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136 Cards in this Set
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Hypersensitivity |
-immune response that injures -can be categorized into 1 of 4 major groups -examples = allergy, autoimmune diseases, immunodeficiency |
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Allergy |
-(allergic reaction) = sensitivity to an allergen -generally harmless substances -involve IgE response |
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Autoimmune disease |
-targets body tissues |
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Immunodeficiency |
-disorder from immune system being too weak to prevent infection |
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Type 1 hypersensitivity (Immediate IgE-Mediated) |
-IgE binds by Fc portion to mast cells or basophils -functions as captured antigen = allows mast cells and basophils to detect invaders -some people more likely to develop allergies (inherited) = specific allergen is due to environmental exposure |
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Binding of IgE |
-triggers release of inflammatory mediators (really good against parasitic worms) -binding to allergens sets off system - inhaled (pollen, mold, etc) - ingested (peanuts, milk, etc) - injected (insect venom, drugs) |
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Allergic reactions |
-occur in sensitized people - have had prior exposure to specific antigen -sensitization = contact induces antibody response
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B cells under mucous membranes....... |
-often switch to IgE production (longer lived than IgG), esp. those prone to allergies - IgE accumulates then attaches to mast cells and basophils - stable for weeks b/c antigen binding sites available to interact w/allergens
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example of a typical sequence of allergic reactions..... |
- pollen grains contact mucous membrane of respiratory tract = IgE production triggered = individual becomes sensitized to pollen |
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LOOK AT SLIDE 5 WHICH SHOWS PROCESS!!!!! |
LOOK AT SLIDE 5!!!!! :D :D :D |
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Localized allergic reactions |
- hives: "wheal and flare" of skin - seen in (+) skin test for allergens - antihistamines block - hay fever: itching, teary eyes, sneezing, runny nose following inhalation of airborne antigen - antihistamines block - asthma: respiratory allergy - inflammatory mediators cause spasms of bronchial tubes, mucus production - antihistamines NOT effective!!! |
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Systemic Anaphylaxis |
- rare but serious form of IgE-mediated allergy - antigen enters blood and spread throughout body - binds to IgE on basophils = release mediators - extensive blood vessel dilation = fluid loss, drop in BP = heart failure, insufficient blood flow to brain/other vital organs - bronchial tubes constrict - suffocation - can usually be controlled by injection of epinephrine |
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most cases of anaphylactic shock occur from.... |
- bee stings - peanuts - penicillin injections |
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Treatments to prevent allergic reactions |
- immunotherapy (alters immune response) - desensitization = causes immune system to produce IgG - IgG binds antigen, prevents IgE binding - involves injections of dilute antigen over time |
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Omalizumab |
-rhuMab = recombinant humanized monoclonal antibody
- form of IgG molecule; binds Fc portion of IgE = blocks attachment to mast cells and basophils |
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Chronic asthma is generally treated with.... |
- steroids!! - steroids slow down immune response = more susceptible to infection |
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When we have a hypersensitivity.... |
- cell-bound IgE molecules react with antigen; cross-link - mast cell releases histamine & other inflammatory mediators (this is called degranulation) - this yields rapid reaction (hay fever, asthma, anaphylactic shock) |
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Type II hypersensitivities (Cytotoxic) |
- antibodies react with molecules on cell surface - this triggers destruction of cells - there are 2 methods for this |
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2 methods of triggering destruction of cells |
1. activate classical pathway of complement system = lead to lysis via membrane attach complexes (MACs)
2. trigger antibody-dependent cellular cytotoxicity (ADCC), lead natural killer (NK) cells to bind to Fc regions of antibodies and deliver chemicals to destroy cell |
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Examples of Type II cytotoxic hypersensitivities |
- transfusion reactions and hemolytic disease of newborn - some autoimmune diseases
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Transfusion Reactions |
- erythrocytes have antigenic determinants on surface - major group is ABO = A, B, AB, O blood types - individuals have antibodies to the antigens they lack (mostly class IgM; appear w/in 6 months of birth) - bind to transfused cells = agglutination |
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Agglutination |
- cells rapidly destroyed by MACs or NK cells; debris can block vessels, initiate clotting - this can lead to kidney damage, fever, respiratory & digestive problems (may be life threatening) |
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Hemolytic disease of the newborn |
- Rh (rhesus) antigen on red blood cells - Rh (+) have antigen; Rh (-) do not - if Rh (-) recipient is given Rh (+) blood, antibodies will develop; future transfused cells are destroyed |
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Pregnant Rh (-) woman carrying Rh (+) baby..... |
- can develop antibodies to Rh antigen - will not affect 1st baby (IgM cannot cross placenta) - BUT, if 2nd baby is Rh (+), anti-Rh IgG antibodies can cross placenta = damage fetal blood cells - maternal enzymes usually protect fetus from toxic products of RBC destruction until AFTER birth
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What is used to prevent hemolytic disease??? |
