Vaccines and pathogens Flashcards
Mechanisms of pathogens
Extracellular:
- encapsulated - can’t be phagocytosed without Ab and complement (Strep pneumo, Strep pyogenes, Staph aureus, Neisseria)
- toxin releasing (Vibrio cholerae)
Intracellular - live within phagocyte without getting digested
- Mycobacterium, Salmonella, Chlamydia
Pathogen breach of mechanical barriers
Usually tight junctions maintain innate immunity
- Burn -> disrupts -> Pseudomonas
- Strep pyogenes -> lipotechoic acid -> attachment/colonization
- Neisseria meningitidis -> endocytosis in nasal epithelium
Pathogen activation of innate response
Early response:
Complement, leukocytes activated by cell walls, LPS, CpG-DNA, viral RNA -> Ifn-g, IL-12
TLRs (pattern recognition receptors) -> pathogen associated molecular patterns (PAMPs)
- ex CpG (hypomethylated bacteria) DNA, viral RNA, LPS, flagellin, lipoproteins
- > TNF-a, IL1, IL6
Pathogens and adaptive immunity
This is where vaccines are active! Innate function (inflammation + presentation) -> priming, memory
Vaccine schedule
Multiple immunizations - super complicated
Combination of killed, subunit and attenuated
Most have multiple boosters to ensure response
Overall vaccine concepts
Need:
- right antigen
- right place (effector memory, directed response)
- induce correct arm of immune system
Closest mimic to pathogen -> most targeted response (also highest risk of infection)
- ex intranasal smallpox -> immunity or death
- vs intradermal cowpox - safer, right route
Also want safe, cheap, stable, long-lasting
Vaccine adjuvants
Required for most vaccines!!
- antigen without costimulation -> anergy vs activation of lymphocytes
Inflammation -> APC response -> cosstimulation
- can be directed towards Th1, Th2
- ex alum (weak), moophosphoryl lipid A (Salmonella LPA)
Functions:
- retention of antigen -> prolonged release and exposure
- aggregates to soluble proteins -> higher density
- TLR agonists -> cytokines, costimulation
- inflammation -> recruits WBCs for more presentation
Herd immunity
Two mechanisms of population protection
- shed live vaccine -> innoculate others (ex oral polio vaccine)
- prevent spread of disease (disrupts transmission)
Antibody vaccine responses
Most common effector response
Usu target to GI, resp or systemic (IM, ID) for blood-borne pathogens
Mechanisms
- prevent binding - ex polio IgA in gut
- direct immune response (opsonize -> macrophages, ADCC)
- block colonization
- block toxins (tetanus, clostridium)
Cell-mediated vaccine responses
Less common but sometimes required for full response
- ex CD8 -> cell apoptosis or lysis before pathogens released
Usually target CD4 -> B cell, macrophage, etc
Types of vaccines
Live attenuated (aka modified live):
- retain complete antigen profile -> most effective (replicate, induce MHC 1 -> CTL response)
- some risk of reversion to virulent -> contraindicated for immune deficient patients!
Subunit:
- produce some CD8 response but less
- ex viral, CpG DNC
Killed:
- not effective inducing CD8, shorter duration
- safer - ex IM polio less effective but no reversion
- how to ensure all are killed
- RSV - killing/fixation altered immunogenicity
- ex rabies, cholera, HIV?
Conjugate vaccines
Polysaccharide (ex bacterial = Penumococcal PCV)
- can’t induce T cell response (not a peptide)
- conjugate to carrier protein -> APC and B cell response (T-cell independent) -> carrier presented to T cell -> T cell response
Often have only polysaccharide for booster (T-cell independent) - can directly re-activate B cell memory
Toxoid vaccine
Attenuate exotoxins (heat, chemical/formalin) -> neutralizing antibodies
Ex: diptheria, tetanus, pertussis (used to be cellular form but caused reactions)
Subunit vaccines
More targeted but also more expensive
Produce specific epitope -> CD8 and antibody responses
- always requires adjuvant for inflammation/costimulation
Flu - isolate viral proteins -> B cell and T cell epitopes
(most effective is attenuated nasal -> broader CD8 response)
Passive vaccination
Provide antibodies directly
Ex: rabies antiserum, RSV for premature neonates
