First step in the immune system response:

• always "on"
• soluble factors followed by cellular response
  • soluble:
    • complements pathway
      • protease cascade (C3 is critical!!)
      • inflammatory (esp. C5a!!)
    • defensins
    • interferons
    • cytokines & chemokines
      • TNFalpha major inflammatory!!
  • cellular:
    • neutrophils (always on)
    • macrophages (need activation)
    • dendritic (DC) cells (shift to immune)
    • langerhans cells

Second step to the immune system response:

• directed by innate dendritic cells (DC)
  • activate CD4 & CD8 T cells
  • CD4 activates other cells
    • B cells make antibodies
    • macrophages at infection site
• T cells mature in Thymus
• B cells mature in Bone marrow
• memory cells are mature T & B cells
  
  • can be reactivated
• plasma cells are pure antibody factories (lotta ER)

Innate reponse immunity cell

• predominant, short-lived phagocytic WBC
• filled w/ granules = "granulocyte"
• inflammatory
• always "on"

Innate reponse immunity cell

• also called "monocyte"
• phagocytic, but must be activated 
• tissue-specific
  • e.g. Kupher cell, osteoclast, etc...

Innate reponse immunity cell

• coordinates shift from innate ---> immune
• different types:
  • myeloid
  • Langerhans - in the skin
  • plasmacytoid - make cytokines
    
  • follicular - "sticky" cell w/ no myeloid origin
    • CANNOT issue immune response

Innate reponse immunity cells

• NK cell
  • no T cell receptors
  • kills infected, antibody-covered cells
  • makes interferon gamma
• NKT & Gamma delta T
  • T cell & NK cell receptors
  • respond to bacterial products/secretions

Immune reponse cell

• mature in Thymus
• CD2, CD3 receptors
• release cytokines
• recognizes T cell receptors (TCR):
  • alpha beta
  • gamma delta
• two important types:
  • CD4 - activatory & phagocytic
  • CD8 - phagocytic

Immune reponse cell

• mature in bone marrow
• have surface Ig & MHC II
• make antibodies

Component of the innate response

• protease cascade ---> activate C3
  • "A is for Activity, B is for Binding"
    
• classified by way of activation:
  • alternate ---> bacterial cell surface
  • lectin ---> bacterial carbohydrates
  • classical ---> IgG or IgM
    • C1 unique to this pathway
• activates inflammatory processes:
  • anaphylaxis
  • chemotaxis
    • C5a = potent inflammatory product
  • Membrane Attack Complex (MAC)

• gram (+) cocci
• catalase (+)
• coagulase (+)
• naturally found on skin, nose
  
  • food poisoning, hospitals!!
• virulence factors:
  • capsule
  • peptidoglycan w/ teichoic acid
  • TSS toxin, enterotoxin
• causes:
  • skin infection (impetigo, foliculitis, furuncle)
  • Toxic shock syndrome (TSS)
    • fever, rash, N&V
  • Pyogenic

• gram (+) cocci
• catalase (+)
• coagulase (-)
• naturally found on skin (hospitals!!)
• virulence factors:
  • capsule
  • peptidoglycan w/ teichoic acid
• causes:
  • skin infection (impetigo, foliculitis, furuncle)
  • UTI
  • Pyogenic

• gram (+) cocci
• alpha hemolytic - incomplete hemolysis
  
• catalase (-)
• virulence factors:
  • capsule
  • peptidoglycan w/ teichoic acid
  • M protein (superantigen)
• causes:
  • pneumonia
  • meningitis
  • Pyogenic

• gram (+) cocci
• beta hemolytic - complete hemolysis
  
• catalase (-)
• Group A (bacitracin sensitive) 
• ubiquitous, mouth & throat
• give Penicillin
• virulence factors:
  • capsule
  • peptidoglycan w/ teichoic acid
  • M protein (superantigen)
• causes: (most pathogenic)
  
  • Scarlet fever
  • Strep throat
  • Glomerulonephritis
  • Puerperal fever
  • Rheumatic fever (later heart disease)
  • Pyogenic

• gram (+) rods
• ubiquitous anaerobe
  
• endospores
• virulence factors:
  • Tetanospasmin (A-B toxin)
    
