Midterm 1 Flashcards
Innate immunity components
Skin resource competition, mucosal surfaces, phagocytes, cytotoxic cells
Mucosal surface types
GI, respiratory, urogenital, conjunctiva (eyes)
Phagocyte purpose and types
Ingest and kill bacteria
Monocytes = blood, develop into macrophages
Macrophages = Stuck in tissue (liver, lymph, etc.)
PMNS/Neutrophils = Abundant in blood, 1st to infection
Cytotoxic cell types
CD8+ T Cells = deliver toxic granules (specific)
NK (Natural T-Killer) = deliver toxic granules (variety)
WBC count
Range 4500-10000/uL, leukocytes in blood
Granulocytes
Mostly phagocytic neutrophils, some eosinophils and few histamine releasing basophils
Agranulocytes/PBMC
Mostly lymphocytes (B-T-NK) and some monocytes
Mast cells
Not technically granulocytes (fixed in tissue) but have granules and release histamines - found in connective tissue
Complement purpose and production
Produced in liver, recruit phagocytes, facilitate phagocytosis and stimulate inflammation
C3a purpose
Recruit phagocytes, vasodilation (move phagocytes), anaphylatoxin (histamine release from mast cells)
C3b purpose
Phagocyte uptake and opsonization, bind to bug and recognized by phagocytes
C5a purpose
Like C3a, vasodilation, recruitment and anaphylatoxin
C5b-C6-C9 complex
MAC (Membrane attack complex) forms membrane pores and kills Gram -
Classical complement pathway
Ab driven, IgG binds to Ab on variable bug surface, C1 binds and starts complement cascade, C3 cleaved into C3a and C3b, MAC forms pores and kills Gram -
Where does C5b bind
LPS
Where do C6-C9 bind
Membrane with C5
Alternate complement pathway
C3b driven, C3 is hydrolyzed to C3a and C3b, C3b binds to LPS Or TA, C3b further stimulated to cleave C3
Mannose binding lectin pathway
Lectins bind to mannose and other sugars on bug, stimulate C3 cleavage, MBL binding clumps bacteria and allows elimination via phagocytes
Control of complement
Factor H binds to C3b to form complex, degraded by factor I
Gram - bacteria
Inner and outer membrane, small cell wall, LPS attached to OM
Gram + bacteria
Cytoplasmic membrane, large cell wall, LTA attached to membrane and TA attached to cell wall
Phagocytosis mechanism
Engulfed into phagosome, fusion with lysosome
PAMPs
Pathogen associated molecular patterns recognized by phagocytes like LPS, LTA, and flagella, which stimulate TLRs and cytotoxic cell production
Phagocyte activation
LPS bind to LPS binding protein, LPS-LBP complex bind to CD14 receptors and activate TLR4. PMNs released from marrow, margination inside blood vessels, extravasation to squeeze into tissue, oxidative burst
What causes septic shock
Not enough oxygen because of hypoperfusion (low blood flow)
Stage 1 sepsis / organ dysfunction
Acute SOFA score change, respiration, coagulation, liver, CNS, kidneys, and GCS motor responses
Stage 2 septic shock
Complement cascade and vasodilation, cytokine production, disseminated intravascular coagulation (DIC), hemorrhaging, MODS (multiple organ dysfunction syndrome bc of low blood flow and ARDS (acute respiratory distress syndrome) bc of lung inflammation/ leaking leads to death
Early therapy for sepsis
Early antibiotics but symptoms are non-specific, no effective therapy to stop shock
Supportive therapy for sepsis
Ventilators to support oxygen, fluid administration and vasopressors/epinephrine to constrict vessels and bronchodilation by inducing fight/flight response
IgG
Best at opsonization and toxin neutralization, smallest, most abundant, can cross placenta, in the blood and LRT
IgM
Best at activating complement via classical pathway, pentamer, in blood
sIgA
Best at trapping bug in mucin, toxin neutralization, secreted into mucosa NOT in blood
IgE
