How Do Microbes Cause Disease Flashcards
what is the standard pattern for stages of disease?
*Incubation period
-Asymptomatic period
-Toxins produced
*Prodromal stage
-Vague feelings of discomfort
-Nonspecific complaints
*Period of illness (invasion)
-Symptomatic and more specific signs and symptoms
-Effect of toxins
*Convalescence
-Persons immune system responds to infection (or medical intervention)
describe the complement system + its function. how do pathogens resist + subvert these host immune responses and persist in any host
complement system= its made up of plasma proteins (i.e. blood soluble proteins), the plasma proteins react with one another to opsonise pathogens + induce a series of inflammatory responses to fight infection [part of first response of Innate Immune system]
3 main functions of complement:
1- opsonisation (C3b) and pathogen clearance by phagocytes
2- MAC : membrane attack complex (C5b) and direct lysis of pathogens
3- enhancing inflammation (C5a): activation and recruitment of phagocytic cells by anaphylatoxins (C5a, C3a) released by digestion of complements components
explain how bacterial toxins induce damage to the host + contribute to disease
- bacteria can prevent phagocytosis by macrophages by inhibitting chemoattractants, inhibiting chemotaxis e.g. Streptococcus pyogenes degrades C5a-specific serine protease
- bacteria can prevent being ingested by phagocytosis by killing phagocytes, having capsules that protect them from opsonisation,
- bacteria can escape from endosome-phagosome and grow in cytoplasm
- bacteria can destroy antibodies e.g. IgA proteases {enzymes that break down antibodies are produced by following bacteria):
*H. influenzae
*N. meningitidis
*S. pneumoniae
What are the 2 major factors of bacterial adherence to a host cell
1) PILI + FIMBRIAE
pili (singular: a pilus) is a hair-like microfiber appendage found on the surface of many bacteria and archaea.Pili only occur on gram -ve bacteria. Pilli are long and thick. Pili aid in bacterial conjugation
fimbriae= tiny, bristle-like fibers arising from bacteria. Fimbriae occur in both gram +ve and gram -ve bacteria. Fimbriae are short and thin. Fimbriae attach the bacterium to the substrate
SO BOTH THESE SURFACE STRUCTURES ARE A WAY IN WHICH THE BACTERIA ATTACK THE HOST CELL (these are a major factor of bacterial adhesion)
2)AFIMBRIAL ADHESIN
*membrane or mebrane bound glycoproteins or glycans that interact with host cell receptors via a bridging molecule{bring the bacteria in close contact to our cells} and help bacteria to adhere + attack them
what are biofilms? why are they clinically relevant?
Structured community of bacteria that produce a sugar polymer, known as extrapolymeric substance (EPS), that allows the biofilm to attach to a surface
clinical relevance
* biofilms have extreme resistance to antibiotics + other anti-microbial agents
* high resistance to host immune defences
some bacterial pathogen produce degradative enzymes (spreading factors) that participate in formation of lesions at the site of colonisation and facilitate growth and spread of the pathogen - They do not kill host cells.
What are the following spreading factors?
*hyaluronidase
*collagenase
hyaluronidase (spreading factor):
– breaks down hyaluronic acid (intracellular cement of connective tissue)
– e.g., Streptococcus spp, Staphylococcus aureus,
certain Clostridium spp
collagenase breaks down collagen network supporting tissues + promotes spread of infection e.g. some Clostridium perfringens {causes gas gangrene}
explain the 2 main mechanism of bacterial invasion into host cells: Trigger + Zipper
triggered invasion
e.g. used by salmonella bacteria
-bacteria inject virulence factors directly into host cell cytoplasm to activate their own uptake by the cell
-these virulence factors modify host cells to engulf them (i.e. ‘triggering’ cytoskeletal rearrangement in host cell)
zippered invasion
e.g. used by Listeria or Yersinia bacteria
-cell wall of bacteria has these high affinity receptors on it that recognise + BIND TO host cell receptors
-so now they are bound together + the bacteria activates signalling pathways inside host cell that encourage the host cell to take the bacteria in (zips its way in)
define opsonization of pathogens
Opsonization is an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes. Without an opsonin, such as an antibody, the negatively-charged cell walls of the pathogen and phagocyte repel each other
what is a zymogen
a zymogen is an inactive substance which is converted into an enzyme when activated by another enzyme
how does h.pylori invade the gastric mucosa
Helicobacter pylori is a gram-negative, flagellated, microaerophilic bacterium that selectively colonizes the gastric mucosa.
