Module 7 - Depth Study Flashcards
monocytes
- type of WBC formed in bone marrow
- turn into macrophage or dendritic cell after moving from bloodstream into tissues in response to infection
- mac + dend are APCs (participate in acquired immunity)
neutrophils
- first to move to site of infection to inactivate pathogens
- produce neutrophil extracellular traps to bind + trap pathogens, preventing further spread
- recruits other immune cells to SOI but not APCs (self-destruct after a few days)
leukocytes =
lymphocytes =
WBCs
type of leukocyte
NK cells
innate immune system
- don’t attack pathogens directly but destroy infected host cell
- cytotoxic - contain cytoplasmic granules filled with perforin + proteases
- once it detects a ‘non-self’ cell it attaches to it + releases these cytotoxic molecules causing the lysis (rupture) + death of target cell
Dendritic cells (DC)
- presents antigens on surface (APCs) - located in tissues - common points for infection - triggers adaptive immune response
- messenger between the innate and adaptive immune system
CD4T
‘helper’ T cells - they do not neutralise infections but rather trigger the body’s response to infections
CD8T
adaptive immune system
- during an infection, naïve CD8+ T cells are initially stimulated by interacting with APCs within lymphoid organs
- CD8T cells are cytotoxic T cells that induce cell death either by lysis or apoptosis
Interleukin (IL)
- naturally occurring proteins that mediate communication between cells
- can elicit many reactions in cells and tissues by binding to high-affinity receptors in cell surfaces
cytokine
small, short-lived proteins (made in response to pathogens)
- released by one cell to regulate the function of another cell, thereby serving as intercellular chemical messengers
D.I.C.
Disseminated Intravascular Coagulation = implication of Cytokine Storm
- a serious disorder in which the proteins that control blood clotting become overactive
- abnormal clumps of thickened blood clots form inside blood vessles (use up clotting factors) –> can lead to massive bleeding in other places
A.R.D.S.
Acute respiratory distress syndrome = CS can cause ARDS
- a serious lung condition that causes low blood oxygen
- fluid buildup and break down of surfactant prevent the lungs from properly filling with air and moving enough oxygen into the bloodstream and throughout the body
Anaemia
- condition where the # of RBCs or haemoglobin concentration within them is lower than normal
–> decreased capacity of the blood to carry oxygen to the body’s tissues
Cytokine storm
- excessive, uncontrolled immune response characterised by a widespread release of many pro-inflammatory cytokines
–> overactivation of other immune cells like T-cells, macrophages, and natural killer cells
–> (can) tissue damage, organ dysfunction, and sometimes death
how antiviral drugs work
Rather than killing a virus directly, antivirals usually inhibit the growth, development and multiplication of viruses at different points
- anti-entry
- protease inhibitors
- anti-RNA polymerase
- anti-viral release
= do not cure the disease but slow down the progress allowing the body’s natural defences to take over
why viruses mutate
all organisms mutate (natural selection)
- by becoming more effective in moving from host to host + reproducing faster, a virus can extend its life
- mutation can help viruses evade immune responses + vaccines + antivirals
why virus mutation problem for antivirals
- viruses have high mutation rates
- mutation might give virus antiviral resistance to a drug = certain antiviral has lower effectiveness in inhibiting the spread + harm of a particular virus
reasons viruses are genome-mapped
- help to track the way a virus is spreading + changing
- easier to develop vaccines (don’t need actual sample)
- compare current and past viruses
viral diseases with antiviral drugs (6)
- coronaviruses, e.g. COVID-19
- ebola
- flu
- genital herpes
- hepatitis b and hepatitis c
- HIV
two antiviral drugs for COVID-19 in Australia
primarily used for people with mild COVID-19 who have a high risk for developing severe disease, reducing the need (or lowering the risk) for admission to hospital
oral:
* Paxlovid (most effective oral treatment to date)
* Lagevrio (molnupiravir)
covid - rna or dna virus?
