Micro I Flashcards
What are the mechanisms that bacteria and protozoa use to resist complement mediated killing?
- Capsule and long LPS O antigens: the outer capsule prevents complement activation; Long LPS O antigens prevent complement receptors of the phagocytes from obtaining access to fixed C3b on the microbe
- Coating in immunoglobulins (S.aureus, S.Pyogenes)
- Membrane bound enzymes can degrade the complement
**whenever the bacteria has something coming off of its surface, it is usually to avoid opsonization or to facilitate adhesion to the host
What are the mechanisms by which bacteria and protozoa use to resist phagocytosis?
- Release of toxins that kill phagocytes (S.aureus, S.Pyogenes)
- Release of catalase to prevent oxidative killing (S.Aureus)
- Escape from the phagolysosome and live in the cytoplasm of the macrophage (and replicate there within the phagocyte; T. Cruzi)
- Prevention of Opsonization by releasing molecules (ie: protein A) that interact with the antibodies so that the organism doesnt, thus preventing phagocytosis
- Inhibition of fusion of phagosome and lysosome
- Prevention of contact with phagocyte via a capsule
- Defense against cytokines: ie: PLasmodia secretes IL-2 receptors that prevent T-cell activation during malaria; pseudomonas aeurinosa secretes enzymes that cleave IL-2 and IFN- G
How do persistent infections thrive?
persistent = reside in their host for long periods (years);
- The shed of persistent microbes into the environment can be continuous (ie: Hep B into blood), or intermittent (ie: Tubercle bacillus)
- Very relevant when it comes to viruses, which are well adapted to be persistent infections, for example, Hepesvirus may latently infect dorsal root ganglia becoming re-activated later; or it may be shed into salivary secretions and infect other
What are the strategies that microbes use to evade (avoid) the host immune response?
They attempt to conceal their antigens by:
- interfering with the display of Ag on the surface of infected cells (HIV)
- Readily shed, therefore making the Ag less accessible to circulating lymphocytes (ie: Skin and secretory duct colonizers)
- Molecular mimicry (molecules that cross-react with human proteins)
- Coat themselves with host proteins (ie: S.Aureus coats in Fc receptors to bind immunoglobulin; Viruses can secrete Fc receptors to bind immuoglobulins to the surface of infected cells)
- Induce tolerance or anergy (No B/T Response)
ie: Cytomegalovirus infects during embryonic life; Coccidiodes inmitis produces large quatities of antigen, thus inducing anergy
What are some molecules that produce Fc Receptors? what is the function of this?
= staphlococci, steptococci, herpes simplex virus, varicella-zoster, cytomegalovirus;
The point is so that antibodies attach to the microbe (that has Fc receptors on its surface) in a “backwards” position so that it doesn’t induce an immune response; The bacteria can avoid neutralization/opsonization/complement
Describe the concept of antigenic variation and its function in infection
= antigenic shift and antigenic drift
= variation of surface components during infection, confounds immune response to pathogen; whatever is on the pathogen’s surface is what the host responds to and produces immunity agains, so if the organism can change its surface characteristics then it can avoid the immune response and it cam lead to WAVES of infection where there is an initial microbial growth, but then an immune response decreases microbial growth rapidly, but then there is an antigen change resulting in a “new” epitope, and thus the cycle repeats itself
Relates to influenza, which can undergo antigenic drift (new mutations in genes) or antigenic shift (new combinations of strains leads to a new strain);
Relates to parasites which may carry unexpressed surface protein genes, in which movement of a gene 3’ to the promotes allows for its expression (thus sequential recombination permits the expression of different antigens during the life cycle)
What is the difference between antigenic drift and antigenic shift?
antigenic drift = the natural mutation over time of known strains of influenza (or other things, in a more general sense) which may lead to a loss of immunity, or in vaccine mismatch. IE: repeated point mutations in hemagglutinin and neuraminidase genes
antigenic shift = two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains.
IE: recombination of different strains of influenza leads to a new strain; CAN LEAD TO PANDEMICS!
What effect do micro-organisms have on the immune system? How do infections cause this?
If viruses infect T/B cells or macrophages, can cause an immunosuppressive effect;
Bacterial toxins can also disrupt the normal immune response by lysing lymphocytes, cleaving immunoglobulins, and inactivating complement;
EX: staph/strep superantigens disrupt the normal immune response
Some viruses (herpesvirus) can encode a cytokine homologue that interferes with the immune system
What are bacterial exotoxins? What are the two classes?
= hydrolytic enzymes that degrade DNA or connective tissue promoting spread of infection; the enxymes are secreted (type I, II, or III secretions), and have an effect somewhere other than the infection site
- Cytolysins
- Cytotoxins
** in Gram negative bacteria, the toxins form in the periplasm!
What is the difference between cytolysins and cytotoxins?
