)

Anxiety Abdominal pain

anaphylaxis1
Anaphylaxis
  • Life-threatening medical emergency d/t rapid constriction of the airway
  • Treatment
    • Epinephrine (adrenaline)
      • Β-2 adrenergic receptors -> powerful bronchodilator
      • EpiPen
        • May also cause tachycardia
type i hypersensitivity reactions1
Type I Hypersensitivity Reactions
  • Atopic reactions
    • Inherited tendency to become sensitive to environmental allergens
    • Allergic rhinitis (hay fever), asthma, dermatitis, urticaria
type ii cytotoxic and cytolytic reactions antibody dependent reactions
Type II: Cytotoxic and Cytolytic Reactions/ Antibody-Dependent Reactions
  • Antibodies produced by the immune system bind to antigens on pt’s own cell surface
  • Involve binding of IgG or IgM antibodies to antigens
  • Antigen-antibody complexes activate the complement system reaction/acute inflammation
  • Mediators of inflammation produce chemicals that lyse (destroy) cells (erythrocytes, platelets, leukocytes)
  • Hours to days
  • Examples
    • Hemolytic transfusion reactions
    • Goodpasture syndrome
    • Hashimoto’s thyroiditis
hemolytic transfusion reactions
Hemolytic transfusion reactions
  • Results from ABO incompatibility
  • Antibodies coat the foreign erythrocytes  agglutination  occlusion of blood vessels
  • Cellular lysis
    •  Acute renal failure
type iii immune complex reactions
Type III: Immune-Complex Reactions
  • Results from antigen-antibody complexes
  • IgG, IgM complexes are deposited in tissue (kidneys, joints, lungs, small blood vessels)  inflammation and cellular destruction
  • Local or systemic
  • Hours-days
  • Associated with systemic lupus erthymatosus (SLE), rheumatoid arthritis (RA)
type iv delayed hypersensitivity reactions
Type IV: Delayed Hypersensitivity Reactions
  • Cell-mediated (not antibody-mediated) immune response causing tissue damage
  • Sensitized T lymphocytes attack antigens and release cytokines which attract macrophages
  • 2-3 days
  • Examples:
    • Contact dermatitis (poison ivy rash)
    • Transplant rejection
allergic disorders
Allergic Disorders
  • Assessment
    • Health History
    • Physical Examination
  • Diagnostic Studies
    • Skin Tests
      • Procedure
      • Results
      • Precautions
chronic allergies
Chronic Allergies
  • Characterized by chronic remissions and exacerbations
  • Allergen recognition and control
    • Skin testing
    • Elimination diet
  • Identification of aggravating factors
  • Medic Alert bracelet
  • Collaborative Care
    • Epi Pen
    • Antihistamines
allergic disorders cont
Allergic Disorders (cont.)
  • Collaborative Care (cont.)
    • Drug Therapy
      • Antihistamines
      • Sympathomimetic/decongestant drugs
      • Corticosteroids
      • Antipruritic drugs
      • Mast cell-stabilizing drugs (cont.)
    • Immunotherapy
      • Mechanism of action
      • Method of administration
systemic lupus erythematosus sle
Systemic Lupus Erythematosus (SLE)
  • Chronic, mulitisystem inflammatory disease
  • Typically affects skin, joints, renal, hematologic, neurologic systems
  • Etiology: unknown
  • Autoimmune reactions are directed against host cells
  • Clinical manifestations are variable
slide30
SLE
  • Clinical Manifestations
