Immunology exam 4

primary syphilis

1 week to 3 months after initial exposure, chancre- usually at site of entry, painless ulceration most often on genitalia, can involve other areas, after 3-12 weeks heals by itself without any other symptoms, painless goes away spontaneously, many ignore it and do not seek medical treatment

mixed essential cryoglobulinemia

1-2% with hep C, immune complexes of virus, Ab, C, and rheumatoid factor, complexes form in cold and dissolve upon warming complexes deposit throughout the body- type III hypersensitivity (rashes and joint pain) raynaud's phenomena- pain, numbness, paleness, and or tingling of fingers/toes when exposed to cold, develop due to cryoglobulinemia

influenza A

18 subtypes of hemagglutinin- H1-H18 11 different neuraminidase- N1-11 most human infections are caused by variants- H1-3/N1-2

common variable immunodeficiency

20-30 different primary immunodeficiencies, results in severe clinical condition rare but 2nd most common primary immunodeficiency low level of IgG, A, and/or M do not produce IgG antibodies to specific protein vaccines when stimulated CVID due to- deficiency in cell-signaling of CD19, 20, 21, 80, mutations in protein TACI most common- TACI- mediated signaling plays a role (B cell activation and regulation) susceptible to infections- lungs, sinuses, ears, bronchi, GI infections lymphoma or stomach cancer can develop associated autoimmune disorders- autoimmune hemolytic anemia, ITP diagnosis difficult and often delayed- infections treated incidentally, patients make own Ig early in life and then stop, often done by exclusion of other immunodeficiencies treatment- Ig IV, infection control

laboratory tests for HIV

3 different aspects of infectious process 1. host antibody levels against virus- HIV-1/HIV-2 frequently combined with p24 antigen testing 2. virus presence- nucleic acid testing (NAT) 3. hosts CD4+ T cell count window period- time between infection and test detecting changes

treponema pallidum

4 subspecies, each causes different disease pallidum (syphilis) endemic (bejel) carateum (pinta) pretense (yaws)

C difficile- associated diarrhea (CDAD)

> 3 loose, watery stools (24 hours) on antibiotics, high fever, abdominal pain, unusual stools (fetid odor) source- often hospital, nursing home- hospital setting for long periods also outpatient setting, community at large transmission fecal-oral, spore, organism resilient

hep summary

A, E- spread through fecal-oral A, E- do not become chronic B, D, C- spread through blood B, D, C- can become chronic >half of chronic liver disease in US is due to B and C further evaluate when clinical signs of hepatitis (elevated liver enzymes) physical s/s of hepatitis, similar regardless of virus- lab results important for treatment, prognosis positive for hep C should receive hep A and B vaccines to protect liver from any further assault positive for hep B should receive vaccine for A if any risk factors hep E- rarely seen in US but consider travelers rapid diagnosis of any hepatitis viruses is important to prevent spread of the disease

lyme EIA and western

CDC recommends two-tier protocol initial ELISA testing followed by specific Western Blot carry out as confirmatory tests for disease

HIV/AIDS

CDC- US >1.1 million living with HIV, world >35 million died of AIDS since 1981, the average time from acquiring HIV to progression to AIDS is 10 years without ART

blood borne hepatitis- hep B

DNA virus- surrounded by a nucleocapsid- surrounded by lipoprotein envelope, nucleocapsid composed of core protein HBcAg Hep B surface antigen (HBsAg) in the lipoprotein envelope HBeAg- between nucleocapsid and lipoprotein envelope acute hepatitis- 90 days after infection (60-150 days) males> females degassed at rate 1.6 times contact with infectious blood/body fluids- mucosal contact or break through skin (percutaneous) dried blood can infect for 7 days after shed persons at risk- can be sexually transmitted, occupationally exposed, hemodialysis patients, travelers to prevalent countries, contacts of infected persons, IV drug users many asymptomatic, symptoms same as general hepatitis (addition of joint pain and rash) fulminant hepatitis and death (0.5-1% of cases) unlike A or E, hepatitis B can be chronic- virus remains in body after acute infection is over, can remain symptom free for many years chronic hep B- scarring (cirrhosis) or cancer (hepatoma) 15-25% with chronic hep B, cirrhosis causes liver failure and death, countries without advanced medical care (hepatoma leads to death in 1 year)

lab for rubella

EIA for antibody to Rubella- IgM or 4-fold rise in IgG titers, used to determine if woman of childbearing age (immune or susceptible if woman is not immune vaccinate before she attempts to become pregnant)

EIA versus Western

ELISA detects abs to mixture of bacterial antigens- does the patient have antibodies to borrelia burgdorferi? Western blot assesses person's abs to specific Borrelis antigens- Which ones and how many? CDC defines positive- IgM against 2 of the following 3 bands (OspC 22-25, 39, 41) IgG reactivity against 5 of following 10 bands (18, OspC 22-25, 28, 30, 39, 41, 45, 58, 66, 93)

Hep B antigens

HBsAg and HBeAg- patient is infectious, part of the virion, HBeAg becomes positive shortly after HBsAg (indicates patient is highly infectious)

AIDS

HIV to AIDS- viremia drastically increases, CD4+ cell counts drastically decrease, increase in cancers (kaposi's sarcoma, lymphomas) virus infects CNS- metabolic encephalopathy= AIDS dementia complex- infection of brain microglia and macrophages, manifests years after HIV infection

laboratory for HSV

HSV PCR, viral culture, immunohistochemical stain serological evidence- HSV diagnosis, used to type 1 or 2, point-of-care tests available for HSV-2 diagnosis

treatment

IM penicillin G tetracyclines, doxycycline, and ceftriaxone can be used

primary- immunoglobulins (Ig)

Ig deficiencies- defect- B cell maturation or activation, results in agammaglobulinemias or hypogammaglobulinemia, occurs at any step in development phase of B cell- stem cell to plasma cell defect in signaling molecules (needed for B cell function) defect in isotope switch- affects production (increase or decrease) of any Ig isotype increase pyogenic (pus-forming) infections treatment- passive transfer of Ig, except for IgA deficiencies

reportable

MMR are reportable

hep C treatment

PEP- no prophylaxis is available, Ig doesn't work because antibodies are not protective- same reason no vaccine developed pegylated interferon with ribavirin- interferon interferes with viral replication, ribavirin is a nucleoside inhibitor, about 55% become negative by molecular assays direct acting antiviral (DAA)- new drugs- sofosbuvir a nucleotide analogue inhibitor of the HCV NS5B polymerase enzyme, genotypes 1-4, simeprevir a protease inhibitor that blocks hep C virus genotype 1 virus replication combination drugs are very effective- first line- elbasvir/grazoprevir (zepatier) mevyret, harvoni, epclusa second line- vosevi cirrhosis does not respond to treatment asymptomatic patients with normal liver enzymes- wait to be treated, however response rate better when low viral load drug treatment is not a trial decision, liver transplant when liver failure is eminent

hepatitis A

RNA virus, acute hepatitis (incubation period= 14-28 days) shed in feces- high concentrations, 2 weeks before, until 1 week after symptoms appear risk related to fecal-oral route- oral-anal contact, international travelers (Mexico, South and Central America, contaminated food, water) children in communities with high rates of disease exposure from infected food-handlers- food handlers- bad hygiene, handled uncooked food, contaminated food after cooking, produce irrigated or processed with contaminated water traveler tips to high-risk regions- prevention- water- drink bottled water- some plastic bottles are reused and filled with local tap; only consume if unsealed when present, some regions use superglue, if doubt drink carbonated water (water with gas) food- destroy by heating 1 minute at 85 C, all shellfish cooked only, fruits, vegetables only if cooked or peeled not chronic, antibody protective so you can't get reinfected, relapsing can occur, hospitalization required (35%) reported deaths (0.8%) mainly in people over age 50, alcoholic or other viral damage to liver cure; nearly 100%, pregnant women- no extra risk, young children frequently asymptomatic, laboratory diagnosis very important for treatment and prognosis (reportable infection, national surveillance)