- RhoGAM - contains anti-Rh antibodies, bind to any Rh (+) erythrocytes that may have entered circulation = prevents stimulation of primary immune response |
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Type III Hypersensitivites (Immune Complex - Mediated) |
- formation of immune complexes - IgG or IgM antibodies bound to soluble antigen - usually removed by phagocytes binding to Fc regions - may occur during variety of bacterial, viral, protozoan infections; also from inhaled dust, bacteria, injected medications (penicillin) |
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Phagocytes binding to Fc regions...... |
- if antigen in slight excess, smaller complexes form & remain in circulation or at sites of formation in tissue - can trigger blood-clotting cascade & activate complement system = recruits phagocytes - phagocytes release pro-inflammatory cytokines, may also release enzymes, toxic molecules |
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Results of Type III |
- produces rashes, joint pains, other symptoms of farmers lung, lupus, bacterial endocarditis, early rubella infection, malaria, glomerulonephritis
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Disseminated intravascular coagulation |
- devastating condition in which clots form in small blood vessels = leads to failure of vital organs |
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Arthus reaction |
- localized immune complex reaction - occurs following injection of antigen into previously immunized individual w/circulating antibody - example = tetanus-diptheria booster given too often
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Serum sickness |
- systemic immune complex reaction - caused by passive immunization - antibodies provided for protection - example = serum from horse |
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Type IV Hypersensitivity (Delayed-type cell - mediated) |
- due to antigen specific t-cell responses - can occur almost anywhere in body - peak 2-3 days after antigen exposure - Example = tuberculin skin test |
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Tuberculin Skin Test |
- detects latent Mycobacterium tuberculosis infections - small quantity of mycobacterial proteins injected = site reddens, thickens (no "wheals") - effector helper t-cells recognize antigens, release pro-inflammatory cytokines
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Delayed-type hypersensitivity in infectious diseases |
- cell-mediated immunity plays central role in combating intracellular microbial infections - effector cytotoxic t-cells destroy infected host cells - prevents spread of infection, but also damages tissue; chronic infections yield extensive damage - example: damaged sensory nerves of leprosy |
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Contact Hypersensitivities (contact dermatitis) |
- caused by effector t-cells responding to small molecules that penetrate intact skin - results in irritating rash, sometimes blisters
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common causes of Type IV |
- nickel jewelry - leather - cosmetics - latex - poison ivy - poison oak |
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Rejection of Transplanted Tissues |
- special case of delayed-type cell-mediated hypersensitivity - most human transplants are allografts - effector cytotoxic T cells, natural killer cells reject |
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Definition of Allograft |
- tissues of donor and recipient are not genetically identical - antigenic differences, especially MHC molecules (lead to rejection of graft) - autografts and isografts avoid these problems - xenografts evoke vigorous response |
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MHC = |
Major Histo Compatibility |
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Autografts = |
graft from elsewhere in the body |
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Isografts = |
graft from identical sibling |
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Xenografts = |
from animals |
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Rejection of transplant |
- minimized by matching donor & recipient - indefinite use of immunosuppressive drugs - these drugs increase susceptibility to infections & cancer |
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Autoimmune Disease |
- development of lymphocytes that respond to self (autoantigens) are normally eliminated - when failure to remove occurs = autoimmune disease - cause not entirely clear |
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Possible causes of Autoimmune Disease |
- deficiency in action or control of regulatory T cells - genetic components, possibly MHC molecules - environmental factors including infections - pathogens ability to evade immune system via mimicry - injury where self antigens are released from privileged sites |
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Spectrum of Autoimmune Disease |
- can be organ specific or systemic (damage results from antibodies and/or cell-mediated immune response) - examples: type 1 diabetes, graves disease, SLE, myasthenia gravis, rheumatoid arthritis |
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Type 1 Diabetes Mellitus |
- organ specific - cytotoxic T cells destroy beta cells of pancreas = cells of body no longer properly take up glucose
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Grave's Disease |
- organ specific - antibodies attach receptors on thyroid gland for thyroid-stimulating hormone (TSH) = activates, leads to increased hormone production and gland enlargement (may show as goiter) |
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Systemic Lupus Erythematosus (SLE) |
- systemic - antibodies made against molecules found in cell nuclei - symptoms include: joint pain, swelling in joints, rashes |
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Myasthenia gravis |
- systemic - antibodies bind to acetylcholine receptors at neuromuscular junctions = block impulses |
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Rheumatoid arthritis |
- systemic - connective tissue targeted (most often joints) - T cells and antibodies target |
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Treatment of Autoimmune Diseases |
- anti-inflammatory or immunosuppressant drugs (these typically interfere w/T-cell signaling or kill dividing cells to limit response; approaches not optimal) - NEED NEW APPROACHES!
