Immunology Flashcards
which cytokine regulates the transition between neutrophil and macrophage dominated inflammation
IL-6
which cytokine is a major mediator of septic shock
IL-6
many vasoactive molecules are made via conversion of ________________
arachidonic acid
what would happen if COX was inhibited
blocked conversion of arachidonic acid to vasoactive molecules, therefore dampening inflammation
TH cells have which CD molecules
CD3, CD4
TC cells express which CD molecules
CD3, CD8
B cells express which CD molecules
CD20
what cells are phagocytic
neutrophils, macrophages, DCs
what cells are APCs
macrophages, DCs, B cells
what cells are sentient
mast cells, macrophages, DCs
regular DCs are produced from a ____________ progenitor whereas plasmacytoid DCs are produced from a _____________ progenitor
regular DCs are produced from a MYELOID progenitor whereas plasmacytoid DCs are produced from a LYMPHOID progenitor
plasmacytoid DCs produce which cytokines
type I IFNs (IFNα/β) - makes them important in antiviral defense
what growth factor regulates production of neutrophils
G-CSF
what binds to what to facilitate ROLLING
L-selectin on neutrophils binds to P-selectin on endothelial cells
what binds to what to facilitate FIRM ADHESION
LFA-1 on neutrophils binds ICAM-1 on endothelial cells
what cytokines do neutrophils release after diapedesis
IL-1, IL-6, TNFα
T/F neutrophils are longer living than macrophages
F
M1 macrophages are ________-inflammatory, and __________________ and are driven by _____________
pro-inflammatory; antimicrobial; IFNγ (and IL-12)
M2 macrophages are _________-inflammatory, and ______________ and are driven by __________________
anti-inflammatory; pro-angiogenic; IL-4 (and IL-13)
role of CD31
expressed by living neutrophils; gives anti-death signal to macrophages (if no signal, macrophages will phagocytose neutrophils)
granulomas are created by the action of _____ macrophages
M2 macrophages
what APP is common to all veterinary species
SAA (serum amyloid A)
role of SAA
enhanced chemotaxis of neutrophils, lymphocytes, and macrophages
what APP sequesters iron
haptoglobin
what are siderophores
produced by bacteria to steal iron from the host
pathogenesis of toxic shock
toxic shock bacteria -> crosslinking of MHC molecules -> non-specific activation of a large number of lymphocytes -> cytokine storm of IL1, IL6, TNFα -> SIRS
what are the three modes that complement is activated
1) classical 2) alternative 3)lectin
what activates classical mode of complement
Ag-Ab complex
what activates alternative mode of complement
pathogen surface
what activates lectin mode of complement
collectins
name three outcomes of complement activation
1) direct cell lysis via MAC
2) increased phagocytosis by binding to complement receptors
3) increased vascular permeability and leukocyte attraction
what mode of cell communication is not used by cytokines
a) autocrine
b) paracrine
c) endocrine
c) endocrine
T/F B cells can only detect protein antigens
F. B cells detect protein, lipid or carbohydrate antigens
T/F T cells can only detect protein antigens
T
which of the following are bad examples of an antigen
a) glycolipids
b) lipids
c) glycoproteins
d) lipoproteins
e) polysaccharides
f) proteins
g) structurally unstable molecules
b, e, g
CD40, CD80 and CD86 are markers of
mature DCs
high IL-12 is a marker of
mature DCs
high Fc receptors/low surface MHC is a marker of
immature DCs
histiocytomas are often caused by
Langerhans cells (macrophages in skin)
what is MHC haplotype
the full set of MHC expressed by an animals cells
MHC in cows is called
BoLA
MHC in pigs is called
SLA
MHC in cats is called
FLA
MHC in dogs is called
DLA
what are the implications of a diverse MHC haplotype
less susceptible to infectious disease but more susceptible to autoimmune disease
what functions as both primary and secondary lymphoid tissue
bone marrow
what CD molecule is expressed by naive T cells but not mature T cells, ensuring naive T cells stay in the lymph node
CD62L
where are the majority of lymphocytes
lymph nodes
what is a mitogen
molecule that induces mitosis and non-specifically activates lymphocytes; bypasses requirements of lymphocytes for BCR/TCR mediated recognition of an antigen
what are 3 ways that NK cells can kill
1) loss of MHC class I expression
2) increase in expression of stress-related proteins (MICA/MICB)
3) Ab binding to CD16, leading to ADCC
