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Immunology > Ch 3: Receptors and Signaling (B and T-Cell Receptors) > Flashcards

Ch 3: Receptors and Signaling (B and T-Cell Receptors) Flashcards

1
Q

Upstream

A

components of a signaling pathway that are the closest to the receptor

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2
Q

Downstream

A

The components of a signaling pathway that are the closest to the effector molecules that determines the outcome of the pathway

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3
Q

Growth factor receptors

A

ligand binding induces a conformational change in the receptor that results in receptor dimerization

cytoplasmic domain has tyrosine kinase activity thus, leads to reciprocal phosphorylation of cytoplasmic regions of the receptor molecules by the dimerization partener

inducible enzyme activity built into receptor

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4
Q

What is different about BcR and Tcr from growth factor receptors

A

They have very short cytoplasmic components and therefore need help from intracellular receptor-associated molecules to induce signal transduction

Iga/Igb heterodimer in B cells and Hexatriomeric CD3 complex in T cells

These are closely associated with their respective antigen receptors and are responsible for transmitting the signals initiated by ligand binding

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5
Q

ITAM

A

immuno receptor tyrosine activation motif

recurrent seqwuence motifs found on many signaling proteins within the immune system

the tyrosine becomes phosphorylated following signal transduction through the associated receptor

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6
Q

CD19/CD21 complex

A

binds to complement molecules covalently attached to the antigen

B-cells -> BcR

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7
Q

How do CD8 and CD4 aid in signal transduction

A

bind to nonpolymorphic regions of the antigen presenting MHC molecule

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8
Q

Lipid Rafts

A

Highly ordered, detergent insoluble, cholesterol and sphingolipid rich membrane regions and are populated by many molecules critical to receptor signaling

Ligand induced clusters of Bcr and Tcr move into here

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9
Q

immunoglobulin structure

A

hyper variable loose strands at the margins and a core structure of antiparallel B-sheets linked by a di-sulfide linkage

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10
Q

Antibody common structure

A

four polypeptide chains, to identical light chains and two identical heavy chains, H and L chains linked with a di-sulfide linkage and non-covalent interactions

antibody molecule forms a Y shape with two identical antigen binding regions at the tips of the Y (both H and L chains contribute to the binding domain)

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11
Q

Fab regions

A

the identical fragments that retain the antigen binding specificity of the original antibody after cleavage via papain

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12
Q

Fc region

A

the non-antigen binding region of an antibody

fragement crystalizable region

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13
Q

Fc receptor

A

on phagocytotic ot cytolytic cells or immune effector molecules

binds the antigen-coupled antibody

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14
Q

antigenic dererminant

A

a region of an antigen that makes contact with the antigen combining region on an antibody

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15
Q

What is the purpose of Th cells

A

guide the behaviour of other immune cells

Whithout them an immune response can see severely damaging due to the lack of directional cues

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16
Q

How does our immune system combat the use of error-prone RNA pol in mirobes

A

the generation of diversity

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17
Q

Myeloid DC’s

A

tissue resident and are professional APC’s

Lymphoid are the IFN secreters

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18
Q

Follicular DC’s

A

NO not act as APC’s for Th cells

Important for the maturation of B cells

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19
Q

What do Th1 detect for

A

intracellular pathogens

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20
Q

What do Th2 detect for

A

Extracellualr patogens

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21
Q

Treg

A

Can quell an immune response

CD4 and CD25

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22
Q

NK cells

A

Part of the innate immune response and do not have any antigen specific receptors

sence the absence of MHC

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23
Q

NKT cells

A

lipid and glycoproteins antigens are recognized by TcR

Express CD4

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24
Q

Th1 cells

A

secrete cytokines that promote differentation and acivation in macrophages and cytotoxic T cells
-> modulation of a cytotoxin immune response

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25
Q

IL-12 and IFN

A

induce Th1 differentation

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26
Q

Th2

A

activates B cells to make antibodies

27
Q

IL-4 and IL-5

A

generation of Th2

28
Q

Th17

A

promotes differentation of activated macrophages an neutrophils and support the inflammatory state

