Blood and immunity Flashcards
What are the components of blood?
Red blood cells
White blood cells
Platelets
Plasma
What does red blood cells do?
Carry oxygen to our cells
What does plasma do?
Carries hormones, enzymes, nutrients, and waste products around the body.
What does platelets do?
Clots blood to prevent blood loss following injury.
What does white blood cells do?
defend the body from infection.
What does blood do?
Helps regulate body temperature.
maintain pH of body fluids.
What did Richard lower do?
Performed first successful blood transfusion in dogs.
Performed first successful blood transfusion in humans (sheep-human).
What did James Blundell do?
Performed first successful human-human transfusion.
What did Karl Landsteiner do?
_observed that blood transfusion would sometimes result in blood clumping in the recipient’s circulation.
Classified the ABO system of blood typing.
Identified the rhesus antigen.
What did Edward Lindeman do?
Discovered that blood could be extracted by needle.
How is blood used?
Clinical transfusion
Identification (forensics/paternity)
How many types of blood are there?
4 main types: A B AB O
8 in total (+/-)
What antigen each blood type has?
Type A> antigen A
Type B> antigen B
Type AB> antigen A and B
Type O> no antigen
What antibody circulate in each blood type?
Type A> antibody B
Type B> antibody A
Type AB> no antibodies
Type O> Antibody A and B
What happens if antibody bind to antigen in RBCs?
Agglutination in vitro
Haemolysis in vivo
What can transfusion of wrong blood type do?
1) Donor’s Antibodies attack recipient’s RBCs (negligible)
2) Recipient’s antibodies attacks donated RBCs.
What does the presence or absence of rhesus antigen mean?
positive (+)> present
negative (-)> absent
How can the presence or absence of rhesus antigen affect blood transfusion?
Rh+ > can receive from both Rh+ and Rh-
Rh- > can only receive from Rh- (they don’t originally have Rh antibodies but they can develop one after first exposure)
How can Rh affect babies of different Rh than their mothers?
If the mother has Rh- and the baby has Rh+ :
first born> no effect
Second born> Haemolytic disease
Because the mothers immune system develop Rh antibodies after exposure to Rh antigen from the first born
What type of RBCs is universal recipient?
AB+
What type of RBCs is universal donor?
O-
What is a venom?
substances produced by predators that causes harm but only when injected into the body of the prey via fangs or stings.
what is a poison?
substances that causes harm when absorbed by the body, via ingestion or contact.
what is a toxin?
the chemical constituent of poisons or venoms that make them harmful.
could drinking too much water kill somebody?
yes, drinking too much water cause hyponatremia leading to hypotonic ECF> cells swell and burst
What is Ecstasy?
a drug (MDMA) that promotes the release of ADH
What are psilocybin and psilocin?
Active compounds in magic mushrooms
What is Lysergic Acid Diethylamide (LSD)?
derived from fungus found on cereal, more potent than psilocybin and psilocin.
What is the relationship between psilocybin, psilocin, and LSD and serotonin?
psilocybin, psilocin, and LSD mimic serotonin
What is the relationship between the methyl group and psychoactive?
more methyl groups> greater lipophilicity> greater membrane penetration> greater psychoactive
What is serotonin?
is a neurotransmitter that exerts inhibitory and excitatory effects in the CNS.
How does the psychedelic drugs act?
suppress the inhibitory pathway in the brain, hence increased excitation
What are some of the fatal fungi? and what are the toxic compounds that they contain?
- Deadly Webcap (orellanine)
- Death Cap (amatoxin)
- Destroying Angel (phallotoxin)
What organs does the toxins in the fatal mushrooms damage the most?
liver and kidneys
mostly the liver because it’s the first organ that encounter the toxin after bein absorbed by the digestive tract and carried to the liver by the hepatic portal vein.
How are colchicine and taxol toxic to the human body? is there potential therapeutic use for them?
disrupt microtubules to inhibit mitosis> cell division.
they could be useful in treating cancer (stop it from growing)
What is digoxin and how it might be dangerous?
is a cardiac glycoside (treat cardiac dysrhythmia) derived from Foxglove.
therapeutic dose very close to toxic dose.
Why buffer fish is deadly?
contains tetrodotoxin (TTX) which block electrical activity in neurons> inhibit nerve communications.
