Exam Flashcards
What is anthrax?
An infectious disease that comes from ingestion of Bacillus anthracis endospores. This bacteria is gram pos and can survive for ages.
Exposure routes of anthrax:
Cutaneous- enters through cuts or abrasions. Will begin as a red spot, oedema will begin and dark spot will form.
Pulmonary- Woolsorters’ disease occurs by inhalation. Faster progression and death. Lesions occur in lymph nodes. Almost always fatal.
Intestinal- ingestion by eating infected meat or food
Injection anthrax- injecting spores accidentally, similar to cutaneous anthrax
Anthrax pathogenesis and molecular basis:
Pathogenesis: spores will enter and resist phagocytosis. Inside the cell, germination begins and the bacteria will form a capsule to prevent engulfment. Exotoxin will be produced
Molecular basis: expression of two virulence plasmids, pXO1 and pXO2. pXO2 encodes proteins for the capsule and pXO1 encodes 3 proteins for anthrax toxin- protective antigen, lethal factor and oedema factor
How is anthrax diagnosed and treated?
Bacteria will be isolated from blood or wounds and detected by nucleic acid test or gram stain.
Can be treated with antibiotics or drugs like Adefovir or Raxibacumab.
Bacteria features?
Single cell prokaryotes that have cell membrane and wall but no membrane bound organelles. Have circular chromosome and divide by binary fission.
How bacteria divide by binary fission:
Chromosome is duplicated, cell grows and chromosomes will separate. Cell will divide.
Which type of bacteria form endospores?
Gram positive
Types of gene transfer between bacteria and result
Antibiotic resistance could occur.
- Conjugation: transfer of genetic material by pili through a mating bridge.
- Transformation: foreign DNA inserts into host DNA from environment
- Transduction: genes from host insert into virus and are carried to another host
What are the features of a virus?
A subcellular particle that can’t multiply outside a host. Has a nucleic acid in a protein capsid that can be surrounded by a lipid bilayers.
Steps of viral infection and replication
- The outer part of the viral particle makes first contact with host cell membrane, attaches to a receptor.
- Virus will enter the cell.
- Genetic material is released into cytoplasm.
- Replication is done by using host enzymes.
- New viral particles are assembled.
- Viral particles are released. This can happen by budding off from the host cell membrane. Enveloped virus must leave the cell via budding.
Replication of positive and negative strand RNA viruses:
- A positive strand RNA virus has single stranded RNA with the same orientation as its mRNA, so the RNA can be directly translated through a ribosome.
- A negative strand RNA virus has single stranded RNA that is complementary to its mRNA and needs to be transcribed before entering a ribosome. Requires an RNA polymerase.
Features of fungi:
Eukaryotes with a chitin cell wall that cause opportunistic infections that can become systemic.
Types of fungal infections
- Superficial- grows on body
- Systemic- internal organs
- Subcutaneous- in nails or skin
- Cutaneous- epidermis, hair
- Opportunistic- internal organs
Define a parasite
Organism that lives in or on a host at their expense. Can be unicellular or multicellular
Define definitive and intermediate hosts
Definitive- harbors adult parasite. Hosts can be humans or animals. Mosquitoes are definitive hosts for malaria.
Intermediate- harbors larval form. Hosts can be insects like flies, mosquitoes, ticks. Molluscs can carry schistomiasis. In malaria, humans are the intermediate hosts
All about protozoa:
Single celled eukaryotes that can cause malaria, giardia, worms or toxoplasma. They have unique surface antigens at each stage of their life cycle (African Sleeping Sickness that mutates after immune system has attacked).
What are prions?
Host-derived glycoproteins that cannot be cultured, are incurable and resistant to disinfection. Can have a sporadic, genetic or acquired cause.
How do prions work?
We have normal proteins that express prion proteins. Coming into contact with an infectious prion protein can trigger conversion of normal protein into infectious protein. There is a snowball effect, plaques of protein form and become internalised in cells.
They do not trigger an immune response as they are protein.
Pros and cons of normal flora?
Prevents pathogenic species growth, helps develop immune system but there is potential to spread into sterile body parts when immunocompromised.
What are the different symbiotic associations?
- Commensalism- one organism benefits, no harm to host. Bacteroides in the large intestine ferment digested food
- Parasitism- one benefits at the others expense. Large intestine, entamoeba histolytica will feed on mucosa causing ulcers.
- Mutualism- both benefit. Rumen of cattle, bacteria will metabolise food to fatty acids and gases which can be used for energy.
Evidence of mitochondria evolution?
Eukaryote cells still have endosymbiotic bacteria. Mitochondria ribosomes are like prokaryotes. Mitochondria control their own division and have similar gene expression to prokaryotes. Antibiotics that affect ribosome bacteria also affects mitochondria ribosomes
Describe how lifestyle changes can affect host-parasite relationships
Altered environments like using air conditioning, food handling and production practices changing, routine use of antibiotics, use of immunosuppressive therapy (opportunistic infection), altered sexual habits, increased ownership of pets, increased journey to tropical countries.
What is in the innate system?
A nonspecific defense system. Has lysozymes, complement proteins, interferons, cytokines, phagocytes, granulocytes, natural killer cells.eosinophils
What is in the adaptive immune system?
