Plagues & Pandemics - Beatty

Pathogen

a microorganism or other biological agent that can cause disease

Endemic

infection that is continually present in a population or geographic area

Epidemic

an outbreak of infectious disease above the normal level of infections that then subsides

Pandemic

infections that spread over more than 3 continents

Protease

enzyme that breaks down proteins and peptides

Phagocytosis

A type of endocytosis where a cell engulfs large particles and fuses with a lysosome for digestion

Plasma

Liquid part of blood; carries proteins, nutrients, and waste

Lymph fluid

What plasma becomes once it enters tissues, washes out debris and pathogens.

Lymph node

bean-shaped organs that filter lymph fluid.

Lymph vessel

thin tubes that transport lymph fluid around the body & to/from the bloodstream after being filtered at the nodes

Lymphatic system

System of lymph fluid, vessels, nodes, tissue, etc

Pathogenesis

The process by which a disease develops and progresses in a host organism.

Inflammation

Innate immune response. Symptom of damage/infection. Caused by an influx of cells, fluid, tissue destruction, or pathogen presence.

Phagocytes

Macrophages, dendritic cells, neutrophils

Macrophage

phagocytes that specialize in engulfing and killing bacteria, activate adaptive immune response

Dendritic cell

phagocyte located in tissues. when a PAMP is detected, they go to lymph nodes to activate the T cells of the adaptive immune system. professional antigen-presenting cells, uptake antigens from tissues to bring to lymph nodes.

Neutrophil

abundant phagocytes for killing bacteria (with enzymes and reactive O2 species). can cause tissue damage because they're sloppy killers. quick in, quick out to avoid residual effect (1-2 days). most important phagocyte for killing bacteria

PAMP (Pathogen Associated Molecular Patterns)

Conserved structures across many pathogens that are difficult for the pathogen to alter. Function like a danger signal to the immune system. Ligands for TLR's.

TLR (Toll-like receptors)

Proteins that detect and bind to PAMPs to signal for the production of cytokines.

Cytokine

Small proteins that are released at the site of infection. Bind to receptors on WBC's to give signal to increase immune response. Too many produced = too many immune cells = shock, death. Too few = failure to contain infection

TNF (tumor necrosis factor)

type of cytokine. too much can cause autoimmune disease

Virus

noncellular obligate parasite.

Bacteria

prokaryotic, single-celled organism, can reproduce independently.

Protozoa

eukaryotic, single celled organism, larger & more complex than bacteria.

Macrophage vs dendritic cell

Macrophages primarily phagocytize pathogens, while DC's mostly focus on antigen presentation.

B cell

Makes antibodies. Can only make one type of antibody for one pathogen.

T cell

Help increase antibody production, kill infected cells.

Antibody aka immunoglobin

protein produced to counteract a specific pathogen. can only bind to specific epitopes on the pathogen's antigens. circulate in the blood and lymph.

Antigen

The specific molecule or part of a molecule on a pathogen that the immune system recognizes as foreign. Not always disease-causing: can be pollen, dust mites, etc.

Antigen vs PAMP

Antigen: unique to a specific pathogen, triggers a highly targeted adaptive immune response. PAMP: common feature across multiple pathogens used by the innate immune system treated as a danger signal.

Epitope

Specific part of an antigen recognized & bound by antibodies.

Fab region

"variable region" of an antibody that binds to antigens.

FC region (effector region)

"constant region" of an antibody that gives certain properties. 4 main types: GAME

Neutralization

Physically block virus from binding to receptors on host cell surface or block the active site of a toxin. Usually high affinity (aka binds well to antigens), mostly Ig G and Ig A

Opsonization

Fc of antibody binds to the FcReceptor on phagocytic cells (mostly macrophages) to increase phagocytosis uptake. Mostly Ig G and Ig E

Complement

A blood toxin that when activated (encounters Ig M-coated bacteria) deposits on the bacteria's surface and kills the pathogen via the toxic effects or increased chance of phagocytosis

CR G

Neutralizes and does opsonization (promotes phagocytosis by macrophages). Circulates in blood

CR A

Neutralizes. Secreted into mucosal sites (thin layer of cells lining lungs, intestines, reproductive sites)

Antigen presentation

When a pathogen replicates inside or is engulfed by a host cell, protein fragments are displayed on the cell's surface. Way for the infected cells to alert the adaptive immune system

MHC's (Major Histocompatibility Complex)

Molecules that do the job of antigen presentation

Professional antigen-presenting cells

Cells that specialize in antigen presentation, ex. dendritic cells, macrophages, B cells

TCR (T cell receptor)

have a variable and constant region. variable region only recognizes antigens presented by MHC's on other cells. Activates T cell

Cognate

Specific combination of MHC and antigen recognized by one TCR

CD4 helper T cells

When its TCR is engaged by its cognate, it will produce cytokines to increase antibody production and/or increase activation of CD8 cytotoxic T cells.

