Immunology Flashcards
Lect 15 onwards
components of first line of defense
chem barriers, mech barriers and reflexes: skin, mucous membranes, secretions, normal microbiota
components of second line of defense
- Innate immune cells: macrophages, neutrophils, eosinophils, basophils, NKC, DC, Mast cells
- Antimicrobial mediators: cytokines like interferons, TNF, IL-6, Chemokines, complement cascade
- processes: phagocytosis, PRR activation (toll-like receptors), inflammation, fever
components of third line of defense
Adaptive immunity: T cells, B cells and antibodies
which lines of defense are specific vs non-specific?
non-specific: first and second line of defense
specific: third line of defense
When and what was the first vaccine attempt
15th century, smallpox crust inhaled or inserted in skin cuts (called variolation), then Jenner realized cowpox made people resistant to smallpox
what do you call it when you reduce pathogenicity of pathogen for vaccination?
attenuation
Humoral vs Cell mediated immunity
Humoral: B cells and antibodies, complement proteins and certain antimicrobial peptides
Cell-mediated: delayed, T cells and macrophages and NKC
what animal was used as model for phagocytosis via macrophages?
starfish larvae
_____ is one of the few vaccines thats efficient even after host has already been infected with pathogen.
anti-rabies
how does immunotherapy work?
blocks tumour cells from deactivating T cells
describe defensins
- small
- cysteine rich
- catatonic (positively charged)
- in plants, vertebrates and invertebrates
- disrupts cell membranes
- found in many compartments of body
- secreted by innate immune cells and epithelial cells
components of skin as first line of defense.
- defensins secreted by dermal cells
- lysozymes destroy cell wall
- sweat makes low skin pH
components of respiratory system as first line of defense.
- mucosilary blanket: mucins and defensins reduce bacterial/viral contact with cells
- alveolar macrophages
- coughing and sneezing reflex
- cilia help move pathogen along
- nitric oxide produced by lungs destroys surface of pathogens
Components of digestive epithelia as first/second line of defense.
FIRST LINE
1. cells replaced often and quickly healed if damaged (important because tissue damage is high)
2. Paneth cells make defensins
3. goblet cells make mucous
SECOND LINE:
1. patrolled by macrophages (engulf invades) and dendritic cells (alert other parts of immune system)
what are defensins?
anti-microbial peptides
what cells make mucous in first line of defense
goblet cells
how does phagocytosis kill pathogen
- membrane envaginated (pseudopod) with bacteria to make phagosome.
- phagosome fuses with lysosome (lysosomal enzymes digest bacteria) and get acidified by mitochondria and peroxisome
- digested products released to recruit more immune cells
top 3 cells that do phagocytosis
neutrophils, dendritic cells and macrophages
TLR4 is/does what?
TLR4 (toll-like receptor 4) is a PRR on the surface of innate immune cells which detects the presence of LPS (exclusive to gram neg cell wall), then initiates second messenger
what does MHC stand for
Major Histocompatability Complex
types of T lymphocytes
- CD4+ - secretes cytokines to promote/regulate immune response
- CD8+ - kills target cells
- T regulartory cells - regulates immune response and prevents harmful response to self-antigens
where do T cells mature
thymus
CD4 TCR binds to ____
MHC II
difference between MHC I and MHC II
MHC I: present in every cell in the body but only goes to surface of cell is infected, bind to CD8 cells
MHC II: present on surface of every antigen presenting cell (macrophage, DC, NKC), bind to CD4
red and white blood cells develop from ____
hematopoietic stem cells (HSC)
describe how hematoxylin and eosin staining works
hematoxylin binds basophilic nucleic acids = blue = WBC because has nucleus
acidic eosin dye binds eosinophilic proteins in granules and cytoplasm = pink = RBC because no nucleus (makes room for O2 transport in cell)
white blood cells are also called ___
leukocytes
neutrophils, eosinophils and basophils are all ______
granulocytes
what portion of the blood contains no cells nor clotting proteins?
the serum
___% of blood cells are leukocytes
1%
Whole blood is made of :
plasma, WBC and RBC
____ and ____ are agranulocytes
lymphocytes (T/B cells) and monocytes (become macrophages)
____% - ____% of WBC in blood are lymphocytes
20% - 40%
- T cells: 7%- 24%
- B cells: 1% - 10%
monocytes make up what % of WBC in human blood?
