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)