- H. pylori expresses Lewis X antigen (LPS=lipopolysaccharide), a normal component of gastric epithelium. Allows unrecognised colonization of gastric antrum.
n.b. the LPS mediates the binding of the bacterium to laminin, and interferes with gastric cell receptor-laminin interaction, thereby potentially contributing to the loss of mucosal integrity
- Antrum: the lower portion (near the small intestine), where the food mixes with gastric juice. Pylorus: the last part of the stomach, which acts as a valve to control the emptying of the stomach contents into the small intestine
what is the difference between an endotoxin and an exotoxin
endotoxins are part of the outer portion of the cell wall of gram -ve bacteria. They are released when bacteria die + cell wall breaks apart
endotoxins include: cell wall components; lipopolysaccharide(LPS), peptidoglycan, teichoic acids
exotoxins are released from live bacteria + are mostly produce by gram +ve bacteria
3 main types of exotoxins:
*Cytolysins with cell membrane targets (stimulate production of cytokines and can drive body into toxic shock)
*Bipartite A-B toxins: intracellular targets
*Toxins acting on host defences (superantigens)
what is cholera caused by and explain the mechanism of the cholera toxin?
Vibrio cholerae bacteria produces Cholera toxin: speeds-up normal excretory process in gut epithelium leading to massive fluids loss with diarrhoea and severe dehydration
how does cholera toxin induce diarrhoea?
* Cholera toxin is an A-B toxin
*ADP-ribosylates large G proteins that regulates cyclic AMP (cAMP)
* Increase of cAMP (up to X100)
*Stimulates chloride ions secretion via cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel
*Water and other electrolytes osmotically follow which cause diarrhea
*Severe cases: up to 12 liters of liquid lost per day
*Untreated cases: mortality about 50%
*Treatment: fluids and electrolytes
what is a superantigen?
Normal situation: antigen is presented by class II MHC and recognized by only a specific sets of T cells with right T cell receptor.
T cells produce and release cytokines locally and activate only B cells specific from antigen.
0.01 to 0.001 % of T-cells activated
super antigen= induces non-specific class II MHC – T-cell receptor binding.
Cause widespread non-specific stimulation of T-cells.
Excessive cytokine release, systemic. Leads to fever, vomiting, diarrhea and circulation/organs failure and death
20 to 30% of T-cells activated
n.b. Toxic Shock Syndromes are mediated by exotoxins which activate the immune system to release inflammatory cytokines. These exotoxins act as superantigens, causing T cell activation and the resulting “cytokine storm” (TNF-alpha, interleukin [IL]-1, and IL-6)
Some viruses incorporate their nucleic acid into the host genome which can cause the development of cancers; what are some examples of viruses that can do this
- Hep B – hepatocellular carcinoma
- Epstein Barr – Burkitts lymphoma
- HIV – lymphoma
- HPV – cervical carcinoma
what are some examples of disease caused by A-B EXOTOXINS
Examples of disease caused by A-B EXOTOXINS
- Diphtheria – caused by Corynebacterium diphtheriae
– Toxin inhibits protein synthesis in heart muscle & other cells
Symptoms= - Tetanus – caused by Clostridium tetani
– Toxin affects neuromuscular junctions → blocks release of inhibitory neurotransmitters (GABA- Glycine) in CNS→ leads to irreversible contraction of muscle and spastic paralysis
Symptoms= - Botulism – caused by Clostridium botulinum
– Toxin affects neuro