recognition response Flashcards

1
Q

what regulates recognition and response

A

Recognition & response are regulated by
surface receptors and intracellular proteins

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2
Q

what do surface receptors on immune cells recognize

A

Surface receptors on immune cells recognize antigens (B & T cells) or
patterns (innate cells)

activation of the receptor induces a response in the cell (signal transduction)

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3
Q

how do receptors interact with ligands

A

through non covalent interactions

h bond
VDW hydrophobic interactions
ionic bond

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4
Q

how is the strength of an interaction quantified between a receptor and a ligand

A

the dissocaition constant kd

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5
Q

what does a high and low kd value mean

A

the lower the kd, the higher the affinity of interaction

Most enzyme ligand interactions: Kd range 10 -3 to 10 -5 M
Ab – Ag interactions: Kd as low as 10 -12 M

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6
Q

what is equilibrium analysis used for

A

to determine antibody affinity

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7
Q

affinity

A

interaction between one ligand and receptor

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8
Q

avidity

A

overall strength of all interactions during multivalent binding

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9
Q

what regulates key steps in receptors binding to antigens

A

Key steps are regulated by
phosphorylation of proteins to form
docking sites, activate enzymes, or
promote degradation/stabilization of
proteins

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10
Q

what does receptor clusering by multivalent Ags do

A

activates signal transduction
a) individual receptors bind a multivalent ligand and nycleate receptor cluster formation
b) multivalent ligand mediates cluster formation

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11
Q

what do membrane microdomains do

A

Membrane microdomains increase organization and efficiency of receptor activation/clustering

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12
Q

what is an example of a membrane mircodomain

A

lipid raft

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13
Q

what are to ways of changing the affinity of receptors for thier ligands

A

Combining different receptor sub-units can change the affinity of receptors for their ligand

Changing the level of
receptor on the cell
surface can also vary
the response of the
cell

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14
Q

what is a protein domain commonly shared by many receptors

A

Many receptors share a
common protein domain-
Immunoglobulin (Ig)
domain

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15
Q

what is the immunoglobulin domain and what is its structure

A

The Ig domain was first described in Antibodies, which is why it
was named “immunoglobulin domain”

The Ig domain is sandwich of 2 b sheets with loops connecting the anti-parallel b strands

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16
Q

how do B lymphocytes interact with antigens

A

via the B cell receptor

this consists of an Ab that recognizes the antigen and molecules inserted into the membrane that communicates with the inside of the cell (signal)

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17
Q

BCR and co-receptors

A

Co-receptors can accelerate or change the
signal sent through the BCR

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18
Q

how do T cells recognize antigens

A

The T cell receptor and co-receptors allow interaction of T cells with peptide Ag;
when the Ag is presented by APC

Molecules that communicate with
the inside of the cell (signal)

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19
Q

what do innate immune cells recognize

A

Innate immune cells recognize pathogen associated molecular patterns (PAMPs) via pattern recognition
receptors (PRR)

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20
Q

what are cytokines

A

Group of low-molecular weight regulatory proteins that function as the ʻmessengers of the immune systemʼ

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21
Q

what cells are cytokines

A

Includes:
* Interleukins (secreted by leukocytes & act on
other leukocytes)
* Monokines (secreted by monocytes &
macrophages)
* Lymphokines (secreted by lymphocytes)
* Chemokines: related but regulate cell migration

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22
Q

how do cytokines act

A

Cytokines act in autocrine, paracrine, or endocrine fashion

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23
Q

how much. cytokines is required to have an effect

A

Cytokine RECEPTORS have
very high affinity for the
cytokine, SO cytokines can
have biological effects at
picomolar amounts