Is targeted to deliver a specific response. Has a ‘memory’ of pathogens, making it effective upon reinfection. Utilises antibodies, cytokines, T (cytotoxic, helper etc.)and B (memory and plasma) lymphocytes.
Distinguish between the three lines of defence against pathogens?
- First line- non specific barriers like skin and stomach acid
- Innate- non specific pathogen killing
3.Adaptive- specific pathogen killing
Define macrophages
Macrophages are phagocytes begin as promonocytes in bone marrow and become monocytes in the circulation. Become mature in tissues and form the mononuclear phagocyte system. Live for a long time. Destroy and recognise pathogens, release cytokines and complement components. Have mitochondria.
Understand neutrophils:
Phagocytes that are the first to respond to pathogens, have no mitochondria and secrete cytokines
How phagocytes work?
Phagocytes will recognise pathogen associated molecular patterns (PAMPs) by their pattern recognition receptors (PRRs) and become activated, will phagocytose. PRR can be in a cell membrane or soluble in blood, extracellular fluid. Major PRR are the toll-like receptors (TLRs). When internalised, the microbe is a target for killing mechanisms and will be killed by degradation mechanisms.
How does the complement system work?
Alternate complement pathway = innate pathway.
C3 protein breakdown will be stabilised by C3 convertase if a microbe is detected and interacts with properdin. Part of C3 when broken down (C3b) will combine with factor B to make C3bBb. When a microbe is present, this complex stabilises C3. This is a positive feedback loop. C3b will activate phagocytes to destroy the bacteria. C3a will act as a signaling molecule acting as a chemotactic factor and increasing permeability.
The c5a and C3a complex will activate mast cells which will release histamine to increase vascular permeability. Macrophages will release cytokines to increase vascular permeability and create adhesion molecules that help neutrophils move into tissue.
What are acute phase proteins?
Soluble factors in blood or tissue that alarm to infection or injury. Mannose binding lectin that will bind to cAMP and C-reactive protein are examples of acute phase proteins. These will attract complement
How does the membrane attack complex work?
In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a ‘multi-hit’ mechanism; however, sub lytic MAC pores on host cells activate signaling pathways
How do B and T cells work?
B cells become plasma cells or memory cells. T cells can become T helper cells or cytotoxic T cells. B cells mature in bone marrow and T cells mature in the thymus- these are primary lymphoid organs. In secondary lymphoid tissues like lymph nodes or the spleen, immune responses are activated. The cells can circulate in the blood through lymphatic vessels and enter blood through thoracic duct. Memory cells are responsible for the results of vaccination (preventing illness and severe illness).
The functions of different T cells?
- T helper cells (CD4+) ensure optimal responses by other lymphocytes
- Cytotoxic T cells kill pathogens by releasing cytotoxic granules
- Th1 helps kill intracellular pathogens, produce interferons that will stimulate NK cells. Stimulate production of more interferon gamma to enhance the macrophage for killing.
- Th2 helps kill extracellular parasites, encourages immunoglobulins, mucous secretion, eosinophils. Secretes proinflammatory cytokines
- Th17 assists extracellular immune response and works against fungi
- Treg secretes anti inflammatory cytokines and regulates the immune system.
What is MHC function?
MHC (major histocompatibility complex) is often referred to as HLA . This complex interacts with T cells→ MHC class I can be found on any nucleated cell while class II are found on antigen presenting cells like dendritic cells, macrophages, B cells. The function is to bind peptide fragments from pathogens and display them on the cell surface for recognition by T cells.
Distinguish humoral and cell mediated immunity
Humoral targets extracellular
Cell-mediated targets intracellular
What is antigen specificity?
Specificity of B and T cells is from receptors which have unique specificity by rearranging DNA in germline cells.
Variable region, diversity region and joining region in B cell DNA all contribute one ‘minigene’, resulting in the differently specific variable regions in the heavy chain. The light chain also has a variable segment. B cells can also add more nucleotides which will change the reading frame and can undergo somatic hypermutations which results in mutation forming easily
T cells generate diversity in a similar way but cannot add nucleotides, don’t secrete TCRs, do not change their constant region (don’t class switch) and don’t have somatic hypermutation.
T cells generate unique receptors in the thymus, which positively selects for T cell receptors that recognise MHC (HLA) complexes and destroys those that react to MHC (HLA) and autoantigens by negative selection
What is clonal expansion?
A small number of precursor cells that recognize a specific antigen proliferate into expanded clones, differentiate and become effector and memory cells, which promote effective immune responses. This happens in secondary lymphoid organs.
How are antibodies produced with and without T cells?
B cells can pick up antigens and be co-stimulated by a T helper cell.
An APC will pick up an antigen and present it to a T helper cell which has a receptor for the pathogen. The B cell will also be stimulated by the primed T cell, triggering clonal expansion of the B cell. There can be antibody production without T cells, but they make the process more effective.
Polyclonal activators can work to stimulate B cells to produce antibodies but they are non specific. Superantigens can also non specifically activate B and T cells, causing a cytokine storm.
How do microbes overcome host defences?
- evolving VERY fast
- antibiotic resistance genes
- exploiting weak points of host defence
- host improves defences at a slow rate
What are the 4 types of microbial infection?
- microbial attachment or penetration mechanism
- entry through biting of arthropod
- skin wound or animal bite
- impaired antimicrobial defenses
What are Koch’s postulates?
