Exam 1 Flashcards
What is an innocuous antigen?
should not illicit an immune response
What are atopic individuals?
predisposed to allergies (IgE)
What is the Hygiene Hypothesis?
lack of early childhood exposure to innocuous, increases the susceptibility to allergic diseases
What is responsible for allergies?
Type 1 HSR
When is gut microbia established?
at birth
Type 1 HSR is mediated by what isotype?
IgE
What receptors recognize pathogens and communicate and provide signals to TH cells?
pattern recognition receptors
What are the 3 steps to choosing a Th subset?
- APC binds to antigen + polarizing cytokines
- transcription factors induced
- production of effector cytokines
Biased Th subsets are required to eliminate a pathogen/allergen. How are these subsets chosen?
pattern recognition receptors on APCs
What are the polarizing cytokines for Tregs?
IL-2
TGF-B
What are the polarizing cytokines for TH17?
IL-1
IL-6
IL-23
TGF-B
What is the polarizing cytokine for TH2?
IL-4
What are the polarizing cytokines for TFH?
IL-6
IL-21
What are the polarizing cytokines for TH1?
IL-2
INF-g
IL-18
What are the effector cytokines for Treg?
IL-10
TGF-B
What are the effector cytokines for TH17?
IL-17A
IL-17F
IL-22
What are the effector cytokines for TH2?
IL-4
IL-5
IL-13
What are the effector cytokines for TFH?
IL-4
IL-21
What are the effector cytokines for TH1?
INF-g
TNF
What cytokine regulates immune supression?
TGF-B
When in development (fetal–>adult) are Tregs and TGF-B the highest?
fetal stage
When is immune tolerance the highest in development (fetal–>adult)?
fetal stage (lots of Tregs TGF-B present)
When is protective immunity the highest in development (fetal–>adult)?
adult stage (low Tregs and TGF-B because immune system has developed)
What is intrauterine IPEX?
inactivation of FOXP3 causing no Treg production = no tolerance developed
What is the fetal immune system controlled by?
Tregs
Atopic individuals have a ______ bias towards TH2 cells (overactivated)
skewed
What are some examples of factors that can cause immune skewing?
age
sex
obesity
pre-disposition
prior exposure
microbiome
What are the 5 mucosal surfaces the microbiome colonizes?
- oral epithelium
- airway epithelium
- intestinal epithelium
- reproductive epithelium
- skin epithelium
What is the largest mucosal surface with the most microbiome?
intestinal epithelium
What 5 ways are intestinal microbiome help to the host?
- enhances nutrion
- provides competitive growth
- produces metabolites
- regulates local immune response
- regulates immune homeostasis
What are 4 mucosal protection stratagies?
- tightly packed epithelial cells
- limited immune response to host bacteria
- antimicrobial peptides
- production of IgA
What is immune homeostasis?
balance between Tregs and Teffectors
What does immune imbalance look like =? (Tregs v. Teffectors)
More T effectors that T regs
What is tonic signaling?
immune system skewing above baseline set by barrier surfaces and other factors (like age or sex)
- more bad bacteria than good bacteria
What is an example of how pathology doesn’t always describe the mechanism?
weak and excessive immune responses result in immunopathology (wrong response)
What does K means?
equilibrium constant
- strength of non-covalent interactions between 2 molecules
Are covalent or non-covalent interactions irreversible?
covalent
Are covalent or non-covalent interactions sharing of electrons with extensive orbital overlap?
covalent
What is an example of covalent interactions in immunology?
C3b binding to pathogen surface
Are covalent or non-covalent interactions weaker?
non-covalent
What are 4 examples of non-covalent interactions?
- hydrogen bonds
- ionic bonds
- hydrophobic interactions
- van der Waal interactions
What does hydrogen bonding require?
donor
acceptor
hydrogen
What is a hydrogen bond?
2 electronegative atoms compete for the same hydrogen
What amino acids do hydrogen bonds occur between?
polar AA
What is an ionic bond?
bond between a cation and anion
What amino acids do ionic bonds occur between?
charged AA
What is a hydrophobic interaction?
hydrophobic molecules are attracted to one another
What amino acids do hydrophobic interaction occur between?
uncharged non-polar AA
What is a van der Waal interaction?
packing of atoms together
What amino acids do van der Waal interactions occur between?
all amino acids
What is Ka?
association constant
What is Kd?
disassociation constant
What is Ka measured in?
M-1
What is Kd measured in?
M
What is the equation for Ka?
[RL] / [R][L]
What is the equation for Kd?
[R][L] / [RL]
What is the relationship between Ka and Kd?
they are inverses of each other
Kd = 1/Ka
What does it mean for the [RL] formation if the Ka is large?
more RL formed
What does it mean for the [RL] formation if the Kd is small?
more RL formed
What is the equation for (f)?
f = Ka [L] / 1+Ka[L]
What does f tell us?
the fraction of RL complexes formed at a given [L]
Which axis is f and [L] on in a binding curve?
f = y axis
[L] = x axis
Using a binding curve, Kd = [L] when?
50% of RL complexes are formed
If 10% of RL is formed, ____x Kd
0.1 x Kd
If 50% of RL is formed, _____x Kd
1 x Kd
If 90% of RL is formed, ______ x Kd
10 x Kd
If 100% of RL is formed, _______ x Kd
100 x Kd
Kd or Ka is a constant?
Ka
If Ka is a constant, why does the binding increase with increasing concentrations?
there is a higher chance of R and L interacting if there is more ligand
How can you tell if a ligand has a stronger affinity than another?
If it can reach Kd (50% saturated) with less [L] then its stronger
* smaller Kd = stronger
If affinity or avidity stronger?
avidity
What is apparent Kd?
(avidity) when expected Kd is different from ther actual Kd
Why is avidity stronger?
grabbing 2 ligands at once is much stronger (multivalent/multiple binding interactions)
* like doing a pull up with both hands instead of 1
What 2 things are required for avidity?
- R or L to be attached to a surface
- other component has to have multiple binding sites
Does avidity or affinity have a smaller Kd if its the same interaction?
avidity (stronger)
What is responsible for the different affinities between molecules?
non-covalent interactions
What is the most important interaction for specificity?
van der Waal
How can antibodies disrupt non-covalent interactions to neutralize a microbe?
antibody will have higher affinity (lower Kd) for receptor where microbe wants to bind and blocks it
What is a hypersensitivity reaction?
when the immune system responds inappropriately to innocuous antigens
What does anaphylaxis stand for?
against protection
What is the recognition molecule for type 1 HSR?
IgE
What is the effector mechanism for type 1 HSR?
granulocytes degranulation
What are the 3 phases of type 1 HSR?
- sensitization phase
- early effector
- late phase
What happens during the sensitization phase of type 1 HSR?
exposure to antigen
What happens during the early effector phase of type 1 HSR?
- mast cell degranulation mediated by IgE–FcERI
- release of primary and secondary mediators
What happens during the late phase of type 1 HSR?
- cytokine production
- granulocytes recruitment