Immune Function

1

• Immune FunctionHIV

2
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

3
Acute Inflammation

• Short term process characterized by the classic
  signs of inflammation
• Swelling
• Redness
• Pain
• Heat
• Predominant celltype neutrophils

4
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

5
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.

6
Lymphoid Organs

• Central lymphoid organs
• Thymus
• Bone marrow
• Peripheral lymphoid organs
• Tonsils
• Gut-, genital-, bronchial-, skin-associated
  lymphoid tissue
• Lymph nodes
• spleen

7
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

8

• 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

9

• Antigens that get past the external barriers are
  targeted for destruction by the immune system

10
Antibodies

• Attach to specific antigen
• Make it easier for phagocytes to destroy antigen

11
Acquired Immunity

• Is when the body is exposed to various antigens
  and builds a defense that is specific to that
  antigen

12
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

13
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

14
Altered Immune Response

• Immunocompetence
• ? immunity
• Immunodeficiency diseases
• Severe infections
• Malignancies
• ? immunity
• Hypersensitivity disorders
• Allergies
• Autoimmune diseases

15
Hypersensitivity Reactions

• Autoimmune Diseases
• Four Types
• Type 1, II, III are immediate and humoral
• Type IV is a delayed hypersensitivity and
  cell-mediated

16
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

17
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

18
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

19
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

20
Anaphylaxis

• Life-threatening medical emergency d/t rapid
  constriction of the airway
• Treatment
• Epinephrine (adrenaline)
• ?-2 adrenergic receptors - powerful
  bronchodilator
• EpiPen
• May also cause tachycardia

21
Type I Hypersensitivity Reactions

• Atopic reactions
• Inherited tendency to become sensitive to
  environmental allergens
• Allergic rhinitis (hay fever), asthma,
  dermatitis, urticaria

22
Type II Cytotoxic and Cytolytic Reactions/
Antibody-Dependent Reactions

• Antibodies produced by the immune system bind to
  antigens on pts 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
• Hashimotos thyroiditis

23
Hemolytic transfusion reactions

• Results from ABO incompatibility
• Antibodies coat the foreign erythrocytes ?
  agglutination ? occlusion of blood vessels
• Cellular lysis
• ? Acute renal failure

24
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)

25
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

26
Allergic Disorders

• Assessment
• Health History
• Physical Examination
• Diagnostic Studies
• Skin Tests
• Procedure
• Results
• Precautions

27
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

28
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

29
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

30
SLE

• Clinical Manifestations
• Dermatological, M/S, Cardiopulmonary, Renal,
  Nervous system, Hematologic, Infection
  susceptibility

31
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

32
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

33
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

34
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

35
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

36
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.

37
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

38
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)

39
Effects of Corticosteroids contd

• 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

40
(No Transcript)
41
HIV and AIDS
42
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.

43
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.

44
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.

45
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 cells normal DNA and
  takes over the cells machinery.
• The invaded lymphocyte then produces HIV particles

46
The HIV Retrovirus contd

• 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

47
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

48
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 (normal 800-1000 mm3) or
• Development of an AIDS defining illness

49
Typical Untreated HIV Course
50
HIV and AIDS

• AIDS diagnosed when individual with HIV develops
  at least one of the following Table 14-1)
• CD4T count of less than 200 cells/µl
• Healthy adults have CD4T count 1,000
• Development of opportunistic infection (OI)
• Development of opportunistic cancer
• Wasting syndrome
• Loss of 10 of total body mass
• Development of dementia

51
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

52
AIDS Defining Illnesses contd

• 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

53
AIDS Defining Illnesses contd

• Malignancies
• Most frequently seen AIDS-related malignancy is
  Kaposis Sarcoma (KS)
• Tuberculosis
• Leading cause of death from AIDS worldwide
• Can affect any body siteusually lungs
• Needs to be treated aggressively with drugs and
  isolation to prevent its spread to others

54
(No Transcript)
55
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

56
Pneumocystis Pneumonia
57
Kaposis 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

58
Kaposis 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

59
Kaposis Sarcoma
60
Collaborative Care

• Monitoring HIV disease progression and immune
  function
• Initiating and monitoring highly active
  antiretroviral therapy (HAART)
• Preventing and detecting opportunistic infections

61
Collaborative Care

• Preventing and treating complications of
  therapies
• Ongoing health assessment
• Baseline data including HP, immunization
  history, psychosocial and dietary evaluation

62
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

63
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

64
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

65
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)

66
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

67
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

68
NRTIs

• Combivir
• Emtriva
• Epivir
• Epixicom
• Hivid
• Retrovir

• Trizivir
• Truvada
• Videx EC
• Viread
• Zerit
• Ziagen

69
Protease inhibitors (PIs)

• Block protease
• Protein needed for HIV replication
• Introduced December, 1995
• Approved for use in combination with NRTIs

70
PIs

• Agenerase
• Aptivus
• Crixivan
• Fortovase
• Invirase
• Keletra
• Lexiva

• Norvir
• Prezista
• Reyataz
• viracept

71
Antiretroviral drugs
72
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

73
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

74
Dyslipidemia

• Most patients with HIV infected patients who
  arent on HAART have lipid abnormalities
• PIs are most often associated with dyslipidemia
• Can lead to accelerated atherosclerosis

75
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

76
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

77
Independent Nursing Interventions

• Most important interventions for reducing
  cardiovascular risk
• Teaching patients about smoking cessation
• Encouraging exercise
• Optimal weight control

78
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

79
Smoking and HIV

• When nurses advise and encourage hospital
  patients who smoke to quit, 15 - 20 of them
  quit, compared with 3 who dont receive
  counseling at all.
• 4 As 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

80
Other HIV/AIDS drugs
81
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

82
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

83
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

84
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

85
Thats all folks.

• Study and do well!!