Many of life's failures are men who did not realize how close they were to success when

they gave up.

- Thomas Edison

THE IMMUNE SYSTEM

Demuel Dee L. Berto, RN,MD

Humoral Immunity

Im m u n oc o m pe te nc e

Cell Mediated Immunity

Inflammation

IMMUNITY - the ability of the human body to resist almost all types of organisms or toxins that tend to damage the tissues and organs.
2 Types of Immunity:
Natural or Innate Immunity Acquired Immunity

NATURAL OR INNATE IMMUNITY

Not produced by the immune response You were born with it

 Results from general processes, rather than from processes directed at specific disease organisms:
Phagocytosis of bacteria Destruction by the acid secretions of the stomach Resistance of the skin to invasion by organisms

 Presence in the blood of chemical compounds or toxins

Lysozyme Basic polypeptides react & inactivate certain types of G+ bacteria Complement complex a system of about 20 proteins that can be activated in various ways to destroy bacteria. Natural killer cells

ACQUIRED IMMUNITY
Gained after birth Can be either active or passive ACTIVE ACQUIRED IMMUNITY: produced by the host after either natural exposure to an antigen or by immunization.

ANTIGENS
Substances that the immune system recognize as foreign or non-self. On infectious agents (viruses, bacteria, fungi, or parasites)

On non-infectious agents (pollens, foods, & bee venoms)

On drugs, vaccines, transfusions, transplanted tissues

ACTIVE ACQUIRED IMMUNITY

1. By injecting dead organisms: no longer
capable of causing disease but still have their chemical antigens

(typhoid fever, whooping cough, diphtheria, and other bacterial diseases)

2. By injecting toxins: chemically treated so that their

toxic nature has been destroyed even though their antigens for
causing immunity are still intact. (tetanus, botulism, etc)

3. By injecting live, attenuated organisms:

organisms have been grown in a special media or have been passed through a series of animals until they have mutated enough that they will not cause disease but still do carry the specific antigens. (poliomyelitis, yellow fever, measles, and

other viral diseases).

PASSIVE ACQUIRED IMMUNITY

Does not involve the hosts immune response. Achieved without injecting any antigen. Infusion of preformed antibodies or activated T cells

Examples
1. Passage of maternal antibodies to the fetus 2. Preformed antibodies (from human or animal)
Administered in the form of immune serum (antibody containing blood from which the clotting factors and cells have been removed).

 Antibodies last for 2 3 weeks and during this time the person is protected against the invading disease. Activated T cells last for a few weeks if transfused from another person & for a few hours to a few days if transfused from an animal.

Lymphocyte
The basis of acquired immunity. Found most extensively in the lymph nodes Also found in special lymphoid tissues (spleen, sub-mucosal areas of the GIT & the bone marrow). Constitute approx 36% of the total leukocyte count.

2 major populations
1. T-lymphocytes - form activated lymphocytes that provide cell-mediated immunity, a major defense against infections due to viruses, fungi, tubercle bacilli, also against tumors. 2. B- lymphocytes - form antibodies that provide humoral immunity, a major defense against bacterial infection.

SPECIAL ATTRIBUTES OF THE B-LYMPHOCYTE SYSTEM

Humoral Immunity

Formation of Antibodies by Plasma cells

Phagocytosis by macrophages Phagocytized antigen presented to adjacent B lymphocytes

Antigen

Enlargement of B lymphocytes (lymphoblast)

Plasmablasts Plasma cell precursor

divide once every 10 hrs

Plasma cell
- Produces antibodies (about 2000 molecules per sec.)

Antibodies are secreted into the lymph & carried to the circulating blood.

Formation of Memory Cells

Antigen
Phagocytosis by macrophages Phagocytized antigen presented to adjacent B lymphocytes

Enlargement of B lymphocytes (lymphoblast)

Plasmablasts

Memory Cell

Plasma cell -produces antibodies

Remain dormant until exposed to the same agent

Primary Response (in forming antibodies) - Occurs on first exposure to a specific antigen.
- There is a delay in the appearance of the primary response - Has weak potency & is short-lived

Secondary Response - Occurs after a second exposure to the same antigen.

- Rapid after exposure to the antigen (often w/in hours)
- Far more potent and forms antibodies for many months, rather than only a few weeks.

CLASSES OF ANTIBODIES
TYPE IgA FUNCTION Secretory; Inhibits bacteria and viruses from adhering to skin and mucous membranes Activated Receptor on B lymphocytes Degranulation of mast cell and basophil; clearance of parasites

IgD IgE

CLASSES OF ANTIBODIES
TYPE IgG FUNCTION Activates complement; neutralizes toxins;enhances phagocytosis;sustained immunity against viral and bacterial infections Activates complement; clears antigens through precipitation; possibly mediates auto-immunity; mediates ABO incompatibility

IgM

How will ANTIBODIES destroy foreign invaders?