hepatitis D (delta) virus

RNA virus, requires co-infection with Hep B virus to replicate- uses envelope proteins of Hep B to assemble into new particles and attach and enter new cells RNA genome codes for only 2 proteins- RNA binding proteins, host cell supplies rest of proteins needed for replication transmitted0 like hep B, percutaneous or mucosal exposure acquired with hep B- it is a co infection if acquired while in the chronic hep B state it is called a super infection if patient has both B and D- worse prognosis for acute and chronic Hep B- 2% mortality of acute hep, 20% with chronic hep assay for anti-HDV antigens in hep B patient, no separate vaccine for hep D, prevent with vaccine for hep B

nontreponemal screening tests

VDRL test- screening to detect anticardiolipin antibodies, flocculation technique RPR- also measures antibodies to cardiolipin, agglutination technique

primary- XLA

X-linked agammaglobulinemia inherited from mother (40%)- rest are spontaneous mutations also celled bruton's agammaglobulinemia; bruton's disease, males, 1:250,000 lack of mature B cells- pre-B cells in BM but lack circulating B and plasma cells, impaired B cell development- lack of tonsils, poorly developed lymph nodes lack of Ig or all isotypes, T cells, NK cells, CD4/CD8 are normal, congenital defect in an enzyme- bruton's tyrosine kinase (critical role in cell signaling, maturation fo B cells from precursors) infections in early life (once maternal Ab cleared out 6-9 months) lack of tonsils- diagnostic criteria prognosis- live well into 40s, better with early treatment- Ig replacement IV, treating infections aggressively

secondary

acquired AIDS, malnutrition, radiation exposure, immunosuppressive therapy

symptoms

acute respiratory disease- mild to severe runny nose, muscle or body aches, sore throat, cough, diarrhea, fatigue, sometimes fever, vomiting complications- ear infections, sinusitis, bronchitis, asthma and congestive heart disease worsen

agammaglobulinemia

administer pooled or selected gamma globulins

treponemal tests

agglutination, fluorescence, and EIA- treponema pallidum particle agglutination assay (TP-PA)- cross reactivity other Treponemas can occur, uses gelatin particles sensitized with treponema antigens

chronic infection

anti-HBcAg IgM is negative, anti-HBcAg IgG is positive, HBsAg is positive- virus antigen should have disappeared prior to development of IgG anti-HBcAg anti-hepatitis D antigen (anti-HDV) indicates co-infection with Hep D virus IgM anti-HBcAg and HBsAg measurements used in screening donor blood antibody to HBeAg (patient is recovering from infection) antibody to HBsAg- measured after disappearance of HBsAg- indicates recovery, this antibody provides protective immunity antibody to HBsAg- present without any other markers in vaccinated, not produced in chronically infected individuals can become reactivated- corticosteroids or chemotherapy, IgM anti-HBcAg may reappear in serum, HBeAg or HBV DNA indicate active viral replication

testing for antibodies

antibodies against HIV used diagnosis- window period is critical, false negatives- tested too early, person can still transmit virus to another even though no antibodies detected HIV infected individuals- develop anti HIV antibody within 30-60 days after exposure, almost 100% infected show antibody 3 months after infection, detectable production of antibodies to HIV is called seroconversion

laboratory tests for T pallidum

antibodies in blood- nonspecific screening tests, detects antibodies to cardiolipin (lipid generated from damaged cells non-treponema tests) venereal disease research laboratory (VDRL) test, and rapid plasma reagin (RPR) test other conditions cause false positives- virus (hepatitis, measles, varicella) disease (TB, malaria, chaga's disease, endocarditis) sample contamination

anti-DNAse B

antibodies to DNAse B- elevated in rheumatic fever and post streptococcal glomerulonephritis, classical method used to detect antibodies- DNAse B can degrade DNA, current method- immunonephelometry

hep B

antigens detected by EIA capture- competitive or sandwich assays used IgM detection- direct competitive assay- Ag coated on plate, patient's antibody added, enzyme labeled Ab to Ag is added, patient Ab competes with kit Ab for binding Ag both acute and chronic hep B are nationally reportable diseases treatment- acute- no treatment because high spontaneous recovery rate, antiviral therapy may be given for severely ill, chronic with active viral replication- interferon alpha, lamivudine, adefovir dipivoxil, entecavir, and telbivudine lamivudine (3TC)- reverse transcriptase inhibitor hep B has a step in its lifecycle- viral RNA produced by a cellular RNA polymerase from viral DNA, then replicated to DNA via a viral reverse transcriptase, reverse transcriptase inhibitors- used for hep B, adefovir dipivoxil, televudine, entecavir, do not work for HIV do not cure chronic Hep B, they do decrease viral replication, monitor chronic infection- progress to liver cirrhosis or liver cancer fulminant acute HBV infection- liver transplant, high-dose passive transfer (human anti-hep B immunoglobulin) antivirals

treatment

antiviral therapy-decrease the symptoms oral- acyclovir, valacyclovir, famciclovir topical- decreases viral shedding and improves healing time IV acyclovir- severe infections, infections of infants

antigens and antibodies for testing

assays- IgM and IgG to epstein-barr viral capsid antigen (VCA) IgM to epstein-barr virus early antigen (EA) antibody ti epstein-barr nuclear antigen (EBNA)

prevention

avoid tick areas if bitten early tick removal- infection depends on tick feeding for > 24 hours, remove tick close to skin as possible without crushing or severing head from body

HIV infection

binding of virus to host cell- interaction of gp120 with CD4 causes structural change in viral envelope, expose domains of gp120 that bind to chemokine receptors interaction of gp120 viral protein with chemokine coreceptors- fuse viral envelope+ cell membrane virus attaches to cell- gp41 protein in virus penetrates cell membrane- fusion results in a hole in the membrane, virus enters cell, virus releases its RNA and its enzymes reverse transcriptase converts RNA into viral DNA, viral DNA transported into the nucleus, integrates into host cells DNA by viral integrase transcription by reverse transcriptase- susceptible to numerous errors "errors" contribute to genetic variability of HIV (drug resistance and or immune evasion)

H pylori invasive testing

biopsy during endoscopy and a rapid urease test- histology exam and culture to detect H pylori

immunopathology of lyme disease

bite site, bacterium protected by tick saliva, inhibits initial localized immune responses (neutrophil migration) after B burgdorferi in dermis- inflammatory response causes Erythema Migrans rash (bull's-eye) strong immune response, humoral and cellular- not effective on eliminating organism, responsible for clinical symptoms of disease remains in host months-years, evades immunity- down regulates expression of bacterial proteins that are immunogenic, antigenic variations of some of these proteins, interferes with action of complement

TORCH

causes hepatosplenimegaly, fever, lethargy, difficulty feeding, anemia, jaundice at birth infants tested at birth- toxoplasmosis, other infections, rubella, cytomegalovirus, herpes simplex virus