Binds to mast cells and basophils to stimulate histamine release and vasodilation like C3a and C5a, located below epithelial surfaces NOT in blood
Antibody timing
IgM produced by immature B cells quickly to activate complement, IgG produced after a week and is very specific
Macrophage/T cell activation mechanism
MHC (Major histocompatibility complex)
MHC II
Ag complex on APC surface stimulate CD4+ Th cells, Th1 produces interferon gamma and activates Mac/CD8+ T cells, Th2 produces interleukin 4 and stimulates Ab production
MHC I
Ag complex on nucleated cells stimulates CD8+ T cells to release toxins into infected host cells with perforin to make pores and granzymes inducing apoptosis
CHO capsules
Bind directly to B cell surfaces produce antibody, no Th cell activation, cant be engulfed unless opsonized, babies cant make antibodies to CHO
Bacterial endotoxin
LPS
Bacterial protein toxins
AB exotoxins, membrane disrupting toxins, SAgs (superantigens)
Clostridium classification
Gram +, spore forming, anaerobe, in soil
What causes botulism
BoNT (Botulinum neurotoxin) produced by C. botulinum
BoNT feature
Most toxic known toxin, biowarfare agent
Botulism pathogenesis
Spores germinate in food and replicate, bug produce toxin which is ingested and enters blood, BoNT causes symptoms, flaccid paralysis, respiratory and heart failure
BoNT mechanism
Cleaves SNARE proteins at vesicles in nerve endings of PNS, prevents acetylcholine release, no muscle activation
BoNT serotypes
ABEF humans, CDE animals
Botulism symptoms
Appear within 1-3 days, slurred speech, double vision, vomiting
Botulism treatment/prevention
No vaccine, treatment with ventilator and HBAT antitoxin from horse, prevention is to boil canned food
Infant botulism
Ingest bee honey with spores, GI tract colonization and produce BoNT
Wound botulism
Spores enter wound, colonization, BoNT produced
Treatment for colonization botulism
Antibiotics for bacteria in addition to antitoxin
Botox
Uses low dose of BoNT
What causes tetanus
TeNT (Tetanus neurotoxin), NOT contagious person to person
Tetanus reservoir
Spores in soil, animal feces and intestine
Tetanus transmission
Spores to wound
Tetanus pathogenisis
Spore enters wound, bug colonizes and produces TeNT, which enters bloodstream, respiratory failure and death
TeNT mechanism
Cleave SNARE proteins in CNS inhibitory neurons, muscle always active and uninhibited
Tetanus symptoms
Spastic paralysis, lockjaw, respiratory failure and death at high rates
Tetanus treatment
TIG (tetanus immune globin) from human immunized donor, antibiotics, vaccinate with toxoid
Tetanus vaccine
Inactivated TeNT toxoid, part of DTaP
Model for membrane disrupting toxin
C. perfringens
C. perfringens disease
Gas gangrene, infection of muscle tissue and production of carbon dioxide from bug, 100% fatal w/ no treatment
C. perfringens reservoir
Soil, human and animal intestine
C. perfringens pathogenesis
Spore enters wound and bug colonizes, alpha toxin disrupts membrane, necrosis, spread, death
C. perfringens alpha toxin
Phospholipase disrupts phospholipid bilayer
C. perfringens treatment
Surgery
Superantigen purpose
Aggressively activate host immune response
Staphylococcal menstrual TSS (toxic shock syndrome)
Old superabsorbent tampons promoted anaerobic bug growth, produce TSST1 (toxic shock syndrome toxin) which entered blood and caused fever, shock, possible organ failure and death
Streptococcal TSS (toxic shock syndrome)
S. pyogenes growth in wound, bacteria enter bloodstream, release SpeA (S. pyogenes exotoxinA) leading to organ failure and death
Superantigen mechanism
Normally MHC-II+antigen complex binds to T cell to stimulate specific response, superantigen toxins bind conserved regions of T cell receptors and MHCII and cause cytokine storm/massive immune response
