Exam 5 Flashcards
any situation in which a microbe is established and growing in a host; begins at mucous membranes found throughout the body
infection
pathogens adhere to mucosal surfaces through interactions between
pathogen and host macromolecules
4 adherence factors
capsule/slime layer, adherence proteins, lipoteichoic acid, fimbriae pili
Steps in pathogenesis
- Exposure to Pathogen
- Adherence
- Invasion
- Colonization & Growth
- Toxicity OR Invasiveness
- Tissue Damage/Disease
Describe invasion… what is needed?
pathogen penetrates the epithelium; needs nutrients and right growth conditions
substantial microbial growth in host tissue; dependent on location in the body
microbial colonization
microbial growth at the site of invasion
localized infection
spread of microbe throughout body via blood or lymphatic systems; more difficult to treat/ more likely to be deadly
systemic infection
microbe that cause disease; colonization early in life could be fatal
pathogen
microbe that causes disease when host defense is absent or compromised; some are resident flora (Staphylococcus or Candida)
opportunistic pathogen
damage or injury to the host that impairs host function; preceded by infection
disease
ability of a pathogen to cause disease
virulence
the number of pathogen required to kill 50% of the population
Lethal Dose 50
anything made by the pathogen to help it cause disease
virulent factors
help pathogen attach to host cell (ex. fimbrial protein subunit of E. coli)
adherence factors
help pathogen to invade host tissue (ex. Clostridium hyaluronidase breaks own hyaluronic acid that holds cells together)
invasive factors
help pathogen grow within host tissue (ex. Vibrio cholera secretes a protein (TcpF) that allows colonization of the small intestine)
Colonization Factors
help pathogen avoid phagocytosis (ex. Encapsulated Bacillus anthracis, Treponema pallidum binds host fibronectin for disguise)
Cell Surface Structures
soluble chemical excreted by viable pathogen
exotoxins
causes lysis of host cell (ex. Staphylococcal alpha-toxin)
cytolytic toxins
composed of two proteins covalently bound: B subunit binds to host cell and transfers the A subunit into the host cell to cause damage (ex. Diphtheria toxin produced by Corynebacterium diphtheriae)
A-B toxins
exotoxins that affect the small intestine, causing changes in intestinal permeability that lead to diarrhea (ex. Cholera toxin produced by Vibrio cholera)
enterotoxins
How is the cholera boxing produced by Vibrio cholera
- Normal ion movement, Na+ from lumen to blood, no net Cl- movement
- Colonization and toxin production
- Activation of epithelial adenyl cyclase by cholera toxin
- Na+ movement blocked, no net CL- movement to lumen
- Massive water movement to the lumen
stimulate large numbers of immune response cells causing extensive inflammatory reactions (ex. Staphylococcus aureus TSST-1 causes TSS)
superantigen toxin
toxic bacterial structural component released upon bacterial cell death; lipopolysaccharides derived from the outer membrane of gram-Neg bacteria
endotoxin
how do you detect endotoxins?
LAL assay
loss of virulence that can be attained by genetically engineered vaccines or naturally under non optimal growth conditions
attenuation
the ability of an organism to resist infection (ex. Bone marrow stem cells produce leukocytes)
Immunity
leukocytes
phagocytes & lymphocytes
4 types of phagocytes
dendritic cell
macrophage
neutrophil
mast cell
2 types of lymphocytes
t cell
plasma cells
where do all leukocytes come from
bone marrow stem cell
what body fluid systems transport immune cells throughout the body
circulatory and lymphatic systems
what is the first line of internal defense against pathogens
innate (non-specific) immunity
contact virus, bacterium, tumor cells; release perforin and granzymes to kill
Natural Killer Lymphocytes
if there is MHC 1 recognition, then the NK cell is deactivated
recognition of cells by Natural Killer cells
What happens when the Natural Killer cells recognizes cancer & viral infected cells
stress protein receptor recognizes stress protein on cell, then NK cell kills the cell
Neutrophils & Monocytes (macrophages and dendritic cells) that destroy the pathogen by phagocytosis
Phagocytes
pore forming protein
perforin
exogenous serine proteases
granzymes
steps in phagocytosis
- Phagocyte pattern-recognition molecules recognize pathogen-associated molecular pattern on pathogen
- phagocytosis
- Lysosome fuses with phagosome and secretes enzymes into the phagosome to digest the pathogen
What do phagocytes have on their cell surface to recognize pathogens?
phagocyte pattern-recognition molecules
What part of a pathogen is recognized by a phagocyte?