- suspected agent must be absent from healthy animals
- agent must be isolated from diseased organism and cultured
- cultured agent must cause same disease in a healthy organism
- same agent must be isolated from the new diseased organism
What does transmission primarily rely on?
Number of microbes.
Describe the innate response:
- Complement activation
- C-reactive protein is produced by liver cells in response to cytokines, will pull macrophages to an infection
- Macrophages recognise bacteria (PAMPS) through toll like receptors (TLRs)
- NK cells control viral and intracellular infection
- Phagocytes (neutrophils and macrophages) engulf, kill and digest through oxidative and non oxidative mechanisms. Neutrophils can trap bacteria through ‘NETS’ (neutrophil extracellular trap) or kill by phagocytosis.
- Cytokines like interferons activate macrophages and induce killing of bacteria. NK cells are a source of interferons until T cells take over.
How does oxidative killing happen in phagocytosis?
Phagosome will have an enzyme NADPH oxidase that reduces oxygen to a superoxide, creating free radicals that will damage lipids and protein of the pathogen cell wall. Lysosomes and peroxisomes can also fuse and bring more enzymes that will oxidize and create more free radicals
How does non oxygen dependent phagocytosis happen?
Proteases, lipases will attack lipids in the bacteria.
What are the three types of interferon and how do they function?
Interferons are antimicrobial cytokines. There is gamma, alpha and beta.
Alpha and beta are secreted by infected cells, alerting that there is an infection and increasing MHC class 1 complexes on the cell surface with the viral antigen. MHC class 1 alert cytotoxic T cells and MHC class 2 present to CD4 T helper cells which will secrete interferon gamma, increases activity of NK cells and encourages surrounding cells to switch off genes for viral replication. IFN switches on genes, triggering production of enzymes that will degrade viral mRNA and switch on genes for protein kinases and phosphates, inactivating EIF 2, involved in protein synthesis. Stops protein synthesis.
How do the complement system, cytotoxic T cells and NK cells have lytic mechanism?
Complement has membrane attack complex form pore in membrane while T and NK cells secrete granules with perforin to form pores
How do microbes spread to CNS?
They cross the blood brain barrier by entering peripheral nerves and traveling up axons
How do microbes evade innate defences?
Interfere with cilia, complement alternative pathway and can block interferons, capsule to prevent phagocytosis, phagocyte killed by toxin
How do microbes conceal antigens?
Colonising privileged sites that have little immune responses. Outer noncellular material like in cysts won’t cause an immune response. ‘Molecular mimicry’ by microbes in which its antigen is similar to an antigen already in the body. Ability to produce Fc receptors which will bind the constant part of antibodies - this is useless
What is antigenic variation?
- antigens change after an immune response is built up for one antigen. Variation can occur by mutation (drift) and recombination (shift)
Influenza has major change in surface antigen from recombination.
All about bacterial toxins:
damage cells and alter metabolic machinery. Some toxins block protein synthesis, others cause water loss and diarrhea, others affect nerve impulses
- Hemolysins produce alpha toxin, damaging phospholipids and hence the plasma membrane. Other alpha toxin can form pores in cell membranes.
- Diphtheria toxin have an AB structure. B=binding to cell, A=active part. This toxin prevents normal functioning, knocking out protein synthesis. Cholera has the same structure, converts ATP to cyclic ATP and causes salt and water pumps in membrane to work overtime, causing diarrhea.
- Tetanus toxin inhibits release of inhibitory transmitters, resulting in constant stimulation of muscles. Botox toxin blocks muscle stimulation
Benefit of diarrhea for host and microbe?
- host can rapidly get rid of microbe
- microbe can spread to other hosts
What happens in the different types of hypersensitivity?
I- sensitisation of mast cells causing allergic reaction, minutes. IgE antibodies activated when antigen is presented
II- antibodies directed against particular cells, hours. Example is hemolytic disease in newborns when baby and mother are rhesus positive and rhesus negative. Mother’s antibodies can attack newborn.
III- immune complexes cause disease when lodged in tissue or blood vessel, hours. Example is the Arthus reaction in which antigen and antibody form immune complexes which end up in vascular system triggering clotting, activating immune cells that will destroy tissue. Serum sickness is caused by similar mechanism.
IV- T cell immune response can cause tissue destruction, days. T cells exposed to antigen, and the second time around macrophages become activated by t cells. Granuloma in tuberculosis is another example. SARS coronavirus causes damage in alveoli and cause loss of CD4 and CD8 cells, also causes massive activation of macrophages.
Hypotheses of allergy?
- Hygiene hypothesis- improved hygiene are positively associated with allergies
- Old friends hypothesis- early life exposure to pathogens develops immune system from T helper 2 dominated response to a more defensive T helper 1 response
- Microbiota hypothesis- microbiome helps develop a tolerogenic immune status, lower diversity in microbiome causes allergy
Examples of cancer causing virus?
- DNA and RNA viruses can cause cancer
- Human T cell lymphotropic virus type 1 is associated with adult T cell leukemia
- EBV associated with nasopharyngeal carcinoma and also Burkitt’s lymphoma
- HPV associated with cervical cancer and skin carcinoma
- Hep B and C cause hepatocellular carcinoma. Infected cells cause chronic inflammation and damage
- Kaposi’s sarcoma causes by human herpes virus 8. Can have direct on cell causing uncontrolled cell division. Growth factor and growth factor receptors become upregulated.