    • Dermatological, M/S, Cardiopulmonary, Renal, Nervous system, Hematologic, Infection susceptibility
polymysitis dermatomyositis
Polymysitis & Dermatomyositis
  • Diffuse, idiopathic, inflammatory myopathies of muscle  weakness
  • Clinical manifestations
    • Fatigue, weakness
    • Classic cyanotic heliotrope rash
    • Joint pain
  • Diagnostic Studies
    • CK
    • ESR
  • Nursing Management
    • Assistive
sjogren syndrome
Sjogren Syndrome
  • Autoimmune disorder that targets moisture producing glands  dry mouth, dry eyes
  • Usually affects women over the age of 40
  • “gritty” sensation of eyes
  • Symptomatic treatment
immunodeficiency disorders
Immunodeficiency Disorders
  • Immune system does not adequately protect the body
  • Impairment of 1 or more immune mechanisms
  • Primary Immunodeficiency Disorders
    • Immune cells are improperly developed/absent
  • Secondary Immunodeficiency Disorders
    • Deficiency based on illness or treatment
  • Graft-versus-Host Disease
    • Transfusion or transplantation with immunocompetent cells
immunosuppressive therapy
Immunosuppressive Therapy
  • Goal: adequately suppress immune response to prevent rejection while maintaining sufficient immunity to prevent overwhelming infection
    • Calcineurin Inhibitors
    • Sirolimus
    • Mycophenolate Mofetil
    • Polyclonal Antibodies (Antithymocyte Globulin and Antilymphocyte Globulin)
    • Monoclonal Antibodies
    • New Immunosuppressive Therapy
corticosteroidal therapy
Corticosteroidal Therapy
  • AKA “steroids”
    • Prednisone
    • Solu-medrol
  • Discovered in 1948
  • Believed to be “miracle cure” for arthritis
  • Used to relieve the signs, symptoms of many diseases
  • Long-term use leads to serious complications and side effects
    • Became known as “scaroids”
corticosteroids
Corticosteroids
  • What Are They?
    • Corticosteroids are drugs closely related to cortisol, a hormone which is naturally produced in the adrenal cortex (the outer layer of the adrenal gland).
  • How Do They Work?
    • Corticosteroids act on the immune system by blocking the production of substances that trigger allergic and inflammatory actions, such as prostaglandins. However, they also impede the function of white blood cells which destroy foreign bodies and help keep the immune system functioning properly. The interference with white blood cell function yields a side effect of increased susceptibility to infection.
corticosteroids1
Corticosteroids
  • What Conditions Do They Treat?
    • Corticosteroids are widely used for many conditions. They are also used to control inflammation of the joints and organs in diseases such as:
      • rheumatoid arthritis
      • lupus (systemic lupus erythematosus)
      • ankylosing spondylitis
      • juvenile arthritis
      • inflammatory bowel disease
      • polymyositis
      • mixed connective tissue disease
      • polymyalgia rheumatica
      • scleroderma (systemic sclerosis)
      • vasculitis
effects of corticosteroids
Effects of Corticosteroids
  • Anti-inflammatory Action
    •  circulating lymphocytes, monocytes and eosinophils
    • Inhibit accumulation of leukocytes at site of inflammation
    • Inhibit release of substances involved in inflammatory response