pathogen-associated molecular pattern
4 ways the pathogen can protect itself from phagocytosis
- Pigments to neutralize singlet oxygen (Staph aureus, carotenoids)
- Molecules scavenge toxic oxygen (Mycobacterium tuberculosis, cell wall glycolipids)
- Leukocidins kill phagocyte (Streptococcus pyogenes)
- Capsule prevents the adherence of phagocyte to the bacterial cell (Streptococcus pneumoniae)
localized nonspecific response to noxious stimuli (toxins, pathogens)
inflammation
arrive at site first in response to chemokine released from damaged host cells; release proteases, phospholipase, and collagenases to destroy bacteria; secrete chemokines such as Macrophage Inflammatory Proteins to signal macrophages to come help
neutrophils
secrete inflammatory cytokines (increase vascular permeability, swelling, reddening, heat); phagocytosis ensues if pathogen is present
macrophages
release histamines and cause vasodilation (increase in vascular capillary diameter)
mast cells
a systemic inflammatory response; life threatening
septic shock
main cause of septic shock
rupture of the large intestine causing leakage of gram negative enteric bacteria into sterile areas
adaptive (specific) immunity is defined by 3 properties
specificity, memory, and tolerance
immune cells recognize and react with antigens via direct molecular interaction
specificity property in adaptive immunity
memory T cells and B cells allow for faster and stronger secondary response
memory property in adaptive immunity
immune cells are not able to react with self antigen
tolerance property in adaptive immunity
Steps in adaptive immunity
- initial steps similar to innate immunity
- leukocyte displays digested pathogen peptide (antigen) on its cell surface thereby becoming an antigen-reseting cell
- t–cell recognizes the antigen on the antigen-presenting cell
- pathogen is destoyed
type of leukocytes and t cells in cell-mediated immunity
Leukocytes: Macrophages and Dendritic cells
Type of T-Cells: T-cytotoxic and T-helper 1 cells
type of leukocytes and t cells in antibody-mediated (humoral) immunity
Leukocytes: B cells
Type of T-Cells: T-helper 2 cells
positive selection in T cell tolerance
retains T-cells that recognize self MHC proteins
negative selection in T cell tolerance
retains T-cells that do not bind tightly to MHC/self-antigen complex
when T-cell receptor binds to antigen/MHC complex, T-cell:
- becomes activated
- divides to make more T-cells….
Effector Cells and Memory Cells
short lived and carry out function of T-cell
effector cell
remain inactive until they encounter the same antigen in the future; long-lived
memory cell
2 types of T-cell function in cell-mediated immunity
- t-cytotoxic cells destroy antigen-presenting cell (MHC 1 antigen presentation)
- t-helper 1 cells increase phagocytosis and cause inflammation (MHC 2 antigen presentation)
steps in antibody-mediated immunity
- Initial antigen exposure and primary response that leads to the production of antibodies and memory cells
- Secondary antigen exposure
- Subsequent antigen exposure
Steps of initial antigen exposure and primary response
- B cell uses antibody to recognize and bind antigen
- Antigen-antibody complex is internalized
- Antigen is processed and loaded onto MH II protein
- MHC-antigen complex is presented on the B cell surface
- Th2 Cell recognizes MHC-antigen complex stimulating cytokine production by Th2 Cell
- Cytokines stimulate nearby antigen-specific B cells to make antigen-specific antibodies (mostly IgM)
make antibodies in the primary response, short-lived
plasma cells
used upon future exposure to antigen, long-lived
memory cells
faster than primary response, doesn’t require T-cells, memory cells transform into plasma cells and begin producing IgG
secondary response induced by reexposure to antigen
over time, antibody titer _____
decreases
subsequent antien exposure will lead to another
secondary immune response
proteins activated by innate and adaptive immunities
complement proteins
classical complement activation
uses antigen-antibody complex
- Antibody binds antigen and complement protein
- sequential binding of other complement proteins
- bacterial cell membrane damage and lysis
alternative pathway of complement activation
host serum proteins bind to bacterial cell surface; C3 binding initiates binding of other complement proteins
binding of antibodies or C3 enhances phagocytosis because phagocytes have antibody receptors that recognize constant domain and C3 receptors
opsonization
inappropriate immune response resulting in host damage (four types)
hypersensitivities
pathogen proteins that cause widespread stimulation of immune cells resulting in a massive inflammatory response damaging the host
superantigen