Both are exotoxins
Cytolysins = disrupt mammalian cell membrane and cause the cell to lyse (form a pore that causes loss of nutrients and filling of water, or they cause enzymatic lysis of the cell membrane)
Cytotoxins = classic bacterial toxins with an AB subunit (A = active portion; its an enzyme that gets translocated into the cell and produces effect. B = binding portion, it binds to a receptor so that A can be secreted)
- They disrupt the mammalian cellular physiology by modifying some substrate, usually by transferring ADP-ribose group from NAD to a substrate
- The effects range including: inhibition of protein synthesis, increase in cytosolic cAMP (causes hyperactivity), disruption of nerve transmission
What is bacterial endotoxin? What is its effect on the immune response?
= Gram-negative Lipopolysacharride (LPS)
Range of effects on immune response including: fever and vascular collapse (shock); primarily due to cytokines IL-1 and TNF
**staph and strep superantigens induce similar physiologic responses
HOW?
LPS on organism binds to macrophages which promote IL-1 and TNF secretion to cause fevers and increased adhesion of PMNs on endothelial cells; also they increase vascular permeability and vasodilate
Describe the damage response of microbial pathogenesis
A curve where Host damage/benefit = y axis, and host response = x-axis.
IF the host response to the microbial pathogen is too strong/too weak then there is lots of host damage; if the response is intermediate, then there is little host damage, but there isn’t any benefit;
IF the reponses is too weak, damage is due to the pathogen, if the host response is too strong, damage is due to the immune system damaging tissue
What is a macule?
flat, red with inflammatory response to microbe or toxin (has infiltrating leukocytes)
What is a papule?
raised, red with more marked inflammation than a macule; involves the invasion of neighboring itssue
What is a vesicle?
a blister; microbe invades the epithelium; includes HSV and VZV infections
What is a furuncle?
a boil; microbe invades the dermis by colonizing the hair follicle (folliculitis);
There is coagulation of fibirin around the lesion
= pus-filled bumps that form under your skin when bacteria infect and inflame hair follicles. Boils (furuncles) usually start as red, tender lumps. The lumps quickly fill with pus, growing larger and more painful until they rupture and drain.
What is a carbuncle?
A carbuncle is a cluster of boils that form a connected area of infection under the skin, and infect hair follicles;
- focal suppuration (decay in tissue forming pus; an abcess)
- May lead to entry of organism into bloodstream via lymphatics
What is impetigo?
a bullous, crusted, or pustular eruption; HONEY COLORED
What is erysipelas?
Well-defined, spreading inflammation of DERMAL LYMPHATICS
What is cellulitis?
acute inflammation due to infection of subcutaneous fat
What is Necrotizing fascitis?
inflammatory response in soft tissue below the site of infection
What dictates how aggressive a pathogen infects the host and the depth of the tissue of invasion?
VIRULENCE FACTORS!!! especially cytolysins
What are some of the virulence factors relevant to Staph infections?
- Alpha toxin:
pore-forming cytolysin that kills RBC and WBC; its a pore that assembles in the pepmbrane and permits fluid loss from the cell (complement-like MOA) - Toxic Shock Syndrome Toxin (TSST-1) :
pyrogenic exotoxin from Group A step; its a superAg (NOT A TYPE AB EXOTOXIN!) that cross links T-cell receptor and MHC II causing massive cytokine release enhancing endotoxic shock (IL-2, IFN-G, IL-1, TNF-A) - Exfoliative Toxins (in Staph Scalded Skin Syndrome SSSS):
2 types: chromosomal and plasmid encoded: induce intercellular splitting at desmosome between stratum spinosum and stratum granulosum causing bullous lesions - Exoproteins for spread:
Hyaluronidase that hydrolyzes CT, or staphylokinase that promotes fibrinolysis - Antiphagocytic components:
Protein A bind the Fc portion of IgG (to turn off immune response);
Coagulase promotes surface polymerization of fibrin to resist phagocytosis
Catalase neutralizes H2O2 - Quorum sensing to regulate virulence factor expression in response to cell density: causes upregulation of coagulase at LOW cell densities for colonization (promotes surface polymerization of fibrin), and upregulation of staphylokinase at HIGH densities for spread (promotes fibrinolysis)
How are skin/soft tissue infections transmitted?
- via skin/nasal carriage because there isn’t any acquired immunity here
- via fomites (inanimate objects)
What is scalded skin syndrome?