Death occur from asphyxiation (respiratory muscle failure)
What are the deadliest venoms?
Cobra’s, Rattlesnake’s, Viper’s
What are the venom constituents? and what is their function?
- Haemotoxins: clotting the blood
- Neurotoxins: disrupt transmission at the nerve cells (neuromuscular junction), paralyses the prey
- cytotoxins: eases digestion of prey
What constituent of venom has a therapeutic potential as an analgesic?
neurotoxin
What is Botox? and what are its uses?
Botulinum Toxin
cosmetic, therapeutic, bioterrorism
How does Botox work?
blocks acetylcholine release into the neuromuscular junction> blocks muscle contraction.
what are the disease causing organisms?
pathogenic bacteria, fungi, viruses
what do we need protect from?
bacteria, viruses, parasites, fungi, cancers
what is the rapid response system and how does it work?
innate immune system
immune cells with pattern recognition receptors (PRR) recognises pathogen associated molecular patterns (PAMPs)
How many invariant receptors are there?
less than 100
how many many molecular patterns are recognised?
around 1000
what are microbes’ common characteristics of PAMPs?
bacterial and fungal > cell wall component
bacterial and viral > RNA and DNA
What are the cells of the innate immune system with PRR?
phagocytes > neutrophils and macrophages
dendritic cells
What are common PAMPs in bacterial cell wall?
liposaccharide (LPS) and peptidoglycan
what is the name of the mechanism in which macrophages destroy pathogens?
phagocytosis
how does phagocytosis occur?
1) phagocyte sensing a pathogen
2) phagosome
3) fuse of phagosome and lysosome
4) toxic enzymes and proteins within the lysosome breakdown the pathogen
what is the largest circulating population of white blood cells?
neutrophils
Where does the neutrophils get produced?
bone marrow
what is the first line of defense against microbial pathogens?
neutrophils
What is the life span of neutrophils?
1-2 days
what is pus?
dead neutrophils and pathogens
what are the killing mechanisms of neutrophils?
phagocytosis (intracellular)
degranulation (inra/extracellular)
NETs (neutrophil extracellular traps) (extracellular)
What killing mechanism does eosinophils use and how does it work?
Exocytosis
releasing lysosome vesicles containing toxic enzymes and proteins to destroy larger pathogens
What are the differences between the innate immune system and the adaptive immune system?
innate:
rapid response
1000 pattern recognised
no memory
adaptive:
needs time to prepare
100 million antigens recognised
has memory
what is an antigen?
part of the pathogen that can be recognised by the B and T lymphocytes of the adaptive immune system
What are the component of antibodies?
heavy chain, light chain
How can B cells create different antibodies?
As they develop, they choose random gene segments for the heavy and light chain from many possible segments. as the gene segments are joined together, extra nucleotides added/deleted at the junction, hence junctional diversity.
What is the function of antibodies?
tag the pathogens so that they get destroyed by other immune cells
What is the function of the memory B cells?
memory B cells created after the primary response recognise the same pathogen and respond more rapidly and strongly.
Which antibody type is higher in number (IgM or IgG)?
IgG
How do t cells work?
1) dendritic cell phagocytose pathogen
2) pathogen antigen goes to dendritic surface
3) helper T cell bind to the antigen
4) helper T cell activated
5) helper T cell release cytokine
6) cytokine activate cytotoxic T cells
7) cytotoxic T cells kill viruses and tumour cells
what are cytokines?
- communication mechanism
- act locally or at distance
- secreted by many cell types (especially immune system cells)
- stimulated in response to microbes or other cytokines
- powerful molecules - act at nanomolar level
what are the effects of cytokines on blood vessels?
help recruitment of more immune cells to the tissue
what are the effects of cytokines on recruited immune cells?
activate them more
mention examples of powerful cytokines generated by the innate immune system:
TNF, IL-1, IL-6
What are the systemic protective activities of cytokines TNF, IL-1, IL-6?
brain > fever
liver > acute-phase proteins (produced in response to infection or inflammation)
bone marrow > leukocyte production
what are the systemic pathological effects of TNF?
heart > low output
endothelial cells/ blood vessels > increased permeability/ thrombosis
metabolic abnormalities > insulin resistance
What is cytokine storm and why does it occur?
if cytokine production is too great
septic shock, severe covid-19
what is sepsis?
severe infection which enters the blood stream
what is a septic shock?
severe and frequently fatal form of sepsis
what are the characteristic of a septic shock?
