Bacterial Pathogenesis Flashcards
1
Q
What is a pathogen?
A
organism that has the capacity to cause disease:
- opportunistic
- primary
2
Q
What are opportunistic pathogens?
A
- rarely cause disease in healthy hosts regularly cause disease in compromised hosts:
- burn victims susceptible to infection with pseudomonas aeruginosa
- HIV patients more susceptible to intracellular bacteria (mycobacteria)
- hospitalized patients on broad spectrum antibiotics (clostridium difficile)
3
Q
What are primary pathogens?
A
cause disease in healthy individuals
- have virulent mechanisms to overcome, mechanical, innate and adaptive immune responses rarely associate with their host except in the case of disease
- bacillus anthracis
4
Q
Infectious disease?
A
- damage or loss of tissue or organ function due to infection or host inflammatory response
- symptoms of infections are caused by the microorganism or by the immune response of the host
5
Q
Contact with organism does not always lead to disease, what could it lead to?
A
- elimination by host defense
- part of normal flora
- carrier state
- disease
6
Q
Whether or not disease results depends on what?
A
- virulence of pathogen
- environmental factors
- host factors
7
Q
What is virulence determinate?
A
properties that enable an organism to enter, replicate and persist in a host:
- expression of capsule, LPS, or pili
- elaboration of exotoxins that kill WBCs, proteases, siderophores
- generation of DNA inversions that lead to antigenic and phase variation
8
Q
How do we determine what properties of an organism are necessary or involved in the disease process?
A
there are scientific processes that we can go through to determine whether or not a virulence factor is required for that organism to cause disease or whether it facilitates ability to cause disease -some have several factors
9
Q
Stages of infection?
A
Transmission
Colonization
Multiplication
Invasion
Dissemination
Damage
10
Q
Congenital transmission?
A
transmission from mother to child
11
Q
Colonization?
A
- the ability to resist physical removal during infection
- establishment at site of infection can be mediated by specific receptor mediated interactions or biofilm formation
12
Q
Receptor mediate adhesion?
A
- adhesion: macromolecules on the surface of bacteria (pili, MSCRAMMs)
- receptor: specific carb or peptide on the surface of host cell that is bound by the adhesion
- bacterial adhesions mediate host specific adherence (E coli 987P only cause diarrhea in young pigs) and tissue specific adherence (E coliP pili mediate adherence to urinary tract)- gram -
13
Q
Microbial surface components recognizing adhesive matrix molecules?
A
- MSCRAMMs
- superfamily of surface adhesions that target host extracellular matrix proteins such as fibrinogen, fibronectin, collagen for adhesion
- only been studied in Gram + bacteria (lipoteichoic acid binds fibronectin)
- very specific
14
Q
Biofilm formation?
A
- aggregate of bacteria that bind to each other on a surface within a slime layer
- many difficult to treat infections are caused by bacteria in biofilms
- bacteria can communicate with other bacterial species in biofilms
- within biofilms bacteria resist:
- antibiotic attack
- being flushed away
- phagocytosis and complement attack
15
Q
How can bacteria acquire iron?
A
- secrete chelator called siderophore that bind ferric ions for transport into cell, can steal iron
- some bacteria have membrane proteins that have more affinity for iron than lactoferrin or transferrin, they take the iron
- multiplication: acquisition of iron
16
Q
What bacteria invade cells?
A
- facultative intracellular bacteria- invasion of cells is part to pathogenesis (bloody diarrhea instead of watery)
- obligate intracellular bacteria- invasion of cells required for growth or survival (can’t make their own ATP), chlamdyia trachomatis
17
Q
What are exoenzymes?
A
- allow organisms to degrade certain structures in the body, such as DNA
- facilitate dissemination
- Hyaluronidase- breaks down hyaluronic acid the ground substance of connective tissue
- Deoxyribonuclease (DNase)- thin pus made viscous by DNA released by dead WBC
- Streptokinase- activates plasminogen and converts it to plasmin which attacks fibrin clots allowing spread
18
Q
What can direct damage due to infection be the result of?
A
- by products of bacteria growth (acids, gas)
- secretion of exoenzymes that break down cells intracellular matrixes of host tissues
- secretion or elaboration of bacterial toxins (endo and exotoxins)
- damage by the immune response (host mediated pathogenesis)
19
Q
Bacterial toxins?