antibody mediated; allergy; occurs within minutes of secondary antigen (allergen) exposure; reactions are mild to life-threatening
type I, immediate hypersensitivity
primary response of type I, immediate hypersensitivity
allergens stimulate Th2 cells to secrete cytokines causing B cells to release IgE which bind to mast cell receptors
secondary response of type I, immediate hypersensitivity
if allergen binds to nearby IgE antibodies to cross-link them, then degranulation occurs
treatment of Type I, immediate hypersensitivity depends on severity
removal of allergen, antihistamines, steroids to reduce inflammation, adrenaline, desensitization
activate abnormally large amounts of T cells; excess cytokine production causing systemic inflammatory reactions
superantigen
Examples of Staph aureus as a superantigen
Food poisoning and TSS
individual receives antibodies but did not make the antibodies
passive immunity
natural passive immunity example
fetus gets IgG from mother in utero; newborns get IgA from breast milk
artificial passive immunity example
injection of antiserum or antitoxin
individual is exposed to antigen and memory cells are produced
active immunity
natural active immunity example
infection
artificial active immunity example
immunization
found that milkmaids exposed to cowpox were immune to smallpox, so he started vaccinating people with cowpox
Edward Jenner
resistance of a population to infection due to immunity of a high proportion of the individuals in that population
herd immunity
What percentage of herd needs to be vaccinated to have herd immunity to measles
90%
7 types of vaccines
- Toxoid
- Surface Protein
- Killed Bacteria Cel
- Inactivated Virus
- Live Cells/Activated Virus
- Purified Polysaccharide (Conjugated)
- Recombinant Antigen
- DNA Vaccine
chemical modified exotoxin retains antigenicity but no toxicity (ex. Tetanus, Diphtheria, Anthrax)
Toxoid vaccine
Formaldehyde create proteins from the bacteria (ex. Pertussis)
Surface Protein vaccine
formaldehyde, heat (ex. Typhoid Fever)
Killed Bacteria Cell vaccine
formaldehyde (ex. Rotavirus, IPV, flu)
Inactivated Virus vaccine
attenuated strains; more effective for viral immunity (MMR, Var, BCG)
Live Cells/Active Virus vaccine
antigenic polysaccharide from capsule is attached to a protein (ex. MCV4, PCV7, Hib)
Purified Polysaccharide (Conjugated) vaccine
pathogen gene that codes for an antigen is put into a harmless microbial host (yeast) to make lots of th antigen (ex. HAV, HBV, HPV)
Recombinant Antigen vaccine
bacterial plasmid containing a pathogen antigen (ex. HIV clinical trials)
DNA vaccine
viral size
~20-44nm; smaller than their host cell
viral structure
a nucleocapsid made of nucleic acid (viral genome) surrounded by a protective protein coat (capsid)
made of capsomeres containing one or more proteins; arranged to give vision symmetry
capsid
rod-shaped; protein subunits twist up; length of virus is determined by length of nucleic acid
helical symmetry
roughly spherical; 20 equilateral triangles with 3 or more capsomeres in each
Icosahedral symmetry
outer membrane (lipid bilayer) around capsid derived from the host cell
enveloped viral structure
multiple parts of the viral structure assembled separately
complex viral structure
What are the two forms of a virus? In which form does the virus do harm?
- extracellular and intracellular
- the virus does harm in the intracellular
how are viruses classified?
their genomes and how they make DNA
Steps in viral replication of a virulent phage
Attachement, Penetration, Synthesis of nuclei acid and protein, Assembly and packaging, Release (lysis)
bacteriophage that leaves by budding
M13
bacteriophage act injects a phage and kills it
T4
Packaging of DNA into T4 phage head
Packaging motor attaches to proceed. dsDNA moves into the head by a proton motive force. Scaffold proteins discarded. Other assembly steps. Packaging motor discarded.
Temperate virus infects the cell and has two options
Lytic Cycle or Lysogeny
viral genome integrates into host chromosome
lysogeny
the virus when its genome exists as part of host genome
prophage
host cell that harbors prophage
lysogen
transfer of a specific region of bacterial chromosome to another bacterium via a virus; requires a lysogen to be moved incorrectly (rare)
specialized transduction
represses genes involved in lysis; required in low concentrations to maintain lysogeny
CI (lambda repressor)
represses genes involved in lysogeny; needed in greater amount than CI to force lambda into lytic cycle
Cro
when lysogeny occurs, this can survive in a dormant host cell while virulent phages need active host cellular biosynthetic machinery
prophage
When does Lysis occur?
if cell has DNA damage.
in nutrient-rich environments when many proteases are present in the host cell.