Examples of upper and lower respiratory tract infection?
Upper tract infection= common cold, sore throats, infectious mononucleosis, mumps
Lower = laryngitis and tracheitis, diphtheria, pneumonia, influenza, tuberculosis
What are the defensive structures of the respiratory system?
- Macrophages protect alveoli
- Lower respiratory tract is sterile
- Mucociliary system
- Flushing action of saliva
- Lysozymes
- Surfactant
- Antimicrobial peptides
- MALT
Symptoms of upper tract infection?
- rhinorrhea (runny nose, cough sore throat)
- fever, sneezing, hoarseness
- breathing difficulty
- lethargy
Rhinovirus and coronavirus.
- > 50% of colds, transmission by droplets,aerosol or virus contaminated hands. Symptoms like runny nose or cough, fever, sneezing.
Pathogenesis of common cold: viral surface molecules bind and attach to host cells, cilia or microvilli, spreading to neighbor cells and new sites by surface secretions. Epithelial damage and secretion of fluid with inflammatory mediators cause symptoms of cold.
Diagnosis typically only important for lower respiratory infections. Might do a PCR or use clinical appearance.
No vaccine is available. Symptomatic treatment
Pharyngitis and tonsillitis.
- 70% of sore throats caused by viruses.
Throat is sore when overlying mucosa is infected or because of inflammatory immune responses. Bacteria cause pharyngitis.
Lab diagnosis not necessary for these.
Infectious mononucleosis.
- Tonsils and uvula become swollen and petechiae form. Fever, sore throat, anorexia and lethargy are symptoms.
Diagnosed by detection of viral capsid Ag IgM , atypical lymphocytes in blood smear, EBV DNA found in PCR.
Treatment is symptomatic.
Parotitis (mumps)
single stranded RNA paramyxovirus that is spread by air borne droplets. Causes abnormal or foul tastes, less ability to open mouth, fever, pain, redness and swelling. Diagnosis done by virus isolation in cell culture or viral RNA detection, or detection of mumps specific antibody. Vaccine available. Treatment symptomatic.
Laryngitis and tracheitis.
may follow upper tract infection, caused by parainfluenza viruses primarily and Staphylococcus aureus. Tracheitis is a bacterial infection of trachea and can obstruct the airway especially in young children.
Diphtheria
caused by toxin producing strains of Corynebacterium diphtheriae. Can cause respiratory obstruction, while the toxin can cause heart failure and polyneuritis. Treated immediately with antitoxin and antibiotic. Vaccine available. Toxin has two fragments (A and B) which A fragment will inhibit protein synthesis in the host cell, causing it to die.
Pneumonia
-microbes reach lungs by inhalation or blood.
Bacterial pneumonia cause is typically Streptococcus pneumoniae but there are other bacteria. Viral pneumonia is caused through lung invasion that can damage respiratory defenses.
Pneumonia is caused by attachment to the respiratory epithelium.
Patients have fever, chest pain, shortness of breath. Sputum is collected before contamination occurs at breakfast and is gram stained. Atypical pneumonia confirmed by serology.
Treatment uses antimicrobial therapy.
Community acquired pneumonia has pathogens arrive in alveolar space and multiply. Macrophages will produce cytokines and recruit neutrophils to alveolar space. Inflammation response will occur and cytokines will be released into bloodstream.
Four types of pneumonia:
- Lobar- involves specific region of lung. Polymorph exudate formed in response to the infection clots in alveoli and makes them solid.
-Bronchopneumonia- can spread in lung.
-Interstitial- invasion of lung interstitium, characteristic of viral infection
-Lung abscess- destruction of lung parenchyma.
Influenza
three types- A,B,C. Changes as it spreads through host species (antigenic drift or shift). Has hemagglutinin and neuraminidase spikes.
Transmission by droplet inhalation.
Damage to respiratory epithelium and causes secondary bacterial infection.
NAAT diagnosis. Vaccine available and antiviral agents can prevent.
Tuberculosis
Disease of the lungs that is transmitted by aerosol droplets through coughing sneezing or speaking.
Primary tuberculosis is often asymptomatic. Secondary is reactivation of dormant bacteria due to impaired immune function.
Spread to lymph or blood is the concern. Granuloma formation can occur when macrophages surround and try to engulf an infected macrophage but they become infected themselves. Chemoprophylaxis is important for prevention
Need to treat with Isoniazid, Rifampin (Rifadin, Rimactane), Ethambutol (Myambutol), Pyrazinamide. Diagnosed by microscope examination of acid-fast rods and culture of Mycobacterium tuberculosis. X rays can diagnose too
Function of hemagglutinin and neuraminidase?
Hemagglutinin: bind to host cell and fuse the viral envelope to the cells plasma membrane to cause infection
Neuraminidase: releases virus from cell surface.
Antibodies against hemagglutinin are more effective than against neuraminidase. Structure of H changing makes antibodies previously made ineffective.
Symptoms of UTI?