    • Therefore, suppress manifestations of inflammation (redness, tenderness, heat, swelling, local edema)
effects of corticosteroids cont d
Effects of Corticosteroids cont’d
  • Immunosuppression
    • Cause atrophy of lymphoid tissue
    • Suppress cell-mediated immune responses
    • Decrease production of antibodies
  • Blood pressure
    • Vasoconstriction
    • Retention of Na (and water)
  • Carbohydrate and Protein Metabolism
    • Increase hepatic glycogenesis
    • Increase insulin resistance
    • Redistribute fat in cushingoid pattern
aids in the u s
AIDS in the U.S.
  • Centers for Disease Control (CDC) estimated that in 2007 about 1 million people in US are living with HIV or AIDS
    • 46% estimated to be men who have sex with men
    • 31% estimated to be adults/adolescents infected through heterosexual contact
    • Blacks who make up 13% of population accounted for almost ½ of the number of HIV/AIDS cases diagnosed
  • In US and countries where latest therapies are available, many patients have been managing their HIV infection with antiretroviral therapy (ART) for more than 20 years.
aids worldwide
AIDS Worldwide
  • The magnitude of the global HIV/AIDS epidemic vastly exceeds that in the United States.
    • At the end of 2001, more than 40 million people were estimated to be living with HIV/AIDS, and
    • More than 20 million had already died from AIDS.
    • Nearly three quarters of those with the disease are living in sub-Saharan Africa, where access to antiretroviral therapy is limited.
hiv and aids1
HIV and AIDS
  • The primary causative agent of AIDS is HIV
  • HIV infects lymphocytes and results in severe immunodeficiency.
  • Immunodeficiency can lead to infections, cancers and neurological manifestations.
the hiv retrovirus
The HIV Retrovirus
  • HIV retrovirus has a particular affinity for helper T lymphocytes (cells that control the functions of other immune cells)
  • Once inside T lymphocytes, HIV produces abnormal DNA and fuses with the cell’s normal DNA and takes over the cell’s machinery.
  • The invaded lymphocyte then produces HIV particles
the hiv retrovirus cont d
The HIV Retrovirus cont’d
  • These viruses exit the dying cell and repeat the process in other T lymphocytes
  • Without treatment, T lymphocytes become depleted as HIV particles increase
  • The person develops an infection or malignancy
transmission of hiv
Transmission of HIV
  • Major routes of transmission
    • Through human blood
      • Including infected needles
    • Sexual Transmission
      • Through exchange of semen, vaginal and cervical fluids
    • Perinatal Transmission
      • During pregnancy, labor, delivery or breast-feeding
disease development
Disease Development
  • Typical course of HIV/AIDS is defined by three phases
  • Primary infection phase
    • Flu-like symptoms
    • Few days  two weeks
  • Chronic asymptomatic/latency phase
    • Little or no symptoms of illness
    • Lasts average of 10 years
  • Overt AIDS phase
    • Occurs when person has a CD4 count < 200 mm3 (normal 800-1000 mm3) or
    • Development of an AIDS defining illness
hiv and aids2
HIV and AIDS
  • AIDS diagnosed when individual with HIV develops at least one of the following Table 14-1):
    • CD4+T count of less than 200 cells/µl