Diphtheria classification
Gram + club, no spores
Diphtheria nickname
The strangler bc of neck swelling
Original dog sled race
Delivering the horse antitoxin to Alaska
Diphtheria reservoir
Human asymptomatic carriers
Diphtheria transmission
Aerosols
Diphtheria pathogenesis
Aerosols or contact, throat colonization, form adherent pseudo membrane, produce DT which enters bloodstream which causes respiratory and heart failure
Diphtheria toxin
AB toxin binds to HB-EGF (Heparin binding epidermal growth factor) precursor and ADPR EF2 to kill cell
DT target
Heart/organs, since HB-EGF is present in many cell types
Diphtheria treatment
DAT (diphtheria antitoxin) on unbound toxin and antibiotics
Diphtheria vaccine
DT toxoid elicits IgG response, part of the DTaP series
DT conjugate vaccines
Link DT to CHO capsules to give effective antibody response
Hib characterization
Gram - rod causing infant meningitis
Hib transmission
Aerosols causing colonization of oropharynx
Hib disease
Infant meningitis and pneumonia
Hib vaccine
Hib CHO capsule linked to DT toxoid
Immunotoxins
DT A fragment linked to antibodies that recognize only cancer antigens
Yersinia characterization
Gram - rod w/ capsule
Y. enterocolitica disease
Appendectomy in children / general food poisoning
Y. enterocolitica transmission
Contaminated food/water
Y. enterocolitica pathogenesis
Diarrhea caused by YST (Yersinia stable toxin) and growth in mesenteric (abdominal) lymph nodes causing inflammation
Y. pestis defining characteristic
Causes black death, DIC black skin lesions
Y. pestis reservoir
Wild rats
Y. pestis transmission
Infected fleas, direct contact with fluids, aerosols
Bubonic plague
Flea feeds on infected rodent, inject into human, growth in lymph nodes
Septicemic plague
Progressed stage of bubonic plague, enter and multiply in blood, infect multiple organs
Pneumonic plague
Human aerosols can infect, severe pneumonia, bloody sputum
Plasmids in all Yersinia
pYV (plasmid yersinia virulence) T3SS, injectisome to secrete toxins into host, repress inflammatory genes and inhibit phagocytosis
V antigen activate IL-10 to repress inflammation
Y. pestis specialized plasmids
pPla (plasminogen protease activator), converts plasminogen to plasmin and allows disemination from bite source [CLOT BUSTING like Tpa for heart attacks]
pMT (murine toxin) F1 antiphagocytic protein capsule, phospholipase D promotes flea colonization
Staph. aureus classification
Gram+ coccus, hemolytic with yellow colonies
Staph. aureus diseases
Most common cause of sepsis, most are skin infections. Also causes SE (food toxicosis), systemic infection and toxicosis
Staph. aureus reservoir
Normal skin flora, GI and URT, infected animals
Staph. aureus transmission
Close contact, occasionally from animals
Staph. aureus blocking opsonic phagocytosis
Alpha toxin/hemolysin pore forming toxin to ADAM-10, leucocidin pore forming toxin to Mac complement receptor, staphylokinase degrades complement and antibody and converts plasminogen to plasmin, protein A binds to IgG-Fc
Nuc staphylococcal nuclease degrades NETs (traps)
Polysaccharide capsule blocks opsonization
Staph. aureus disemmination
Hyaluronidase cleaves hyaluronic acid to increase tissue spread
Staph. aureus superantigens
SE (staphylococcal enterotoxin) causes food poisoning, SE-TSS produced systematically and SEB is a biowarfare agent
TSST1 causes menstrual and non menstrual toxic shock
MRSA
Methicillin resistant Staph. aureus, vancomycin used instead, acquired in hospital and community
VRSA
Vancomycin resistant Staph. aureus
Streptococci classification
Gram + aerobic coccus
Streptococci identification
RBC alpha (partial), beta (complete), or gamma (no) hemolysis
Lancefield cell wall carbohydrate grouping (GAS,GBS, etc.)
