Innate Immunology/Bacteria Flashcards
Superficial skin infections of S. pyogenes
Impetigo, erysipelas
Deep skin infections of S. pyogenes
Cellulitis, necrotizing fasciitis, myositis
Main infection associated with S. pyogenes
Pharyngitis
Toxin-mediated disease of S. pyogenes
Scarlet fever and streptococcal toxic shock syndrome
Post-streptococcal disease (non-suppurative)
Rheumatic fever and glomerulonephritis
Pharyngitis
Abrupt onset of sore throat, fever, and headache; posterior pharynx erythematous with exudate; tender cervical adenopathy
Scarlet fever
Diffuse erythematous eruption; sandpaper rash beginning on chest and extending towards extremities and strawberry tongue; mediated by strptococcal pyrogenic exotoxin (SPE)
Acute rheumatic fever/heart disease
Erythema marginatum (pinkish erythematous rash involving trunk and sometimes limbs, but not face)
Glomerulonephritis
Acute inflammation of renal glomeruli with edema, hypertension, hematuria, and proteinuria; deposition of immune complexes triggers complement activation and inflammation
Impetigo
Primary - direct bacterial invasion of previously normal skin
Secondary - infection at sites of minor skin trauma; nonbullous (most common, papules surrounded by erythema»pustules that enlarge and break down to form golden crusts
Erysipelas
children and young adults; Superficial skin infection with lymph node enlargement and systemic symptoms; skin raised with clear demarcation
Cellulitis
Rapidly spreading infection of dermis and subcutaneous fat with poorly defined, flat borders; erythema, pain, warmth, swelling; risk factors - breaks in skin, chronic skin disease
Necrotizing fasciitis
bacteria infect fascia; high mortality; progresses rapidly over several days (skin changes color, breakdown with bullae, cutaneous gangrene may be seen); risk factors - penetrating wounds, surgical wounds, immunosuppression, diabetes, obesity
Streptococcal TSS
Initial manifestation - inflammation, pain, fever, chills, nausea, vomiting, diarrhea
Subsequent manifestations - shock and organ failure, bacteremic, necrotizing fasciitis; risk groups - HIV, cancer, diabetes, heart/pulm disease, VZV infection, and drug/alcohol abusers; SpeA and C facilitate disease
Pseudomonas aeruginosa clinical diseases
SSTI: hot tub folliculitis, ecthyma gangrenosum (neutropenic), burn wounds
Pulmonary, UTI, ear, eye, bacteremia and endocarditis
General CoNS infections
Bacteremia (nosocomial) in neonates mostly, infections in patients with medical devices
S. epidermidis clinical diseases
Implanted device infections, Subacute endocarditis
S. saprophyticus clinical diseases
UTI
S. haemolyticus clinical disease
implanted device infections
S. lugdunesis clinical diseases
Endocarditis similar to S. aureus
S. aureus clinical diseases
Abscesses, cellulitis, folliculitis, furuncles and carbuncles, impetigo, scalded skin syndrome (Ritter’s disease), TSS
Abscess formation
Inflammatory response to S. aureus, S aureus attacks PMNs, continued recruitment of immune cells to site, buildup of necrotic PMNs and cell debris (liquefactive and coagulative necrosis); formation of fibrous capsule
Folliculitis
Cutaneous abscesses in and around hair follicles (papules - discreet elevation or pustules - accumulation of pus in a blister can form)
Furuncles
Boils (large, painful, raised nodules); purulent material extends through dermis into subcutaneous tissue and a small abscess forms; pus drains spontaneously or after incision
Carbuncles
Clusters of furuncles; deeper subcutaneous tissue involved; treatment: incision and drainage, trimethoprim/sulfamethoxaozole or clindamycin or doxycycline
Bullous impetigo
Vesicles enlarge to form flaccid bullae with clear yellow fluid that later becomes darker and more turbid; caused by exfoliative toxins
Scalded skin syndrome
Skin tenderness, large bullae, and desquamation or epithelium; blisters contain fluid with no bacteria as symptoms are due to exfoliative toxins A and B
TSS