Healthy adults have CD4+T count >1,000

    • Development of opportunistic infection (OI)
    • Development of opportunistic cancer
    • Wasting syndrome
      • Loss of > 10% of total body mass
    • Development of dementia
aids defining illnesses
AIDS Defining Illnesses
  • Opportunistic Infections (OIs)
    • Develop in people with weakened immune systems, including people with HIV disease
    • Most common opportunistic infections are:
      • Pneumocystis carinii pneumonia (PCP)
      • Oropharyngeal or esophageal candidiasis (thrush)
      • Cytomegalovirus (CMV)
      • Infections causing diarrhea
aids defining illnesses cont d
AIDS Defining Illnesses cont’d
  • Neurological disorders
    • Affect between 40 -60% of all people with AIDS
    • Most common: AIDS-related dementia
      • Mechanism by which HIV infects the central nervous system is not known
      • Characterized by progressive cognitive dysfunction with motor and behavioral alterations
      • Onset is insidious and follows and unpredictable course
aids defining illnesses cont d1
AIDS Defining Illnesses cont’d
  • Malignancies
    • Most frequently seen AIDS-related malignancy is Kaposi’s Sarcoma (KS)
  • Tuberculosis
    • Leading cause of death from AIDS worldwide
    • Can affect any body site—usually lungs
    • Needs to be treated aggressively with drugs and isolation to prevent its spread to others
pnuemocystis pneumonia pcp
Pnuemocystis Pneumonia (PCP)
  • Most common opportunistic infection requiring hospitalization
  • Caused by pneumocystis jiroveci, formerly known as pneumocystis carinii
  • PCP is the indicator condition in 38% of AIDS pts
  • Classic triad of symptoms:
    • Fever, exertional dyspnea, nonproductive cough
kaposi s sarcoma
Kaposi’s Sarcoma
  • Once considered rare
    • Usually seen in elderly men or organ transplant patients
  • In the past 20 years cases have been associated with HIV infection
  • With prophylaxis and treatment, the number of cases d/t to HIV infection has ’d by ~85%
kaposi s sarcoma1
Kaposi’s Sarcoma
  • Typically causes tumors to develop in the tissues below the skin surface, or mucous membranes lesions
  • Lesions typically
    • Raised blotches or nodules
    • Purple, brown or red
    • Sometimes associated with painful swelling
  • Skin lesions are disfiguring but not life threatening
  • Can be life threatening when it involves lungs, liver or GI tract
    • Bleeding
    • Difficulty breathing
collaborative care
Collaborative Care
  • Monitoring HIV disease progression and immune function
  • Initiating and monitoring highly active antiretroviral therapy (HAART)
  • Preventing and detecting opportunistic infections
collaborative care1
Collaborative Care
  • Preventing and treating complications of therapies
  • Ongoing health assessment
    • Baseline data including H&P, immunization history, psychosocial and dietary evaluation
collaborative care2
Collaborative Care
  • Education about spectrum of HIV, treatment, preventing transmission, improving health, and family planning
  • Repeating and clarification of information is necessary due to shock and denial
antiretroviral therapy art
Antiretroviral Therapy (ART)
  • Rapid development of new drugs, combinations
  • Since the introduction of ART survival with AIDS has improved dramatically
    • From an average of 3.1 years to >13 years
  • New recommendations are to start antiretroviral therapy later than previously thought
    • Drug resistance
    • Medication side effects
    • Uncertain benefit
antiretroviral therapy
Antiretroviral Therapy
  • In the US alone, ART has saved an estimated total of at least 3 millions years of life.
  • ART associated with clinically important adverse reactions
antiretroviral therapy1
Antiretroviral Therapy
  • Side effects are considerable
  • Most common and serious s/e include
    • Diabetes
    • Cardiovascular disease
    • Cytopenias
    • Pancreatitis
    • Peripheral neuropathy
    • Hypersensitivity (rash, fever, risk of death)
    • Hepatitis
    • GI toxicity (diarrhea and nausea)
antiretroviral therapy2
Antiretroviral Therapy
  • Different drug groups used to treat HIV
  • Work at different points along the replication cycle
    • Nucleoside reverse transcriptase inhibitors (NRTIs)
    • Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
    • Protease Inhibitors
    • Fusion Inhibitors
  • Most critical, modifiable factor affecting success: patient adherence to drug regimen
nucleoside reverse transcriptase inhibitors nrtis
Nucleoside reverse transcriptase inhibitors (NRTIs)
  • Block reverse transcriptase, a protein HIV needs in order to replicate
  • As NRTIs were introduced and used in combination
    • survival increased
    • Increase in drug related complications
      • Nausea
      • Vomiting
      • Painful neuropathies
      • Life-threatening pancreatitis
nrtis
Combivir

Emtriva

Epivir

Epixicom

Hivid

Retrovir

Trizivir

Truvada

Videx EC

Viread

Zerit

Ziagen

NRTIs
protease inhibitors pis
Protease inhibitors (PIs)
  • Block protease
    • Protein needed for HIV replication
  • Introduced December, 1995
  • Approved for use in combination with NRTIs
slide70
Agenerase