S. pyogenes classification
GAS, forms chains beta hemolysis, causes strep throat and skin infections
S. pyogenes / GAS reservoir
Mouth/throat and other parts of the body
S. pyogenes / GAS transmission
Person to person nasal/saliva in crowded conditions
S. pyogenes / GAS diseases
Skin infection, flesh eating disease, strep throat, middle ear, scarlet fever, pneumonia, meningitis
S. pyogenes / GAS cytokine degradation
C5a protease (ScpA) inhibit phagocyte recuitment
S. pyogenes / GAS blocking opsonic phagocytosis
M proteins bind to Fc of IgG, Streptolysin lyse macrophages, Sda1 DNAse degrade NETs, hyaluronic acid capsule
Streptokinase clot busting like Ppla
SpeA causing TSS and scarlet fever
S. pyogenes/ GAS dissemination
Cleave hyaluronic acid to penetrate tissue and increase lesion
Rheumatic fever (RF)
Caused by M epitopes reacting with heart in some untreated GAS infections, need to treat strep throat with antibiotics
PSGN
Post-streptococcal glomerulonephritis, GAS epitopes Ag-Ab complexes react and damage kidney glomeruli
Rapid Strep Test
Throat swab to detect GAS Lancefield CHO, backup throat culture PCR/NAAT takes days
S. pyogenes / GAS prevention & treatment
Hand washing, sanitation, treatment with antibiotics
S. agalactiae / GBS characterization
Leading cause of neonatal meningitis, alpha beta or gamma hemolytic, forms chains
GBS reservoir
Human GI tract and vagina
GBS transmission
Prenatal, early, and late onset
Prenatal GBS
Invasive procedure or pregnancy trauma, bloodstream invasion
Early onset GBS
Exposure during delivery
Late onset GBS
From caregivers or invasive devices
GBS vagina colonization
Nisin protease cleaves Lactobacillus nisin and allows colonization, beta hemolysin aids colonization
GBS virulence
Beta protein binds factor H to degrade C3b, C5a peptidase, beta hemolysin stimulates meningitis, sialic acid capsule binds immune cell lectins to downregulate immune response and C3b opsonization
GBS urine culture
Treat asymptomatic bacteriuria early in pregnancy
GBS late pregnancy test
Vaginal and rectal swab, IAP (intrapartum antibiotic prophylaxis) if positive right before delivery
GBS meningitis diagnosis
Blood or spine tap culture/PCR
GBS treatment
Antibiotics, no vax
Enterococcus / GDS characteristics
leading cause of hospital/nosocomial bacteremia, very hardy, inherently resistant, Gram +, nonhemolytic, clot buster
Enterococcus reservoir
Colon in humans and animals
Enterococcus transmission
Fecal/oral and direct contact with contaminated surfaces and fluids
Enterococcus diseases
Nosocomial bacteremia, UTI, pneumonia, surgical infection
Enterococcus virulence
Cytolysin membrane disruptor, gelatinase E degrades E-cadherin in tight junction, hyaluronidase, polysaccharide capsule
Enterococcus antibiotic resistance
VRE (vancomycin resistant enterococcus) in hospitals, necessitate specific protocol
Enterococcus diagnosis
Bile/optochin resistance (differentiation from S. pneumoniae) and PCR
S. pneumoniae / pneumococcus classification
Similar to enterococcus, alpha hemolytic, no Lancefield classification
S. pneumoniae / pneumococcus danger
Kills more people than vaccine preventable diseases combined, most common cause of community acquired pneumonia, causes middle ear infections in children
S. pneumoniae / pneumococcus reservoir
Human nasopharynx as normal flora
S. pneumoniae / pneumococcus transmission
Aersosols
S. pneumoniae / pneumococcus diseases
INFLAMMATION, most common cause of bacterial pneumonia, infant meningitis, ear infections, MID EAR TO NASOPHARYNX PATH
S. pneumoniae / pneumococcus pathogenesis
Adherence to nasopharynx, inhalation into lung, replication, pneumonia, incite inflammation and generate pus, bacteremia and meningitis, septic shock
S. pneumoniae / pneumococcus virulence
CpbA (choline binding protein) for adherence, CHO capsule binds Factor H, proinflammatory thick cell wall, pneumolysin inflammatory pore forming cytotoxin, NA cleaves sialic acid, sIgA protease, autolysin
S. pneumoniae / pneumococcus tests
Quellung test capsule serotyping via Ab+bug capsule swelling, bile and optochin test, UAT (urinary antigen test) for cell wall components, NAAT/PCR
S. pneumoniae treatment
Antibiotics with steroids because of autolysin releasing inflammatory components
S. pneumoniae vaccines
Prevnar 13 or 15 for children, DT linked to capsule serotypes, PCV20 for elderly, PPSV23 old design without DT linkage
