Mumps encephalitis causes perivenousdemyelinization and perivascular mononuclear cuffing.
Poliovirus Unencapsulated RNA virus of Enterovirus Transmitted by fecal-oral route 3 major strains Infects people but not other animals Briefly shed Do not undergo antigenic variation EFFECTIVELY PREVENTED BY IMMUNIZATION
Special Consideration 1 : 100 infected invades the CNS Due to VIREMIA or RETROGRADE TRANSPORT VIA AXONS TO MOTOR NEURONS Motor Neurons of Spinal Cord SPINAL POLIOMYELITIS Brain Stem BULBAR POLIOMYELITIS
Features: Cause Acute Infection Followed by Latent Infection Viruses persist in a Non-Infectious Form With Periodic Reactivation & Shedding of Infectious Virus Latency defined Inability to recover Infectious particles from cells that harbor the virus
Pathophysiology of Latency Viral DNA remains w/in Nucleus of Sensory Neurons No viral protein are produced Only Latency–Associated viral RNA transcripts are synthesized ( LATS ) Confer Resistance to Apoptosis Contribute to viral persistence in sensory neurons Reactivation may occur in presence of host immunity Virus Developed ways to avoid Immune Recognition
ESCAPE or Elude Immune System DownModulating MHC class I & II molecules Hide from immune system Producing Homologues of TNF receptor, IL-10 and MHC class I receptors Actively Suppress immune response
Cytomegalovirus Usually produce Asymptomatic infxn except Immunocompromised Found in All Secretions include Milk Can carry the usual dormant virus for life Transmission 1. Transplacental 4. Venereal Route 2. Cervical or Birth Canal 5. Organ transplant 3. Breast Milk 6. Blood transfusion 4. Saliva (children-day care)
Diseases: Congenital CMV- acquired in Utero 95% asymptomatic Mother w/ primary infection CID develops Classic cytomegalic inclusion disease CID Similar to erythroblastosisfetalis
Diseases: Perinatal Infections Passage birth canal/breast milk Majority asymptomatic due to ( +) Ig from mother Many continue excrete CMV in urine/saliva x years Pneumonitis Later in life Hearing loss noted CMV- mononucleosis like illness Fever, atypical lymphos, mild hepatitis, Lymphadenopathy CMV in Immunocompromised Disseminated CMV- lungs, GIT, Retina
HBV- Pathogenesis HBV integrate in host genome Cause Hepatic injury is due to immune response not cytopathic effect of virus Cytotoxic T lymphocytes eliminate infected cells Evasion of immune system Inhibiting IFN-beta downregulation of viral gene expression High mutation rate
HBV- Pathogenesis Chronic Infxn 5-10% Adults Up to 90 % Perinatally infected Children Carrier State Occur when CTL response is Dormant
Other Staph species Opportunistic infection Prosthetic valves Catheter D rug addicts Polysaccharide capsule – attach artificial materials UTI in young women Staph epidermidis Staph saprophyticus
Pathogenesis- Staph aureus Clumping Factor Binds fibrinogen, Fibronectin, Use as bridge Adhere host Endothelial cells Enzymes - Lipase Degrade skin lipids Protein A Binds the Fc portion of immunoglobulins – Escape Ab-mediated killing
Pathogenesis- Staph aureus Superantigens Stimulate 2 0 % of Lymphos Release of large amounts of TNF, IL-1 Septic Shock Toxins –Damage host cell Membrane damaging toxins
Strep Pharingitis Epiglottal swelling & abscess Cervical LN Strep Pyogenes Major antecedent of PoststrepGlomerulonephritis Ag-Ab complex deposit in glomerulus Poststrep Rheumatic fever Antistreptococcal M protein antibodies & T cells that cross react with cardiac myosin
Strep pyogenes:VirulenceFactors Capsules M proteins – prevents phagocytosis C5a peptidase – Degrade chemotactic C5 Antistreptococcal M protein – Ab that cross react w/ cardiac Myosin ( RHD)
Other Streptococcal Infection Strep. Pneumoniae Common cause of CAP & Adult Meningitis Lobar Pneumonia Otitis media, Sinusitis Often preceded by viral infection that injure ciliated epithelium Has capsule- prevent phagocytosis Pneumolysin Inserts on target cell membrane Lysis Activates Classical pathway Reducing complement available for Opsinization