2% - 12%
neutrophils make up what % of WBC in human blood?
50% - 70%
what types of cells each make up less than 1% of WBC in human blood?
basophils and mast cells
what are the first cells to arrive at an infection site
neutrophils
neutrophil function
Phagocytosis
how do neutrophils kill ingested bacteria?
Granule contents
- reactive oxygen intermediate (prim gran)
- reactive nitrogen intermediate (prim gran)
- antimicrobial peptide (defensin) (sec gran)
- lysozyme (prim. gran.)
- hydrolytic enzymes (prim gran)
- cytokines
Describe netosis
when neutrophil overwhelmed by pathogen, it releases its large DNA strands into environment (and granule content) which forms a net to trap pathogens
what cell coordinates defense against multicellular parasite?
eosinophil
name of non-phagocytic granulocytes
basophils
name of rare but strong innate responder?
basophils
- histamine increases blood vessel permeability which aids immune cells accessing infection site
what type of immune cells are released into blood are immature precursors? where do they differentiate”
mast cells ; epidermis
what innate immune cell has a horseshoe nucleus?
monocyte
what are the best APC and why?
dendridic cells, dont need activation
platelets come from what type of cell (precursor)?
megakaryocyte
_____ are derived from lymphoid precursor, have granules containing _____ and ______, and are a part of innate immunity
NKC ; perforin ; granzyme
“CD” in CD4 stands for ____?
cluster of differentiation
3 functions of APC (macrophages and dendritic cells)?
- secrete chemokines and cytokines to attract and activate other immune cells
- phagocytosis and present antigens on MHC II molecules
- upregulate co-stimulatory molecules needed for optimal activaton of CD4+ (like cytokines)
Which cells express the following: CD3, CD4, CD8, CD19, CD45?
CD3: Th and Tc
CD4: Th
CD8: Tc
CD19: B cells
CD45: B, Th, Tc and NKC
plasma cells have an enlarged organelle. which one is it and why?
Enlarged ER because that’s where proteins are made, and plasma cells make lots and lots of soluble antibodies (which are proteins), so enlarged ER allows more to be made quicker
What are the primary, secondary and tertiary lymphoid tissues? What are their purposes?
primary: thymus and bone marrow
- maturation of lymphocytes
Secondary: lymph nodes, spleen and mucosal-associated lymphoid tissue (MALT) and gut-associated lymph tissue (GALT)
- location of trapped antigen, allows mature lymphocytes to interact (and antigen-dependent maturation of T and B cells to occur). Resevoir of lymphocytes
Tertiary: cutaneous-associated lymphoid tissue (CALT)
- has less lymphoids than secondary, but can import during inflammatory response
most important hematopoietic site before vs after birth.
fetal liver vs bone marrow
cells and fluid move through lymphatic vessels by ____ movement of ______ ____ surrounding the vessels. _______ prevents backflow.
peristaltic ; smooth muscle ; valves
efferent lymphatic vessels take lymph fluid from lymph nodes via _______ into _______ circulation.
thoracic duct ; venous
in the lymph node, the B cell zone is called ___ and the T cell zone is called _____
B cell zone: Follicle
T cell zone: Paracortex
what prevents microorganisms that enter lymph nodes from entering blood stream?
phagocytosis
purpose of lymph nodes
where T and B cells can interact with antigens, mature, and produce antibodies
where is spleen in abdominal cavity?
upper left quandrant.
purpose of spleen and different components.
purpose: where immune responses are mounted against antigens in the blood, and old/defective RBC are phagocytosed and recycled.