- collapse of blood vessel
- widespread blood clotting
- metabolic disturbance
- multiple organ failure
what is allergy?
hypersensitivity to environmental antigens
what are some of allergic diseases?
asthma, eczema
How does allergy happen?
innate cells are triggered by allergens to release their mediators
what are the effects of histamine release?
sneezing and itching
what are the ways in which autoreactive immune responses prevented?
- autoreactive lymphocytes eliminated as they develop
- no responses unless accompanied by a danger signal
- regulatory cells suppress an autoreactive response
what happen if autoreactive T cells left unsuppressed?
autoimmune diseases
how do autoimmune diseases develop?
immune system targets self antigens in genetically susceptible individuals
what is primary immunodeficiency?
mutation in genes coding for major components of the immune system
what causes secondary immunodeficiency?
age, malnutrition, drugs, AIDs
what is passive immunity?
transfer of antibodies from immune individuals
What are the advantages/disadvantages of passive immunity?
advantages:
* gives immediate protection
* quick fix
disadvantages:
* no immunological memory (short-term)
* serum sickness (foreign antigen)
examples of natural passive immunity:
maternal antibody (transferred to foetus across the placenta)
examples of artificial passive immunity:
- snake or spider bites, scorpion or fish stings
- primary or secondary deficiency in antibody
- rabies antibody
- Ebola antiserum from survivors
what is active immunity?
vaccination/ immunisation
what is vaccination?
administration of antigenic material to stimulate an individual’s immune system to develop adaptive immunity to a pathogen
what are the advantages of vaccination?
long-term
faster and better response next time
what are the types of conventional vaccines?
- killed whole organism
- attenuated whole organism (not safe)
Types of vaccines:
inactivated
live attenuated
subunit
toxoid
viral vector (nucleic acid)
which virus has been officially eradicated:
smallpox
what are the common diseases we vaccinate against?
measles-mumps-rubella (MMR vaccine)
(MMRV) > addition of varicella (chickenpox)
What is the second most common cause of cancer deaths in females?
cervical cancer
what causes cervical cancer?
human papilloma virus (HPV)
uses of monoclonal antibodies:
- treatment for many diseases: cancer, autoimmune diseases
- diagnostic kits (pregnancy, COVID-19)
what is a B cell hybridoma?
immortalised B cell
how can hybridoma be produced?
fusion of myeloma and isolated B cells from immunised mouse with antigen of interest
what is the benefit of B cells hybridoma?
produce monoclonal antibodies
what properties do myeloma must have to consider fit for hybridoma technology?
- don’t have HGPRT enzyme
- don’t secrete its own antibodies
why hybridoma cells are put in HAT medium?
so only hybrids (myeloma + B cells) can grow
( B cells have HGPRT enzyme so they can grow in HAT medium)
Why mice used to produce monoclonal antibodies should be engineered?
to produce humanised antibodies (so they don’t be recognised as foreign)
examples of monoclonal antibody therapy:
- Humira (anti-TNF > rheumatoid arthritis)
- Herceptin (HER2 > metastatic breast cancer)
- Avastin (anti-VEGF > inhibits angiogenesis > eye disease)
what are magic bullets:
antibody-drug conjugate (antibody take drug to targeted cell)
what is the checkpoint inhibitor?
anti-cancer drug
targeting inhibitory molecule
inhibitory molecule stops T cells from killing other cells including cancer cells (potential for immune related adverse effects)
what are bispecific antibodies?
antibodies that bind to more than one target (one target immune-related to boost the immune system)
catumaxomab > ovarian cancer
how could the immune system be manipulated to attack tumours more effectively?
1) pulse labeling a dendritic cell with tumour antigen in vitro and then inject back
2) encode dendritic cells with tumour antigen
3) dendritic transferred to recipient with cytokine that promotes immune response
how does tumour immunotherapy with T cells work?
- isolate T cells
- modify so they can identify tumour antigen
- proliferate
- transferred back to patient
how can allergy be treated with immunotherapy?
desensitization with repeated small doses of antigen
how does desensitization therapy with peptides work?
peptides induce immune regulatory cells to dampen down the immune system