Neisseria gonorrhea Surface pili that form barrier against phagocytosis Encapsulated gm(-) diplococci STI – Men - Urethritis, Pharyngitis, Proctitis Urethral strictures, chronic infection of Male genitals STI – Women - Salpingitis Tubo-ovarian abscess Scar Sterility or Ectopic pregnancy Perinatal Ophthalmic infxn
Neisseria - Evasion of immune response Use antigenic variation of OPA proteins to escape immune response A single clone of bacteria several multiple antigenic types Pili Protein are altered by genetic recombination
Whooping cough Gram (-) coccobacilli Acute highly communicable Paroxysm of violent cough followed by loud inspiratory whoop Colonizes the brush border of bronchial epithelium Laryngotracheobronchitis Virulence is regulated by BVG locus
Virulence factor :Regulated by Bordetella virulence gene locus (bvg) PertusisExotoxins paralyze cilia
Pseudomonas Infection Opportunistic gram-negative bacterium Frequent, deadly pathogen of patients with cystic fibrosis, severe burns, or neutropenia. Coregulatedpili Adherence proteins that mediate adherence to epithelial cells and lung mucin Endotoxinthat causes the symptoms and signs of gram-negative sepsis.
Syphilis- Treponemapallidum Sexual intercourse is the usual mode of transmission Transplacental transmission of T. pallidum occurs readily, & active disease during pregnancy results in congenital syphilis.
Clostridial Infections Clostridium species are gram-positive bacilli There are four types of Clostridium that cause human disease: 1.Clostridium perfringens (welchii), septicum 2.Clostridium tetani 3.Clostridium botulinum 4.Costridium difficile
Clostridium perfringens (welchii) Anaerobic cellulitis – foul , thin discolored exudate, quick tissue destruction ( versus pyogenic ) Myonecrosis (gas gangrene)- 1to 3 days after infection Invade traumatic and surgical wounds Contaminate illegal abortions Cause uterine myonecrosis, Cause mild food poisoning, Infect the small bowel of ischemic or neutropenic patients to produce severe sepsis.
Clostridium tetani Proliferates in: puncture wounds umbilical stump of newborn infants Releases a potent neurotoxin, called tetanospasmin causes convulsive contractions of skeletal muscles (lockjaw).
Clostridium botulinum Grows in inadequately sterilized canned foods Releases a potent neurotoxin that blocks synaptic release of acetylcholine Causes a severe paralysis of respiratory and skeletal muscles (botulism).
Clostridium difficile Overgrows other intestinal flora in antibiotic-treated patients Releases multiple toxin Causes pseudomembranous colitis
Clostridium Botulinum- Neurotoxin Are released when the organisms die and autolyse Act at the peripheral nerve endings, Cleaving either synaptobrevin (as described for tetanus toxin) or synapse-associated proteins, called SNAP-25 and syntaxin.
Unable to release acetylcholine at the neuromuscular junction and at the synaptic ganglia and parasympathetic motor end-plates of the autonomic nervous system Descending paralysis from the cranial nerves down to the extremities.
Clostridium difficile Produces toxin A Which is an enterotoxin a potent chemoattractant for granulocytes toxin B a cytotoxin, which causes distinctive cytopathic effects in cultured cells and is used in the diagnosis of C. difficile infections
Obligate Intracellular Bacteria Chlamydia trachomatis is an obligate intracellular pathogen Venereal urethritis, lymphogranulomavenereum, and trachoma Lymphogranulomavenereum results in granulomatous inflammation of the inguinal and rectal lymph nodes. Trachoma or chronic keratoconjunctivitis, a leading global cause of blindness, is a disease of poverty and overcrowding, transmitted from eye to eye by aerosols or by hand contact.