CI is destroyed by host protease -> Cro Protein accumulates -> lytic cycle begins
How does a dsDNA virus make new dsDNA genomes and mRNA
The DNA of the viral genome enters the cell’s nucleus. New viral DNA is synthesized in the nucleus. Transcription produces mRNAs that are translated on cytoplasmic ribosomes into capsid and spike proteins. Capsid proteins enter the nucleus and combine with viral genomes to form new nucleocapsids. The viruses bud through eh nuclear membrane but do no acquire their final envelope and spikes until reaching a Golgi Complex.
What is the structure of a typical retrovirus
RNA and enzymes surrounded by a core protein, surrounded by a core shell protein, surrounded by a lipid membrane bilayer with surface envelope proteins and transmembrane envelope proteins
What is the genome of a retrovirus?
ssRNA
has a Gag, Pol, and Env regions
makes structural proteins like protease
Gag
makes reverse transcriptase and integrase (DNA endonuclease)
Pol
makes envelope glycoproteins
Env
Replication of a retrovirus
- Entry and uncoating of the retrovirus
- Reverse transcriptase (2 steps)
- Viral DNA enters nucleus and integrates into the host genome
- Transcription by host RNA polymerase forms viral mRNA and genome copies
- Translation of mRNA forms viral proteins; new nucleocapsids assembled and released by budding
Where does the envelope come from that surrounds some viruses?
from host cytoplasmic membrane
Destruction of host cells (ex. Pox viruses, Poliovirus)
Lytic
enveloped viruses, new visions leave host by budding, cell does not die but remains infected and will produce visions indefinitely, influenza virus
Persistent
virus is not actively replicating, formant; some integrate into host cell genome, but others don’t. Symptoms appear only when virus emerges from latency. (ex. Herpes simplex, Varicella-Zoster), herpesvirus, HIV
Latent
Virus can transform from a norma cell to a cancer cell. Genetic changes that relate growth. (ex. Human Papillomavirus, Epstein-Barr, Cytomegalovirus)
Oncogenic
genes who products are key components of signaling pathways that stimulate cell proliferation
oncogene normally found in cells
normal gene that can be converted into an oncogene
Proto-oncogene (Oncogene normally found in cells)
extra genes not needed for viral replication
oncogene found in oncogenic viruses
misimpression of oncogene in the wrong cell type or prolonged expression can lead to
uncontrolled cell proliferation
oncogene off ->
normal cell growth an division
oncogene on ->
uncontrolled cell growth and division (tumor)
protein particle, no nucleic acid; cause animal neurodegenerative diseases called transmissible spongiform encelphalpathies
prions
Creutzfeldt-Jakob Disease
human disease caused by prions
Bovine Spongiform Encephalopathy
mad cow disease, vCJD if transmitted to humans ….. caused by prions
chronic wasting disease
disease in deer and elk caused by prions
3 ways to get prion disease
- Infectious - ingestion of nervous tissue from infected animal
- Sporadic - having a mutation in the prnp DNA of a neuronal cell
- Inherited - mutation in germ line cells
smallest known pathogens; circular, ssRNA; no protein; cause plant diseases
viroids
Host defense from viruses in eukaryotes
immune system; RNA interface (RNAi)
dsRNA nuclease
dicer
short interfering RNA
siRNA
RNA-induced silencing complex
RISC
ssRNA nuclease
slicer
the CRISPR antiviral defense system
DNA is transcribed into CRISPR RNA. Cutting of DNA by Cas proteins. Foreign sequence is recognized by CRISPR RNA. Can proteins cut and destroy foreign nucleic acid
Host defense from viruses in prokaryotes
Restriction & Methylation
using restriction endonuclease to cut viral dsDNA at specific sequences
Restriction defense in prokaryotes
DNA methylates to methylate their own DNA to prevent cleavage by their own and viral restriction endonucleases
methylation defense in prokaryotes
unaffected by restriction systems
ssDNA and RNA
modify their DNA to avoid digestion by the host’s restrict endonuclease
dsDNA viruses
disguising with sugar
glucosylation
encode proteins to inhibit host restriction systems
viral genomes
3 Anti-HIV drugs
Fusion inhibitors, Reverse transcriptase inhibitors, Protease inhibitors
synthetic peptide that binds to an HIV membrane protein preventing the viral membrane from binding to the host cell membrane
fusion inhibitors
bind HIV protease, preventing the protease fro processing viral polypeptides
protease inhibitors