erythematous rash; purpura fulminans (large purpuric skin lesion and disseminated intravascular coagulation); treatment - empiric with IV clindamycin and vanco (MSSA - IV clindamycin plus oxacillin; MRSA - IV clindamycin plus vanco)
Extracellular TLRs
1,2,4,5,6
Endosomal TLRs
3,7,8,9
Lipopeptide TLR
1,2,6
Peptidoglycan TLR
2
LPS TLR
4
Flagella TLR
5
Glycoprotein TLR
2,4
HSPs and HMGB1 (DAMPs) TLR
2,4
Unmethylated CpG DNA TLR
9
RNA TLR
3,7,8
NLRs
peptidoglycan, flagellin, unmehtylated CpG DNA, RNA
RLRs
RNA
IL-1
Secreted by: macrophages, PMNs, and endo cells; endo cells increase E-selectin, induce APP in hepatocytes, induce fever
TNF-alpha
Same as IL-1 but secreted mostly by macrophages, integrin increase affinity on PMNs
IL-6
Secreted by: macrophages, PMNs, endo cells, fibroblasts; induce APP production, stimulate PMN production in marrow; induce fever; naive T cell differentiation
IL-8
Secreted by: monocytes, macrophages, PMNs; chemokine that recruits PMNs via increased integrin affinity
IL-12
Secreted by: DCs and macrophages; stimulates IFN-gamma production in NK and T cells; enhance NK and CD8 T cells cytotoxic function; differentiation of naive T cells
Histamine
Secreted by mast cells; increase vascular permeability and vasodilation
PGD2
Secreted by mast cells; vasodilation and increase vascular permeability; PMN recruitment
Leukocyte recruitment
- ) Selectin-mediated rolling of leukocytes on endothelium
- ) Integrin conformational change to high affinity state
- ) Integrin-mediated arrest of leukocytes on endothelium
- ) Transmigration of leukocytes through endothelium (diapedesis)
Pathogen phagocytosis recognition
- ) PRRs
- ) FcgammaRI (recognizes Fc portion of antibodies)
- ) CR1 complement pathways
Phagocytosis steps
- ) Microbe detected, phagocyte membrane surrounds via receptor-mediated endocytosis
- ) Phagosome forms
- ) Phagosome fuses with lysosome to form phagolysosome
- ) microbe digested by microbicidal molecules (oxygen-dependent via phagocyte oxidase complex and iNOS or oxygen-independent via proteolytic enzymes, elastase, cathepsin G, lysozyme, phosphatases, or defensins)
Acute phase proteins
CRP (phosphoylcholine), MBL (lectin complement), fibrinogen (clot formation), SAP (phosphatidylehtanolamine), and complement pathway proteins
Functions of complements
Opsonize microbes, stimulate inflammation, lysis of microorganisms
Alternative
C3»C3b»microbe (or degrade by H2O)»factor B recruited and cleaved by factor D»forms C3bBb (C3 convertase)»stabilized by properdin»recruits C3 for more C3b»induces formation of C3bBbC3b (C5 convertase)»C5 produces C5a and b»C5b recruits C6»C7»C8»C9 forms pore»microbe dies by osmotic lysis
Classical
C1q(r2s2) associates with IgG or IgM»r2s2 cleave C4 and C2 and C4b and C2a bind to membrane»forms C4b2a (C3 convertase)»recruits C3 and cleaves into a and b»C3b binds and forms C4b2a3b (C5 convertase)»cleaves C5»C5b recruits C6»C7»C8»C9 forms pore and microbe dies by osmotic lysis
Lectin
MBL recognize polysaccharide»MBL associates with MASPs»cleave C4 and C2»form C4b2a (C3 convertase)»C3 recruited and cleaved»C3b binds and forms C4b2a3b (C5 convertase)»recruits and cleaves C5»C5b recruits C6»C7»C8»C9 forms pore and microbe dies by osmotic lysis
DAF
associates with C3b or C4b to competitively inhibit Bb or 2a from binding to form C3 convertase
MCP/CR1
Associate with C3b, enables factor I (or H) to proteolytically cleave C3b to iC3b
CD59
Associates with C7/8 to prevent MAC formation
C1 INH
Sequesters C1r2s2 complex to prevent activation of classical complement pathway (also targets MASP so lectin also affected)
Integrins
PMNs, monocytes, naive B and T cells express LFA-1 binds to ICAM-1 on endo eclls, lymphocytes, DCs and macrophages; monocytes express VLA-4 binds VCAM-1 on endo cells; monocytes express Mac-1 which binds ICAM-1
Selectins
Endo cells express P and E-selectin bind to sialyl Lewis X ligand on monocytes, PMNs, and effector T; monocytes, PMNs, and naive B/T express L-selectin bind to sialyl Lewis X ligand on endo cells