White Pulp: generation of T and B cell responses against blood-borne antigen. made up of marginal zone and PALS (T cell zone)
Red Pulp: Macrophages phagocytose bad RBC and pathogens
Marginal Zone: DC trap blood-borne antigens and transport them to white pulp
What’s PALS? What does it stand for?
Periarteriolar lymphoid sheath is the T cell zone of white pulp in the spleen (secondary lymph tissue)
cytokines were originally called _____
interleukins
chemokines vs cytokines: which one is bigger, which one is older, and which one has more receptors?
cytokine: bigger, newer, each fam has own receptor
chemokine: smaller, older, 1 type of receptor for all
whats the response once a cytokine binds to a receptor?
- causes changes in expression of adhesion molecules and chemokine receptors on target membrane
- induce cell proliferation or differentiation
- tells cell to survive or die
- can modulate cell effector functions
3 ways cytokines can act
- endocrine
- paracrine
- autocrine
example of membrane bound cytokine family
TNF (tumor necrosis factor) family - lead to necrosis or apoptosis
4 types of cytokine based on their effects
- pleiotropy - 1 cyto, multiple effects
- redundancy - many cyto, same effect
- synergy - 2+ cyto work together to produce effect
- antagonism - 1 cyto inactivates effects of another
chemokine function and receptor type.
function: direct leukocyte migration
receptor: GPCR
first MS drug to reduce inflammation
IFN-beta (class 2 cytokine fam)
are all antigens immunogens?
non
intrinsic and extrinsic factors that determine immunogenicity of antigen
Intrinsic
1. size: bigger is better (hapten too small) EXCEPT for TCRs… they only recognize small that are bound to MHC
2. complexity: more complex is better (dna too simple)
3. physical form: insoluble is better bc aggregates
extrinsic
1. dose (mg to g)
2. route (injection more effective than oral)
bivalent ligand causes :
faster and stronger B cell activation
3 major parameters that affect avidity.
- affinity of antibody for epitope
- valency of antibody and antigen (more binding sites means greater avidity)
- structural arrangement of the parts that interact (do they allow benifical conformational changes?)
what’d different between BCR and antibody?
C terminus of heavy chain is different (membrane bound BCR has hydrophobic region there, whereas soluble antibody cannot have free hydrophobic end)
antibody functions
- opsonization for phagocytosis
- fix complement to enhance pathogen death via lysis (MAC attack)
- block attachment
- neutralize toxins via precipitation
Which antibody passes through the placenta to give foetus immunity?
IgG
IgG is _____% of total Ig pool, whereas IgM is _____% and IgA is ____%
70-75% ; 10% ; 15%
IgG functions
- fix complement
- opsonization for phagocytosis
- block attachment
IgM function
- blocking attachment
- fixing complement
BAD at opsonization because all constant regions (Fc) that would bind to macrophage are bound to each other to make pentamer
primary IgA function
blocking attachment to protect mucous membranes (in saliva, tears and milk)
what antibody causes allergic reaction? how?
IgE binds Fc(epsilon)R on mast cells after binding to allergen to cause reaction
what mechanisms ensure the high diversity of Ig?
- somatic recombination
- somatic hypermutation (D genes have high mutation probability, only in B cells)
- secondary diversification: gene conversion in variable region, or class switch in constant region
where are complement proteins made
liver
what class are complements
class A, C1-9 and D
what does MAC stand for
membrane attack complex
C3a and C5a dont only work as complement proteins to induce _____, they also function as ________
inflammation ; chemokines to created a gradient
what draws WBC to inflammation site?
- cytokines (TNF alpha, IL-1beta, IL-6)
- lipids (protaglandins
- histamine
- chemokines (like C3a and C5a)
4 characteristics of inflammation
- redness
- swelling
- pain
- heat
which cytokines cause fever? (hint: same cytokines that cause inflammation)
TNF-alpha
IL-1beta
IL-6
what are fever causing cytokines called?
pyrogens
how does fever help infection?