HIV and immune responses

cell-mediated, humoral immune response can help but also can contribute to infection (establish viral reservoirs) same as response to viruses- cytotoxic T cells kill virus-infected cells (via MHC class I, viral antigen epitope) virus specific helper T cells are also generated- play a role in the maintenance of the cytotoxic T cells and B cells against the virus viral nef gene- protein that inhibits expression of MHC class I and II components on surface infected cell, down regulates host cellular response to virally infected cells antibodies and antigens- used for diagnosis, detected in blood, mucosa, 3-12 weeks for enough antibodies to detect HIV infection in 97% of people (remaining should seroconvert by 3 months) 2-6 weeks for enough antigen in 4th generation tests antibodies- play a role in antibody-dependent cellular cytotoxicity, complement activation, or indirect neutralizing, early antibody response target gag proteins, late antibody responses to viral envelope and some regulatory proteins, limit viral replication (keep virus in check during early asymptomatic stage) titers of neutralizing antibodies (low, specificity is very narrow, only react with a few selected viral epitopes) lack broader cross-reactivity, virus mutates very rapidly escaping Abs, early responses directed against early forms of virus (from the initial infection) not effective against "newer" mutants of the virus initial response can reduce viral replication however immune response cannot eliminate the virus from the host

varicella zoster

chicken pox and shingles herpesviridae family primary infection- blistering rash (250-500 lesions) mostly on head and trunk, fever in most, headache, photophobia, diarrhea may occur highly contagious, spread by aerosols- produced by coughing, sneezing, and by skin lesions both aerosols and direct contact infectious 1-2 days before rash appears remains infectious even when all blisters scab symptoms 2-3 weeks after exposure, somplications- bacterial skin infections, patient scratches blasters, pneumonia and encephalitis

pharyngitis (strep throat)

children 5-15 most common pharyngitis signs/symptoms- fever, chills, sore throat, headache, red pharynx with exudate, anterior cervical lymphadenitis

antibody to strep antigens

common strep antigens- bacterial exotoxins- DNAse B, streptolysin O (oxygen labile toxin beta-hemolysis) streptomycin S for oxygen stable (cardiotoxic exotoxin beta-hemolysis) Hyaluronidase (facilitates bacterial spread- breaks down hyaluronic acid) streptokinase (activates plasminogen, plasmin, which digest fibrin and other proteins) NADase and different pyogenic toxins, which act as super antigens antibodies commonly tested- streptomycin O, DNAse B streptomycin O antibodies- indicates exposure not indicative of active infection streptolysin O antibodies- levels above baseline values= disease, titers start to increase 1-3 week post strep infection, peak in 3-5 weeks, decrease to original levels in a few months

lyme disease

common tick borne disease spirochetes borrelia genus- borrelia burgdorferi, different species cause disease in different geographical areas transmitted to humans by deer tick- acquires organisms during feeding on other animals that at as natural reservoirs most commonly mice and sometimes rats in North America- most US cases- northeastern, common in Europe, Asia, and Australia transmission- very low (1% of tick bites result in lyme disease) requires tick to remain attached and feed (24 hour)

Hereditary angioedema

complement deficiency defect in C1INH- results in a failure to control the classical and lectin pathways, results in the release of anaphylatoxins, C1INH also regulated factor X11 and kallikrein results in additional vascular permeability

treatment

control infections, correct whatever cause the condition (replace missing protein, missing cell type or cell lineage, replace missing or defective gene) replace missing cell type or lineage- BM or hematopoietic cell transplantation (HLA matched donor is needed, avoid GVHD) gene replacement still under development

influenza spread

coughs, sneezes, talks (droplets travel up to 6 feet away) inhale droplets into lungs, contaminated item then touch nose/mouth spreads 1 day before signs/symptoms

detection and diagnostics for streptococci

culture- sample locus of infection (throat) sheep blood agar plate, halo of beta hemolysis suggests group A strep detect the organism- antigen immunological assays or DNA testing, detect antibodies in infected individual

acute proliferative glomerulonephritis (AGN)

damage to small blood vessels of kidney sequelae of strep- more common after impetigo, strep throat also causes it damage from type III hypersensitivity reaction- deposition of immune complex following infection, immune complexes adhere to basal membrane of glomeruli, activation of complement results in glomeruli destruction symptoms vary-type and severity- hematuria, decreased urine flow, hypervolemia, edema, hypertension, fever, headache, malaise, anorexia, nausea, vomiting, renal necrosis, renal failure urinary sediment- dysmorphic RBCs, RBC casts, leukocytes, occasionally leukocyte casts

primary- complement deficiency

defective complement components- early components of classical pathway (C1q, C1r, C1s, C4, C2, C3) late components (C5-9) alternative pathway components (factor D, properdin) defective opsonization, any defect causing diminished production of complement components causes decreased opsonization defects in C3- high rate of morbidity, key role in each pathway in lysis and opsonization

immunodeficiency

defects in immune response, one or more components of the immune system malfunction, partial or total loss of immune function, prevents system from protecting host from potential threat

evaluate cell mediated immunity

delayed hypersensitivity test (DHT) intradermal injection common Ag (tetanus toxoid) cell-mediated immunity reaction (localized appearance at site of injection induration and inflammatory reaction) done at physician office

CMV diagnosis

detect CMV by PCR or viral culture test for IgM or IgG to CMV- IgM levels positive- initial infection, secondary infection, undergoing reactivation of previous infection 4-fold IgG rise indicates current infection low affinity IgG indicates acute infection treatment- valganciclovir

rapid strep test

detect carbohydrate antigens to group A strep- swab throat, place stab into reagent that extracts carbohydrate antigen, detect antigen- immunochromagraphic sandwich immunoassay highly specific- over 95% sensitivity only 80%, negative rapid test (follow with culture)

polymerase chain reaction (PCR)

detects presence of organism- detects genetic material from borrelia burgdorferi, specificity of PCR 100%, PCR used only when diagnosis is very difficult (limited to test CSF and synovial fluids) detect organism in tick removed from bitten person

diagnosis and lab

diagnosis- clinical appearance, lab testing- severe disease, atypical disease, disease may have exposed a high risk individual direct immunofluorescence with fluorescently labeled Ab to viral antigens on swabs from lesions PCR on same material viral culture antibody testing- increase in paired titers, high titer IgM (acute infection)

spirochetes

disease-causing spirochetes- treponema pallidum (syphilis) treponema pallidun pretenue (yaws) borrelia burgdorferi (lyme disease) borrelia recurrentis (relapsing fever) leptospira species (leptospirosis)

lyme and the immune system

disseminated secretion of cytokines (IL-6, TNF-a)- symptoms of disease (inflammatory, neurological)

rickettsiae

diverse- exhibits different shapes (threads, cocci, rods) obligate intracellular parasites- survives and replicates within host's cell must culture in tissues (chicken embryos) susceptible to antibiotics transmission- ticks, lice, fleas, anthropoids diseases- typhus, rocky mountain spotted fever typhus- R typhi, R prowazekii spotted fevers- R rickettsii, R askari

primary-Tcell

dysfunction of T cell- multiple effects to other aspects of immune system (T cells affect other cells) dysfunction of T cells "only" are hard to identify

diagnosis

early stages- antibodies do not indicate active disease- IgM, IgG, at low titers, may be present after recovery, cross-reactivity to different antigens from other organisms (false-positives results)

treatment

early treatment- cure for disease- antibiotics (doxycycline, erythromycin, amoxicillin, ceftriaxone) treatment- 10 days to a month neuroborrelliosis- B burgdorferi may cross BBB, antibiotics that can cross (minocycline)