By direct attack on the invader
Agglutination Precipitation Lysis Inactivation - Neutralization

By activation of the complement system

Chemical special action force

Complement Fixation
Complement
A system of about 20 proteins (many of which are enzyme precursors) Principal actors
11 proteins (designated C1 C9, B,D)

 Enzyme precursors:
Normally inactive, but can be activated through:
CLASSICAL PATHWAY ALTERNATE PATHWAY

Classical Pathway

Alternate Pathway

SPECIAL ATTRIBUTES OF THE T-LYMPHOCYTE SYSTEM

Cell Mediated Immunity

 CMI help provide protection to the body through its highly developed ability to differentiate self from non self Important in preventing the development of cancer and metastasis after exposure to carcinogens

TYPES OF T CELLS 3 major groups: 1. Helper T Cells - most numerous of the T cells (75%) - serve as the major regulator of virtually all immune - functions by forming a series of protein mediators called CYTOKINES :

Examples: IL 1-6, Granulocyte-monocyte colony stimulating factor, Interferon .

2. Cytotoxic T Cells Direct-attack cell capable of killing microorganisms Most effective against self cells infected by parasitic organisms such as viruses or protozoa Creates holes in the membrane of the infected cells and delivers a lethal hit of enzymes to the infected cells

3. SUPPRESOR T CELLS - capable of suppressing the functions of both cytotoxic & helper T cells. - serve the purpose of regulating the activities of other cells, keeping them from causing excessive immune reactions that may be damaging to the body. - classified as regulatory T cells.

- may also play an important role in limiting the ability of the immune system to attack a persons own body tissues

Natural Killer Cells - not considered a true T cell subset

- important in providing CMI

- direct cytotoxic effects on target non self cells - exerts cytotoxic effects even without undergoing a period of sensitization

- commonly affect virus infected cells and cancer cells

TRANSPLANT REJECTION

Hyperacute Rejection
Begins immediately on transplantation and is an antibody-mediated response
Antigen antibody complexes form in the

blood vessels of the transplanted organ The host has pre-existing antibodies to one or more of the antigens present in the donated organ

 Occurs primarily in transplanted kidneys

Manifestations become apparent within

minutes of attachment of the donated organ to the hosts blood supply Rejected organ must be removed as soon as diagnosis is made

Acute Rejection
Occurs within 1 week to 3 months after transplantation 2 mechanisms
Antibody mediated Which results in vasculitis within the transplanted organ Cellular Host cytotoxic and NK cells enter the transplanted organ through the blood and infiltrate the organ cells and cause lysis of the organ cells

 Diagnosis is made by laboratory tests indicating impaired function of the specific organ along with the biopsy of the graft An episode of acute rejection after solid organ transplantation does not automatically mean that the client will lose the transplant.

Chronic Rejection
Functional tissue is replaced with fibrotic, scarlike tissue The organ fails to perform its normal function Longstanding and occurs continuously as a response to chronic ischemia caused by blood vessel injury Accelerated graft atherosclerosis major cause of death in clients who have survived 1 or more years after heart transplant

Treatment
Maintenance Therapy
Immunosuppressants Very specific cyclosporine Less specific azathioprine Steroids Prednisolone Monoclonal antibodies Directed against the interleukin-2 receptor site on activated T lymphocytes Basiliximab , clizumab

 Rescue Therapy
Reduces the hosts immunologic responses

during the rejection episodes

Antilymphocyte globulin Muromonab
Antibody directed specifically against the human T cell cell-surface antigen CD3 Most effective against rejection during the first episode

Tacrolimus/FK 506
Used in maintenance and rescue therapy after liver transplantation

DISORDERS OF THE IMMUNE SYSTEM

HYPERSENSITIVITY REACTIONS

Type I. Anaphylactic Type Type II. Cytotoxic Type Type III. Immune Complex-Mediated Type IV. Cell-Mediated Type V. Stimulatory Reactions

Type I. Anaphylactic (Rapid) Hypersensitivity Reactions

Rapidly developing immunologic reaction occurring w/in minutes after the combination of an antigen w/ antibody bound to mast cells or basophils in individuals previously sensitized to the antigen.

 may occur as a systemic or as a local reaction. Systemic reaction : usually IV injection of an antigen to which the host has already become sensitized state of shock can be produced within minutes (may be fatal)

Local reactions: depend on the portal of entry of the allergen. May take the form of: 1. localized cutaneous swelling (skin allergy, hives) 2. nasal & conjunctival discharge (allergic rhinitis and conjunctivitis) 3. hay fever 4. bronchial asthma 5. allergic gastroenteritis (food allergy)

Allergen

IgE production by B lymphocytes (at the site of entry of antigen & draining LNs)

IgE antibodies attach to mast cells and basophils

The person is sensitized to that allergen. Memory cells are generated.