A
- alter metabolism of host cells
- exaggerate normal physiological functions
- stop cell growth
- some cause disease by themselves (purified toxin)
two categories:
- endotoxins
- exotoxins
20
Q
Endotoxins?
A
- LPS, lipid A-moiety toxic
- Gram negative
- outer membrane
- chromosomal, necessary gene
- weakly antigenic- cannot purify lipid A to immunize someone
- no toxoid, no vaccine
- weakly neutral by antibodies
- stable at high temps
- effect of LPS is the same regardless of bacterial origin
- immune response is responsible for disease
- liberated when bacteria lyse and/or released as part of membrane fractions
21
Q
Exotoxins?
A
- proteins
- Gram negative and Gram +
- extracellular- excretes it
- frequent phage or plasmid- acquired from
- highly antigenic
- can make toxoid vaccines
- neutralized by antibodies (IgG)
- unstable by high temperatures
- effects vary depending on bacterial origin
- different specificities, different diseases
22
Q
What is lipid A part of?
A
LPS- this is the toxic portion
-liberated when bacteria lyse and released as part of membrane fractions
23
Q
Lipid A is what?
A
PAMP- pathogen associated molecular pattern
-bind to and are recognized by PRR of the innate immune system
24
Q
Examples of PAMPs?
A
- LPS, lipoteichoic acid, lipoproteins, mycobacterial lipoarabinomannan
- peptidoglycan, flagella
- DNA (unmethylated CpG motifs not in mammalian DNA), toxins
25
What are toll like receptors?
- pattern recognition receptors (PRR)
- many that bind extracellular bacteria **(TLR-4 for LPS)**
26
Mechanism that LPS stimulates immune system (lipid A induces cytokines)?
- different than with super antigens
1. lipid A binds to LBP
2. binds to CD14 and TLR-4
3. signal is sent inside cell to stimulate NF-kappaB to release TNF-alpha (coagulation) and IL-1 (fever)
4. could cause septic shock
27
TNF and IL-1?
- primary mediators of endotoxemia
- produced by macrophages when stimulated by endotoxin
- endotoxin shock is usually associated with systemic spread of organisms:
local release -\> containment and removal of infection
systemic release -\> hypotension, DIC, systemic shock (septic)
28
Characteristics of exotoxins?
- secreted or membrane bound and released upon lysis, not integral part of structure of organism
- specifically destroy or inhibit cell functions or tissue components
- vary in specificity (neuro, cyto, entero- gut)
- many, but not all, possess enzymatic activity
29
routes of entry of exotoxins?
- mucosal infections
- wound infections
- intestinal infections
- food poisoning (intoxication)
30
Exotoxin structures and mechanism of action?
A is the active unit responsible for specific action in the cell that interferes with cell
B- specific binding unit to receptor pore forming
- bind to surface, cause pores, water leaves cell, lyses superantigens
- inappropriate association with TCR and MHC molecule so response is polyclonal and large number of T cells and cytokines respond, toxic shock
31
What is diphtheria toxin?
- blocks protein synthesis
- A is the active unit, B is binding unit
- only cells with a receptor B, will be affected by A
- toxin expressed on a prophage, only diphtheria strains with phage are pathogenic
- toxin converted to toxoid -part of DTap vaccine
32
What does cholera toxin result in?
- massive loss of water from intestinal epithelial cells
- AB toxin
- get it through drinking water, bacteria gets into gut -enterotoxin
- causes increased adenylate cyclase, increased cAMP
- watery diarrhea, rice water stools (vibrio cholera)
33
What are hemolysins?
- bind to surface of cells and cause holes in cells
- toxins that damage cell membranes enzymatically or by the insertion of pore forming molecules
- clostridium perfringens (gas gangrene)
34
What are super antigens?
- powerful polyclonal T cell mitogens, get more activation, more aggravation, more cytokines
- stimulates nonspecific T cell responses
- binds to MHC class 2 molecule and T cell receptor **outside** of antigen binding sites (outside of cleft)
- leads to improper immune response and a toxic cascade of cytokines (toxic shock syndrome)
- increase TNF-alpha
35
Evasion of antibody?
- intracellular residence
- antigenic and phase variation
- bind antibody inappropriately (S Aureus)
- elaboration of Ig A protease
- molecular mimicry
- bacteria must overcome/survive constitutive and induced defenses to successfully cause infection
36
Mechanisms microbes use to prevent harmful effects of complement?
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