what cytokine stimulates NK cells
IFNγ
what cytokine do activates NK cells produce
IFNγ
do NK cells have memory
yes - adopt epigenetic changes after exposure to a virus that allow them to respond better to future viral infections
importance of ILC1-3
greatest pound-for-pound cytokine producers, so they play a role in regulating immune responses
what activates NKT cells
glycolipids presented via CD1d to an invariant TCR on the NKT cell surface
what is the trimolecular complex involved in NKT activation
CD1d, glycolipids, invariant TCR
dogs have CD4 on which cell types
TH cells, macrophages and neutrophils
what cytokine is best associated with TH1 cells
IFNγ
what cytokine is best associated with TH2 cells
IL-4
what antibody isotype provides systemic defense and is most abundant in serum
IgG
what antibody isotype has the longest half life
IgG
what antibody isotype is best at activating complement
IgM
what antibody isotype is associated with the primary immune response
IgM
Predominant Ig isotype in colostrum and why
IgG; systemically protective
Predominant Ig isotype in ruminant milk and why
IgG; ruminants have IgG at the mucosa therefore the main type in milk after the gut closes (get best type at the mucosa)
Predominant Ig isotype in non-ruminant milk and why
IgA; predominant isotype at mucosal surfaces therefore the main type in milk after the gut closes (get best type at the mucosa)
What Ig isotypes are not prominant in milk and why
IgE (antiparasitic not important in neonates) and IgD (function unknown)
colostrum intake protects against ___________ disease whereas milk intake protects against _________ disease
colostrum intake protects against SEPTICEMIC disease whereas milk intake protects against ENTERIC disease
Turbidometric immunoassay and snap tests assess for
Success/failure of passive transfer in horses
What to do if low Ig
watch very closely and treat with antibiotics at the first sign of infections
What to do if very low/complete failure of Ig
intensively feed alternative source of colostrum
Outcomes of in utero infection with non-cytopathic BVD
If early on, get persistent infection; if later on, immune system will clear and get healthy calf
Outcomes of in utero infection with cytopathic BVD
If early on, mummification, still birth or absorption; if later on, malformation; if even later on, healthy calf
How does the microflora contribute to development of the neonate immune system
Dendritic cells present microbial antigens to Th cells. Microflora generates PAMPs that activate PRRs; both of these processes promote tolerance
How is IgY transported to a chick embryo
Through the serum directly into the chicks circulation (during fluid yolk phase): ends up in circulation
How is IgA/IgM transported to a chick embryo
Through albumin into the amniotic fluid; gets ingested by the chick: ends up in gut
What is neonatal isoerythrolysis in foals
Mother is pre-exposed to foal RBC antigens and creates antibodies against the foal RBCs; gets passed to colostrum; ingested by foal; erythrolysis of foal RBCs between 24-36h
How to manage detection of NI in foals before 24h
Use a different colostrum source; cease ingestion of mothers colostrum
How to manage detection of NI in foals after 24h
Blood transfusion
How to proactively test for NI in foals
Use an indirect coombs test
How to diagnose NI in foals after it occurs
Direct coombs test
Why is vitamin D needed to fight tuberculosis
Vitamin D binds to Vit D receptor on macrophages (upregulated through TLR 1/2 signalling) to activate Vit D hydroxylase, which produces antibacterial cathelicidins
What are the three mechanisms of antifungal immunity
Primary, skin and other surfaces; primary, lungs; secondary and opportunistic
What are the effector cells against fungal infections
NK cells, TH17 cells, TH1 cells
What cells promote formation of a granuloma
Th1 cells
Describe cyclic parasitemia
Parasite constantly mutates to form a new antigen; immune system has to form a primary immune response each time this occurs; eventually the parasite will mutate in a way that compromises its own survival
What two ways does an infectious agent cause symptoms of disease
1) damage to host cells, tissues or organs
2) damage to tissues from immune response
What three effector cell types clear intracellular bacteria
Tc, NK, M1 macrophages
What is required to clear helminth infections (2 cells and an antibody isotype)