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Possible new approaches to treatment of autoimmune diseases |
- induce tolerance (decrease reactivity or specific antigen) - oral approach holds promise = let immune system "learn" to tolerate antigen as with other foods - transplantation of insulin-producing cells of pancreas - requires immunosuppressive agents - use of stem cells to produce beta cells holds promise |
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Immunization |
- process of inducing immunity - greatest impact on human health of any medical procedures - example of how knowledge is power - useful applications of immunological reactions in diagnostic tests |
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Immunity is acquired..... |
-naturally = normal events (exposure to infectious agent) - artificially = inducing via immunization - passive = antibodies through another person - active = your immune system fights against infection |
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Active Immunity |
- follows antigen exposure - natural (infection) or artificial (immunization)
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Passive Immunity |
- antibodies from another person - Natural (mothers IgG antibodies cross placenta; breast milk contains secretory IgA) - no memory in natural = protection is lost once antibodies degrade - Artificial = injection of antiserum (contains antibodies) |
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Artificial Passive Immunity |
- can prevent disease before or after likely exposure - limit duration of certain diseases - block action of microbial toxins - antitoxins = antiserum that protects against a toxin - hyperimmune globulin (antibodies to specific disease) - immune globulin (IgG fraction from many donors; variety) |
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Vaccine |
- preparation of pathogen or its products - used to induce active immunity - protect individual; prevent spread in population - responsible for dramatic declines in childhood diseases - can reappear and spread as results of failure to vaccinate children - effective vaccines should be safe & have few side effects - give long lasting protection - ideally low in cost, stable, easy to administer |
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Herd Immunity |
- develops when critical portion of population is immune to disease; infectious agent unable to spread due to insufficient susceptible hosts
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The two general categories of vaccines are.... |
- attenuated (live virus/bacteria)
- inactivated (non-infectious microbe) |
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Attenuated Vaccines (definition) |
- elicit stronger immune response, but can sometimes cause disease |
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Inactivated Vaccine |
- elicits weaker immune response, but cannot cause infections |
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Attenuated Vaccines |
- weakened form of pathogen - weakens in recipient (disease is undetectable or mild) - growth under conditions resulting in mutations or genetically manipulated to replace genes
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Advantages of Attenuated Vaccines |
- single dose usually induces long-lasting immunity due to microbe multiplying in body - can also inadvertently immunize others by spreading |
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Disadvantages of Attenuated Vaccines |
- can sometimes cause disease in immunosuppressed individuals - can occasionally revert or mutate (become pathogenic) - generally not recommended for pregnant women - usually require refrigeration to keep active
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Examples of Attenuated Vaccines |
- measles - mumps - rubella - chicken pox - yellow fever - sabin vaccine against polio |
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Inactivated Vaccines |
- unable to replicate - advantage = cannot cause infections or revert to pathogenic forms - disadvantage = no replication, so no amplification in vivo; immune response is limited (several booster doses usually needed) (often contain adjuvant to enhance immune response) |
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Multiple different types of inactivated vaccines |
- toxoids - subunit vaccines - recombinant vaccines - VLP vaccines - polysaccharide vaccines - conjugate vaccines
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Toxoids |
- toxins treated to destroy toxic part, retain antigenic epitopes - includes: diphtheria and tetanus |
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Subunit Vaccines |
- consist of key protein antigens or antigenic fragments from pathogen - avoids cell parts that may cause side effects - examples: acellular pertussis (aP) vaccine |
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Recombinant Vaccines |
- subunit vaccines produced by genetically engineered microorganisms - example: hepatitis B virus; yeast cells produce part of viral protein coat |
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VLP (virus-like particle) Vaccines |
- empty capsids produced by genetically engineered organisms - example: human papillomavirus (HPV) |
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Polysaccharide Vaccines |
- made from capsules - not effective in young children; polysaccharides are T-independent antigens, which elicit poor response - example: pneumococcus vaccines for adults |
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Conjugate Vaccines |