Re-exposure to the allergen

Binding of allergen to 2 adjacent IgE molecules on the surface of a basophil or mast cell

Destortion of the cell membrane causing them to degranulate

Release of vasoactive amines (histamine) into the circulation.

Histamine
Increased capillary permeability Increased mucus secretion Pruritus and erythema

Edema, facial puffiness

Watery nasal and conjunctival discharge

Primary Phase

Secretion of leukotrienes and prostaglandins

Stimulation of more WBC

Generalized inflammatory reaction

Secondary Phase

Allergic Rhinitis
Rhinorrhea , stuffy nose and itchy, watery eyes Watery , clear nasal discharge Post nasal drip Headache or pressure in the sinuses

Latex Allergy
Protein found in processed natural latex rubber products Avoid products containing latex (surgical gloves, tubings, condoms etc.) Other interventions similar to hypersensitivity reactions

Laboratory
CBC
Increased WBC eosinophil count

Increased serum IgE levels

Normal values 39IU/ml Does not determine indicate specific antigen

Radioallergosorbent Test (RAST)

Determines the blood concentration of IgE directed against a specific antigen and thus can determine specific antigen

Allergy Testing
Skin Testing
Scratch Test
Results in an immediate hypersensitivity reaction to an allergen Discontinue antihistamines for 5 days before the test Allergens are introduced through a superficial scratch or prick cause a localized reaction (wheal) when the test result is positive Serious reactions are rare

 Wash the solution from the skin Topical steroids and oral antihistamines are administered to reduce itching (sedation)

Intra-dermal Testing
Reserved for substances that are strongly suspected of causing allergy but did not test positive during scratch test Greater risk for anaphylaxis occurs

 Oral Food Challenge

Effective for some individuals in identifying specific allergens when skin testing has been inconclusive Eliminate suspected foods for 7-14 days before testing Eat a defined food for at least one day and monitor clients reaction

 In Vitro Testing
Drawing blood from a client and exposing it to different panels containing food and mold allergens After incubation the cells are checked Positive reaction
Increase WBC size by 12 % Increased platelet aggregation

Collaborative Management
Avoidance Therapy

 Medications
Decongestants vasoconstriction in the inflamed tissue thereby reducing the edema
Caution in patients with HPN, glaucoma

Antihistamines- blocks histamine from binding with its receptor preventing vasodilation and capillary permeability
Sedation

Corticosteroids decrease inflammation by preventing the synthesis of mediators Mast Cell Stabilizers Leukotriene Inhibitors

 Desensitization
The most common form of desensitization involves subcutaneous injections of small amount of the allergen An increasing dose is usually given weekly until the patient is receiving a 0.5ml dose Recommended course of treatment is approximately 5 years

 The mechanism of action to reduce allergic responses by desensitization is thought to be competition. Instead of IgE , IgG is produced and binds with the allergens so as not to cause degranulation of mast cells or basophils.

Anaphylaxis
Generalized pruritus and urticaria Erythema and angioedema Bronchoconstriction, mucosal edema and excess mucus production Wheezes , crackles Anaphylactic shock

Collaborative Management
Establish and maintain airway High fowlers position Apply tourniquet immediately proximal to the allergen point of entry when possible O2 by mask Start IVFs
Plain NSS or LR

 Administer medications as ordered

Epinephrine .3-.5ml subcutaneously is the DOC Antihistamines diphenhydramine IM or IV Aminophylline theophylline IV for severe bronchospasm Corticosteriods hydrocortisone, solumedrol IV B2 agonists nebulization Salbutamol, terbutaline,

Type II. Cytotoxic Type

Mediated by auto-antibodies directed toward antigens present on the surface of cells or other tissue components. Hypersensitivity results from the binding of antibodies to normal or altered cell-surface antigens

Examples: Type II Hypersensitivity 1. Transfusion reactions 2. Erythroblastosis fetalis

3. Autoimmune hemolytic anemia, agranulocytosis, throbocytopenia 4. Drug reactions
antibodies are produced that react w/ the drug.

Collaborative Management
Discontinue the offending agent Plasmapheresis
Filtration of the plasma to remove specific substances like auto-antibodies

Symptomatic Treatment

Type III. Immune ComplexMediated

Induced by antigen-antibody complexes having the capacity to activate a variety of serum mediators, principally the complement system. Wherever the immune complex lodge it causes tissue damage

 Generalized
if immune complexes are formed in the circulation & are deposited in many organs

Localized to particular organs:

Kidney (glomerulonephritis), Joints (arthritis), Small blood vessels of the skin if the complexes are formed and deposited locally (local Arthus reaction) Wherever complexes deposit, the tissue damage is the same: complement cascade and the elaboration of biologically active fragments.