- subjective - pain, distress, nausea, fatigue, cough, fever
- Acute lower - dysuria (pain when urinating), urgency to pass urine, frequency of micturition (urination)
- Recurrent infections occur to relapses or infection by different organism
- Acute bacterial prostatitis- fever and low back pain (systemic symptom), dysuria, frequency
- Pyelonephritis (kidney infection) causes fever and lower urinary tract symptoms. More severe
UTI- Cause, transmission, pathogenesis, diagnosis and treatment
A bacterial infection (commonly e.coli, a gram negative rod) from urethra to bladder. Viral and parasite causes too. In hospital settings, Staphylococcus and enterococcus.
Pathogenesis: mechanical factors, obstruction to complete bladder emptying, catheterization (runs risk of introducing bacteria to bladder) can play factor in UTI.
Virulence factors for uropathogenic E.coli (UPEC) = PAP pili for adhesion and attachment, capsular acid polysaccharide antigens helps avoid phagocytosis, antigens, and hemolysin production that causes damage.
- Catheter use: must use aseptic technique so that bacteria cannot enter urethra and is not pushed in. Urine samples in the patient are taken from hose instead of bag as bacteria will collect there.
Diagnosis: detection of bacteria through a midstream urine sample or microscopic examination. Special urine samples needed to detect M tuberculosis and Schistosoma. Can use a culture, though the significance depends on collection, storage, antibiotic treatments taken by patient, fluid intake and the specimen.
Treat: oral antibacterial and drink water, systemic antibacterial agent for a complicated UTI (kidney infection)
Prevent: regularly empty bladder, prophylactic antibiotic use could work but not recommended due to resistance, good catheter care (avoid if possible, use intermittently if possible, use good aseptic technique, maintain gravity drain)
Symptoms of STI’s- gonorrhea, chlamydia, HPV, HIV
Gonorrhea
- skin lesions that begin as papules and can become pustular
- septic arthritis of ankle with erythema
- dysuria
Chlamydia
- inflammatory response
HPV
- genital warts
- associated with cervical cancer as it integrates into the genome and other genital cancers
- cervical lesions visible by colposcopy must be removed
HIV- human immunodeficiency virus
- mild mononucleosis type illness on primary infection
- untreated: acute immune response like mononucleosis or CNS illness like meningitis. A latency period before a chronic illness stage with weight loss, fever
Gonnorhea
STI of epithelium and manifests as cervicitis, urethritis, proctitis, conjunctivitis. Initially asymptomatic. Can cause infertility if untreated.
- Caused by Neisseria gonorrhoeae, a gram negative coccus.
- Spread due to virulence factors: pili that help attachment to epithelium, por proteins that form pores in outer membrane, opa protein that assist binding, LOS endotoxin, Rmp protein, IgA protease and the capsule to resist phagocytosis.
- Pathogenesis Immune response: Gonococci interact with epithelial cells inducing cytokine, chemokine production. Some invade subepithelial space where macrophages dendritic cells and neutrophils will be encountered.
- Diagnosis from microscopy and culture from urethra and vaginal discharge. rapid test available but not as reliable.
- Treated by antibacterial ceftriaxone and fluoroquinolones
Chlamydia
- Caused by Chlamydia trachomatis, a gram negative bacteria that enters host through small abrasions in mucosal surface and enter cells by endocytosis after they bind to receptors.
- Pathogenesis: inside the cell, fusion of chlamydia containing vesicle with lysosome is inhibited, and it will begin to develop and become metabolically active, dividing by binary fission and releasing contents to extracellular environment.
- Immune response:
1. infection causes production of pro inflammatory cytokines that increase expression of endothelial adhesion molecules. Macrophages contribute to cytokine release
2. Neutrophils, NK cells and monocytes are recruited. MMPs
3. Nk cells, interferons, antibody production, tissue becomes damaged
4. when infection resolves inflammation goes down but scarring of tissue can result - Diagnosed by cell cultures. Iodine will stain inclusion bodies brown. Can use fluorescent microscopy.
- Treated by doxycycline or tetracycline
HPV
Caused by human papillomavirus that is not enveloped, has icosahedral capsids and have a double strand DNA.
Transmission: sex
- Pathogenesis: Enters skin cells by microabrasions, cells are infected, replicates.
Basal cells are infected, viral DNA replicates and is transcribed, virions are assembled in nucleus and released when cells are shed.
- Treatment: HPV vaccines reduce infection
HIV
- A single stranded RNA retrovirus that causes AIDS. Infects cells with CD4 surface antigen and requires chemokine co receptors (CCR5).
- Cells killed by virus and made vulnerable to immune attack by Tc cells. Defects in antigen presentation as dendritic cells become infected.
- Enters cell by fusion with cell membrane at cell surface or by uptake into vacuole and release in the cell. Has glycoprotein (gp120) that is important for its attachment. Can be taken into cells by penetration or vacuole. Integrates to host DNA
- Transmitted by unprotected sex, drug addicts, blood transfusion, pregnancy and non sterile instruments. Homosexual and bisexual males most at risk.
- Lab tests involve Ag, Ab and genome detection.
- Antiretroviral therapy improves disease diagnosis. Latency can be established. Prophylactic measures can be taken by taking PrEP
How do hospital infections occur and how do we prevent them?
Hospital acquired (nosocomial) infection is acquired in hospital 48 hr after admission or discharge. Can happen from another patient or the environment (exogenous) or a self/autoinfection (endogenous).