    • neuro-exotoxin => block NT release
  • Tetanolysin
    • hemolytic exotoxin
  • peptidoglycan (w/ teichoic acid)
• causes:
  • Tetanus (spastic paralysis)
    
  • respiratory failure
    

• gram (+) bacillus
• ubiquitous anaerobe (soil, food)
  
• endospores
• virulence factors:
  • 7 types of A-B toxin (A-G)
    
    • affect NMJ => block ACh release
  • peptidoglycan (w/ teichoic acid)
• causes:
  • Botulism
    • descending motor loss, flaccid paralysis

• gram (+) bacillus
• ubiquitous anaerobe (soil)
  
• endospores
• virulence factors:
  • lethal toxins (a,b,e,I)
  • degradative enzymes
  • peptidoglycan (w/ teichoic acid)
• causes:
  • Myonecrosis (gas gangrene)
    • life-threatening!
    • rapidly spreading edema, necrosis, CO2
  • cellulitis
  • fascitis/myositis
    

• gram (+) bacillus
• normal gut flora, anaerobic, common to hospitals
  • pathology when it overpopulates => too much antibiotics
    
• give vancomycin
  
• endospores
• virulence factors:
  • peptidoglycan (w/ teichoic acid)
• causes:
  • diarrhea
  • intestinal infections

• gram (+) bacillus, very large
  
• always pathogenic
  
• endospores, aerobic & anaerobic
• virulence factors:
  • Anthrax toxin
    
    • factor I - edema factor (EF) 
    • factor II - protective antigen (PA)
    • factor III - lethal factor (LF)
      • can cause TSS
        
  • capsule
  • peptidoglycan (w/ teichoic acid)
  • S-layer => unique protein coat
• causes:
  • Anthrax
    • cutaneous easily resolved
    • GI & pulmonary extremely fatal

• Gram (-) 
• oxidase (-)
• variable O-antigen
• Lactose fermenting:
  • (+) E. coli, Enterobacter, Klebsiella, Citrobacter, Serratia
  • (-) Salmonella, Shigella, Proteus
• ubiquitous to gut => pathogenic elsewhere
  • EXCEPT Salmonella (never natural)
• virulence:
  • LPS (endotoxin)
  • cytotoxins, enterotoxins
  • O-antigen
  • siderophores
• causes:
  • gastroenteritis
  • UTI
  • sepsis
  • pneumonia
  • meningitis
    

• Gram (-) 
• oxidase (-)
• O-127 antigen
  
• Lactose fermenting (+)
  
• ubiquitous to gut => pathogenic elsewhere
• attach and disrupt microvilli
  
• virulence:
  • LPS (endotoxin)
  • cytotoxins, enterotoxins
  • O-antigen
  • siderophores
• causes:
  • diarrhea (infantile & watery)
    

• Gram (-) 
• oxidase (-)
• O-127 antigen
  
• Lactose fermenting (+)
  
• ubiquitous to gut => pathogenic elsewhere
• attach and disrupt microvilli
  
• virulence:
  • LPS (endotoxin)
  • enterotoxins, heat labile/stabile (LT-1 & Sta)
    • LT activates adenylate cyclase (cAMP)
      
    • Sta binds guanylate cyclase (cGMP)
      
  • O-antigen
  • siderophores
• causes:
  • diarrhea (watery)

• Gram (-) 
• oxidase (-)
• O-127 antigen
  
• Lactose fermenting (+)
  
• ubiquitous to gut => pathogenic elsewhere
• similar to Shigella (not as bad)
  
• virulence:
  • LPS (endotoxin)
  • cytotoxins, enterotoxins
  • O-antigen
  • siderophores
• causes:
  • diarrhea (watery)

• aka Shigatoxin E. coli (STEC)
• Gram (-) 
• oxidase (-)
• O157:H7 antigen => can't ferment sorbitol
  
• Lactose fermenting (+)
  
• invades macrophages => initiates inflammation
  • spread aided by host cell actin
    
• virulence:
  • LPS (endotoxin)
  • Shiga toxin (Stx I & II)
    • A-B toxin
    • inhibits protein synthesis
      