 Rheumatoid arthritis Systemic Lupus Erythematosus Serum sickness

Occurs after the administration of a foreign serum or certain drugs Collection of immune complexes deposited in the walls of the blood vessels, skin, joints, kidney Most common cause is penicillin and animal serum antitoxins

Collaborative Management
For serum sickness
Self limiting Symptomatic treatment
Aspirin for pain Antihistamines for pruritus Steroids

Type IV. Cell-Mediated

Initiated by specifically sensitized T lymphocytes which respond to an antigen by producing and releasing certain lymphokines which recruit, retain and activate macrophages to destroy the antigen Antibodies and complement are not involved Occurs hours to days Self limiting

1. Tuberculin reaction - the best known example of delayed-type hypersensitivity - produced by intracutaneous injection of tuberculin - In previously sensitized individual: reddening and induration of the site(8-12 hours), peaks in 24-72 hours, and thereafter slowly subside.

2. Transplant rejection 3. Contact dermatitis 4. Poison Ivy skin rashes 5. Local response to insect stings

Patch Testing
Used to identify the allergen Skin contact with substances to which the client is potentially allergic Contact with a specific allergen results in a delayed reaction that develops in 48-96 hours Substances applied under occlusive tapes Localized erythema, blister, swelling

Collaborative Management
Removal of the offending antigen Monitor reaction site and sites distal to the reaction for circulation adequacy Antihistamines minimal benefit Steroids

Type V. Stimulatory Reactions

Inappropriate stimulation of a normal cell surface receptor by an autoantibody, resulting in an continuous turned-on state for the cell Example Graves Disease
An autoantibody binds to TSH receptor sites in the thyroid gland stimulating it to produce thyroid hormones continually

Collaborative Management
If one organ is involved like in Graves disease ,surgical removal or radiation can be done If more than one organ is involved then immuno-suppresion is warranted

AUTOIMMUNE DISEASES

IMMUNE TOLERANCE
Ability to recognize or distinguish self (selfantigens) from non-self (foreign antigens) like bacteria or viruses. Immune system is tolerant to the hosts tissues but is able to reject foreign tissues and destroy infectious agents.

AUTOIMMUNE DISEASES
Failure of the tolerance mechanism Immune reaction against self-antigens Usually occurs after destruction of some of the bodys tissues release of self antigens that circulate in the body acquired immunity (activated T cells or antibodies)

Sjogrens Syndrome
Keratoconjunctivitis sicca dry eyes Xerostomia dry mucous membranes of the nose and mouth Vaginal dryness Autoimmune destruction of the lacrimal, salivary and vaginal mucus producing glands Associated with RA and fibromyalgia NO CURE!!!

 Women 35-45 years old Viral triggers Insufficient tears cause inflammation and ulceration of the cornea, insufficient saliva cause decreased digestion of CHO, promotes tooth decay and increases incidence of infections Vaginal dryness cause infection and dyspareunia

Collaborative Management
Immunomodulation
Methotrexate Cyclophosphamide Steroids Cyclosporine

Symptomatic treatment
Artificial tears and saliva Lubricants

Moisturizers Systemic pilocarpine for dry mouth Blockade of tear outflow NSAIDS for pain

Goodpastures Syndrome
Auto-antibodies are made against the glomerular basement membrane and neutrophils Organs affected are the Lungs and Kidney More common among males SOB, hemoptysis, oliguria, hypertension, tachycardia

Collaborative Management
Immunomodulation
High dose corticosteroids mainstay of drug therapy

Plasmapheresis IV immunoglobulin Dialysis Renal transplantation

Lupus Erythematosus
Lupus = Wolf Chronic, systemic, progressive inflammatory connective tissue disorder that can cause major body organs and systems to fail 2 main classifications
Discoid lupus erythematosus (DLE) Systemic Lupus Erythematosus

 Anti nuclear auto-antibodies are produced and react with the DNA within the cell nuclei Immune complexes invade directly the organs or cause vasculitis which deprives the organs of arterial blood and O2 Leading cause of death is kidney failure

 Affects women between the ages of 15-40 at 8-10 times more often than men Onset occurs most often during the childbearing years NO CURE!!!

The 1982 Criteria for SLE

S erositis (Pericarditis, Pleuritis) O ral ulcers A rthritis P - photosensitivity R enal disorder (Proteinuria) A ntinuclear antibodies I mmunologic disorder (+ LE prep) N eurologic disorder (seizures) M alar rash D iscoid rash H ematologic disorder (anemia,leukopenia)

 If four of these criteria are present at any time during the course of the disease, a diagnosis of SLE can be made with 98% specificity and 97% sensitivity.