- polysaccharides linked to proteins - converts polysaccharides into T-dependent antigens - example: Haemophilus influenzae b (Hib) has nearly eliminated Hib meningitis in children; streptococcus pneumonia vaccine promises to do the same |
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Campaign to eliminate Poliomyelitis (Polio) |
- 3 types of poliovirus (enter through mouth) - virus infects throat and intestinal tract (invades blood) - from blood, can then invade nerve cells & cause disease - Salk vaccine (mid 1950's) contains inactivated viruses of all three types = dramatically lowered rate of disease but required series of injections for max. protection - Sabin attenuated vaccine available in 1961 |
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Sabin attenuated vaccine |
- cheaper oral vaccination, although still 3 doses - induced better mucosal immunity (secretory IgA response), so better herd immunity - attenuated viruses can mutate; approx. 1 out of 2.4 million doses results in poliomyelitis - can cause cases of the disease (rare), but gives much better protection against transmission of wild-type - Salk vaccine allows wild-type virus to replicate in intestines - disease can be transmitted to others, spread rapidly |
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Sabin vaccine (continued) |
- campaign highly successful - wild-type eliminated from United States by 1980 ("no spreading cases") (Salk vaccine doses followed by Sabin vaccine - eliminated from western hemisphere by 1991 - original goal of global eradication by 2000 was not achieved, but efforts continue |
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Importance of Childhood Vaccinations |
- prior to vaccinations, numerous deaths & disabilities - many still become ill or die from preventable diseases - some parents refuse to vaccinate children (fear harm) - vaccine victims of their own success, have lulled people into false sense of security (risk of vaccine seems greater than risk of disease) |
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Importance of Childhood Vaccinations (cont.) |
- benefits greatly outweigh very slight risk - child w/measles has 1:2000 chance of serious brain inflammation vx. 1:1,000,000 chance from vaccine - between 1989-1991, immunization rates dropped 10%; outbreak of 55,000 cases resulted in 120 deaths - routine pertussis immunization yielded significant decrease in incidence (saved many lives) |
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Routine Pertussis Immunization |
- because of some adverse reactions to killed whole cell vaccine, many parents refused to vaccinate - by 1990, highest incidence of pertussis in 20 years, deaths of some children - safer acellular subunit vaccine is now used - NO EVIDENCE OF LINK BETWEEN VACCINES & AUTISM |
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Current progress in immunization |
- recent advances yielding safer, more effective vaccines - example: conjugate vaccines that enlist T-cell help - new adjuvants being developed - administering of cytokines w/vaccine - novel types being actively studied: - peptide vaccines - edible vaccines - DNA-based vaccines |
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Peptide vaccines |
- key antigenic peptides from pathogens |
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Edible vaccines |
- transfer genes for key antigens into plants; could eliminate global difficulties of transport, storage |
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DNA-based vaccines |
- inject into muscle tissue, which expresses for a short time |
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Immunoassays |
- use antibody-antigen specificity - can test individual for unknown but suspected pathogen - binding of known antibodies identifies unknown pathogen - can test patient for infection of known pathogen - binding of patient's antibodies to known pathogen demonstrates current or previous infection - example: tuberculin skin test (Mantoux test) for tuberculosis |
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Seronegative |
- individual not yet exposed to antigen - has no specific antibodies to that pathogen
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Seropositive |
- individual has been exposed - has produced specific antibodies to pathogen |
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Seroconversion |
- process of producing antibodies, takes about 7-10 days; rise in titer is characteristic of infection - small, steady antibody level indicates previous exposure |
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Serology |
- study of in vitro antibody-antigen interactions
- serum is fluid portion of blood after blood clots - plasma is fluid portion of blood treated to prevent clotting - other specimens (cerebrospinal fluid, tissues) also tested |
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Epidemiology - Rates of disease in population |
- epidemiologists less concerned with absolute number of cases than rate (consider small vs. large city) |
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Attack rate |
- percentage of people who become ill in population after exposure - reflects infectious dose, immune status of population |
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Incidence rate |
- number of new cases/time/population - measure of risk of an individual contracting a disease |
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Prevalence |
- total number of cases at any time or for a specific period in a given population - reflects overall impact of disease on society; includes old and new cases, as well as duration of disease - both expressed as cases per 100,000 people |
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Morbidity |