Malaria Intracellular protozoan parasite Plasmodium falciparum is a worldwide infection that affects 100 million and kills 1 to 1.5 million persons per year and so is the major parasitic cause of death. Other types (P. vivax, P. ovale, P. malariae) Transmitted by more than a dozen species of Anopheles mosquitoes widely distributed throughout Africa, Asia, and Latin America.
Malaria P. vivax and P. malariae mild anemia in rare instances, splenic rupture and nephrotic syndrome. Acute P. falciparum infections produce high parasitemias, severe anemia, cerebral symptoms, renal failure, pulmonary edema, and death.
Features of P. falciparum Infect rbc of all ages Versus young rbc for other species High parasite burden Profound Anemia Infected rbc clump together Stick to Endothelial lining of small blood vessels ( Sequestration ) Block blood flow Form KNOBs on rbc surface (PfEMP 1) Plasmodium falc. Eryhtrocytememb protein Bind Ligands on blood vessel wall Cause poor perfusion to the brain ( Cerebral malaria )
Features of P. falciparum Stimulates production of HIGH levels of Cytokines Induce fever Suppress rbc production NO prodn Tissue damage Induce expression of endothelial receptors for PfEMP 1 Increasing sequestration
Morphology P. falciparum initially Splenic congestion and enlargement of the spleen Infected rbc taken byreticuloendothelial cells. The liver becomes progressively enlarged and pigmented with progression of malaria. Kidneys often enlarged and congested pigment in the glomeruli and hemoglobin casts in the tubules.
Addendum Sporozoites – Infectious stage During feeding SporozoitesReleased in blood w/in minutes Bind to and invade liver cells by binding to the hepatocyte receptor for the serum proteins thrombospondin and properdin, located on the basolateral surface of hepatocytes The binding is accomplished because of the presence of sporozoite surface proteins that contain a domain homologous to the binding domain of thrombospondin. Within liver cells, malaria parasites multiply rapidly, so as many as 30,000 merozoites (asexual, haploid blood forms) Merozoites released when the hepatocyte ruptures
Addendum Merozoites bind by a parasite lectin-like molecule to sialic residues on glycophorin molecules on the surface of red blood cells. Merozoitesrelease multiple proteases from a special organelle called the rhoptry. Within the red blood cells, the parasites multiply in a membrane-bound digestive vacuole, Hydrolyzing hemoglobin through secreted enzymes that include an aspartate protease Most malaria parasites rupture the cell infect new red blood cells Some parasites sexual forms called gametocytes infect the mosquito when it takes its blood meal.
Addendum Maturation change morphologic from ring to schizont form secrete proteins that form 100-nm bumps on the red blood cell surface, called knobs called sequestrins Sequestrins bind to endothelial cells by ICAM-1, the thrombospondin receptor, and the glycophorin CD46 cause malaria-infected red blood cells to be removed from circulation Red blood cells containing immature ring forms of the parasite flexible pass through the spleen, circulate in the blood Red blood cells containing mature schizonts, rigid sequestration in the spleen.
Schistosoma S. mansoni / japonicum eggs liver disease. 1. Substances released from schistosome eggs Are directly hepatotoxic, 2. Carbohydrate antigens from eggs induce Granuloma formation mediated by TNF and TH 1 and TH 2 helper cells. TH 2 helper T cells secrete IL-4 Induce IgE synthesis eosinophilia, mastocytosis, and high levels of serum IgE in human schistosomiasis Resistance to reinfection by schistosomes after treatment correlates with IgE levels Whereas eosinophil major basic protein may destroy larval schistosomula
3. Eggs release factors that stimulate lymphocytes secrete a fibrogeniclymphokine Stimulates fibroblast proliferation and portal fibrosis. This exuberant periportal fibrosis, which is out of proportion to the injury caused by the eggs and granulomas, Pipestem Fibrosis Occurs in 5% - 10% of persons heavuly infected with schistosomes Hallmarks of severe schistosomiasis: Portal hypertension Esophageal varices, Ascites
S. haematobium infection, Bladder inflammatory patches due to massive egg deposition and granulomas cause hematuria The most frequent complication is inflammation and fibrosis of the ureteral walls leading to obstruction, hydronephrosis, and chronic pyelonephritis.