Laboratory Assessment
ANAs best screening test Anti ds-DNA and anti-Smith are more specific CBC pancytopenia Check serum electrolytes, creatinine, BUN, liver enzymes, CXRay, clotting factors, urinalysis

Collaborative Management
Pain and fatigue glucocorticoids Arthralgias, arthritis, myalgias, fever, serositis NSAIDS, ASA Dermatitides, fatigue, arthritis antimalarials (chloroquine) Rash sunscreens (SPF>15), topical or intra-lesional glucocorticoids

 Life threatening manifestations high dose glucocorticoids For disease control, reducing flare ups, reducing steroid dependence cytotoxic drugs ex. Azathioprine, Cyclophosphamide Lupus nephritis glucocorticoids and cyclophosphamide

Rheumatoid Arthritis
Second most common connective tissue disease and is the most destructive to the joints Chronic , progressive, systemic inflammatory process that primarily affects the synovial joints

Clinical Manifestations
Early Manifestations
Pain in affected joints, aggravated by movement is the most common manifestation in established RA Typical pattern of joint involvement is bilateral and symmetric Fatigue, generalized weakness, stiffness, anorexia and weight loss of 2-3 pounds

 Late Manifestations
Morning stiffness (gel phenomenon) Soft joints because of synovitis and effusion Spindle like fingers Subluxation of the cervical spine

 Joint Manifestations
Boutonnierre Swan neck Ulnar deviation Bakers cyst Carpal tunnel syndrome

Laboratory Tests
Rheumatoid factor
Measures IgG and IgM 2 methods
Rose Waaler more specific Latex agglutination more sensitive

Anti nuclear antibody titer

Measures the unusual antibodies against nuclei of cells that cause tissue death

 ESR
20-40mm/hr mild inflammation 40-70mm/hr moderate 70-150 mm/hr - severe

Serum complement
Attaches to immune complexes in an attempt to destroy them In vasculitis there is decreased serum complement

 Serum Protein Electrophoresis

Level of alpha globulin is raised in acute inflammation Gamma globulin is raised in chronic inflammation

Arthrocentesis
Fluid is aspirated from the joints and analyzed for inflammatory cells, immune complexes, RF

Collaborative Management
Aspirin NSAIDS Disease Modifying Agents
Slow the disease or produce disease remission Anti-malarials chloroquine
eye exams every 3-6 months

Penicillamine

 Cytotoxic drugs
Methotrexate
Mainstay for advancing and sustaining RA because it is inexpensive ,less toxic and effective May cause PCP

Cyclophosphamide Azathioprine

 Gold salts
Reduces pain and inflammation Gold sodium thiomalate

Steroids Etanercept
Binds to TNF and blocks its effects TNF is involved in inflammatory and immune response Subcutaneous

 Infliximab
Neutralizes the activity of TNF Given as a single IV infusion over several hours

Rest, Positioning, Ice and Heat Enhancement of body image

Communicate acceptance of the client Use personal items Coping strategies

Secondary Immunodeficiency

Acquired Immune Deficiency Syndrome (AIDS) A retroviral disease characterized by profound immunosuppression that leads to opportunistic infections, secondary neoplasms and neurologic manifestations

Risk Groups for AIDS

Homosexuals or bisexuals 57% Intravenous drug users 25% Hemophiliacs .8% Recipients of blood and blood products 1.2% Heterosexual contacts of members of other high risk groups 10%

AIDS is not the same as HIV infection Not everyone infected with HIV has AIDS Criteria
Infection with HIV Clinical disease that indicates cellular immunodeficiency CD4 + T lymphocyte count < 200/mm3 or CD4 + T lymphocyte total % < 14

Progression

May take months to years depending on how HIV was acquired Transfused blood contaminated by HIV faster progression Single sexual encounter longer latency period

Etiology
2 subtypes of HIV
HIV 1 USA, Europe, Asia, Central Africa HIV 2 West Africa

Retrovirus
Contains only RNA Contains an enzyme called Reverse Transcriptase

CD4 lymphocytes regulate activity of all immune system cells Destruction of these cells suppress immune function resulting in lymphopenia and abnormal T cell function, production of incomplete and non functioning antibodies and abnormally functioning macrophages

Finally resulting into increased susceptibility to opportunistic infections and cancer Mortality rate is 60%

NO CURE!!!!

