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Epidemiology
Finding the causes of diseases, including infectious and non-infectious diseases.
Miasma Theory
The old idea that disease was caused by âbad air.â
Germ Theory
Idea that microbes cause disease
Epidemic
An outbreak of infectious disease that then subsides
Epidemic
An outbreak of infectious disease within a community or region
Big 3
HIV, TB, malaria
Innate immunity
Limits the spread of pathogens during initial infection, activates adaptive immune system
Adaptive Immunity
Can eliminate specific pathogens, creates memory for faster responses during future infections
DNA
ATGC, preferred genetic material
DNA base pairing
AT, GC
RNA
AUGC, used in many viruses
Central dogma
DNA â RNA â Protein
Triplet code
3 nucleotides = 1 amino acid
Retroviruses
Makes DNA from RNA template through reverse transcription; HIV
RNA viruses
Makes direct copies of RNA through RNA replication
Prions
Proteins capable of replicating without DNA or RNA`
Gene
segment of DNA/RNA that gives rise to protein
Genome
All nucleic acids passed from parent to offspring, includes DNA that isnât genes
Virus
Infectious pathogen (HIV)
Bacterium
Prokaryotic pathogen (TB)
Protozoan
Eukaryotic pathogen (malaria)
Morbidity
Illness/complications caused by disease, ex. parasitic worms may cause morbidity w/o directly causing death
Phagocytes
WBC that âeatâ pathogens/material through phagocytosis
Macrophage
Performs phagocytosis, presents antigens, removes old/dying cells, repairs wounds, stimulates adaptive immunity, detects pathogens, and orchestrates inflammation
Macrophage killing
Kill when activated by cytokines
Dendritic cell (DC)
Takes up antigens @ peripheral infection sites, presents them in lymph nodes, helps initiate adaptive immunity
Neutrophil
Major/common phagocyte responsible for killing bacteriaNeut
Neutrophil granules
contain toxic proteins & enzymes that kill bacteria
Neutrophil Disadvantage
Toxic contents can cause substantial damage to surrounding healthy tissue
Neutrophil Lifespan
Short-lived, rapidly repleted from bone marrow
Lysosome
Contains enzymes that digest engulfed material
B cell
Only cell type capable of producing antibodies
Antibody
Protein produced by B cells that binds to an antigen
FAB region
Variable region of an antibody that specifically binds an antigen
Fc region
Constant region of an antibody that determines its isotype/functions
Antibody isotypes
IgM, IgG, IgA, IgE
Antibody diversity
10^11 different antibodies
B Cell specificity
Each B cell creates one kind of antibody
Neutralization
antibodies bind pathogens/toxins & block their function
Opsonization
Antibodies make pathogens easier for phagocytes to engulfC
omplement
Can promote opsonization, phagocytosis, or lysis
Antibody-dependent cellular cytotoxicity
Antibodies coat a target cell & recruit cytotoxic(CT) WBCs to destroy it
Cytotoxic T Cell
Kills infected cells, especially virally infected cellsCD
CD8+ T cell
Cytotoxic T cell that kills phagocytes
CD4+/T helper cells
produces cytokines & regulates adaptive immune responses
T cell receptor (TCR)
Recognizes antigen when presented by MHC
major histocompatibility complex (MHC)
displays pathogen fragments on host cell surfaces
Professional antigen-presenting cells
dendritic cells, B cells, macrophages
DC movement
picks up pathogens @ infection sites â brings to regional lymph nodes/spleen
CTL recognition
when a cytotoxic T cellâs TCR recognizes antigen on MHC, it kills the infected cell
CTL specificity
Provides highly specific killing without widespread non-specific damage
Active immunization
vaccination that establishes immune memoryP
Passive immunization
transfer of antibodies, does not establish immune memory
Passive immunity duration
protection lasts as long as antibodies remain, 3-6 months
Preventetive vaccine
given to healthy/naive individuals to prevent disease from primary infection
Therapeutic vaccine
Given to infected individuals to prevent/reduce disease or stimulate anti-tumor response
vaccine goal
establish memory B/T cells to provide protection from future infection
immunodominance
identifying key antigens that generate strong T/Bcell responses
Vaccine challenge
Must avoid excessive immune pathology(when body reacts too strongly), overactive immune response can cause disease
Route of immunization
Most vaccines are intramuscular/subcutaneous, some can be oral (rotavirus & polio)
Adjuvant
Crucial in non-replicating vaccines to enhance immunogenicity
Adjuvant mechanism
Activates TLRs, promotes inflammation, activate antigen-presenting cells, increases CD4 T cell & antibody responses
Antigenic Variation
Changes in pathogen antigens, caused by high viral mutation rates
Attenuated/live vaccine
Weakened pathogen with a reduced ability to cause disease (OPV, MMMR, VZV)
Advantage: low dose, no adjuvant, authentic antigen presentation, effective CTL response
Disadvantage: Possible reversal of virulence
Inactivated vaccine
Killed/inactivated organism/toxin (influenza, hep A, pertussis, IPV, tetanus & diphtheria)
advantage: cannot be reverted to virulence
disadvantage: doesnât replicate & provides poorer antigen presentation for CTL
Live vector vaccine
Inserts genes from a pathogen into a well-categorized vaccine vector (vaccinia, adenovirus, salmonella, ebola..)
advantage: self-replicating, may not require adjuvant
disadvantage: possible pathogenesis
Recombinant protein vaccine
Uses immunogenic proteins (envelope/outer-membrane proteins) produced in large quantities (Hep B, HPV, malaria)
Advantages: safe & relatively easy to produce
Disadvantages: usually requires adjuvants/boosters, may not produce long-term memory
SARS-CoV-2 vaccine target
spike protein â major target of neutralizing antibodies
mRNA vaccine
uses lipid nanoparticles to deliver mRNA in to host cells, allowing cells to produce the target protein
advantage: fast production & easy adaptation to new pathogens
disadvantage: must be encapsulated in lipids/sugars
AstraZeneca vaccine
viral-vector vaccine; 79% efficacy against symptomatic COVID 19
Johnson & Johnson vaccine
Targets adenovirus/spike, 66-72% efficacy
Sputnik V
Adenovirus causing 2 different adenovirus for priming & boosting, 91.7% efficacy
Sinovac/CoronaVac
Inactivated vaccine, can be stored in refrigeration