How do Microbes Cause Disease (2) ? Flashcards
what first response of innate immune system?
The innate immune system is made of defenses against infection that can be activated immediately once a pathogen attacks. The innate immune system is essentially made up of barriers that aim to keep viruses, bacteria, parasites, and other foreign particles out of your body or limit their ability to spread and move throughout the body. The innate immune system includes:
Physical Barriers: such as skin, the gastrointestinal tract, the respiratory tract, the nasopharynx, cilia, eyelashes and other body hair.
Defense Mechanisms: such as secretions, mucous, bile, gastric acid, saliva, tears, and sweat.
General Immune Responses
such as inflammation, complement, and non-specific cellular responses. The inflammatory response actively brings immune cells to the site of an infection by increasing blood flow to the area. Complement is an immune response that marks pathogens for destruction and makes holes in the cell membrane of the pathogen. Check out our video that explains inflammation and complement, which we will touch on later.
The innate immune system is always general, or nonspecific, meaning anything that is identified as foreign or non-self is a target for the innate immune response. The innate immune system is activated by the presence of antigens and their chemical properties
what is the complement system?
what are the three main functions?
- *group of blood soluble proteins:**
- 30 proteins circulate in inactive forms
- activated by pathogens detection
- chain reaction: activated proteins activate other proteins by cleavage
- *functions:**
- opsonisation (C3b and IGG): opsonins tag foreign pathogens for elimination by phagocytes
- membrane attack complex (MAC) (C5b): formation at surface of invading microbes of clustering of complement molecules. create a pore in microbe. leads to lysis and death
- enhance inflammation: activation and recruitment of phagocytic cells by anaphylatoxins (C5a & C3a), released by digestion of complement components
how does phagocytosis occur?
what antimicrobial lysosomal enzymes used?
- microbe detected by receptor on phagocyte
- engulfment of microbe in vesicle: phagosome
- lysosome with degradative enzymes binds to phagosome: phagolysosome
- toxic substances, like reactive oxygen species: (superoxide, H2O2), nitric oxide and lysosomal enzymes (cationic peptides, alpha defensins) destroy them
how do some microbes resist phagocytosis by macrophages?
- **inhibit phagocyte mobilization
- **inhibit chemoattractants. e.g. Streptococcus pyogenes degrades C5a
- inhibit chemotaxis. e.g. Pertussis toxin causes intracellular rise in cAMP in neutrophils to impair chemotaxis -
avoid ingestion:
- kill phagocytes
- capsules protect from opsonization
- stealth: bacterial capsules that resemble self (need to know e.g.s?)
give an example of stealth strategy by microbes
- S. aureus* produces protein A in its membrane
- protein A binds to Fc portion of host antibody
- prevents ingestion and phagocytosis
what are ways that microbibes can evade host defences when INSIDE the host? (4)
microbiocidal effects
- escape from endosome-phagosome and grow in cytoplasm: Listeria / Shigella
- inhibition of phagosome-lysosome fusion: Leigonella pneumophilia
- survive within phagolysosome
4. replicate within phagolysosome: Salmonella
how can some microbes survive detoxifcation of oxygen derived harmful substances?
detoxifcation of oxygen derived harmful substances from the host:
e.g. some microbes have:
- superoxide dismutase (SOD): neutralises free radicals such as O2
- *- catalase** (breaks down H2O2): e.g. Staph. aureas
how do some microbes destory antibodies?
- create IgA proteases
- these destroy IgA (IgA coat foreign microbes with mucous)
where do pathogens get their nutrients from?
what is hard to find for them :( - how do they get around this?
- sugar and fatty acids abundant in host
- hard to get Fe :(
- get around this by: produce siderophores - have v high affinity for Fe (take it from ferritin (where Fe naturally found))
what are microbial toxins?
main 2 categories? when are each released?
microbrial toxins: virulence factors that damage host:
- Endotoxins: cell wall components of bacteria. main one: lipopolysaccharide (also: peptidoglycan, teichoic acids). only released when bacteria die
-
Exotoxins: actively released from live bacteria
3 main types:
- cytolysins: target cell membrane
- bipartite A-B toxins: intracellular targets
- toxins acting on host defences
which bacteria produce lipooploysaccharide (LPS)?
where located in bacteria?
made of? which part is toxic?
gram negative bacteria
location: outer membrane of bacteria cell wall
structure: lipid A, core polysaccharide, O antigen
lipid A = toxic
how does LPS inflict damage?
activates complement and stimualtes producion of cytokines: results in septic shock, ferver, intravascular coagulation = haemorrage and endotoxin shock.
what happens when have too much endotoxin LPS produced?
what are the 3 main type of exotoxins?
- toxins that damage membranes: cytolysines and pore forming toxins. help spread of bacteria
- toxins that act as enzymes: A/B toxins, more diverse group of toxins
- toxins that activate immune response: superantigens
explain how A/B toxins work
what are the different subunits and what are their functions?
act as enzymes: most toxins acting as enzymes are A-B toxins
- 2 subunits: A&B
- A = enzymatic activity
- B = binds to cell membrane (allows A to go into cell(
cholera toxin:
- *-** produced by?
- what does it do in the body?
- does it induce ^?
Cholera toxin
produced by: Vibrio cholerae
effect: speeds up normal excreotry process in gut epithelium: massive fluid loss. diarrhoea
induces diarrhoea by:
- A-B toxin
- A part activates cell’s G-protein, modifies G-protein and keeps it in active state
- causes more and more production of adenylate cyclase: causes more cAMP
- this stimulates CFTR channel to have more Cl- leave cell: imbalance of electrolytes
- water follows Cl- and electrolytes
- causes severe diaarhea
- treatment: fluodsa and electroyltes