Stages of Infection
Acute infection = Primary HIV = Seroconversion
No symptoms

Early Disease no symptoms, CD4 count > 500/ml Middle Disease usually no symptoms, CD4 count 500-200/ml

Late Disease symptomatic, CD4 count 200-50/ml Advanced Disease usually symptomatic, CD4 count < 50/ml

Seroconversion
People infected with HIV usually develop antibodies 4 to 6 weeks after being infected, but it may take as long as 3 months for antibodies to develop

The period of time between when a person is infected with HIV and when the antibody test result is positive is called the "window period. Despite being seronegative, the person may be infectious during the window period

Global Epidemiology of HIV/AIDS

In 2003: AIDS killed 3.1 million people

In 2004:
An estimated 39.4 million people were living with HIV 4.9 million people acquired HIV

Incidence in the Philippines

Since the first cases of HIV/AIDS were reported in 1984, 1,515 HIV infections, including 508 AIDS cases and 196 HIV/AIDS related deaths, had been reported by June 2001. The epidemic in the Philippines has been classified as low level.

Prevention
The most important aspect for prevention of HIV transmission is education HIV is primarily transmitted
Sexually genital, anal, oral Parenteral sharing of needles, equipment contaminated with blood Perinatal from placenta, contact with maternal blood and body fluids during birth, breast milk

HIV has been isolated in:

Blood Semen Vaginal secretions Breast milk Amniotic fluid Urine Feces Saliva Tears CSF Lymphnodes Corneal tissue Brain tissue

Not transmitted through casual contact, sharing of household utensils, towels, linens, toilet facilities or insect bites.

Sexual Transmission
Abstinence and mutually monogamous sex with a non infected partner are the only absolute safe methods of preventing HIV infection through sexual contact Most easily transmitted when infected body fluids come into contact with mucus membranes or non intact skin

The vagina has more mucus membranes than the penis thus HIV is more easily transmitted from infected male to uninfected female than vice versa Specific sexual acts
Oral sex Anal sex fissuring or tearing
Whether male or female

Safer sex practices include

Using a latex condom for genital and anal sex A condom or latex barrier (dental dam) over the genitals or anus during oralgenital or oral-anal sex Latex gloves for finger or hand contact with the vagina or rectum

Parenteral Transmission
Risk of transmission of AIDS via needle prick Never reuse or recap needles Screen all blood donors and products
Screen for HIV antibody but false negative results can occur because of the time lag in antibody production

Perinatal Transmission

Risk 14-45% for each pregnancy Occurs trans-placentally in utero Intra-partally during exposure to blood and vaginal secretions during birth Post-partally through breast milk

Transmission and Health Care Workers Needle stick injuries are the primary means of HIV infection for health care workers Transmission through exposure of non intact skin and mucus membranes to blood and body fluids

Transmission Rates of Disease Due to Needle Stick Injuries

Hepatitis B 30% Hepatitis C 3% HIV/AIDS - .3%

Physical Examination and Clinical Manifestations Pathogenic Infections

Caused by virulent microorganisms and occur even among people whose immune system are functioning at an optimal level

 Opportunistic Infections
Caused by microorganisms that are continually present as part of the normal environment and are kept in check by normal immune function

 Only when immune function is depressed or compromised are such organisms capable of causing infection Opportunistic infections do not pose a threat to the immunocompetent health care worker caring for a client with HIV infection or AIDS

Protozoal Infections
Pneumocystis Jiroveci Pneumonia
Most common opportunistic infection in people with AIDS DOB, tachypnea, persistent dry cough and fever Fatigue , weight loss and crackles

Toxoplasmosis Encephalitis
Toxoplasma gondii Contaminated cat feces or by ingesting infected, under cooked meat Mental status changes, neurologic deficits, headache, fever Seizure ,vision changes, speech and gait change

Cryptosporidiosis

Cryptosporidium Gastroenteritis / diarrhea 15-20 L/ day water loss

Fungal Infections
Candida albicans Normal flora of the GIT Candida stomatitis/esophagitis
Frequent finding Sore throat, dysphagia, retrosternal pain

Cottage cheese like yellow-white plaques and inflammation Endoscopic biopsy

Vaginal Candidiasis Severe pruritus Thick white vaginal discharge

Cryptococcosis
Severe ,debilitating meningitis Cryptococcus neoformans Meningeal irritation, fever, headache, BOV, seizures

Histoplasmosis
Histoplasma capsulatum Begins as a respiratory infection Dyspnea, fever, cough and weight loss hepatosplenomegaly

Bacterial Infections
Mycobacterium Avium Intracellulare (MAC)
Most common bacterial infection associated with AIDS Infects the respiratory and GIT Fever debility, weight loss, malaise, lymphadenopathy

Mycobacterium Tuberculosis
2-10% of persons with AIDS 50% develop extrapulmonary TB A person with TB and a CD4 + count <200/mm3 may not have a positive PPD test because of an inability to mount an immnue response (anergy) CXR, sputum AFB, sputum culture