24
Q

pleiotropy

A

same cytokine acts on different cels to have different effects

25
redundancy
difffrent cytokines have the same effect on the same cell
26
synergy
effect is more than the sum of its parts effect changes
27
antagonism
one cytokine prevents action of another cytokine
28
cascade induction
multiple target cells, multiple secreting cells
29
what do mutations to the IL-2Ry chain cause
X linked severe combined immunodefficiency (XSCID) * IL-2 is essential for activation of T cells * Patients have no T or NK cell activity * Worse than expected if just T cells affected
30
why is the gamma subunit so widely used
Unexpected severity of IL-2Rγ-deficiency explained by common use of γ subunit
31
how do cytokine receptors change gene expression
Cytokine receptors communicate with the nucleus via a signal transduction pathway to change gene expression and influence cell fate & activity
32
JAK
janus kinase
33
STAT
signal transducer and activator of transcription
34
what are some functions of specific cytokines
pyrogens (fever causing) pro inflammatory anti inflammatory anti viral chemokines
35
pygogens
Pyrogens (fever-causing): IL-1, IL-6 and TNF-alpha
36
pro inflammatory cytokines
* Pro-inflammatory: IL-1, IFN-γ, and TNF-alpha
37
anti inflammatory cytokines
* Anti-inflammatory: TGF-β
38
anti viral cytokines
Anti-viral: IFN-γ, IFN-α/β
39
chemokine cytokines
Chemokines: IL-8 attracts neutrophils, MIP-1alpha and MIP-1beta attract monocytes & NK cells
40
what controlls extravasation
chemokines
41
what are the steps of extravasation
rolling activation arrest/ adhesion transednothelial migration -integrins are necessary for adhesion
42
how do cytokines affect chemokine receptors
Cytokines can cause upregulation of chemokine re
43
what are two types of anti inflammatory agens
antibody based therapies corticosteroids
44
antibody based therapies
blocking antibodies that bind integrins or other adhesion molecules * kidney transplantation * autoimmune diseases: crohn’s, MS, Rheumatoid arthritis
45
corticosteroids
* Interact with steroid hormones * Decrease # of circulating leukocytes * lysis of lymphocytes * circulation of lymphocytes * Inhibit secretion of almost all cytokines * block NF-κB activation (transcription factor) = reduced IL-1 secretion * inhibit T cell, macrophage, and neutrophil activation
46
how are cytokines related to hematopoesis
they regulate hematopoesis G-CSF and GM-CSF are used to treat chemotherapy patients and bone marrow recipients.
47
what are cytokine related diseases
septic shock/ sepsis cytokine storm cancers autoimmunity and other immune based diseases
48
septic shock/ sepsis
* Endotoxins produced by gram negative bacteria stimulate DCs and macrophages via TLRs to overproduce IL-1 and TNF-α * Superantigens * Trauma leading to ischemia (lack of blood blow); sterile inflammation * neutralize TNF-α with an antibody * neutralize IL-1 with soluble IL-1 receptor antagonist (IL-1Ra)
49
cytokine storm
influenza, SARS, COVID-19: positive feedback activates too many immune cells; healthy immune system * “Exacerbated lung inflammation due to cytokine dysregulation is the underlying cause of respiratory failure in SARS-CoV-2-infected individuals” Ramasamy and Subbian 2021
50
cancers (cytokine related)
* HTLV (human T cell leukemia virus): IL-2 * myelomas, cardiac myxoma cells, cervical cancer, bladder cancer: IL-6 * enhance proliferation * autocrine * Hodgkin’s lymphoma: IL-5
51
autoimmunity and other immyune based diseases
* SLE (lupus): IL-10
52
cytokine based therapies
cytokine inhibitors/ antagonists reversing cellular deficiencies treatment of immunodeficiencies treatment of T cell leukemia and trasnplant patients
53
cytokine inhibitors and antagonists
*TNF inhibitors, IL-1Ra for RA /chronic inflammation *IL-2R as clinical marker for chronic T cell activation
54
reversing cellular deficienceies
G-CSF and GM-CSF to escalate the rate of reconstitution following chemotherapy or bone marrow transplantation
55
treatmnet of immunodeficiencies
*G-CSF for x-linked agammaglobulinemia, *IL-2 for SCID; IFN-γ for leukocyte adhesion deficiencies *IL-2 antibody stabilizes recombinant (injected) IL-2 in the circulation (paradox)
56
treatment of T cell leukemia and transplant patients
* Blocking antibodies to prevent T cell activation by IL-2 * Conjugate toxin to cytokine analogue to target TH cells that express abnormally high amounts of CD25 (IL-2γ chain) destructino of activated Th cells or supression of T h cell proliferation and Tc cell activation
57