pathogenesis

eclipse phase (window period)- delay before virus is detectable- viral components not easy detected (7-10 days after infection) single virus can initiate infection virally infected cells and free virus arrive at lymph nodes CD4+ T cells get infected- antigen presenting cells (dendritic cells)- internalize virus, present virus to T cells virus spreads to entire body- level of infection- depends on # of cells within lymphoid area, gut lymphoid tissue (rich in CD4+ cells) 80% depleted in first 20 days of infection during high viremia CD4+ cells are low (later return to normal) viral escape from immune system- reservoirs of virus, CD4+ cells, monocytes, macrophages, dendritic cells, microglial brain cells (which are also CD4+), virus causes persistent infection- ultimately depletes virus-infected cells infected cell depletion- elimination by cytotoxic T cells, viral budding destroys cell, virally induced apoptosis, as depletion increases cells can't be replaced fast enough helper T cells CD4+- most affected, depletion affects both arms of immune system (profound immunodeficiency) lack of T cell help for cell-mediated immunity, lack of T cell sending signals to B cells (antibody production to antigens affected)

hep C testing

elevated liver enzymes test for HCV antibody (or HCV RNA)- antibody testing using rapid oral-quick test has similar sensitivity and specificity to the lab conducted assays if negative- recheck in 6 months if positive for antibody test for HCV RNA- if positive current infection, if negative- past

serology for C difficile

enzyme-linked assays- detects toxin A and B in stool, sensitivity 70-100% specificity >90% rapid immunochromatography for toxins real-time PCR- FDA approved, sensitivity and specificity >95%

herpes simplex 1 and 2 (HSV)

epidemic, herpesviridae family, DNA virus "cold sore" at mouth (herpes simplex 1) genital lesions depending on site of infection sexually transmitted (herpes simplex 2) HSV-1/HSV-2 are cross-transmissible symptoms- painful blisters- burst, sores last 2-4 weeks, often reappears more than once, often appears 4 or 5 times the first year after infection, each successive occurrence is usually less severe, symptoms can be very severe in immunosuppressed and can require hospitalization due to disseminated infection, hepatitis, or CNS effects, shedding can occur when no symptoms are present both 1 and 2

herpesviridae family

epstein-barr, cytomegalovirus, herpes simplex 1 and2, varicella zoster DNA viruses, all exhibit latency, all cause lifelong infections

The M protein

evades phagocytosis- blacks complement binding to peptidoglycan >50 types identified by antigenic specificity- major source of antigenic shift/drift bends fibrinogen epitopes that mimic muscle and connective tissues- cross reactive autoimmune conditions autoimmune rheumatic carditis and rheumatic fever

scarlet fever

exotoxin produced by streptococcus pyogenes treat with antibiotics childhood disease; adults lasting immunity fever, sore throat, tongue bright red, resembles a strawberry, rash peels in a few days, chest, armpits, skin folds, groin, ears (face spared)

viral infection and replication

expression of CD4 not sufficient for infection, co-receptor involved certain groups while being high risk remained seronegative- homozygous deletion chemokine receptor CCR5 gene (truncated protein) 2 chemokine receptors, specifically CXCR4 and CCR5 serve as co-receptors for HIV

acquired immunodeficiencies

external factors- malnutrition, infections, anti-inflammatory, immunosuppressant drugs, trauma (splenectomy) environmental conditions (radiation)

hepatitis E

fecal-oral (like hepatitis A) RNA virus contaminated water causes epidemic contaminated food and animals not spread person to person not spread sexually where- southeast and central Asia, India, Mexico, rare in US (travel associated) Middle East, Africa- second to Hep B for viral Hepatitis acute- incubation period 2-10 weeks after infection, looks like Hep A- usually not severe, 40% of infected people become ill, young children often asymptomatic, most recover in a few weeks, does not become chronic, 1% become fulminant (disease is fatal) individuals with chronic hepatitis or other liver damage (mortality rate as high as 70%) rare in US- diagnostic tests not done in US, blood tests available in other countries- serology IgM, IgG to hepatitis E specific antigens, RT-PCR for viral RNA treatment- rest, fluids, no medicines toxic to liver, no alcohol vaccine- available in China only

first stage of lyme disease

first disease- early localized infection, headaches, fever/chills, myalgia, swollen lymph nodes, few days to several weeks, followed by early disseminated infection (spread of organism in blood and to body)

tertiary syphilis

following untreated latent-stage syphilis- about 1/2 develop tertiary syphilis, occurs as early as 1 year after initial exposure, typically decades after gummas (granulomas)- chronic festering balls (pockets of inflammatory molecules and cells) everywhere (bones, tissues, skin) affects anatomy (grotesque deformities) cardiac abnormalities- affect ascending aorta- inflammation, aneurysms, aortic valve dilation, insufficiency and massive left ventricular hypertrophy HUGE enlargement of the heart- For bovine (cow's heart) coronary arteries narrow, secondary effects (diff breathing, diff swallowing, ribcage damage) ruptured aneurysms and heart failure; common cause of death

latent stage

follows secondary syphilis, no symptoms

testing for Hep A

for total anti-HAV Ab- indirect enzyme immunoassays, sandwich immunoassays are most common test for IgM Ab to hepatitis A virus

primary

from congenital defects >80 syndromes lymphoid or myeloid lineages, defects in a single gene or a complex of genes, most diagnosed in children

primary immunodeficiency

genetic anomalies- due to single gene or multiple gene mutations depending in the genetic component- antibody response, cell-mediated immunity, complement activation and function, phagocytic function, cell trafficking, organ development

diagnostic tests and serology

genital ulcer, history- diagnostic work-up dark field microscopy of lesion fluid- positive syphilis, negative

Hep A- post exposure prophylaxis (PEP)

given to individuals who are in close contact with an infected person Ig injection if 1-40 years old, receive Hep A vaccine vaccine preferred because of long-term protection given within 2 weeks of exposure

pandemic rubella

global pandemic- 1962-1965 >12 million cases of rubella in the US congenital rubella syndrome- mental retardation, cataracts, deafness, heart malformations, spleen, liver damage 1969- live attenuated rubella vaccine licensed in US 1989- improved 2 dose vaccine schedule 2004- end to endemic in US <25 cases in US associated with cases abroad

helicobacter pylori

gram negative very common resident of stomach- 2/3 of world population, more prevalent in developing countries, >3/4 asymptomatic, causes most duodenal (90%) and gastric (80%) ulcers associated with stomach cancer penetrates mucosal lining of stomach, H pylori burrow into mucosal layer of stomach, survives harsh environment of stomach urease- enzyme that cleaves stomach urea to produce ammonia and CO2, further chemical reactions produce bicarbonate- neutralizes stomach acids, ammonia damages the epithelial cells other pathogenic substances- different enzymes (mucinases, proteases, phospholipase) vacuolating cytotoxin A (VacA) injects CagA into epithelial cells- disrupts cell cytoskeleton- interferes with cell's intracellular signaling mechanisms and expression of different cell genes, contributes to immune and inflammatory response because it is highly immunogenic strong inflammatory reaction at site where it colonizes- increased production of gastrin hormone- increases acid in the stomach, damage result of- bacterial products, inflammatory responses, fluctuations of gastric acid

clostridium difficile

gram-positive, spore forming bacteria normal human intestinal commensal in 3-5% infection- antibiotics destroy normal flora, take over with C diff, antibiotic- associated severe diarrhea (pseudomembranous colitis series inflammation of colon) toxins cause clinical manifestations- toxin A (enterotoxin) Toxin B (cytotoxin) inflammation, bloating, diarrhea toxins- mild to severe, life threatening in some particularly older patients, simple cases spontaneous resolution by stopping antibiotics causing the problem, more serious cases metronidazole or vancomycin (fecal transplant for resistant patients)

differentiation of strep species

hemolysis (break down blood)- species oxidize iron in hemoglobin (alpha-hemolytic green-colored halo blood agar) species completely destroy RBCs (beta-hemolytic clear halo forms blood agar) species don't hemolyze (gamma-hemolytic)

viruses

hepatotoxic (liver-seeking) viruses- hepatitis A, B, C, D (delta), E A,E- spread through fecal- oral route B, C, D- spread by bloodbourne route