Recurrent Pneumonia from Bacterial Infections 2 or more episodes of pneumonia in a 12 month period is an AIDS case definition Chest pain, productive cough, fever, dyspnea

Viral Infections
Cytomegalovirus
CMV retinitis BOV, blindness CMV colitis diarrhea CMV encephalitis

Herpes Simplex
Perirectal , oral, genital areas Numbness, tingling at the site of infection up to 24 hours before vesicle formation Painful vesicles which ulcerates

Varicella Zoster
Present in nerve ganglia , enters body fluids and other tissues causing shingles Chicken pox Pain , burning along dermatome nerve tracts Large fluid filled vesicles form and crust over

Malignancies
Kaposis Sarcoma

Most common malignancy associated with AIDS Clients with hemophilia and HIV low incidence Men infected through homosexual contact highest incidence

Mucocutaneous lesions
Small, purplish brown, raised lesions, non tender, non pruritic Diagnosed through biopsy

Non-Hodgkins Lymphoma
- Patients extremely at risk are those whose CD4+ counts are below 50/uL

AIDS Dementia Complex

70% of persons with AIDS Direct infection of cells within the CNS Slow thinking, memory loss, wandering attention Loss of coordination, loss of balance, leg weakness Apathy , irritability

Wasting Syndrome
Due to altered metabolism from malignancy or opportunistic infection Diarrhea , malabsorption, anorexia, oral and esophageal lesions

Laboratory Assessment
Lymphocyte count
5000-10000 cell/mm3 Lymphocytes 30-40% or 1500-4500 In AIDS WBC <3500, lymphocytes >1500

CD4/CD8 counts
Normal 500-1600 cells/mm3 Ratio 2:1 Low CD4 and low CD4/CD8 ratio increases clinical manifestations

Antibody test
Measures the clients response to the presence of the virus (antigens) rather than measuring parts of the virus or the virus itself After infection 3 weeks to 3 months for a person to test positive for HIV antibodies Some 36 months before detection

Enzyme Linked Immunosorbent Assay (ELISA)

Clients serum is mixed with HIV and grown in culture If client has antibodies, they will bind with the HIV antigens and can be detected (+) False positive results have been reported in multi-parous/pregnant women, IV drug users, malaria, lymphomas

Western Blot
If ELISA is positive, confirmed by western blot Not widely available because expensive and complex More specific (+) presence of antibodies to at least 2 of the major HIV antigens

If a person has a positive test result for HIV antibodies, it does not mean that he or she has AIDS. It means he/she has been infected with the virus.

Viral Culture

Measures reverse transcriptase activity over a 28 day period More RT present more active replication

Viral Load Testing

Measures presence of HIV viral genetic material or other actual viral protein in the clients blood Useful in monitoring disease progression and treatment

P 24 Antigen

The test is used to detect HIV antigens in children younger than 18 months Test can be useful at any age Two or more positive results are diagnostic for HIV infection

Management
Anti-retrovirals

Inhibits viral replication but DOES NOT KILL THE VIRUS Multiple drug regimen/ Highly Active Antiretroviral Therapy is done to improve duration or quality of life

Drug Therapy for AIDS related Opportunistic Infections

Nucleoside Analog Reverse Transcriptase Inhibitors Non-Nucleoside Analog Reverse Transcriptase Inhibitors Protease Inhibitors Ribonucleotide Reductase Inhibitors

PRIMARY IMMUNODEFICIENCIES

 May be genetically determined and affect specific immunity Most manifest themselves 6 months to 2 yrs old Noted because of the susceptibility of infants to recurrent infections.

X-Linked Agammaglobulinemia of Bruton

Absence of serum immunoglobulins Restricted to males Severe recurrent infections at 6 months of age when infant becomes depleted of maternal immunoglobulins.

 Most common infections are pyogenic (Staphylococcus, H. influenzae) First signs and symptoms are recurrent sinusitis, pharyngitis, otitis media, meningitis, bronchitis, pneumonia, and skin infections. Viral and fungal infections are handled normally because cell mediated immunity is normal.

