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
Q

redundancy

A

difffrent cytokines have the same effect on the same cell

26
Q

synergy

A

effect is more than the sum of its parts
effect changes

27
Q

antagonism

A

one cytokine prevents action of another cytokine

28
Q

cascade induction

A

multiple target cells, multiple secreting cells

29
Q

what do mutations to the IL-2Ry chain cause

A

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
Q

why is the gamma subunit so widely used

A

Unexpected severity of IL-2Rγ-deficiency
explained by common use of γ subunit

31
Q

how do cytokine receptors change gene expression

A

Cytokine receptors communicate with the nucleus via a signal transduction
pathway to change gene expression and influence cell fate & activity

32
Q

JAK

A

janus kinase

33
Q

STAT

A

signal transducer and activator of transcription

34
Q

what are some functions of specific cytokines

A

pyrogens (fever causing)
pro inflammatory
anti inflammatory
anti viral
chemokines

35
Q

pygogens

A

Pyrogens (fever-causing): IL-1, IL-6 and TNF-alpha

36
Q

pro inflammatory cytokines

A
  • Pro-inflammatory: IL-1, IFN-γ, and TNF-alpha
37
Q

anti inflammatory cytokines

A
  • Anti-inflammatory: TGF-β
38
Q

anti viral cytokines

A

Anti-viral: IFN-γ, IFN-α/β

39
Q

chemokine cytokines

A

Chemokines: IL-8 attracts neutrophils, MIP-1alpha and MIP-1beta attract monocytes & NK cells

40
Q

what controlls extravasation

A

chemokines

41
Q

what are the steps of extravasation

A

rolling
activation
arrest/ adhesion
transednothelial migration

-integrins are necessary for adhesion

42
Q

how do cytokines affect chemokine receptors

A

Cytokines can cause upregulation of chemokine re

43
Q

what are two types of anti inflammatory agens

A

antibody based therapies
corticosteroids

44
Q

antibody based therapies

A

blocking antibodies that bind integrins or other adhesion molecules
* kidney transplantation
* autoimmune diseases: crohn’s, MS, Rheumatoid arthritis

45
Q

corticosteroids

A
  • 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
Q

how are cytokines related to hematopoesis

A

they regulate hematopoesis

G-CSF and GM-CSF are
used to treat
chemotherapy patients
and bone marrow
recipients.

47
Q

what are cytokine related diseases

A

septic shock/ sepsis
cytokine storm
cancers
autoimmunity and other immune based diseases

48
Q

septic shock/ sepsis

A
  • 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
Q

cytokine storm

A

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
Q

cancers (cytokine related)

A
  • 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
Q

autoimmunity and other immyune based diseases

A
  • SLE (lupus): IL-10
52
Q

cytokine based therapies

A

cytokine inhibitors/ antagonists
reversing cellular deficiencies
treatment of immunodeficiencies
treatment of T cell leukemia and trasnplant patients

53
Q

cytokine inhibitors and antagonists

A

*TNF inhibitors, IL-1Ra for RA /chronic inflammation
*IL-2R as clinical marker for chronic T cell activation

54
Q

reversing cellular deficienceies

A

G-CSF and GM-CSF to escalate the rate of reconstitution
following chemotherapy or bone marrow transplantation

55
Q

treatmnet of immunodeficiencies

A

*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
Q

treatment of T cell leukemia and transplant patients

A
  • 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
Q
A