Cytomegalovirus (CMV)

herpesviridae family US- 50-80% of adults by age 40, most asymptomatic, some- sore throat, fatigue, fever, swollen glands, symptoms similar to infectious mono serious immunocompromised- major cause of death and disease- transplant recipients, people with HIV, people with lymphoproliferative diseases, associated diseases- pneumonia, retinitis, GI disease unborn- most important viral cause of birth defects, 80% born with congenital CMV infection are asymptomatic at birth and remain asymptomatic, 20% develop problems 50% symptomatic at birth- experience liver, spleen and or lung problems, microcephaly, seizures at birth, hearing and or vision loss, lack of coordination, seizures, death remaining 50% asymptomatic at birth but develop vision and hearing problems that appear up to 2 years after birth

paul-bunnell antigen

heterophiles antibodies agglutinate sheep, horse, bovine RBCs antigen on these RBCs reacts with infectious mono serum led to develop an inexpensive assay other sera that react with sheep RBCs- 2 other types of serum cause agglutination of sheep/horse RBCs- normal patients with antibody to forssman antigen, people who had serum sickness and react with an antigen on sheep or horse RBCs due to previous stimulation with animal serum

HIV drugs

highly active antiretroviral therapy HAART-now called ART- combine 3 antiHIV drugs from at least 2 drug categories successful in reducing viremia and restoring counts- drastically reduces # of infections and overall mortality

jaundice

hyperbilirubinemia- jaundice- yellowing skin, whites of eyes, excess bilirubin is excreted in urine, stools turn clay colored as blockage increase PT (prothrombin time) elevated in severe hepatitis bilirubin- breakdown product of heme, from RBCs, excreted in bile, liver damage and bile duct blockage (increased serum bilirubin) increases can be due to RBCs lysis

shingles

illness caused by reactivation occurs most often in individuals > age 60 can occur in younger people especially immunocompromised painful blisters- occur in limited area, area enervated by one or two nerves, one side of the body, head or trunk complications- pneumonia, blindness, encephalitis persistant pain in some- does not resolve when lesions resolve, contagious- not nearly as primary chicken pox infection

clinical latency

immune response reduces viral numbers- virus not totally eliminated, remains in lower numbers in plasma and lymphoid tissues asymptomatic CD4+ cell # return to normal levels- viral transmission from person to person still occurs, virus still actively infecting host cells last for several years (average of 10) some remain asymptomatic- others mild infections or mild chronic symptoms virus multiplies, destroys immune cells- risk of opportunistic infections, affected individual develops AIDS

serology of lyme disease

immunofluorescence of ELISA used to detect abs to borrelia "positive" titer of 1:256

chronic hep C

impact- >2.4 million chronically infected people in US, 15-25% will clear the virus after infection without treatment, 75-85% develop chronic infection, 60-60% will progress to chronic liver disease, 10-20% will develop liver cirrhosis, 1-6% will die (liver cirrhosis or hepatoma) number of deaths (>18,000 cases in the US per year) most people do not have symptoms, as liver damage progresses symptoms occur, cirrhosis with hepatomegaly and splenomegaly, jaundice, muscle wasting, ascites (fluid in the peritoneal cavity)

congenital syphilis

in utero infection- mother with secondary or early latent syphilis untreated- miscarry, stillbirth, premature, death of newborn babies develop- seizures, developmental delays, deformities, problems in dentition, enlargement of liver and spleen, jaundice, anemia, rashes, lesions; infectious rare- infants develop tertiary syphilis

syphilis

incidence increasing, transmission sexual contact, transmission mother to child through placenta (congenital syphilis) obligate parasite depends on host for survival, cannot live without it contains 100x less surface proteins- difficult to create vaccine, organism able to either escape or survive immune response physical barriers most effective protection (skin, mucosa)- innate and acquired immunity play a role in defense antibody responses often ineffective, can survive host for many years, T cells, cytokines, phagocytosis (macrophages) play a role in eliminating organism from lesions antibiotic treatment is successful, without treatment disease progresses- widespread damage to many organs, tissues (brain, heart, major arteries, eyes, bones, death) common manifestation- dermatological- genitals, extra genital lesions

primary- hyper-IgM syndrome

increased IgM, very low G, A and E defect in isotype switching, switching requires the T cell help- the failure in switching is most commonly due to- T cells CD40 ligand (binds to CD 40 on B cells, involved in B cell activation and isotype switching) treatment- gamma globulin replacement therapy, infection management

serology and diagnostics of Rickettsia

indirect immunofluorescence test- most commonly used, species and antibody isotype specific, need to demonstrate a 4-fold IgG titer increase for confirmation PCR- detect and differentiate different Rickettsiae groups, difficult with rocky mountain spotted fever (requires biopsy of lesion)

fluorescent treponemal antibody absorption (FTA-ABS) test

indirect immunofluorescence with antibody serum CSF or serum is absorbed to remove non-specific antibodies added to a slide with fixed T pallidum organisms washed fluorescent anti-IgG antibody is added along with a second fluorescent antibody to stain the treponema

infectious mononucleosis

infection- symptoms in 35-50% malaise, sore throat, enlarged tonsils, fever, swollen glands, enlarged spleen, liver (hepatitis) can occur (splenic rupture can occur) symptoms can act for 1-2 months diagnosis- elevated lymphocyte count, atypical lymphocytes, symptoms (age of patient) heterophile antibodies- antibodies that react with antigens from 2 or more species in a pattern without evolutionary relatedness, IgM antibodies

streptococci

infections- strep throat, endocarditis, meningitis, pneumonia, skin infections (erysipelas) dental caries, necrotizing fasciitis ("flesh eating") many species harmless- normal flora (respiratory, digestive) many kinds- clinically relevant- alpha hemolytic streptococci (S pneumonia) beta hemolytic group A strep (S progenes) beta hemolytic group B strep (S agalactiae)

epstein-barr virus

infectious mononucleosis- direct contact with saliva of infected person (shared drinking glasses, straws, kissing) not through air or blood, symptoms begin 30-50 days after exposure also causes- burkitt's lymphoma- requires additional co-factor thought to include malaria, nasopharyngeal carcinoma- requires additional genetic ad or environmental co factors possible cause for MS along with a genetic predisposition and environmental effects such as vitamin D deficiency infection in children is usually asymptomatic, infection in teenagers/young adults results in infectious mono, 50-65% of the time mild or asymptomatic disease

Hepatitis

inflammation of liver, injury of liver liver enzymes elevated- leak from damaged or dying liver cells, ALT (alanine aminotransferase) AST (aspartate aminotransferase) alkaline phosphatase alkaline phosphatase may also be elevated when bile duct obstructed

later stage of lyme disease

joint and bone pain, irregular heartbeats, palpitation, dizziness neurological problems (neuroborelliosis) more severe cases (10% untreated)- partial facial paralysis, meningitis, memory loss, sensitivity to light, lack of sleep, mood swings rash at sites other than site of tick bite- if untreated or treatment unsuccessful disease develops into late stage serious condition- affects different tissues and organs- heart, brain, muscles, joints, nerves, extreme tiredness, arthritis (usually knees) cognitive difficulties, shooting pains, tingling, delusional behavior, some forms of psychosis, lost sense of reality, permanent damage, paralysis lower body (paraplegia)

primary- LAD

leukocyte adherence deficiency- autosomal recessive genetic defect most common- gene that encodes for CD18, role in adhesive and emigration of leukocytes to extravascular sites, neutrophils cannot cross the endothelial barrier 1:100,000 persons, recurrent bacterial infections in early childhood- lungs, peritoneal cavity, gingiva, have abscesses diagnosis- unexpected recurrent infections, analysis of immune function- cellular and humoral should be normal, increased neutrophils because unable to leave circulation, evaluate CD18 expression on surface leukocytes (flow cytometry) treatment- BM transplantation, gene replacement under consideration

