Action & characteristics of pathogens Flashcards
Where do bacteria try to hide from immune response?
- Sites poorly protected by immune cells: e.g., cholera in GI tract, salmonella in intestinal and biliary tracts
- w/in cells (intracellular bacteria) – in macrophages (Brucella, Listeria, M. leprae, M. TB) or other cells (Yersinia, Shigella, Listeria, E. coli)
How do intracellular bacteria survive in macrophages
- Salmonella secrete products that alter environment of phagolysosome
- N. gnorrhoeae, Brucella bortus, S. aureus produce catalase and superoxide dismutase to destroy toxic oxygen products produced by the hexose monophosphate shunt
- S. aureus also produces cell-bound pigment (carotenoid) that quenches singlet oxygen
- Some bacteria escape cell –> secrete lysins to break down phagosome membrane and bacteria are relased into cytoplasm to multiply
- Some prevent phogosome-lysosome fusion (TB, T. gondii)
Surface coats as a pathogen defense mechanism
Polysaccharide Capsule that suppress complement activation to inhibit phagocytosis, also have surface receptors to bind host cells, and toxins (e.g., e coli)
Important consideration when treating hypermutable genes like pseudomonas
- Need TWO antibiotics. W/in 24-48 hrs, producing a strain resistant to first abx. You see them getting better then suddenly fever back and WBC back. C&S shows resistant to abx
- Esp important if pt is immune compromised, pseudomonas – potential for shock. IF you miss it, give 2 new ones.
Important factors that affect bacterial virulence and infectivity
- Iron – needed to multiply
- Polysaccharide capsules
- Toxin production
- Presence in blood (bacteremia or septicaemia)
What do bacteria need from the host to multiply and how does this sometimes manifest in the host?
- Must have iron to multiply – they have siderophores (iron receptors)
- Septic patiens sometimes present with false iron-deficient anemia:
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Examples of pathogenic bacteria that normally reside in humans w/o causing disease
Streptococcus pyogenes (pharyngitis), S. pneumonia (pneumonia, meningitis), Neisseria meningitides (meningitis), Haemophilus influenzae type b (meningitis)
Gram pos vs Gram neg bacteria
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- Gram neg
- thin peptidoglycan capsule.
- LPS coat (an endotoxin), causes most of immunogenicity
- Gram +
- thick peptidoglycan layer
- surface protein on top of peptidoglycan layer
- both capable of mobility
Action and characteristics of exotoxins
- Enzymes released during bacterial growth causing specific responses
- Include cytotoxins, neurotoxins, pneuotoxins, enterotoxins, hemolysins
- Immunogenic
- Elicit antitoxin production (Abs try to neutralize)
- –> vaccines available for many exotoxins
- Elicit antitoxin production (Abs try to neutralize)
Action and characteristics of endotoxins
- Lipopolysaccharides contained in the cell walls of gram-negative organisms
- Lipid A component responsible for toxic effects
- Pyrogenic effects –> why they’re called “pyrogenic bacteria”
- Can be released during bacterial membrane during growth or tx w/antibx, so antibiotics cannot prevent toxic effects
- Activates almost every aspect of inflammation!!
- Behind gram- sepsis/septic shock!
What type of toxins are behind septic shock?
- Gram negative! (most often)
- The lipopolysaccharides/endotoxins elicit a number of responses – activate coagulation cascade (DIC), induce release TNF-alpha (cachectin) by macrophages
Image: What do macrophages do in response to LPS exposure?
- Try to eat. Produce lots of TNF and IL-1 which lowers iron and induces fever. TNF and IL-1 also incite T cells to release INF-gamma, which stimulates macrophages to get more involved.
- TNF, IL-1, IFN-gamma circle is very important!
Effect of LPS on PMNs
Mobilize PMNS –> significant inflammation in epithelial cells –> increased vascular permeability
Effect of LPS on mast cells
IgE mechanisms from LPS triggers mast cell mediators –> vascular permeability.
Effect of LPS on PLTs
- Release of mediators leading to vascular permeability
- Leads to DIC thrombosis
Effect of LPS on liver
Hypoglycemia
LPS and DIC thrombosis
d/t interaction btwn LPS, PLTs and clotting factors
What cytokines does LPS trigger
- Successive waves of cytokine production
- TNF, IL-1, IL-6, IL-8
- Also NO, PAF, other mediators
How do macrophages interact with LPS?
- LPS binding protein presents bound LPS to toll-like receptors on the macrophages
- In conjunction with CD14, they create a complex capable of producing IL-1, TNF, IL-6, IL-8 and PLT activating factors (macrophages are what get platelets involved!)