- increases circulation rate (more WBC to infection site)
- some pathogens can’t tolerate the heat so damaged or die
- increases transferrins, which isolate iron away from pathogens to limit growth
_____, found in gram ____ bacteria, can be dangerous as they trigger release of pyrogens which can lead to cytokine storm
LPS ; negative (-)
does systemic inflammation increase or decrease blood pressure? what is the result?
decreases blood pressure because increased vascular permeability. causes low levels O2 to go to organs, which can lead to organ failure (kidneys go first)
PRR recognise _____
PAMPs - Pathogen-associated molecular patterns
PRRs are found in ____ and _____, but not in _______
higher plants ; vertebrates ; invertebrates
what are the extracellular domains of TLR made of?
leucine-rich repeats (LRR) in the shape of a C (hetero or homo dimers)
Name of transcription factor activated in response to TLR binding? where is it located?
NFKB in nucleus
there is viral dsRNA mediated activation of which TLR? this leads to activation of what?
TLR 3/3
IRF3 and IRF7 activated
there is viral ssRNA mediated activation of which TLRs? this leads to activation of what?
TLR 7/7 and TLR 8/8
IRF7 activated
result of pathogen binding to TLR?
Phagocytosis
give an example of a soluble intracellular PRR
NOD-like receptor (NLR).
floats in cytoplasm, identifies pathogen, activates NFkB transcription factor
NLRP1, NLRP3, NLRC4 form inflammasome, activates caspase-1, cleaves IL-1beta precursor, mature IL-1beta released
where are vesicles containing class II MHC found??
in cytoplasms of APC
follicle light zone vs dark zone
light zone - Th cells and B cells interact, there is class switching
dark zone - Proliferation of B cells and somatic hypermutation of antibodies
Extracellular bacteria is fought via ___ and ____ immunities, whereas intracellular bacterial is fought via ____ immunity
innate ; humoral (antibody-mediated) ; cell-mediated
the _____ is the site of response to blood-borne pathogens because of ____________
spleen ; exchange of blood in red pulp area
what disease prevents phagosome lysosome fusion
tuberculosis
what is a mature granuloma made of?
macrophages, T helper cells, infected cells, and bacteria
Describe inducible protection against viral infection
virally infected cell produces interferons: IFN alpha and IFN beta. these diffuse to nearby cells to stimulate expression of antiviral genes. this way, once virus enters cell, it is immediately attacked and degraded by antiviral proteins
describe cell-mediated protection against viral infection
NKC detects lack of MHC I on infected cell, as well as stress protein (via stress protein receptor). Its like okay you’re sus, so then it causes apoptosis via perforins/granzymes
what is perforin and granzyme?
both secreted by NKC and induce apoptosis in infected cell from inside out (enter cell via endocytosis)
perforin
- pore forming protein
granzyme
- serine protease
what does cross-presentation via DC mean?
DC sees antigen, presents it on MHC I cell. DC cell also phags antigen and presents it on MHC II for CD4 cells
how do CTL kill cells?
same way as NKC, via perforin and granzyme from granule after TCR binding
alternative pathway: Fas/FasL pathway
- does same thing as perforin and granzyme
Human MHC alleles are highly ______, and their expression is _______
polymorphic (many different alleles) ; co-dominant / polygenic (and its rare both alleles are the exact same)
why is it important that MHC molecules are diverse?
- pathogens adapt fast, so we need receptors that adapt equally as fast to stop them from evading immune system.
- No MHC presentation = no adaptive immune response
antibodies cause aggregation for phagocytosis. where and by who are these aggregated cells removed?
monocytes and myeloid cells in liver phag aggregated cells
what two viruses kill/inhibit T cell activity?
- Human T lymphotropic virus 1 and 2
- HIV
An indirect ELISA is used to assess presence of HIV in a person. what are bound to the microtiter plate as antigens?
- recombinant enveloppe
- core proteins
what type of ELISA is used to quantify cytokine concentration in a tissue?
Sandwhich ELISA
what are two diseases that were wiped out in canada after vaccines became available?
polio and diphtheria
does smallpox have an RNA or DNA genome?