vaccine

live attenuated virus part of measles mumps rubella vaccine (MMR)- mumps virus is difficult to attenuate so it is least effective but still around 88% not recommended for already pregnant women

testing for hep B

measure Ag and Ab to viral antigens- different in acute resolving infections and infections that become chronic hep B surface Ag (HBsAg)- first measurable sign of infection- disappears in 4-6 months if the patient is recovering but stays if the patient develops chronic hep B anti-hepatitis B core Ag (anti-HBcAg)- antibodies against HBc antigen, develops with symptoms, antibody lasts for lifetime (isotyping needed to determine present vs past infection) same in acute and chronic

anti-streptolysin O

method of choice- immunonephelometry- serum is mixed with purified streptolysin- antibodies present= immune complexes, increasing light scattering of sample, measured by nephelometer, extrapolate amount of antibody present

antigenic drift

minor changes, mutations in the genome of the virus

mycoplasma pneumoniae

mollicutes- lack a cell wall, cell membrane similar to eukaryotic cells susceptible- erythromycin, fluoroquinolone, tetracyclines common- all ages contagious- respiratory droplets, in families, spreads quickly atypical pneumonia (walking) inflammation of pharynx, bronchi, lungs, remains for months symptoms slow progressing- bronchitis, sore throat, headaches, chills

H pylori disease

most asymptomatic- eventhough have chronic gastritis, ulcers develop in 15% treatment- proton pump inhibitors, antibiotic regimens

Selective IgA immunodeficiency

most common Agammaglobulinemia middle-east decent, european decent, rate of its occurrence vary from population to population, males>females more than 1 cause- variable patterns of transmission- autosomal recessive, autosomal dominant, sporadic chromosomes 18, 14, or 6 abnormalities associated, strong association with certain HLA haplotype associated with different B cll or T cell abnormalities not necessarily catastrophic- most are asymptomatic, compensatory mechanisms involved- secretory IgM levels increase secretory IgA- predominant, extravascular secretion, mucosal system- enormous surface area (portal of entry for many pathogens, residence of commensal microorganisms) protects against pathogens, maintains homeostasis in GI tract severity of symptoms vary- involve respiratory and GI tract- mild to severe (respiratory infections, digestive infections, diarrhea) severe- permanent damage airway and intestines severe deficiency- 30-40% produce anti-IgA antibodies- anaphylactic rx after transfuse blood containing IgA, before blood transfusion test for anti-IgA IgE antibodies, washed or RBCs or plasma blood products from IgA deficient donors lab- low IgA below 5-7 mg/dL are low assays for low levels (immunonephelometry capture enzyme) IgG and M levels are normal diagnosis- levels of serum IgA, most asymptomatic- family history, unexplained recurrent infections, found to be associated with a # of different autoimmune disorders treatment- control infections, gamma globulin infections- NO, cannot replace IgA at mucosal interfaces, injection of IgA would cause IgE to IgA

X-linked SCID

most common form of SCID- still very rare very low to absent T cells and NK cells non-functioning B cells severe susceptibility to infections from infancy fatal in very early childhood mutations in gammac chain subunit of IL-2 receptor- defects in IL-2 signaling, gammac chain subunit shared by receptors for IL-2,4,7,9,15,21- affect functions of all these cytokines treatment- BM transplant, gene therapy is still being developed and has limited success along with failures

HIV transmission

most common transmission is sexual exposure to genital or rectal mucosa, people who inject drugs around 9% contact with blood, pre-seminal fluid/semen, rectal fluid, vaginal fluid, breast milk these fluids must come in contact with a mucous membranes damaged tissue or injected into blood HIV crosses mucosal barriers- dendritic cells are implicated not transmitted by casual contact or being around an infected individual, not transmitted by air, water, food, or mosquito, fragile; does not survive outside the blood to body fluids

initial stage of lyme disease

multiple and diverse signs/symptoms- initial- tick bite- few days to 1 month after bite, painless "bulls eye rash" (erythema migrant EM) not seen in 20% of cases

symptoms of hepatitis

nausea, abdominal pain, fever, malaise, anorexia, dark urine, clay-colored stool, jaundice, hepatitis with jaundice= icteric hepatitis without jaundice= anicteric

viral budding

new virions release- process reversed from viral entry- env protein transported via ER to golgi, cleaved generating new gp120 and 41 (gp41 attaches to 120 to infected cell membrane) virion buds out of the cell, maturation of new virion new viruses infect other cells

test for H pylori

noninvasive testing- antibodies against organism, test for microbial antigens, stool testing carbon-urea test- relies on bacterial urease, which breaks down urea releases CO2, radioactively labeled (14C or 13C) urea ingested- H pylori urease breaks it down, releases 14C or 13C labeled, CO2 detected in breath stool testing- monitor elimination of H pylori in feces, EIA tests for antigens serologic testing- antibodies to H pylori, most commonly detect IgG, chemiluminescence

ART

not a "cure" HIV can "hide" from immune system and drugs- integrate into various cellular reservoirs lifetime administration never fully eradicate virus virus can develop resistance to drugs- rendering drugs ineffective side effects- immune reconstitution inflammatory syndrome, asthma, drug allergies and hypersensitivity, liver and kidney toxicity, gastric disturbances

CD4+ counts

not really test for HIV measures cells most affected by HIV infection (CD4+ T cells)- numbers decrease drastically in acute HIV, recover somewhat after viremia decrease, decline throughout the years during clinical latency, eventually drop to irrecoverable levels CDC- to classify AIDS, <200 CD4+ T-cell counts range between 500 and 1500 cells/ul, monitoring CD4+ counts- to monitor antiviral therapy efficacy, to anticipate opportunistic infections, flow cytometry used

HIV rapid tests

oraquick- provides results in 20 mins, oral fluids analyzed in a testing apparatus shaped like a stick, detects the presence of HIV antibodies in saliva, home test-OTC

influenza

orthomyxoviridae RNA surface contians- hemagglutinin (H), which binds to surface silica acid, neuraminidase (N), cleaves silica acid for virus exit from the cell 3 groups- based on internal nucleoprotein (A,B,C) influenza A most widespread- pandemics, influenza B less, influenzas C mild; is not widespread reasons for repeat waves of influenza infection- changes in surface hemagglutinin and neuraminidase antigens, 2 different factors cause changes (antigenic shift and antigenic drift)

measles (rubeola)

paramyxoviridae family- mumps and RSV also single stranded negative RNA MMR vaccine US- very few get measles 131 cases Jan 1, 2008- july 31, 2008 112 not vaccinated- 63 not vaccinated but to parents beliefs worldwide- leading cause of child death, measles initiative has resulted in a steady decrease in the incidence of measles unvaccinated population- one case of measles spreads to 12-18 people, if person not vaccinated and not protected by herd immunity person will probably get measles- her immunity- significant percentage of population is immunized >90% spread through respiratory secretions- AIR BORNE, coughs, sneezes, dense rash on face, turns, arms, legs sore throat, high fever (up to 105) cough, runny nose, red eyes, light sensitivity signs/symptoms occur 7-18 days after infection kopek spots seen in mouth- red spots with bluish white centers

mumps

paramyxovirus RNA protection against mumps provided by MMR- not as robust as protection against measles and rubella, cases of mumps seen in vaccinated signs and symptoms- 15-20% are asymptomatic, swollen parotid salivary glands, submaxillary sublingual salivary glands mat be enlarged, fever, headache, muscle aches, loss of appetite, fatigue complications- orchitis, mastitis/oophoritis, encephalitis, meningitis spread- direct contact with secretions, indirect by contaminated items (fomites) contagious- 1-2 days before swelling up to 5 days after swelling apparent lab- lab analyses to detect virus- viral culture RT-PCR to detect RNA, lab to detect immune response- anti mumps IgM, 4-fold rise in IgG, seroconversion IgG from negative to positive

neurosyphilis

paresis, changes in behavior and personality, changes in emotional reactions, psychotic symptoms hyperactive reflexes irregularities in function of pupils gradual degeneration of sensory neurons- affects nerves that help maintain sense of position, direction, standing, vibration, touch commonly found with HIV infections; antibiotic treatment has kept the number of neurosyphilis cases under control

congenital HSV

part of TORCH mother with obvious genital herpes infection deliver by c-section primary herpes during pregnancy increase risk to baby transmission risk low but if transmitted to baby- baby can develop disseminated disease, blisters with red base that burst and crust over, 35% of infected babies have CNS effects, 25% progress to disseminated disease (50% mortality rate, 50% long term developmental defects)