Role of macrophages in LPS
Center piece responsible creation of all mediators and eventual septic shock. This is why recent ICU weapons are anti-TNFs
Book: what does LPS trigger at low, moderate, and high quantities of mediators?
- Low: local - monocyte/macrophage/neutrophil activation, endothelial cell activation, complement activation (C3a, C5a)
- Moderate: more systemic inflammatory responses – fever, acute phase reactants, leukocytosis
- High: septic shock and death– low cardiac output, low peripheral resistance, blood vessel injury, thrombosis, DIC, ARDS
Bacteremia or septicemia
- Presence of bacteria in the blood due to a failure of the body’s defense mechanisms
- Toxins released in the blood cause the release of vasoactive peptides and cytokines that produce widespread vasodilation
What type of bacteria usually causes bacteremia or septicaemia?
Gram negative
Common gram positive organism
Staphylococcus aureus
Common infections of Staph aureus
Infection produced may depend on toxin produced
Folliculitis
- Scalded Skin Syndrome (Exfoliative Toxin) (SSS)
- Food Poisoning (Enterotoxins A-G)
- Toxic Shock Syndrome (TSST-1):
- Endocarditis
- Pneumonia
- Carbuncle, Furuncle
- Impetigo
- Wound Infection (esp DM)
Concern with folliculitis d/t Staph aureus
If toxic, can lead to scalded skin syndrome
Enterotoxin: presentation and duration
not that dangerous but looks like it. Lots of cramps, feel like death. Appears w/in hours of ingestion, lasts 7-8hrs.
Pneumonia d/t S. aureus: characteristics
- Uncommon in community
- only common if hospital acquired – then MRSA
- presents bilaterally w/some lobar consolidation and effusion
UTI: S. saprophyticus vs staph aureus
- S. saprophyticus often UTI in young healthy female. Fairly benign. Or staph epidermis from skin, foley cath;
- But staph aureus in urine, remember came from the blood! = staph bacteremia until proven otherwise
Gram positive direction of infection
- **parachutes from blood to urine – never other way around; gram+ travel. This will save lives!!!*** e.g. staph aureus
- e.coli , gram neg travel, can go other way, urine to blood, can cause sepsis (urosepsis
Weapons of Staph aureus
- Engage: Attachment Proteins – good at engaging us and tissue for infection. Gets in blood, why it’s so good at reaching heart
- Shield: Capsule protects against phagocytosis (difficult to phagocytize)
- Neutralize: Staph Protein A binds IgG
- Slow down the enemy: Complement Evasion, Staph proteins inhibit complement (C3, C5 Convertase, C5, C2, C5a receptor)
- Poison: Enterotoxins (abd cramps, pain, diarrhea)
- Invade: membrane damaging alpha toxins, lipase, leukocidin (toxic to leukocytes), hemolysin (lyses RBCs), beta toxin, exfoliative toxins, etc)
- Beta Lactamase: destroys Penicillin (if they see PCN, they produce beta lactamase in response). Breaks down PCN ring/beta lactam ring. Idea behind methicillin resistant SA
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What components of complement does S. aureus inhibit?
C3, C5 Convertase, C5, C2, C5a receptor
Infective endocarditis: acute vs subacute course
- acute course; Health individual Came to hospital for CA Pneum, or line placement, S.a. introduced à
- signif fever, chills, deterioration w/in 24-48hrs. At risk for rupture & death.
- Subacute: IV drug users. Weeks of fever, chills, weight loss. Do echo and see huge vegetation on valve. Survive after IV antibx. Needle exchange programs reduce risk.
- Irony: healthy host dies, IV drug user lives. They survive b/c mortality is often from immunogenicity of staph aureus that kills! IV drug user has had number of low dose repeat exposures, so immune response is blunted and we see subacute course.