Th2; IgE, eosinophils
What is the virome
Non-pathogenic viruses that make up the microflora
T/F Type I IFN responses use autocrine, paracrine and endocrine mechanisms
T
What is the Type I IFN receptor
IFNAR
What cell type produces the most Type I IFN
Th1 cells
What is the key effector cell in an antiviral immune response
CD8+ Tc cells
Autograft
Same individual
Allograft
Same species
Isograft
D/R are genetically identical
Xenograft
different species
in what cases do we not need to worry about graft rejection
Isograft and autograft
Triggers of allograft rejection
1) mismatched MHC antigens
2) blood group antigen mismatches
3) foreign antigens presented by MHC
What are the four types of graft rejection
Hyperacute, accelerated, acute, chronic
Hyperacute rejection occurs within ________ and is due to _________
Minutes-hours; pre-existing antibodies
Accelerated rejection occurs within __________ and is due to ____________
Days; memory cells
Acute rejection occurs within ___________ and is due to ________________
Weeks; T cell responses
Chronic rejection occurs within ________________ and is due to ________________
Months; antibodies
Why do liver transplants tend to be rejected slowly
Hepatocytes produce a lot of IDO
what is the umbilical cord rich in
neonatal stem cells
why do skin allografts take longer to be rejected
no established blood supply at time of transplant
why dont corneal allografts require tissue typing or immunosuppression
immunopriveleged site
how is allogenic bone marrow transplanted
1) treat host with radiation to kill off their bone marrow
2) inject host with donor bone marrow
3) prophylactic antibiotics until the new immune system is reconstituted
what is graft-versus-host-disease
when transplanted bone marrow results in cells that recognize host tissue as foreign and attack it (occurs when there is a large degree of MHC mismatch)
concordant vs discordant xenografts
concordant: closely related species; discordant: non-related species
why doesn’t sperm get rejected in the uterus
it is immunosuppressive (prostatic fluids inhibit complement)
What is sensitivity
Probability a test will be positive when a disease is present
What is specificity
Probability a test will be negative when a disease is absent
What does FSC determine in flow cytometry
Relative size of the cell
What does SSC determine in flow cytometry
Relative granularity or internal complexity
What does FL1, FL2… determine in flow cytometry
Relative flourescence
What does indirect ELISA detect
antibodies in serum
What does a sandwich ELISA detect
antigens in serum
What must a virus express in order to cause hemagglutination
hemagglutinins
What is a false positive
Test came up positive even though the animal does not have the pathogen
What is a false negative
Test came back negative even though the animal has the pathogen
What can flow cytometry be used to diagnose
Hematological malignancies (lymphocyte vs monocyte vs granulocyte cancer)
T/F ELISA can be miniaturized into rapid tests
T
T/F The immune system ignores self
False; the immune system will destroy self-derived but dangerous cells (ex. cancerous cells)
T/F carnivores have a higher incidence of cancer
T
Which of the following may be the strongest correlate to cancer risk
a) longevity
b) body size
c) nutrition
C
What are the three E’s of immunoediting
Elimination, equilibrium, escape
Elimination: killing cancer cells _____ cancer cell proliferation
>
Elimination represents
successful immunosurveillance
Equilibrium: killing cancer cells _______ cancer cell proliferation
=
During equilibrium what happens
TUMOUR EDITING: Cancer cells acquire immuno-evasive properties
Escape: killing cancer cells ______ cancer cell proliferation
<
Escape represents a shift from ________ cancer to ___________ cancer
subclinical cancer to clinical cases of cancer
Role of TILs in cancer
Help move from equilibrium -> elimination
Escape is promoted by a loss of (3)
- IL-12
- IFNγ
- T cells
What is an IDEAL antigen for immunotherapies (3)
- expressed on all cancer cells
- expressed only on cancer cells
- expressed in a variety of cancers
What is a less ideal antigen for immunotherapies and what is the best outcome
TAAs
1. expressed in a higher concentration on cancer cells
2. expressed during different stages of development
3. expressed in healthy cells in immunopriveliged sites