  • O157:H7
  • siderophores
• causes:
  • bloody diarrhea
    
  • hemolytic uremic syndrome (HUS)
  • dysentery
    

• Gram (-) 
• oxidase (-)
• Lactose fermenting (-)
  
• NOT normal flora
• immediately leaves the gut upon ingestion
  
  • invade lamina propria --> peripheral immune system
  • intracellular growth (immune-evading)
    
• virulence:
  • LPS (endotoxin)
  • Salmonella pathogenecity island (SPI)
    
  • Salmonella plasmid virulence (spv) genes
    • antigen switch (immune-evading)
      
• causes:
  • Typhoid fever
  • primary bacteremia --> septicemia
    • GI symptoms, headache, myalgia, etc..
      

Lactose fermentor test

• active fermenting => pink or red
  • E. coli releases bile as well
• use to differentiate gram (-) bacteria
• Recall,
  • (+) E. coli, enterobacter, klebsilla, etc...
  • (-) Salmonella, shigella, proteus

Lactose/sucrose fermentor test

• lactose/sucrose fermentors = yellow/orange
• H2S producers = black
• good for gram (+) differentiation
  

Mannitol fermentor test

• only Staphylococci survive high [salt]
• S. aureus = yellow

Mycobacteria test

similar to Middlebrook agar

Mycobacteria test

similar to LJ medium

• Gram (-), pleomorphic coccobacillus
• needs low temp, Cys for growth
• virulence:
  • LPS (endotoxin)
  • grows intracellular (ameoba, macrophages)
• immune response requires T cells
• causes:
  • pneumonia
  • fatigue, diarrhea, confusion

• Gram (-) bacilli
• Oxidase (+)
• grape-like, corn tortilla odor
• ubiquitous; soil, water, hospitals
  • biofilm => blue/green slime
• resistant to most antimicrobials
• virulence:
  • capsule
  • pili
  • LPS (endotoxin)
  • cytotoxins & exotoxins
  • elastase
  • Alginate - hallmark of chronic infection
    • immune evasion
  • biofilm
• causes:
  • respiratory disease (e.g. pneumonia)
    • immunocomprised/hospitalized
  • septic shock
  • UTI
  • endocarditis
  • osteochondritis

• Gram (-) diplococci
• "coffee bean" morphology
• Oxidase (+)
• Catalase (+)
• Maltose & Glucose fermentor
  
• Lipooligosaccharide (LOS)
• normal oral flora
• virulence:
  • capsule (need spleen)
  • LOS (endotoxic)
  • intracellular growth
    • immune evasion
• causes:
  • meningitis
    • fever, arthritis, lesions
  • Waterhouse-Friedrichson syndrome
  • septic shock
    

• Gram (-) diplococci
• "coffee bean" morphology
• Oxidase (+)
• Catalase (+)
• Glucose fermentor only
• likes chocolate agar
• Lipooligosaccharide (LOS)
• normal oral flora
• virulence:
  • capsule (need spleen)
  • pili => adherence
  • beta-lactamase
    
  • LOS (endotoxic)
  • intracellular growth
    • immune evasion
• causes:
  • gonorrhea => discharge
  • skin lesions
    

• Gram (-) comma-shaped rods
  
• Oxidase (+)
• facultative anaerobe
  
• lives in water
• virulence:
  • cholera toxin (A-B toxin)
  • pili
  • chemotaxis, zona occludens toxins
  • LPS (endotoxin)
• causes:
  • cholera => watery diarrhea, cramps, N&V
  • dehydration

• Gram (-) spirochetes
• stain w/ aniline dyes (Giemsa or Wright)
• obligate anaerobe
• grows in ticks
• virulence:
  • flagella
  • LPS (endotoxin)
  • gene heterogeneity for protein C
    • antigenic shift => immune evasive
      
• causes:
  • Lyme disease ("bulls-eye" bite mark)
    
  • chronic, recurrent fever
    

Immunoglobin G

• H chain = γ
• most functional/useful Ig
  • most prevalent, longest half-life
• early neonatal protection => babies get from Mom
• antigen clearance (agglutination, opsonization)
• T-cell dependent
• slow immune response
• associated w/ immune memory
  • levels MUCH higher upon 2nd infection