- caused by staph (SSSS)
- comes from the hands of HCW that have EXFOLIATIVE TOXIN on them, coming into contact with NEONATES and CHILDREN;
- causes a bullous impetigo that is localized
- exfoliative toxin induces intercellular splitting at desmosome between stratum spinosum and stratum granulosum causing bullous lesions
What is toxic Shock syndrome caused by?
-casued by TSST-1, a superantigen that colonizes vagina or wound infection and causes a huge T-Cell response that can lead to shock
How does wound contamination lead to infections?
- spreads into bloodstream via lymphatics (bacteremia)
- endocarditis, osteomyelitis, meningitis, and pulmonary infections result from bacteremia
What are the different tests performed for a suspected Staph infection?
- Collect the specimen: surface swab, blood, pus cultured on blood agar
- Determine Gram staining (Gram + in clusters = Staph/Strep in clusters);
- Catalase Test: to determine Staph vs. Strep:
+ = production of O2 bubbles when H2O2 added to culture; = STAPH - Coagulase Test: to determine the different strain of Staph (S. Aureus = highly virulent vs. S. epidermidis and S. Saprophyticus = low virulence)
- Tests the coagulation of citrated plasma by culture; if the serum coagulates, then its is the high virulent staph (S. AUERUS) if it does NOT coagulate = low virulence staph - Test Antimicrobial susceptibility (to see if what drug and what dose is the best to give the patient, so that higher resistant strains aren’t produced)
What is M-Protein and how is it related to skin and wound infections?
-Mediates binding to epidermis
Viruses, parasites and bacteria are covered in protein and sugar molecules that help them gain entry into a host by counteracting the host’s defenses. One such molecule is the M protein produced by certain streptococcal bacteria.
M proteins embody a motif that is now known to be shared by many Gram-positive bacterial surface proteins. The motif includes a conserved pentapeptide which precedes a hydrophobic C-terminal membrane anchor (anchored in peptidoglycan of well wall);
The Amino terminus is variable due to genentic recombination which leads to antigenic variation and type-specific immunity
M protein is strongly anti-phagocytic and is a major virulence factor. It binds to serum factor H, destroying C3-convertase and preventing opsonization by C3b. However plasma B cells can generate antibodies against M protein which will help in opsonization and further the destruction of the microorganism by the macrophages and neutrophilis. Cross-reactivity of anti-M protein antibodies with heart muscle is the basis for acute glomerulonephritis
-several factors embedded in the cell wall, including M protein, lipoteichoic acid, and protein F (SfbI) facilitate attachment to various host cells.[10] M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators. The M protein found on some serotypes is also able to prevent opsonization by binding to fibrinogen.[1] However, the M protein is also the weakest point in this pathogen’s defense, as antibodies produced by the immune system against M protein target the bacteria for engulfment by phagocytes. M proteins are unique to each strain, and identification can be used clinically to confirm the strain causing an infection.
What is protein F?
A protein on the surface of Step Pyogenes that acts as a virulence factor by mediating fibronecting binding at wound sites
What is Steptolysin O (SLO) and Steptolysin S (SLS)
A protein on the surface of strep pyogenes that acts as a virulence factor
- causes Beta hemolysis on blood agar plates
- SLO is a cytolysin that attacks cell membranes and forms large pores, it is oxygen labile (sulfhydryl-activated)
- Ab to SLO mediate self-attack and augment cell lysis
What is Streptococcal Pyrogenic Exotoxins (Spe-A-C)?
- A virulent factor
- SpeA is produced by lysogenized (bacteriophage-carrying) Group A Strep
- it is superantigen that has a sequence homology with staph pyrogenic exotoxin
- induces cytokine release leading to fever, rash, T-cell stimulation, endotoxin sensitivity (Character of scarlett fever)
How are hydrolytic enzymes act as a virulent factor for strep? what is a hydrolytic enzymes of importance?
- responsible for the thin, runny pus in streptococcal infections; pus due to break down of DNA
- streptokinase dissolves fibrin to facilitate spread (used therapeutically because it also dissolves blood clots)
- Seen in impetigo as the honey crusted lesions `
What causes Impetigo (what is the pathogenesis?)
- infection through minor trauma, insect bite typically on face and/or lower extremities
- small vesicle that ruptures leading to serous exudate (secretion), superficial spread, honey colored crust (dried up serum)
- caused by strep pyogenes infection of skin
- Epidemics occur with children 2-5 y/o due to hot, humid climate, poor hygiene, crowding (HIGHLY CONTAGIOUS)
- Transmission is person-peron, and by fomites (shared towels)
- S. Aureas can be bullous (blister) impetigo, or contaminate stepcoccal lesions
- causative M protein types differ from respiratory serotypes