Common: surgical wound infection, respiratory tract infection, UTI- most common, bacteremia.
Causes: Staphylococci and E.coli most common. antibiotic resistant gram positive organisms, drug resistant gram negative organism
Sources and spread: humans, environmental. Could be air borne, droplets, direct contact.
Prevention:
- excluding infection sources from hospital- sterile instrument
- interrupting transmission of infection from source to host- control air borne transmission, aseptic technique
- enhancing the ability to resist infection by the host- passive immunisation, prophylactic antibiotic, care of invasive devices
Symptoms of gastrointestinal tract infections?
**Gastroenteritis: symptoms that include abdominal pain, nausea, vomiting, diarrhea
**Diarrhea: abnormal frequent fluid fecal discharge
**Dysentery: inflammatory disorder of GI tract, blood and pus in feces with pain and fever
**Enterocolitis: inflammation of mucosa in small and large intestine
**Helicobacter pylori and gastric ulcer disease: a gram negative spiral bacterium that is associated with duodenal and gastric ulcers, pain in upper abdomen
**Parasites and gastrointestinal tract: acute or chronic diarrhea, inflammation, disease caused by spread of parasite to other organs
**Systemic infection initiated in GI tract (hep A,B,C):damage to liver
- Worm: chronic mild intestinal discomfort, intestinal obstruction from large numbers of Ascaris, Trichuris can cause chronic diarrhea, hookworm can cause iron deficiency anaemia as well as dermatitis
- **Hepatitis: Inflammation and damage to liver. Can be asymptomatic or symptomatic with malaise, anorexia, nausea, abdominal pain, liver failure, jaundice (yellow tinge of skin as liver cannot transport bilirubin into the bile, causing increased levels in fluids.
Defensive mechanisms of intestinal tract?
- mouth uses saliva, lysozyme
- esophagus uses flow of liquid
- stomach has acidic pH
- small intestine has peristalsis, flow of gut contents, mucus, lymphoid tissue, normal flora
- large intestine has peristalsis, normal flora, mucus
Diarrhea
- Happens in non infectious conditions. Bacteria produce toxins that activate adenylate cyclase in crypt enterocytes, causing elevated cAMP and chloride channels becoming stuck open. Water will be secreted massively resulting in diarrhea. Most common outcome of GI tract infection
Causes- e.coli which has six different groups. (EPEC, ETEC, EHEC, EIEC, EAEC, DAEC). E= entero, T=toxigenic, H=hemorrhagic, A=aggregative, P=pathogenic, D=diffue-aggregative, I=invasive. EPEC and ETEC most important in global incidence. Ecoli needs to attach first and then proliferate. Antibacterial therapy not needed.
- EPEC adheres to intestinal mucosal cells and produce bundle forming pili, an adhesin and an associated protein. These virulence factors allow atatchment and then disruption of microvillus
- EHEC- causes bloody diarrhea, treatment is urgent and needs dialysis, renal failure can result.
- Also Cholera, caused be vibrio cholerae which is found in unclean drinking water. Has serotypes based on somatic antigens. Symptoms caused by enterotoxin. Diagnosing cholera needs a culture. Treatment is rehydration by fluids and electrolytes.
- Non bacterial gastroenteritis and diarrhea usually caused by virus which are specific to humans and are transmitted by fecal oral pathway →
Pathogenesis of rotavirus: Damages transport mechanisms in the gut to cause diarrhea. Attaches to cells and causes damage. Will resolve by itself, thought to be from the immune system. Can be detected by PCR or ELISA
Pathogenesis of cholera: large enough amount of bacteria ingested, small intestine colonised (production of mucinase and atatchment to receptors), toxin production and a result of fluid and electrolyte loss
Can be treated with fluid and electrolyte replacement.
Parasite
Protozoa and worm parasites. Transmission maintained by release of life cycle stages in feces, so hygiene is important. Transmission by contaminated food or water, penetration through skin by larvae, eating animals that are infected.
H.pylori
- Caused by gram negative spiral bacterium. Diagnosed by histological examination of biopsy specimens or urea breath test (h pylori produces urease). Has virulence factors like cytotoxin, acid inhibiting protein, adhesins and urease that aid survival in acidic environment.
Pathogenesis: promotes damage by inflammatory and immune mechanisms. Tissue damage from immune complexes, t cells, chemokines
Worms
- can be infected from either swallowing infected eggs or by skin penetration by infectious larvae moving from lung to intestine. Transmission favoured by inadequate disposal of feces, contaminated water, using feces as fertilizer, low hygiene standards. Caused by Ascaris, Strongyloides and Trichuris that lay eggs in intestine- this is expelled in feces and hatch in intestine when swallowed by other host.
Diagnosed by finding characteristic eggs or larvae in stool. Pinworm diagnosed by eggs on perianal skin. Barium meal will fill defect and help define roundworm
Treated by anthelmintic drugs for intestinal nematodes. Prevention through hygiene and sanitisation
Hepatitis A, B, C
(A)- transmitted by fecal-oral, poor hygiene, anal intercourse or contamination of food or water and virus can enter blood from GI tract, replicates, infects liver cells and passes into biliary tract to reach intestine. Preventable and recoverable. Detected by HAV specific IgM antibody in serum. Vaccination available.