Immunoglobin M

• H chain = μ
• first class made by neonates
  
• early defense, primary response
• antigen clearance (agglutination, opsonization)
• T-cell independent
• fast immune response

Immunoglobin A

• H chain = α
• actively secreted
  • protects mucosa
• antigen clearance (agglutination, opsonization)
• T-cell depedent
• slow immune response
• associated w/ immune memory

Immunoglobin D

• H chain = δ
• B-cell activation
  
• early defense, primary response
• T-cell independent
• fast immune response

Immunoglobin E

• H chain = ε
• anti-parasitic
• activates Mast cells
  
  • associated w/ allergies
• T-cell dependent
• slow immune response
• associated w/ immune memory

• Class switch requires T cell help
• T interacts w/ B cell, directs expression via cytokines
• does NOT change VDJ (antigen-binding)
• combines VDJ w/ new heavy chain region

Deficiency in any one complement can result in a susceptibility to bacterial infections:

• C3 = worse, all bacterial infections
• C1-C4 = pyogenic infections
• C5-C9 = Neisserial infections (meningitis, gonorrhea)

• Clostridium perfringens
• Clostridium tetani
• Clostridium botulinum
• C. difficile
• Bacillus anthracis
• Bacillus cereus

• enterobacteriaceae
  • ETEC, EHEC, EIEC, EAEC
    • bacteremia, UTI, neonatal meningitis
  • Salmonella typhi (human -> human)
  • Salmonella typhimurium (animal -> human)
  • Shigella
• Vibrio cholera
• Pseudomonas

• Neisseria meningitidis
• Neisseria gonorrhoeae
• Borrelia burgdorferi
• Treponema pallidum

• Mycoplasma pneumoniae
• Mycoplasma (other)
• Rickettsia rickettsi
• Rickettsia prowazecki
• Chlamydia trachomatis
• Chlamydophila pneumoniae
• Chlamydophila psittaci

• tiny, tiny, tiny => cannot stain
• NO cell wall => resistant to cell wall antibiotics
• slow growing aerobe, require sterols
• human reservoir 
• virulence:
  • P1 adhesion protein
  • NO cell wall => antibiotic resistant
  • intracellular growth
• causes pneumonia
  
  • primary in respiratory tract
  • fever, chills, malaise
    

• Gram (-) weak, coccobacillus
  
  • half-breed => some LPS, some peptidoglycan
• tiny => intracellular growth (endothelial cells)
• ticks are main reservoir
• virulence:
  • peptidoglycan, some LPS
  • intracellular growth (endothelial cells)
• causes Rocky Mountain spotted fever
  • fever, headache, chills, myalgia, rash

• Gram (-) weak, coccobacillus
• part bact, part virus (energy parasite)
• tiny => intracellular growth
  
• little LPS, peptidoglycan
• human reservoir => most common STD
• two forms = elementary & reticulate
  • elementary is infective, spore-like
• virulence:
  
  • intracellular growth (epithelial cells)
  • inhibits phagosome/lysosome fusion
  • variation of outer membrane proteins
• causes Chlamydia
  • UTI, conjunctivitis, trachoma (eye)

• NR to Gram stain!
  • too small, use dark field microscopy
  • clinically => use serology (cannot culture)
• small, coiled spirochete
• humans only => STD
• virulence:
  • small
  • adherence proteins
  • hyaluronidase
• causes syphilis
  • painless lesions (remissions possible)
  • can spread to other systems
    

• Gram (+) - weak, rods, non-spore, acid fast
  • lipid coat reduces Gram stain
• complex, thick cell wall
• slow growing, antibiotic resistant
• human reservoir (immunocompromised)
  • most infected asymptomatic
• virulence:
  • thick cell wall => antibiotic resistant
  • intracellular growth
    • inhibit phagosome fusion w/ lysosome
  • granulomas
• causes Tuberculosis (no vaccine)
  
  • primary in respiratory tract
  • only affects 5% infected
  • malaise, weight loss, night sweats
  • tissue degeneration, can spread (hip, knee, spine)