Common organisms: URIs
- Corynebacterium diphtheriae (diphtheria), Gram +, facultative anaerobic, extracellular
- Haemophilus influenzae, Gram -, facultative anaerobic, extracellular
- Streptococcus pyogenes (group A), Gram +, facultative anaerobic, extracellular
Common organisms: otitis media
- Haemophilus influenzae, Gram -, facultative anaerobic, extracellular
- Moraxella catarrhalis, Gram -, aerobic, extracellular
- Streptococcus pneumonia, Gram+, facultative anaerobic, extracellular
Common organisms: Lower respiratory tract infections
- Bacillus anthracis (pulmonary anthrax), gram+, facultative anaerobic, extracellular
- Bordetella pertussis (whooping cough), gram-, aerobic, extracellular
- Chlamydia pneumoniae, not stainable, aerobic, extracellular
- E. coli, gram -, facultative anaerobic, extracellular
- H. influenzae, klebsiella pneumonia, Legionella pneumophilia, M. tuberculosis, M. pneumoniae, N. meningitides, P. aeruginosa, S. agalactiae, S. pneumoniae, Y. pestis (Table 10-4)
Common organisms: inflammatory GI tract infections
- Bacillus anthracis (GI anthrax), Gram+, facultative anaerobic, extracellular
- C. difficile, Gram+, facultative anaerobic, extracellular
- E. coli 0157:H7, Gram-, facultative anaerobic, extracellular
- V. cholerae, gram-, facultative anaerobic, extracellular
- V. parahaemolyticus, Gram-, facultative anaerobic, extracellular
Common organisms: invasive GI tract infections
- Brucella abortus, gram-, aerobic, extracellular, leads to sepsis, heart infxn
- Campylobacter jejuni, gram-, microaerophilic, extracellular
- Francisella tularensis, Gram-, strict anaerobic, facultative intracellular
- H. pylori, gram-, microaerophilic, extracellular
- Listeria monocytogenes, gram+, aerobic, intracellular
- Salmonella typhi, gram-, anaerobic, extracellular
- Shigella sonnei, gram-, facultative anaerobic, extracellular
Common organisms: food poisoning
- Bacilus cereus, gram+, facultative anaerobic, extracellular
- Clostridium botulinum, gram+, facultative anaerobic, extracellular
- C. perfringens, gram+, anaerobic, extracellular
- S. aureus, gram+, facultative anaerobic, extracellular
Common organisms: STIs
- Chlamydia trachomatis (PID), not stainable, aerobic, intracellular
- N. gonorrhoeae (urethritis), gram-, aerobic, facultative intracellular
- Treponema pallidum (spirochete; syphilis), gram-, aerobic, extracellular
Common organisms: Skin & wound infections
- Bacillus anthracis (cutaneous anthrax), gram+, facultative anaerobic, extracellular
- Borrelia burgdorferi (Lyme dz, spirochete), gram-, aerobic, extracellular
- C. tetani, gram+, anaerobic, extracellular
- C. perfringens (gas gangrene), M. leprae, pseudomonas aeruginosa, Rickettsia prowazekii, S. aureus, S. pyogenes (Table 10-4)
Common organisms: eye infections
- Chlamydia trachomatis (conjunctivitis), not stainable, aerobic, obligate intracellular
- Haemophilus aegyptus (pink eye), gram-, facultative anaerobic, extracellular
Common organisms: Zoonotic infections
B. antracis, B. abortus, B. burgdorferi, Listeria monocytogenes, R. rickettsia, R. prowazekii, Y. pestis (Table 10-4)
Common organisms: Nosocomial infections
- Enterococcus faecalis, gram+, facultative anaerobic, extracellular
- Enterococcus faecium, gram+, facultative anaerobic, extracellular
- E. coli (cystitis), gram-, facultative anaerobic, extracellular
- Pseudomonas aeruginosa, gram-, obligate anaerobic, extracellular
- S. aureus, gram+, facultative anaerobic, extracellular
- S. epidermidis, gram+, facultative anaerobic, extracellular
Primary cause of necrotizing fasciitis
- Group A Streptococcus
- Severe and rapid tissue destruction d/t combined effects of bacterial toxins and enzymes released from damaged cells.
- Need rapid surgical debridement
Which type of bacteria produce some of most powerful toxins?
Clostridia
Bacterial superantigens
- Increase adherence btwen MHC class II protins on APCs and T cell receptor. Effect independent of Ag, so many T cells produced and these overproduce proinflammatory cytokines (IL1, IL6, TNF-alpha)
- Responsible for some food poisoning, TSS of s. aureus, and scarlet fever
Viruses: implications of being obligate intracellular parasites
- Dependent on host cells
- No metabolism or incapable of independent reproduction
- Permissive host cell
- Virion binds to receptors on the plasma membrane - uses cell for reproduction. Cell bursts and virus spreads
- Usually a self-limiting infection
- Spreads cell to cell
How does viral replication take place?
- DNA or RNA, Single or double stranded
- Protein receptor–binding site
- Virus uncoats once inside cell
- Most RNA viruses directly produce mRNA
- DNA “provirus” enters nucleus is are transcribed into mRNA (cell doesn’t realize it’s enemy mRNA)
- Translation of mRNA results in the production of viral proteins
- New virions are released through budding
- Viral DNA that is integrated in host cell DNA is transmitted to daughter cells by mitosis
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Why are DNA viruses more dangerous than RNA viruses?