DNA
passive vs active vaccines
active: stimulate immune system by giving attentuated pathogen, or part of pathogen, to patient
passive: giving antibodies from a previous natural or synthetic infection, thought to lessen the disease of the patient (not formally approve, trump did this when he got covid-19)
prophylactic vs therapeutic vaccines
prophylactic: build immunity to repel infection, “preparing” immune system for battle
therapeutic: treatment and prevention (like anti-cancer drugs)
What’s the mathematical calculation for transmission potential?
Ro = # of people a sick person will infect
Ro<1 - infection can disappear
Ro=1 - infection is endemic (maintained)
Ro>1 - infection can be epidemic
criteria for viral eradication
- no animal reservoir
- easy to detect - makes it easy to contain
smallpox route of transmission
- aerosols
- direct contact
poliovirus route of transmission
- water-borne
- fecal-oral route
- respiratory droplets
why was polio so hard to eradicate?
95% of people were asymptomatic
What are the two types of polio vaccines? what are their names? where are they grown?
- Inactivated - IPV or Salk vaccine
- grown in monkey kidney cells, then inactivated via formalin and administered intradermally
- SAFER - Attenuated - OPV or Sabin vaccine
- grown at sub-physiological temp in cell culture, causes mutations, delivered orally, virus replicates in gut but doesn’t affect nervous system
- STRONGER IMMUNE RESPONSE, EASIER DELIVERY (no needles)
- HARDER TO MAKE
What’s HPV? what type of dna does it have? What’s its shape?
Human papilloma virus - causes genital warts and sometimes cervical cancer
small circular dsDNA
icosahedral symmetry
3 HPV vaccine names and how many strains they protect from
- Cervarix (bivalent, protects from 2)
- Gardasil (quadrivalent, protect from 4)
- Gardasil-9 (nonavalent, protects from 9)
How are HPV vaccines made?
They are VLP vaccines.
1. the L1 protein coding region of HPV genome is transfered into yeast plasmid
2. yeast makes L1 proteins, which self-assemble into virus outer shell
3. empty VLP administered and elicits high # of antibodies
what’s the covid-19 vaccine made of?
- spike mRNA in a vesicle
- lipids to keep mRNA intact and stable
3. pH regulators
most deadly species of malaria
plasmodium falciparum
two drugs to prevent malaria
Doxycycline and Malarone
how do we diagnose malaria?
but looking for ring structure an infected RBC makes. If found, treatment should be immediate because patient could be dead in 48horus
2 types of malaria (plasmodium falciparum)
- cerebral malaria
- decreased deformability and increased attachment motifs of RBC to cerebral endothelium causes clots and neurological damage - blackwater fever
- kidney damage (hemorrhage), inflammation, tubular necrosis
how is the malaria parasite able to evade immune system so well?
antigenic shift. has 60+ alleles for sticky antigen protein, but only expresses one, and expresses a different one after each round of replication, so newly made antibodies with previous sticky antigen don’t work
protozoans vs metazoans
protozoans - unicellular eukaryotes
metazoans - helminths or worms
what are the 2 biggest challenges posed to immune system by parasites?
- antigenic structure (antigenic shift, or parasite at different stage in life cycle so looks different)
- location over time (moves in the body)
How do Trypanosomes escape the immune system?
by changing surface glycoproteins: VSG group
what type of parasites influence activation and induce cell death in T cells?
helminths (metazoan parasites). they induce switch to IgE and non-protective IgG
Th0 to Th1 mediated by ____. Th1 produces what cytokines, and is what type of immune response?
IL-12
Cytokines: IL-2 and IFN gamma
Cell mediated response
Th0 to Th2 mediated by ____. Th2 produces what cytokines, and is what type of immune response?
IL-4
Cytokines: IL-4, IL-5, IL10
Humoral Immunity
tapeworms are also called ____
cestodes
what causes liver inflammation similar to alcoholics?
trematodes. eggs in intestines, adult in liver. no effective immunity against them
the African sleeping sickness is caused by the bite of the ____ fly
tsetse