RNA
RNA viruses vs DNA viruses - mutate
- RNA viruses - replicate using RNA polymerase which doesn’t proofread + makes many mistakes (generally no error correction ability) = mutations accumulate rapidly
- DNA viruses - replicate using DNA polymerase which do proofread + have cell repair mechanisms = much lower chance of mutating
reverse transcriptions
synthesis of DNA from an RNA template
RNA is starting material
link between Anti-RNA polymerase and protein synthesis
- Anti-RNA polymerase refers to substances or molecules that inhibit the activity of RNA polymerase –> disrupts/halts transcription –> decrease/absence of mRNA synthesis
- reduction/absence of mRNA molecules prevents translation –> disrupts protein synthesis
of variants genome mapped to date
13
covid variants
Alpha, beta, gamma, delta, omicron
antibiotic define
A chemical substance, generally produced by a microorganism, that kills bacteria or slows its growth
different classes of antibiotics
- quinolones
- macrolides
- streptogramins
bacteriostatic vs bactericidal antibiotics
- Bacteriostatic antibiotics: slows growth of bacteria by interfering with processes the bacteria need to multiply, e.g. DNA replication, protein production, etc.
- Bactericidal antibiotics: kill bacteria, e.g. by preventing bacteria from making a cell wall, cell membrane or its cell contents
quinolones - bacteriostatic or bactericidal?
bactericidal
macrolides - bacteriostatic or bactericidal?
bacteriostatic
streptogramins - bacteriostatic or bactericidal?
bactericidal
gram + vs gram -
- refers to the classification of bacteria by the colour they turn in the staining method
- gram + has thick peptidoglycan cell wall, more susceptible to antibiotics that target the cell wall BC higher permeability with no outer membrane
- gram - has thin peptidoglycan cell wall, more resistant to antibiotics BC complex cell wall + has outer membrane (selective permeability)
quinolones - research and effectiveness
- interfere with bacteria DNA (!!!) replication + transcription (inhibit bacteria’s ability to grow/infect cells in body)
- broad-spectrum antiobiotic
- quite effective against gram-negative bacteria (e.g. E. coli)
quinolones examples
- ciprofloxacin - treat people exposed to anthrax / certain types of plague
- levofloxacin - treat pneumonia, UTIs, sinus infections
- trovafloxacin - treat pneumonia, abdominal infections, etc.
macrolides - research and effectiveness
- prevents bacteria from producing proteins they need to grow + multiply (done by binding to the 50S subunit of the ribosome)
- relatively poorly absorbed orally; used for infections caused by gram-positive bacteria
- often used to treat people allergic to penicillins
macrolides examples
- erythromycin - used to treat bronchitis, pneumonia, whooping cough
- clarithromycin - used to treat pneumonia, cellulitis, ear infections, etc.
streptogramins - research and effectiveness
- inhibits the synthesis of proteins by bacteria by binding to the 50S ribosomal subunit
- mainly effective against gram positive bacteria
- streptogramin A and streptogramin B (separately are bacteriostatic, together are bactericidal)
streptogramins examples
pristinamycin IIA, pristinamycin IA
- reduced risk of drug resistance
broad vs narrow spectrum antibiotics
- Broad spectrum = affect many different bacteria in the body including useful bacteria in the gut (implication)
- Narrow spectrum = only affecting 1-2 types of bacteria
important features of a bacterial cell
Plasmid, cell wall, cell membrane, genetic material, cytoplasm, ribosomes
If asked to draw, remember to draw pili!
effectiveness of antibiotics as a treatment strategy for control of infectious diseases
- when used correctly = highly effective
- antibiotic resistance (overuse or bacteria mutation) –> less effective
antibodies define
(immunoglobulin)
a type of blood protein naturally produced by B cells in response to a specific antigen, and play a critical role in the immune system’s 3rd line of defence, with the function of neutralising the pathogen
which antibodies treat COVID-19?