(B)- has three important antigens: HB surface antigen, HB core antigen and HB soluble secreted antigen. Transmitted by sex, mother to child, tattooing. Pathogenesis: Virus reaches blood and then liver where inflammation and necrosis occurs. Immune mediated. Blood is infectious for life. Can cause cirrhosis or hepatocellular carcinoma.
Diagnosed by testing for surface antigens.
Antiviral therapy available and immunisations.
(C)- transmission similar to B. Caused by transfusion associated. Diagnosed by serological tests. Pathogenesis:
Treated by pegylated IFNa (interferon) and ribavirin (antiviral)
Conjunctivitis
viruses and bacteria can cause. Chlamydia trachomatis can cause conjunctivitis. Can be transmitted by blood or nervous system. Chlamydia is treated by antibiotics and face washing. Upper lid becomes infected, inflammation occurs with mononuclear infiltration, scar tissue contracts, eyelashes are pulled in which damages cornea.
- Ophthalmia neonatorum comes from mother in birth canal, caused by Neisseria gonorrhoeae, Chlamydia trachomatis and bacteria or virus. Diagnosed by conjunctiva scraping and NAATs. Antibiotics can treat or antivirals for herpes. Host cell is infected, inclusion bodies form, transformation of RB to EB, cell lysis and spread of RB and EB
Bacterial infection of eye
Classified into abscess formation (folliculitis), spreading infections and necrotizing infections (gangrene, gas gangrene).
- Staphylococcal skin infections are most common and result in an intense inflammatory response and is treated by drainage and antibiotics. Diagnosed clinically. Innate immune responses, macrophages eventually contain. Abscess will form. Toxins can also cause this from Staph. Aureus.
- Streptococcal skin infections caused by group A Strep. pyogenes. M protein is virulence factor. Treated with penicillin. Diagnosed clinically. Factors that are involved are, hygiene, crowding, race, age, heat, humidity, minor trauma. GAS factors inhibit complement activation and antimicrobial peptides, help evade immune system. Causes Impetigo and Erysipelas.
Cellulitis and gangrene
Spreading infection of skin involving subcutaneous tissues, caused by Staph. aureus and Strep.pyogenes. Cellulitis is anaerobic so it is concerning. Diagnosed by culture of aspirates from cellulitis, site of trauma, skin biopsies, blood.
Necrotizing fasciitis, myonecrosis and gangrene caused by anaerobes and facultative anaerobes. Amputation may be needed. Antimicrobial therapy required or debridement (surgical removal of foreign matter). Gas gangrene caused by Clostridium spores in soil or animal feces. Damage is from production of lecithinase, an alpha toxin that hydrolyses lipids in cell membranes causing cell lysis and death.
Difference between superficial and cutaneous mycoses?
superficial = confined to outermost skin layers, cutaneous= penetrates into keratinized layers of epidermis.
Herpes simplex
- universal
- Clinical features: vesicles and latency.
- Transmitted by saliva or cold sores
- Virus replicates in mucosa to form virus-rich vesicles that ulcerate. In primary infection, virus particles enter sensory nerve endings, transported to dorsal root ganglion and initiate latent infection in sensory neurons. Lesion will resolve and latent virus remains in sensory ganglion for life.
Herpes simplex and varicella-zoster infection have virus in mucocutaneous nerve endings travel up axon to reach sensory neurons. Virus will reactivate in the neuron, passing down axon to mucocutaneous sites. CD8 and CD4 T cells are retained in ganglia to prevent reactivation
- Reactivation by illness, sunlight, stress, trauma, menstruation, immunocompromise.
- Diagnosed by PCR or viral culture.
- Treated with acyclovir (an antiviral)
Varicella-zoster virus
- causes chickenpox and when reactivated is shingles.
- highly contagious: inhalation of droplets from respiratory secretions and saliva.
- remains dormant in sensory nerve endings in dorsal root ganglia
- shingles is from a reactivation of latent VSV
- Symptoms- macules (not raised) and papules (raised and not containing pus). Vesicles become pustules and then scab.
- Diagnosed clinically by culture, specific-Abs, detection of DNA
- Prevented with vaccines
- Treated by acyclovir, valaciclovir, famciclovir
Measles
- caused by paramyxovirus
- symptoms- respiratory symptoms, Koplik’s spots and rash
- rash from a cell mediated immune response
- Pathogenesis: virus invades body from blood, reaching surface epithelium in respiratory tract and then mucosae (Kopliks spots) and finally in skin (rash)
- opportunistic bacterial superinfections can occur as a secondary response in resource poor countries
- diagnosed clinically
- Treated by antiviral ribavirin
- Vaccine used for prevention (MMR)
What are vector borne disease?
Transmission of disease by blood feeding insects. They inject organisms into humans as they take a blood meal. There are six legged insects and eight legged ticks and mites.
Malaria
Cause of malaria: Plasmodium species. P.falciparum most virulent
Transmission: bite from infected female anopheline mosquito
Pathogenesis: immunosuppressive and interacts with HIV.