- INCIDENCE of disease in population at risk - contagious diseases (ex. influenza) often have high morbidity rate (infected individual may transmit to several)
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Mortality |
- overall DEATH RATE in population - in developed countries, most often associated with non-communicable diseases (ex. cancer, heart attack) - major cause of death in developing countries |
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Case fatality rate |
- PERCENTAGE OF POPULATION that dies from a specific disease - plague, ebola feared b/c of very high rate - rate for AIDS has decreased from improved treatment; prevalence has increased as more with disease survive |
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Endemic diseases |
- CONSTANTLY present in population - example: common cold, measles in US
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Epidemis |
- UNUSUALLY LARGE NUMBER of cases - can be from introduced or endemic diseases |
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Outbreak |
- is group of cases at specific time and population |
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Pandemic |
- global - example: AIDS |
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Reservoirs of Infection |
- natural habitat in which pathogen lives - in or on animal, human or in environment (soil, water) - identification important in disease control (control of rats, mice, prairie dogs prevents plague in US) |
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Human Reservoirs |
- may be exclusive or exist in other animals, environment - often easier to control (example: smallpox) - symptomatic (obvious source of pathogens) - asymptomatic (harder to ID = may not realize = can spread to others) |
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Example of Asymptomatic human reservoir |
- up to 50% of women infected with Neisseria gonorrhoeae are asymptomatic = easily transmit - many people carry staphylococcus aureus |
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Non-Human Animal Reservoirs |
- common (gastrointestinal pathogens, rabies virus) - zoonoses (zoonotic diseases) primarily exist in animals but can be transmitted to humans (example: plague, rabies)
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Environmental Reservoirs |
- difficult or impossible to eliminate - example: clostridium |
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Portals of Exit and Portals of Entry |
- body surface or orifice: entry, exit route for pathogen - intestinal tract: shed in feces (vibrio cholerae) - respiratory tract: exit in droplets of saliva, mucus (mycobacterium tuberculosis, respiratory viruses) - skin: shed on skin cells (staphylococcus aureus) - genital pathogens: semen, vaginal secretions (neisseria gonorrhoeae) - to cause disease, must be transmitted but also colonize surface or enter host |
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Disease Transmission |
- vertical transmission: - horizontal transmission: - direct contact - indirect contact - droplet transmission - food and water - air - vectors |
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Vertical transmission |
- pregnant woman to fetus or mother to infant during childbirth/breast feeding |
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Horizontal transmission |
- person to person via air, physical contact, ingestion of food or water, or vector |
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Direct Contact |
- handshake, sexual intercourse - infectious dose important (for Shigella, 10-100 cells, can happen from handshake) - from hands, can be ingested (fecal-oral transmission) - hand washing considered single most important measure for preventing spread of infectious disease - some pathogen cannot survive in environment, require intimate sexual contact (treponema pallidum, neisseria gonorrhoeae) |
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Indirect Contact |
- inanimate objects, or fomites - clothing, table-tops, doorknobs, drinking glasses |
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Droplet Transmission |
- respiratory droplets generally fall to ground within a meter from release - densely populated buildings (schools, military barracks) - spread minimized by covering mouth when sneezing |
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Food and Water |
- can become contaminated - animal products (meat, eggs) from animal's intestines - cross-contamination: transfer from one food to another - municipal water systems can distribute to large numbers (1993-Cryptosporidium parvum outbreak in Milwaukee) |
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Air |
- respiratory diseases commonly transmitted - particles larger than 10um usually trapped by mucus - smaller particles can enter lungs, carry pathogens - talking, laughing, singing, sneezing, coughing generate (droplet nuclei (microbes attached to dried material) remain suspended) - # of bacteria in air proportionate to number of people - difficult to control - ventilation systems, negative pressure, HEPA filters to help |
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Vectors |
- living organisms that can carry pathogen - most commonly arthropods: mosquitoes, flies, fleas, lice, ticks; can carry internally or externally - can be mechanical or biological - vector control important in preventing disease |
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Pathogen factors that influence the epidemiology of disease |