IgG
IgA
the big fancy pentagonal antibody
IgM
the antibody with the secretory protein
IgA
IgG
(1) location in body
(2) percentage in body/plasma
(1) Found mainly in blood + tissue fluids
(2) 75-80%
IgG function
- provide long-term resistance to disease - level of IgG is raised in body after booster injection of vaccine
- can cross placenta and provide immunity to foetus and child up to age of 6 months
IgE
(1) location in body
(2) percentage in body/plasma
(1) Skin, lungs + mucous membranes
(2) 0.02%
IgE function
- in the presence of specific antigens, binds to high-affinity receptors (located mostly on basophils + mast cells) and low-affinity receptors (B cells, T cells, etc)
- binding sets off chain reaction –> causes cells to release chemical immune mediators (e.g. histamines)
- allergic reaction + fights parasitic infections
IgD
(1) location in body
(2) percentage in body/plasma
(1) Found on the surface of B cells (part of the B cell receptor)
(2) 1%
IgD function
Effective against toxins and allergens + stimulates B lymphocytes to secrete other immunoglobulins
IgM
(1) location in body
(2) percentage in body/plasma
(1) Blood + lymph fluid
(2) 7%
IgM function
- First to appear (when B lymphocytes are stimulated) + produce primary immune response
- IgM levels decline as the body starts producing more IgG antibodies, which are responsible for long-term protection against pathogens
IgA
(1) location in body
(2) percentage in body/plasma
(1) Found in tears, saliva, seminal fluid, urine, mother’s milk and colostrum
(2) 10-13%
IgA function
Provides first line of defence against inhaled and ingested pathogens + fight against invading microbes even before the person is sensitised
Australia vaccine rollout
- people are worried about the Oxford/AstraZeneca vaccine causing blood clots = innoculation process glacial pace
- Atagi changing vaccination advice several times: Pfizer ‘preferred’ vaccine for under 60s –> all adults >18 vaccinated, incl. AstraZeneca if need be
reasons for more deaths in some countries than others
- Lack of public health infrastructure and facilities: not enough doctors, hospitals, equipment especially in ICU
- Lack of systemic testing, social distancing guidelines, public education
- Quantity + success of vaccination rollouts
- Level of pre-COVID income inequality: for those who earn a much lower income, quarantining/social distancing is not a viable option (especially if it is not mandatory)
covid deaths by year
2019: 0
2020: 1,946,419
2021: 3,531,717
2022: 1,238,166
2023: 219,587
1.9m, 3.5m, 1.2m, 0.2m
secondary immune response
- upon meeting their SPECIFIC antigen again, memory cells rapidly proliferate + differentiate into plasma cells
- plasma cells produce abundant quantities of antibodies to clear the antigen
- some memory cells sent to germinal centres for further affinity maturation + class changeover
primary vs secondary immune response
- primary: curve flatter + shorter because it takes some time for naive B and T cells with the appropriate antigen specificities to be identified, activated and then proliferate
- secondary: upon reinfection, memory memory B cells recognise the antigen and quickly differentiate into plasma cells, outputting ten to hundred-fold greater antibody amounts than the number that were secreted during the primary response
no. of antibodies after secondary immune response > after primary immune response
main type of antibody produced during primary immune response
mainly IgM (although small amounts of IgG are usually also produced)
main type of antibody produced during secondary immune response
IgG (although small amounts of IgM are sometimes produced)
vaccination vs immunisation
- vacc: term used for getting the vaccine, either injection or oral dose
- immun: process of getting vaccinated AND being immune to the disease following vaccination
the different COVID vaccines (5)
- Pfizer Bio N Tech
- Oxford AstraZeneca
- Janssen/Johnson & Johnson
- Novavax
- Moderna
types of COVID vaccines (3)
- mRNA
- vector
- protein subunit
COVID mRNA vaccines
- Pfizer Bio N Tech
- Moderna
COVID protein subunit vaccines
- Novavax
COVID vector vaccine
- Oxford AstraZeneca
- Janssen/Johnson & Johnson
how mRNA vaccines work
- mRNA with instructions for making S protein on COVID-19 virus surface developed in lab
- after vaccination, muscle cells begin making S protein pieces and display them on cell surfaces → body produces specific antibodies = bind to virus upon reinfection (stops it replicating)
- once the protein pieces are made, the cells break down the instructions and get rid of them