Management
Overall prognosis is fairly good IV or IM immune globulin 100-400mg/kg every 3-4 weeks Antibiotics

Isolated IgA Deficiency

Most common congenital immunodeficiency 1 out of 600 individuals of European descent Less common in Blacks & Asians Extremely low levels of serum & secretory IgA High frequency of respiratory tract allergy and a variety of autoimmune diseases (SLE and rheumatoid arthritis)

 Since IgA is the major antibody in secretions bacterial infections are primarily seen in the respiratory, GIT and urogenital tracts Basic defect is differentiation of IgA B lymphocytes

Management
Appropriate treatment of infections Selective IgA deficiency should never be treated with exogenous immune globulin because:
Exogenous immunoglobulin contains very little IgA The production of the other antibodies are normal so that a patient might develop severe allergic reactions to exogenous immune globulin

Common Variable Immunodeficiency

Acquired hypogammaglobulinemia Recurrent bacterial infections similar to Brutons agammaglobulinemia Low levels of circulating antibodies Usually appears during adolescence or young adulthood Less severe susceptibility to infections Giardiasis , bronchiectasis, cholelithiasis

Management
IV or IM immunoglobulin Antibiotics

DiGeorges Syndrome (Thymic Hypoplasia)

Example of selective T-cell deficiency derived from failure of development of the 3rd and 4th pharyngeal pouches. 4th pharyngeal pouch gives rise to the thymus, parathyroids, and some cells of the thyroid gland.

 Patients have total absence of cellmediated immune responses due to hypoplasia or lack of thymus. Tetany due to lack of parathyroids Congenital defects of the heart and great vessels

Chronic Granulomatous Disease (CGD)

X-linked or autosomal recessive Deficiency is NADPH oxidase (critical in oxidative burst needed for optimal killing) Results in granulomatous abscesses in lymph nodes, lungs, and liver Greatly increased susceptibility to opportunistic infections Treatment: broad-spectrum antibiotics, antifungal agents, bone marrow transplant

Chediak-Hegashi Syndrome
Autosomal recessive Lysosomal enzymes are low, very large lysosomes in cytoplasm Intracellular killing of microorganisms is delayed Low NK cell function (number is normal) Characterized also by partial occulocutaneous albinism, extreme photophobia, rapid involuntary eye movements, and other CNS abnormalities Treatment: antibiotics.

HEREDITARY ANGIOEDEMA
C1 esterase inhibitor (C1 INH) deficiency Increased kinin-related proteins
Increased vascular permeability

 Recurrent attacks of swelling, especially skin and mucous membranes

intestinal swelling may cause cramps, nausea, vomiting, diarrhea swelling of larynx may be fatal

 symptoms can be induced by trauma, menses, violent exercise, extremes of temperature and anxiety no increase in infections no specific treatment (laryngeal edema tracheotomy) prophylaxis: androgens

Wiskott-Aldrich Syndrome (WAS)

X-linked Very complex disorder, poorly understood Initial T-lymphocyte number may be normal, but protection is low; T cell count tends to decline with time

 IgM level is low (high catabolism rate) Is associated with thrombocytopenia. Abnormal platelets, bleeding, and severe eczema

 Treatment:
antibiotics and antiviral agents topical steroids for eczema platelet transfusion bone marrow transplant

Ataxia-Telangectasia (AT)
Progressive disease Defective repair of DNA damage
Breaks in T cell receptor genes Breaks in heavy chain genes of antibody Highly susceptible to radiation; high incidence of malignancies

IgA is often low Severe cerebellar ataxia (muscle incoordination) spider-like vascular dilation treatment: bone marrow and thymus grafts

Nutrition Related Deficiencies

Protein-Calorie Malnutrition
Adequate and balanced nutrition is necessary for the functioning of the immune system Greatest impairment is noted in cell mediated immunity with a decreased number of T lymphocytes, reduce delayed hypersensitivity and thymic changes Anergy and increased susceptibility to infection

Clinical Manifestations
Leanness and cachexia Decreased effort tolerance Lethargy Intolerance to cold Ankle edema Dry flaking skin and various types of dermatitis

Management
Treat infections first Correct fluid and electrolyte imbalance Gradual but steady repletion of protein and energy is undertaken through TPN Vitamin supplementation

Therapy Induced Immunodeficiencies

Drug Induced Immunodeficiency

Cytotoxic drugs
Used to treat cancer Destroys cancer cells but also normal cells including cells of the immune system

 Corticosteroids
Inhibits inflammation by stabilizing the vascular membrane and decreasing permeability, thereby blocking the migration and mobilization of neutrophils and monocytes Sequester T cells in the bone marrow, reducing the number of circulating T cells and resulting lymphopenia and suppressed cell mediated immunity Interferes with IgG synthesis and binding to antigens

 Cyclosporine
Suppresses the helper T lymphocytes by blocking proliferation and development Used to prevent organ transplant rejection and graft versus host disease

Radiation Induced Immunodeficiency

 Radiation is cytotoxic to proliferating and resting cells Most lymphocytes are sensitive to radiation, exposure can induce profound lymphopenia in lymphoid organs and in the circulation causing generalized immunosuppression Most severe immunosuppression occurs while receiving radiation and chemotherapy

Management
Aseptic technique Hand washing Biologic response modifiers Interventions for those at risk for infection Medications as ordered to treat infections

THANK YOU! My Precious