S pyogenes treatment

penicillin V or amoxicillin erythromycin or deviates if allergic to penicillin allergies cephalosporin- some strains resistant to erythromycin and/or its derivatives

HIV prevention

post exposure prophylaxis- pill take to reduce risk of infection by up to 92%, given to sexual assault victims and exposed health care workers

hep B vaccines

rHBsAg produced in yeasts, if allergic to yeast can't receive vaccine, protection long-lived postvaccination test- protective titers developed- 1-2 months after third dose of vaccine, checked if immunity is very important- infants born to HBsAg+ mothers, health care workers at high risk, sex partners of people with hep B, hemodialysis patients, immunocompromised people (HIV,etc) booster doses can be given if low antibody response- hemodialysis patients, immunocompromised people

diagnosis

rapid influenza tests- detects influenza antigens in respiratory specimens not very sensitive, signs/symtpoms with negative rapid test- additional testing using RT-PCR or viral culture with direct immunofluorescence assay

fulminant hepatitis

rare, liver destruction faster than repair, bleeding disorders, encephalopathy, coma, liver transplant

antigenic shift

reassortment in doubly infected cell in which a virion is packed with a segment of RNA from a different virus, creating a new virus

Hep A vaccine

recommended by CDC most are inactivated virus vaccine protection- >14-20 years in children, > 25 years in adults

treatment

reduce itching- oatmeal baths, calamine lotion avoid aspirin- ASA and VZV combo- reye's syndrome is a very severe disease in children affects brain and liver oral- acyclovir, valacyclovir, famciclovir

HIV treatment

reduces the rate of further transmission by 96%, improves health outcomes multi-class combinations of anti-retrovirals are available reverse transcriptase inhibitors- nucleoside, non-nucleoside inhibitors protease activity inhibitors- interfere with cell fusion viral integrase inhibitors- prevents insertion of viral DNA fusion inhibitor entry inhibitor- CCR5 receptor antagonist

german measles

replicates quickly, most commonly occurs in young children (fever, sore throat, followed by rash) adults (similar to children, joint pain)

rickettsial diseases in US

rocky mountain spotted fever- tick, R rickettsii, very serious can be fatal (1% death rate, immediate treatment critical) symptoms- fever, headache, loss of appetite, vomiting, significant muscle/joint pain, rash treat- antibiotics (doxycycline) rickettsialpox (R akari) milder disease typhus- rare, presents after natural or man made disasters, rickettsia prowazekii, rickettsia typhi, high fever, chills, muscle pain, rashes, severe cough, severe headaches, hypotension, confusion, stupor, delirium, antibiotics (doxycycline)

rubella

rubella- 3-day measles german measles- togaviridae family, single stranded RNA

streptozyme test

screening test for antibodies against- streptokinase, streptolysin O, DNAse, NADase, hyaluronidase detects suspect poststrep conditions (rheumatic fever) detects a number of different antibodies at same time classical hemagglutination test- use sheep RBCs coated with different strep antigens current kit uses latex particles coated with the antigens

rheumatic fever

serious sequelae of untreated pharyngitis inflammatory disease, cross-reacting antibodies to bacteria- type II hypersensitivity reaction to self antigens, cross reactive antigens in heart, joints, skin, brain arthritis, endocarditis, CNS symptoms, skin lesions, subcutaneous antibodies to M protein- cross reacts with cardiac myosin, glycogen from muscles, components of smooth muscle cells in arteries causes extensive tissue damage (cardiac vessels, tissue of myocardium) can occur when bacteria no longer present, symptoms appear 2-3 weeks after strep infection acute rheumatic fever- common in children, although adults affected too

mono-diff (davidsohn differential)

serum sickness and forssman antibodies- react with guinea pig kidney, infectious mono antibodies do not serum sickness and infectious mono antibodies react with bovine erythrocyte stroma- forssman antibodies do not mono-diff test- differentially diagnosis patients with infectious mono first circle on the card- mix patients serum with the indicator RBCs, after 3 mins observe agglutination, if cells agglutinate perform next 2 steps next circle- mix patients serum with guinea pig kidney suspension then add indicator RBCs last circle- mix bovine erythrocyte stroma then with indicator RBCs

primary- SCID

severe combined immunodeficiencies- X-linked SCID, adenosine deaminase deficiency (ADA) janus kinase 3 (JAK-3) ZAP70 deficiency (T cell receptor signaling) omenn syndrome

davidsohn differential

sheep RBCs have all 3 antigens- which is why all 3 agglutinate sheep RBCs, paul-bunnell antigen, forssman antigen, serum sickness antigen guinea pig kidney- serum sickness antigen, forssman antigen, forssman antibody or serum sickness antibodies will bind to guinea pig kidney, none is left to agglutinate sheep RBCs bovine erythrocytes contain the infectious mononucleosis antigen, serum sickness antigen

diagnosis and lab testing

signs/ symptoms- EM facial paralysis, arthritis, history of tick bite of exposure to endemic areas diagnosis difficult- not all exhibit EM, symptoms may be other disease- many different inflammatory/autoimmune diseases (SLE, RA, Crohn's disease, MS) suspect- lab testing, confirmatory approach

hepatits C

single-stranded RNA virus spherical and enveloped acute infection 6-7 weeks after exposure- usually asymptomatic new cases reached a peak in 1992- then decrease with implementation of blood supply screening for hep C virus in US hep C and E used to be a non-A non-B hepatitis number of new cases fell until 2003 when a plateau was reached most cases related to IV drug use- other risk factors for hep C- multiple sexual partners during incubation period, surgery with transfusion before 1992, poor tattoo practices, occupational exposure to blood (1.8% transmission after needle stick) maternal-neonatal transmission during birth (4% transmission rate) 6 main genotypes- >50 subgroups, mutant viruses develop with viral multiplication, genetic variability- difficult to eliminate virus, develop vaccine, or to treat as resistant mutants develop

HIV virology

single-stranded retrovirus, infects CD4+ cells- CD4+ T cell, monocytes, macrophages, dendritic cells, microglial brain cells HIV genome- 3 structural genes (gag, pol, env) 6 regulatory genes (tat, rev, nef, vif, var, vpu) 2 types of HIV- HIV-1 more virulent, HIV-2 less virulent (both can result in AIDS) retrovirus- reverse transcriptase viral RNA to DNA gag gene- encodes for gag protein, parts of viral particle, stabilize viral genome pol gene- encodes for a protein, cleaved to enzymes, integrase, reverse transcriptase, and protease integrase- inserts viral DNA into infected cell DNA env gene- encodes for env protein- cleaved, 2 viral envelope components, gp120 gp41 gp120 binds to CD4 on cells regulatory genes- tat gene- up regulates transcription of HIV genes rev protein- regulation of mRNA splicing, nef gene- virulence factor (bypasses killing of virus infected cells)