how vector vaccines work
for COVID-19
- Material from the COVID-19 virus is placed in a modified version of a different virus (viral vector)
- Injected: viral vector gives cells instructions to make copies of the COVID-19 S protein
- Once cells display the S proteins on their surfaces, the immune system responds by creating antibodies and defensive white blood cells = fight virus upon reinfection
NOTE: Viral vector vaccines can’t cause you to become infected with the COVID-19 virus or the viral vector virus
how protein subunit vaccines work
for COVID-19
- spike protein material removed from virus + inserted into bacteria, yeast or animal cells
- COVID-19 virus spike protein produced by cells + purified + combined with substances to boost immune response
- injected –> spike protein created in muscle cell, recognised by immune system, produces antibodies which bind to virus + stop it from replicating if reinfected
vaccines currently used in Australia for COVID-19
- Comirnaty (Pfizer)
- Spikevax (Moderna)
- Nuvaxovid (Novavax)
types of traditional vaccines (in general) - 6
- live-attenuated
- toxoid
- inactivated
- recombinant
- sub-unit
- conjugate
live-attenuated vaccines - definition and example
use weakened (attenuated) form of the germ that causes the disease –> strong, long-lasting immune response
e.g. measles
toxoid vaccines - definition and example
use toxoids as antigens - immune response targeted to toxin instead of the whole germ
the disease in this case is caused by the toxin secreted by the bacteria
e.g. tetanus
inactivated vaccines - definition and example
use the killed version of the germ that causes a disease - protection not as strong as live vaccines
e.g. rabies
recombinant vaccines - definition and examples
- only uses proteins of a virus to activate the immune system
- proteins made via genetic engineering by cells that use recombined pieces of the viral genetic code to churn out proteins
- proteins injected in person = activate immune system
- e.g. Hepatitis B
sub-unit vaccines - definition and examples
- only uses very specific subunits of a pathogen to cause a strong immune response to key parts of the pathogen
- booster shots needed for ongoing protection
- e.g. Hepatitis B
conjugate vaccines - definition and examples
- made by chemically linking a protein molecule with a tiny amount of the polysaccharide that makes up the cell coating of the bacterium
- combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen
e.g. Hepatitis B
what does lysosome do in adaptive immunity?
- after phagocytosis, lysosomes in the macrophage break down the pathogen/antigen into parts
- one of those parts is used to display on the MHCII molecule on the macrophage
PAMPs vs DAMPs
PAMPs
- molecules associated with pathogens (not presented in host cells) - often repetitive structures
DAMPs
- endogenous (internal cause) molecules released / exposed when cells undergo stress, injury or damage
what happens to viruses if they don’t have protease?
viral cells are unable to self-replicate, and this results in a low viral load
why do viruses need protease?
need protease to develop + mature
- in viral replication, viruses produce large precursor proteins which aren’t fully functional in long form
- viral proteases recognise specific points along precursor proteins, cut them and it becomes smaller, functional pieces which be assembled into new infectious particles
the cool thing about dimeric IgA
additional ‘secretory protein’ = helps antibody from being digested by enzymes (because it exists in high enzyme areas e.g. saliva and tears)
class switching antibody production
B cells can change the type of antibody they produce while maintaining specificity for the same antigen
- B cells start by making IgM antibodies but can switch to making other classes
- Done by reorganising the DNA within the B cell to activate a different antibody gene segment
allergies + antibodies
- The first time an allergy prone person encounters an allergen, a large amount of specific IgE antibodies are produced + attach themselves to mast cells (which contain histamines)
- When allergen is encountered again, the antibodies created after the first exposure bind to it, alerting the immune system that it needs to be destroyed
- But in an allergy response, when the immune system destroys the allergen, it also destroys the mast cells which causes it to release its histamine = allergic response (sneezing, wheezing, sniffling)
- Subsequent exposure to allergens are usually worse
interferon
a cytokine that inhibits viral replication