How to circumvent the fact that not everyone’s immune system will respond the same to immunotherapies
Use a variety that recruit multiple weapons of the immune system
How to circumvent immunotherapies for immunocompromised and immunosensecent individuals
Use passive immunotherapies (ex. antibodies)
How to circumvent cancers in immunopriveleged locations
Leverage mechanisms of the immune system that protect places like the brain
How to overcome antigen loss variants of cancers
Target multiple antigens with immunotherapies
Four catagories of immunotherapies
- vaccines, 2. antibodies, 3. adoptive cell therapies, 4. oncolytic virotherapy
Neoadjuvant vs adjuvant delivery of immunotherapy for surgery
Neoadjuvant = before surgery; adjuvant = after surgery
Atopy
immediate allergic response ex. atopic dermatitis
Urticaria (what is it and what causes it)
Rash of round welts on the skin, usually due to food allergens
Pruritis
Severe itching
What Ig isotype is best for blood typing
IgM (10 binding sites)
When in a rush, should a clinician perform blood typing or cross matching
cross-matching (takes less than 30 minutes)
Even though cows have the most complex blood group system, why is HA relatively uncommon? How does it typically arise
Inbreeding within herds increases genetic similarity; commonly comes from vaccinating the mother with pooled blood from infected calves (can sensitize the mother; passes Ab to calves via colostrum)
Optimal canine donors are negative for
DEA 1.1, 1.2, 3, 5, 7
Want to avoid transfusing type _ blood into cats that are type _, since _% have antibodies against it.
Type A blood into cats that are Type B; 95%
Universal RBC donor
O-
Universal RBC recipient
AB+
Universal plasma donor
AB+
Universal plasma recipient
O-
How do you treat a transfusion reaction?
- stop transfusion immediately
- give fluids and diuretics to promote urine flow
Why does a vaccine that uses cytopathic BVDV grown in bovine kidney cells promote pancytopenia in newborn calves
Grown in bovine kidney cells therefore exposed to bovine MHC; may end up in the vaccine; get cows vaccinated against certain MHC
What is a potential consequence of a drug binding to the surface of an RBC
Acts as a hapten; get targetting of the RBC and anemia
What is a potential consequence of an RBC absorbing a pathogen-derived antigen
The RBC will be removed by phagocytosis
What are rheumatoid factors
Antibodies that bind to novel epitopes on other antibodies (ex. after they bind to their target antigen)
How do microchimerisms induce autoimmunity
Maternal and fetal blood circulation shared -> maternal response to fetal RBC -> cross-reaction with maternal cells (they share 50% of their DNA)
How does milk allergy develop
Infrequent milking -> increased intra-mammary pressure -> backflow of milk protein into blood (not normally present) -> TH2 biased response -> autoreactive IgE -> anaphylaxis
What is the cause of pain in rheumatoid arthritis and systemic lupus erythematosus
Immune complex (autoantibodies against autoantigens) deposition and subsequent inflammation
Purpose of vaccines (3)
- simulate a pathogenic infection
- induce an immune response that prevents against disease
- prevent transmission of the causative agent
The quality of a vaccine is based on its ____________, not on its ___________
Performance; technological platform (conventional vs new)
T/F an ideal vaccine does not require boosting
T
What is the duration of immunity for an ideal vaccine
Lifetime of the animal
What is the duration of immunity
How long protection is maintained against the disease and transmission of the causative agent
Which of the following vaccine strategies is pro-phylactic
a) herd immunity
b) ring vaccination
c) predictive vaccination
a
T/F A vaccine that does not confer immunity can never be used to achieve herd immunity
T
What is relative risk reduction
Degree to which an intervention reduced an unwanted incident within a subpopulation that has a disease
What is absolute risk reduction
Degree to which an intervention reduced an unwanted incident among the total population
What is seroconversion
When pathogen-specific antibodies appear in serum
How do you treat vaccine-induced anaphylactic shock
epinephrine
What are three reasons why vaccines sometimes need to be re-administered
- competing with passive immunity
- boosters
- antigenic variation of pathogens over time
