Med Micro 1.2 Flashcards
Main mechanisms of pathogenesis
Invasion of tissue (entry!) and production of toxins. May be one or both.
Why is adhesion not mentioned in main mechanisms of pathogenesis?
It is a prerequisite for invasion. Goes without saying
Invasiveness factors
Intracellular and extracellular pathogens; capsules; adaptation; extracellular enzymes
Intracellular and extracellular pathogens
Few intra, cause chronic disease; extra- cause acute disease (needs to access nutrients - cause damage)
Endogenous and exogenous antigens and their result
Endogenous presented to cytotoxic T cells by MHC1: show viral infection, etc. Exogenous to T helper cells by MHC2: present results of phagocytosis; T helpers make cytokines, B cells make antibodies
Capsules
hydrophilic gels that inhibit phagocytosis. Usually an essential virulence factor
Adaptation
microenvironments of host provide habitats for bacteria that are capable of selective tissue invasion. Not every pathogen in a region can cause an infection there.
Extracellular enzymes
Help degrade host tissues
Invasins
Basically a spreading factor, can’t stay in same place forever!; enzyme family, help get through tissue matrices and intercellular spaces
Quorum sensing
Need a certain number of microbes. Turns on many other genes. Others can bind
Toxins
Exotoxins: toxic but heat labile; Good immunogens. Endotoxins: complex lipopolysaccharide from cell wall; poorly immunogenic; released when cells lyse; heat stable, mostly in gram negative.
Why is it important that LPS is a poor immunogen?
Immunogen = elicits immune response; most proteins are (except small ones). We don’t have a good response to LPS.
Membrane-damaging exotoxins
Form pores in eukaryotic membranes; streptolysin from streptococcus lyse RBC, WBC, platelets; hemolysin lyses RBC (S. aureus) ; listeriolysin from Listeria helps it evade lysosomes when endocytosed.
How is hemolysin expression regulated?
In response to low iron levels so it can break open RBC and gain some
Defining entry again
Portals of entry are the areas where the pathogen gains access to tissues. Actual entry is invading those tissues, actually getting into the body
A-B toxins
A chain inhibits some cell functions; B chain binds and helps A enter. In cholera
Endotoxin (LPS)
Lipopolysaccharide or Lipid A in gram negative bacteria. Very variable in polysaccharide size even within one type of bac. Need to test for LPS even if bacteria don’t grow
Virulence
combination of invasiveness and toxigenicity producing the ability to overcome host defenses and cause disease
Testing Virulence
measured with LD50. lethal dose: the # of bacteria to kill half of a population
What is the point of an LD50 study?
Gives level of virulence and we can look at virulence factors (mutate the bacteria and perform the test several times), which is needed for vaccine development
Some host defences
Skin, mucous, innate immunity, inducible ; some are specific, others not; vary with alcohol, drugs, nutrition, genetics,
Factors in innate immunity
Inflammatory response, phagocytes, antimicrobials, complement, other WBC (neutrophils), Natural killer cells
Inducible/Adaptive response
Hemoral immunity (ABs from B cells), cell-mediated response
Skin and mucous pupose
Mechanical factors, chemical (eg Lysosyme, sebum), microbial factors (normal microflora are competitive, release antibiotics to compete for resources)
Phagocytic cells
Respond to and release cytokines when they consume pathogens. Cytokines turn on inflammation, neutrophils etc recruited. Monocytes in blood, macrophages/dendritic cells fixed in tissues.
Responses to phagocytosis of a bacterial cell? (lots!)
Signal b/w 2nd and 3rd line of defense. Antigen presentation (humoral); inflammation (interstitial fluid leaks easier, enter lymph to present antigens or bacteria);
Humoral factors - role of antibody mediated defense
Antitoxins. Bacteriolytic antibodies (AB plus complement - make hole in them). Opsonizing AB (coat cell surface and enhance phagocytosis - ie target for phagocytosis). Agglutinating ABs
Cell-mediated factors
Cytotoxic T lymphocytes; NK cells; activate macrophages
Communicability
Source (dormant or latent - carriers?); # infectious agents released from host; capability of surviving transit b/w hosts; Percent of host population susceptible
Superinfector
Someone who doesn’t display symptoms but releases huge amounts of -particles
Triangle of relationships
Humans, drugs, microbes. All interacting, all evolving.