Aptivus

Crixivan

Fortovase

Invirase

Keletra

Lexiva

Norvir

Prezista

Reyataz

viracept

PIs
highly active antiretroviral therapy haart
Highly Active Antiretroviral Therapy (HAART)
  • HAART is a treatment regimen that combines 3 antiretroviral drugs
    • 2 from NRTI class
    • 1 from PI class
  • Widespread use of PIs in 1996, successful treatment of HIV infection extended life by decades
  • HAART also associated with problems
    • Poor oral bioavailability
    • High pill burden
    • Intolerable adverse reactions
    • Long-term toxicities
  • Most of these problems have been minimized
chronic challenges
Chronic challenges
  • Because HAART has significantly reduced mortality, HIV is now considered a chronic, manageable illness
  • Patients and their families must face difficulties of any chronic illness
    • Medication toxicities
    • Exacerbation of mental health issues
    • Complex medication regimens
    • Lifestyle adjustments
  • Lipid and Glucose abnormalities
dyslipidemia
Dyslipidemia
  • Most patients with HIV infected patients who aren’t on HAART have lipid abnormalities
  • PIs are most often associated with dyslipidemia
  • Can lead to accelerated atherosclerosis
insulin resistance
Insulin Resistance
  • ~25% of population has insulin resistance
  • In patients receiving PI therapy, insulin resistance 60-85%
  • Insulin resistance usually appears 10 – 20 years before type 2 diabetes
patient teaching
Patient Teaching
  • Encourage your patient to:
    • Exercise
    • Control his/her weight
    • Reduce cardiovascular risk
      • Quit smoking
      • Use low-dose aspirin therapy
      • Manage lipids
      • Maintain BP within normal limits
      • Monitoring for diabetes
independent nursing interventions
Independent Nursing Interventions
  • Most important interventions for reducing cardiovascular risk:
  • Teaching patients about smoking cessation
  • Encouraging exercise
  • Optimal weight control
smoking hiv
Smoking & HIV
  • Prevalence of adult smokers in US ~21%
  • In HIV population ~72%
  • In HIV-infected I.V. drug users ~96%
  • Besides contributing to C-V disease, smoking is major contributor to:
    • Bacterial pneumonia
    • Abdominal aortic aneurysms
    • Cataracts
    • Periodontal disease
    • Cancers of lung, stomach, uterus, pancreas, kidney
smoking and hiv
Smoking and HIV
  • When nurses advise and encourage hospital patients who smoke to quit, 15% - 20% of them quit, compared with 3% who don’t receive counseling at all.
  • 4 A’s of smoking cessation counseling:
    • Ask about his smoking
    • Advise him to quit smoking
    • Assist him with quitting by providing educational materials, or referral for pharmacologic aids
    • Arrange follow-up to discuss progress toward smoking cessation
nsg diagnosis alteration in comfort nausea
Nsg Diagnosis: Alteration in comfort: nausea
  • Alteration in comfort: nausea related to medications, opportunistic infections
  • Goal: stable/ideal weight
    • Appropriate nutritional intake
  • Interventions:
    • Avoid hot, spicy or greasy food
    • BRAT diet (bananas, rice, applesauce, toast)
    • Eat dry food (crackers, toast, dry cereal)
    • Sip cold, carbonated beverages (ginger ale) or try peppermint, chamomile or ginger tea
    • Antiemetics as ordered
nsg diagnosis alteration in skin integrity rash
Nsg Diagnosis: Alteration in Skin Integrity: Rash
  • Alteration in Skin Integrity: Rash r/t medications (especially NNRTIs)
  • Goal: skin intact
  • Interventions
    • Natural skin moisturizer (aloe)
    • Antihistamines (benadryl) for mild rash
    • Antihistamine Corticosteroid (prednisone) as ordered for severe rash
    • Avoid harsh soaps and perfumes
nsg diagnosis potential for impaired gas exchange
Nsg Diagnosis: Potential for Impaired Gas Exchange
  • Alteration in tissue perfusion r/t anemia, d/t disease process, medications (especially AZT)
  • Goal:
    • Hgb/Hct within acceptable range
    • Acceptable pO2 without supplemental O2
  • Interventions
    • Administration of erythopoietin (Epogen) as ordered
    • O2 as ordered
    • Blood products as ordered
    • Teach to rest between periods of activity
    •  HOB during episodes of dyspnea
nsg diagnosis potential for injury infection
Nsg Diagnosis: Potential for Injury/ Infection
  • Potential for Infection r/t disease or treatment
  • Goal:
    • No signs/symptoms of active infection
    • WBC maintained within acceptable range
  • Interventions
    • “Compromised Host Precautions”: private room, etc.
    • Good handwashing by all visitors and personnel
    • VS q 2 hours
    • Minimize invasive procedures
    • Avoid raw fruits, vegetables and milk products
that s all folks
That’s all folks….

Study and do well!!…

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