- sporozoites injected into human bloodstream
- enter liver parenchymal cells
- lie dormant as hypnozoites
- mature into tissue schizonts
- rupture releases merozoites
- enters RBC
- merozoites mature into ring form
- trophozoite
- schizont
- release merozoites back into circulation
- some mature in RBCs into male and female gametocytes
- male gametocyte exflaggelates in insect gut
- forms male microgametes, fertilize female gamete to form zygote
- invades gut mucosa
- develops into oocyst
- produces thousands of sporozoites
- these are released
- these migrate to salivary glands of insect
Symptoms: fever and sweats
Immune response: antibodies, interferon, interleukin, tumour necrosis factor, reactive oxygen intermediates, reactive nitrogen intermediates, eosinophil cationic proteins
Diagnosis: finding parasitised red cells in blood films
Treatment: vector control for prevention and artemisinin-based combination therapies or chloroquine phosphate
Dengue fever
Cause of Dengue fever: Flavivirus
Transmission: Mosquitos
Pathogenesis: Virus enters arthropod during blood meal from infected vertebrate as passes to slaivary gland where replication occurs. Infectious arthropod transmits virus to other vertebrate. Virus replicates is vascular endothelium, CNS.
Virus replicates in monocytes
Immune response: four types of dengue
Diagnosis:
Treatment: no antiviral available
Aims of microbiology lab?
Good quality specimen needed
- To provide accurate info about presence or absence of microbes that are responsible for disease
- To provide info on antimicrobial susceptibility of isolated microbes
How infectious agents are detected?
Culture: Taking specimen from either normally sterile sites or specimen from sites with commensal flora. Takes min. 18 hrs for a result
Microscopy: important first step. bright field, gram stain, acid fast stains (mycobacteria), dark field (spirochetes), phase contrast, fluorescence, electron (specimen must be embedded in resin, can identify virus)
Detection of microbial antigens: ELISA assay can measure antigen or antibody concentration through binding
Detection of microbial DNA: nucleic acid probes, PCR, real time PCR, DNA sequencing
The presence of antibodies against a particular microbe: Fluorescent antibody test to detect antigens or antibodies against them. Serologic tests that study antibody-antigen interaction, identifies organisms that grow slowly.
What do R values mean?
= Reproductive rate (R0). Determines ability to spread in susceptible population
- Microparasite R0= average number of secondary cases of infection produced by one primary case in a susceptible population
- Macroparasite R0= average number of female offsping produced by a mature female
We refer to R instead of R0 when there are immunity measures in place.
Social and environmental factors that affect disease?
- Transmission between groups is influenced by school terms and holidays
- Incidence peaks happen seasonally or longer term
- Vaccination success influenced by population density, immunization programs
What is selective toxicity?
The aim of antimicrobial therapy is to kill or inhibit the infecting organism without damaging the host; this is known as selective toxicity. This is commonly accomplished through the use of antimicrobial drugs.
List the ideal properties for antimicrobial agents
Antimicrobial properties: selectivity for microbial target, cidal activity, slow emergence or resistance, narrow activity spectrum (won’t affect normal flora)
Pharmacologic properties: non toxic to host, long plasma half life, good tissue distribution, low plasma protein binding (no interaction with host protein), oral and parenteral dosing forms, no interference with other drugs
Define the terms bacteriostatic and bactericidal
bactericidal (kill) or bacteriostatic (inhibit growth)
Explain the mechanisms of bacterial resistance and how these mechanisms can originate and be transferred
Genetic mutation can cause resistance:
- single chromosomal mutation
- series of mutations
Can be transferred through genes carried on transmissible plasmids, acquisition from transposons and other mobile elements, pili conjugation can exchange material, transformation using DNA from environment, transduction of DNA from phages that infect cell and integrate DNA.
Conferred from chromosal mutation, resistance genes carried on donor plasmid, resistance gene on transposable elements that move between plasmids.
Mechanism of resistance:
- altered target site
- altered uptake or increased exit
- drug inactivation by enzymes- beta-lactamases inhibit cell wall synthesis, can alter target
Name the main target sites for antibacterial agents
- Cell wall synthesis- glycopeptides for gram positive organism
- Protein synthesis- glycopeptides, aminoglycosides, tetracyclines, macrolides, lincosamides, streptogramins
- Nucleic acid synthesis- quinolones, rifamycin’s, trimethoprim
- Metabolic pathways-
- Cell membrane function- lipopeptides, polymyxins
Why are antivirals not as effective as bacteria?
All are virustatic (can’t kill)
How do adjuvants work?
Help enhance immune responses by forming depot, inducing cytokine and chemokine, recruiting immune cells, enhancing antigen uptake, promoting antigen transport to lymph node. They’re not needed usually for live attenuated.
Requirements of good vaccine?
Effective, safe, stable and low cost. Must give good immune response and right type of response. Duration of response, safety and stability are important for live attenuated vaccines
What are the types of vaccine?
- Live attenuated- Microbes that are artificially modified to be non virulent. Most common. Stronger immune response
- Microbes with reduced virulence to humans
- Non living- killed microorganism, no issues like live attenuated. god for immunodeficient people.
- Subcellular fragments- like toxin, antigen, chemicals etc (diphtheria and tetanus vaccines against their toxins)
also DNA vaccine, mRNA vaccine, viral vector (RNA in vector has genetic code that will code for protein, cell will produce virus as if it is infected, antigens will activate), immunogenic peptide vaccine from gene cloning and peptide synthesis