- Because Viral DNA that is integrated in host cell DNA is transmitted to daughter cells by mitosis
- why DNA viruses more dangerous). Why T cell surveillance and NK cells are so important. Slight abnormalities on surface
Viral replication cycle, with image
- Bind
- penetrate
- uncoat
- multiply in nucleus
- either burst cells or use cell export mechanisms to infect other cells
HIV tx all target one of these steps
Effects of the virus on the cell
- Inhibition of host cell DNA, RNA, or protein synthesis
- Disruption of lysosomal membranes
- Promotion of apoptosis
- Fusion of infected, adjacent host cells
- Alteration of antigenic properties – very important!! Especially for flu virus.
- Transformation of host cells into cancerous cells - Some viruses can inhibit tumor suppressor actions in cells. E.g., EBV and lymphoma. HIV much higher risk for almost every cancer.
- Promotion of secondary bacterial infections. E.g. viral cold that lingers too long, now turns into a bacterial infection/pneumonia. More common in smokers.
Avian influenza A strain
H5N1
Human transmission in H5N1
Rare – mostly through birds
H5N1 MOA
Infects the lungs and targets type 2 alveolar pneumocytes and macrophages. It also passes throughout the body to the GI tract, brain, liver, blood cells, transplacentally from mother to fetus
Symptoms H5N1
Fever, cough, sore throat, muscle aches, eye infections (conjunctivitis), pneumonia, ARDs, other severe life threatening complications
Diagnosis H5N1
Detection of viral RNA obtained through throat swabs
Mortality rate H5N1
~60%
Theory of how antigenic shift in influenza virus could take place (human/avian)
When human influenza vurus and avian influenza virus coninfect a species permissive for both (e.g., pig). Hybrid would have same genetic info of human virus but also a new HA containing strand from avian virus. Less susceptible to residual immunity providing protection against yearly in flue infections
Characteristics of fungi: size & cell wall
- Large microorganisms with thick cell walls
- Eukaryotes
- Exist as single-celled yeasts, multicelled molds, or both, or dimorphic
Pathogenicity of fungi
- Adapt to host environment
- Wide temperature variations, digest keratin, low oxygen
- Suppress the immune defenses
Mycoses
- Diseases caused by fungi
- Superficial, deep, or opportunistic
Dermatophytes
Fungi that invade the skin, hair, or nails
Diseases produced by dermatophytes
Tineas (ringworm). Named for area found
- Tinea capitis, tinea pedis, and tinea cruris
Deep fungal infection: prognosis
Deep fungal infections are life threatening and are commonly opportunistic. Need systemic tx w/antifungal agents
Clinical manifestations of infectious disease
- Variable depending on the pathogen
- Directly caused by the pathogen or indirectly caused by its products
- Fever
- Resetting the hypothalamus
- Exogenous pyrogens
- Endogenous pyrogens
- Resetting the hypothalamus
- Leukocytosis
- Fever
How is body temp regulated?
- Nervous system feedback to hypothalamus, which functions as a central thermostat.
- Endogenous and exogenous pyrogens can produce fever
- both seem to be mediated by effect of endogenous pyrogens on hypothalamus: raise thermoregulatory set point through stimulation of PG synthesis and turnover in both thermoregulatory (brain) and nonthermoregulatory (peripheral) tissue
Cytokines that have been identified as endogenous pyrogens
IL-1, IL-6, IFN, TNF, etc.
Countermeasures to infection
Vaccines, antimicrobials
How is the influenza vaccine made?
- Antibodies against HA and NA antigens (2 antigenic pieces of influenza)
- H1N1, H1N2, H3N2, H5N1(avian) – all based on Ags
- Done geographically – so one area not necessarily protect in another!
Yearly changes in HA and NA – influenza A vs influenza B
- Both Influ A&B undergo minor change: “Antigenic Drift” from mutations
- B mutates less than A and is exclusively in humans
- A has periodic major antigenic changes: Antigenic Shift, caused by recombination (cannot predict)
How do antimicrobials work?
- Inhibit synthesis of cell wall
- Damage cytoplasmic membrane
- Alter metabolism of nucleic acid
- Inhibit protein synthesis
- Modify energy metabolism – e.g. quinolones and new generation
Classes of organisms infectious to humans, smallest to largest
- Virus
- Chlamydiae
- Rickettsiae
- Mycoplasma
- Bacteria
- Fungi
- Protozoa
- Helminthes