- the dose: minimum # of pathogens required - doses below min. necessary may produce asymptomatic infection; immune system eliminates organism before symptoms appear - very lg. doses (laboratory accident) may produce serious disease even in normally immune individual - the incubation period: influences extent of spread - long incubation period can allow extensive spread (1963-typhoid fever in ski resort in Switzerland) ( 10,000 individuals drank water containing Salmonella enterica serotype Typhi; 10-14 day incubation allowed spread to at least 6 different countries) |
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Host factors that influence disease epidemiology |
- immunity to pathogen - general health - age |
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Immunity to pathogen |
- previous exposure, immunization - herd immunity protects non-immune individuals in population; >90% immunity typically sufficient - antigenic variation can overcome (example = avian influenza) |
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General Health |
- malnutrition, overcrowding, fatigue - developing world more susceptible b/c of crowding, poor food, sanitation |
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Age |
- very young, elderly generally more susceptible - immune system less developed in young; wanes in old - elderly also less likely to update immunizations |
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National Disease Surveillance Network |
- public health departments in each state - have authority to mad ate diseases that must be reported - Washington State health authorities responded rapidly to Escherichia coli O157:H7; epidemic had started in other states - fungus Cryptococcus gattii first appeared in WA in 2007, causes lung infections, meningitis; OR, CA now monitor these as well - other components of the Public Health Network - public schools report absentee rates - hospital laboratories report on isolation of pathogens with epidemiological significance - news media alert public to presence of infectious diseases |
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Worldwie Disease Surveillance |
- World Health Organization (WHO) has 4 main functions: - provide worldwide guidance in field of health - set global standards for health - cooperatively strengthen national health programs - develop & transfer appropriate health technology - WHO provides education, technical assistance - disseminates information via periodicals, books (weekly epidemiological record) |
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Reduction & Eradication of Disease |
- many diseases reduced through improved sanitation, reservoir & vector control, vaccination and antibiotic treatment; smallpox has been eradicated globally - in US, many formerly common diseases are now rare - work underway to eradicate measles, polio, dracunculiasis |
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Healthcare-associated Infections (HAIs) |
- acquired while receiving treatment in healthcare setting - one of top 10 causes of death in US - hospital acquired nosocomial infections problematic throughout history; hospitals are densely populated with unusually susceptible people, where resistant and virulent pathogens may exist - est. 5-10% of patients admitted in US acquire (perhaps 2/3 are from patients' own normal microbiota) |
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Reservoirs of Infectious Agents in Healthcare Settings |
- other patients - healthcare environment - healthcare workers - patient microbiota |
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Other Patients |
- pathogens discharged via skin cells, respiratory droplets, other bodily secretions and excretions |
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Healthcare Environment |
- some gram (-) rods can thrive in sinks, respirators, toilets - pseudomonas aeruginosa resistant to many disinfectants, antimicrobials; requires few nutrients - many nosocomial infections traced to contaminated soaps, disinfectants, other aqueous solutions |
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Healthcare Workers |
- sick workers, carriers of pathogens - example: styaphylococcus aureus, streptococcus pyogenes |
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Patient Microbiota |
- invasive procedures can transmit normal microbiota to sterile body sites; compromised immune system may allow infection to develop |
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Transmission of Infectious Agents in healthcare setting |
- fomite transmission - direct transmission - airborne transmission |
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Fomite Transmission |
- medical devices - often breach first line barriers of defense (catheters, IV, mechanical respirators, inadequately sterilized invasive instruments)
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Direct Transmission |
- healthcare personnel - must be extremely vigilant with hand washing, disinfecting, wearing gloves |
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Airborne Transmission |
- air pressure - careful mopping - HEPA filters |
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Prevention of Healthcare Associated infections |
- important to detect, establish appropriate policies to stop - hospitals have infection control committee; implement policies based on standard precautions and the transmission based precautions - CDC has established healthcare infection control practices advisory committee (HICPAC) |
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Policies on standard precautions & transmission based precautions |
Guidelines on: - hand hygiene - personal protective equipment - respiratory hygiene/cough etiquette - patient placement - patient-care equipment & instruments/devices - care of environment, textiles, & laundry - safe injection practices - infection control practices for special lumbar puncture procedures - worker safety |