Cd8 cytotoxic T cells

When its TCR is engaged by its cognate, it will kill the cell presenting antigens

Lymphocyte

Type of white blood cell important for immune response: includes B and T cells

Result of too much acute inflammation

severe disease, ex. pneumonia (COVID, flu)

preventative vaccine

give pre-infection, protection from primary infection (HPV, flu, Hep B)

therapeutic vaccine

give post-infection, for slow-acting pathogens (BCG for tb)

adjuvent

add PAMPs to vaccines to activate macrophages & DC’s & make the vaccine more effective. currently gives ligands to bind to TLR’s

attenuated/live

weakened form of pathogen that can still slowly cause an immune response → create antibodies without getting sick. ex: MMR, oral polio

inactivated vaccine

killed pathogen, can’t infect → needs an adjuvent to trigger immune response & activate inflammation. ex: flu, current polio shot, tetanus toxoid

mRNA vaccine

vaccine contains mRNA instructions on how to make a viral protein → AB’s. ex: SARS

immunogenicity

the ability of a substance to cause an immune response

pros of inactivated vaccine

no revirulence, good for viruses that change frequently

cons of inactivated vaccine

no replication of pathogen, weak antigen presentation for CTL’s, don’t last as long

pros of activated vaccines

self-replicating, low dosage, no adjuvent, authentic antigen presentation → better at activating CTL’s

cons of activated vaccines

chance of revirulence

live vector vaccine

insert genes from the pathogen into a harmless/weakened virus vector. ex: VSV Ebola

pros of live vector vaccine

self-replicating, no adjuvent

cons of live vector vaccine

possibility of pathogenesis from the live vector

recombinant protein vaccine

piece of DNA is inserted into cell to make immunogenic proteins (usually envelope/membrane proteins), those proteins are put into vaccine, sometimes with adjuvent. ex: HPV, Hep B

pros of recombinant protein vaccine

cheaper, very safe

cons of recombinant protein vaccine

no pathogen replicated and adjuvent/boosters needed because it’s only protein, may not last long-term

SARS vaccine types

Pfizer/Moderna: mRNA

Novavax: recombinant protein

AstraZeneca/J&J: viral vector

pros for SARS mRNA vaccine

fast production - easy to insert new strain into same mRNA vector

mimics aspects of infection; lipid nanoparticles activate TLR’s

safer than most vaccines

cons for SARS mRNA vaccine

must be kept in lipids/sugars

must be kept frozen

not stable once thawed

bacteremia

blood infection (caused staph aureus in healthcare settings)

toxin

type of virulence factor released by bacteria to directly damage host tissues or disrupt normal cellular functions

virulence factor

molecules, structures, or traits that cause disease, invade the host, evade the immune system, or obtain nutrients

staph aureus replication location

outside cells

conditions caused by staph aureus exfoliative toxin

impetigo, SSSS

staph aureus toxins that cause food poisoning

enterotoxins

pneumonia

lung infection (caused by staph aureus in healthcare settings)

endocarditis

heart valve infection (caused by staph aureus in healthcare settings)

osteomyelitis

bone infection (caused by staph aureus in healthcare settings)

serotype/serovar

distinguished by surface antigens

pathovar

distinguished by the disease it causes or host it infects

EHEC/STEC

most pathogenic E. coli, zoonotic from cattle, secreted Shiga toxin, lysed cells clog kidneys → bleeding in urinal tract, kidney failure.

EPEC

childhood diarrhea, human-human, no Shiga toxin

where is EHEC found?

contaminated beef

Stx function & location

injures eukaryotic ribosome & inhibits protein synthesis. found in EHEC

sources of EHEC transmission

cattle/beef, cow poop as fertilizer

characteristics of S. typhimurium (salmonella)

more infections/fewer deaths, localized & acute infection, can cause gastroeneritis (stomach virus) & diarrhea

characteristics of S. typhi (salmonella)

fewer infections/more deaths, typhoid disease, can disseminate into bone marrow/spinal cord/gallbladder, systemic & chronic infection2

2 types of salmonella

S. typhimurium, S. typhi

where does yersina pestis replicate

inside macrophages (intracellular)

transmission of plague

fleas on rodents

forms of plague

bubonic, septicemic, pneumonic

replication location of bubonic plague

lymph

replication location of septicemic plague

blood

replication location of pneumonic plague

lungs, can pass lung-lung

treatment for plague

antibiotics fast (most deaths are from untimely treatment)

survival of yersinia pestis bacteria

virulence factors, creates own endosome

prevention of plague

avoid contact w/ fleas, 1 licensed vaccine

symptoms of TB

bloody cough, weight loss, fever, nausea

disease that has “lethal synergy with TB” & why

HIV kills CD4 TH cells → needed to control TB

pace of TB replication

SLOW - divide once/20hrs

conversion rate of TB from latent → active with HIV

8% per year

characteristics of chest x-ray for TB

for active TB, imprecise, spots can be anything