DiGeorge Syndrome

small deletion of chromosome 22 affects organs and body parts; severity varies- heart defects, neuromuscular problems, palate defects, learning disabilities, aberration in facial expressions childhood infections common dysfunctional or failed development of thymus, defect in development varies- some have very small defects (almost-normal immune response) 1 in 250: complete DiGeorge Syndrome- no T cell function

symptoms and clinical characteristics-early stage (acute phase)

some asymptomatic when first infected, more commonly flu-like symptoms, headaches, sore throat, fever/chills, rash, night sweats, and enlarged lymph nodes, acute HIV syndrome (mistake for other infection lasts 1 week to 1 month) viremia- very high as virus spreads, rapid decrease in # of CD4+ cells

new lyme ELISA

specificity 99% about twice sensitivity of Western Blot in early infection employs peptide (C6) that mimics portion of protein from borrelia burgdorferi

beta-hemolytic group A strep

streptococcus pyogenes most common strep infections- impetigo, pharyngitis, rheumatic fever, scarlet fever, glomerulonephritis, sepsis, pneumonia, meningitis severe- necrotizing fasciitis, death cell wall- proteins- "M protein" Major virulence factor

S pyogenes exotoxin A1 (SpeA1)

superantigen polyclonal activation of different (antigen-specific) T cells superantigen binds to MHC class II (HLA-DQ) components first then to T-cell receptors (TCRs) bypasses antigen-specific presentation- large number of different T cells released (massive response) enormous and detrimental release of cytokines (IL-1, IL-2, TNFa) strong and harmful inflammatory responses- local and systemic, results in rashes, fever, multiple organ failure, death

treatment

symptoms treated, no attempt to decrease viral load (self-resolving disease)

acute hep C

symptoms- general symptoms of hepatitis, 70-80% are asymptomatic, incubation period: 2 weeks- 3 months in some cases 6 months

HIV genotyping

targets gene mutations of viral components, associated with resistance of virus to antiviral drugs

diagnosis for measles

test for measles Ab to determine immune status clinical diagnosis is typically done- characteristic rash and fever, if present ELISA can be used to confirm EIA for antibodies- IgM antibodies= current infection, 4-fold increase in IgG between acute and convalescent viral culture nasal or throat swab PCR- genotyping determines which wild type strain treatment is supportive

hep C molecular techniques

test for viral RNA qualitative- yes or no for viral presence, PCR based quantitative- info about viral load after positive NAT- genotype testing (different genotypes respond differently to treatment) liver biopsy performed- liver cirrhosis will not respond to therapy screen liver cirrhosis for hepatoma (annually)

primary- diagnosis

testing immune functions to diagnose primary immunodeficiencies- drastic reduction in # of T cells- suffusive of a T cell defect, DiGeorge or a SCID, decreased # of B cells and/or a particular antibody or antibodies indicate a deficiency in humoral immunity clinical history of recurrent infections, nature of infection indicates branch of defective immune system antibody deficiencies- antibody responses are evaluated against antigens- diphtheria and tetanus toxoids (measure antibody to toxoid after immunization) other antigens include proteins and polysaccharides (pneumococcal polysaccharide vaccine for T-independent response) maternal antibodies remain for 6-9 months (clinical picture of antibody deficiency occurs after this time) antibody responses evaluated against antigens- if after first immunization Ab not as expected, booster (if booster effective Ab production normal, 4-fold increase in antibody seen in healthy individuals) diagnosis antibody defects- serum protein electrophoresis (SPE)- measure levels of different serum components, based upon the pattern that is observed, further evaluation of specific Ig levels (quantitative nephelometry or enzyme immunoassays) B cell counts- expression of CD19 or 20 Ig- total, isotype specific, specific to particular antigen viral infections of infections by intracellular organisms- T cel function combined infections suggest hematopoietic defect or combined deficiency, medical history, family history

toxic shock syndrome (TSS)

toxic shock-like syndrome (TSLS) streptococcal toxic shock syndrome (STSS)- very serious, potentially fatal, toxins streptococcus pyogenes and staphylococcus aureus signs/symptoms vary and depends on organism- S pyogenes TSS is usually seen in strep skin infections, previously caused by certain tampons, high fever, malaise, hypotension, cognitive problems, stupor, coma, multiple organ failure toxin acts as super antigen- polyclonal activation of many different T cells- massive massive release of cytokines catastrophic organ and system failure requires immediate attention emergency with hospitalization (ICU) treatment- stabilize, vital support, remove source of infection, aggressive antibacterials extreme cases- death in a few hours

C difficile testing

toxinogenic culture- former "gold standard" detects toxins and their effect

enzyme immunoassays for syphilis

treponemal tests- recombinant T palladium antigens- automation of detection better than other methods, high specificity and sensitivity >95% (strip, ELISA plate, microbes, immunochemiluminescent)

secondary syphilis

untreated 25-30% primary cases develop into secondary within 1-6 months most contagious stage, enlarged lymph nodes, fever, weight loss, sore throat, headaches rash- trunk, limbs, palms of hands, soles of feet condymoa latum- wart-like growths on genital areas, lesions contain live organisms (highly infective) more severe rare cases- meningitis, kidney, liver disease, arthritic disease, connective tissue inflammation, especially around bones, inflammation of eyes

flow cytometry

use specific antibodies to a variety of antigens, CD3= T cells, CD19= B cells, CD16= NK cells aberrations in phagocytosis- measure the oxidative ability of phagocyte (NBT test, DHR 13 test) LAD measure expression of CD18 surface marker complement deficiencies- CH50- classical pathway, AH-50- alternative pathway, individual component concentrations flow cytometry- CD3/CD4 for T cell subset= helper T cells, CD3/CD8 for T cell subset= cytotoxic T cells currently available tests described above- used routinely and extensively, sufficient for diagnosis, genetic markers specific for a primary immunodeficiency

treatment

vaccination antiviral treatment- neuraminidase inhibitors- most useful within 48 hours of symptoms- tamiflu, relenza, rapivab

AIDS vaccine

vaccine impediments- HIV infection does elicit immune response, but ineffective in the long run, virus integrates into host genome remains latent for very long periods, rapid mutation of HIV virus- development against a constant viral antigen difficult

Epstein-Barr viral tests

viral capsid antigen (VCA)- IgM appears first, then IgG (lasts a lifetime) IgG to EA occurs in 1 week, disappears quickly, anti-EBNA is slow but lasts a lifetime current infectious mono- positive anti-VCS and negative anti-EBNA, pat infection- positive anti-VCA, and positive anti-EBNA, testing can also be done for EBV DNA

causes

viruses, alcohol, drugs, toxins, autoimmunity

impetigo

young, preschool children "school sores" rare in adults, "bullous impetigo" fluid-filled blister (bullae) yellow crust, not painful may itch, face, lips, legs, arms, trunk, contagious not life-threatening, transmission- direct by nasal carrier or scratch of lesions treatment- local antiseptic, antibiotic ointments, severe- oral antibiotics (dicloxacillin, erythromycin, others) untreated- glomerulonephritis, sepsis, self-limiting rarely

detection of M pneumoniae

"cold agglutinations" autoantibodies from cross-reactive antigens antibodies agglutinate RBCs< body temos not reliable for diagnosis- only 1/2 infected inhibit cold agglutinations, other microbes can also cause cold agglutinations ELISA- most commonly used for IgM and IgG