-> induced by IL-17 and IL-23

29
Q

antigen activated cells

physiological changes

A

antigen activated cells may induce changes in their cell membranes to bear receptors for chemokines

-> only activated cells (in the lymph nodes or the spleen with migrate)

Also will bear receptors for proliferation signals such as IL2 and differentiation factors like IL4

30
Q

What is Caspase 1

A

Cleases IL1 b/a into their mature form

part of the inflammasome

31
Q

What are the gene transcripts and pathway of IL-1 activaiton

A

IL-1
MyD88
MAP kin
AP-1= TF leads to IL-2 secretion

32
Q

What do all three types of interferon have in common

A

all 2 increase the expression of MHC complex proteins

33
Q

What is IFNb secreated by

A

secreted by actived macrophages and DC’s and virus infected cells

34
Q

Type 1 IFN

A

IFN a/b

Both are secreted by cells which have activated PRRs

a and b “interfere” by producing anti-viral ribonucleases and shutting down protein synthesis in the host cell

kills the host cell and the virus in it

35
Q

Type 2 IFN

A

IFNg and IL10

produced by activated T and NKcells

BIases T cell help toward Th1, induces macrophages and the destruction of intracellular pathogens and differentiation of cytotoxic T cells

36
Q

IL-10

A

type 2 IFN

secreted by macrophages as well as T, B and DC cells

Similar in structure to IFNg

37
Q

Type 3 IFN

A

IFN lambda, IL-29, IL-28 a/b

upregulate the expression of genes controlling viral replication and host cell proliferation

38
Q

TNFa

A

Proinflammatory

produced by activated macrophages

leads to expression of MHC and adhesion molecules

Secreted in response to infection, inflammation and environmental stressors

39
Q

CD40L

A

Expressed on the surface of T cells and is required to signal for B cell differentaiton

40
Q

Fas = CD95

A

binding of Fas ligand induces apoptosis when bound to its cognate receptor

41
Q

Purpose of “decoy receptors”

A

Soluable TNF receptors exist to soak up XS TNF

the IL-1 receptor family also has this

allows fine tuning and modulation of the cytokine response. Can limit diffusion such that cytokine is only secreted and taken up effectively in a localized area

can also to prevent cytokine storms by reducing total amount of cytokine that is effectively absorbed

42
Q

Why do lymphocytes express Fas on their cell surface once an infection has been cleared

A

TNF-R1, CD40, BAFF and April = life or death receptors

for the purpose of cell death via apoptosis

this minimizes inflammation, note that apoptosis is mediated through caspase-8

43
Q

IL-17 family

A

proinflammatory, thus activated by NFkB -? MAP Kin -> Il-17

Released by activated T cells

Stimulates production of pro-inflammatory state
-> IL-6
as well as neutrophil mobilizing cytokines

44
Q

IL-17E

A

is an exception to the IL-17 family

induces the Th2 response and suppresses the Th17 response

45
Q

Il-6

A

Pro-inflammatory cytokine and anti-inflammatory mitokine

46
Q

What is the general signal transduction cascade for Il-2 secretion through NFAT

A

PRR activation = dimerization and reciprocal phosphorylation via ITAM like domains
-> Phos = allows docking molecules to bind

BcR/ TcR clustering increases their affinity for lipid rafts
-> Lyn can then phosphorylate the iga and igb domains
(Lck does a similar thing in T cells)

PRR-> NFAT (nuclear factor activating T cells) -> activation of genes encoding IL-2 which can then modulate T-cell proliferation

47
Q

PKC activates NFkB

A

Ikb is an inhibitor of NFkB and is bound

when a cell is activated, ikb gets Phos and is then ubiquitinated for degradation

Then NFkB can bind promoter = proinflammatory and citation events as well as the secretion of Il-2

48
Q

Ras/ MAP kin

A

activaiton of AP-1 = TF that is important for IL-2 secretion

Ras is a G-protein

49
Q

Tcell activation

A

Needs TcR as well as the co-receptor CD28 to be stimulated

CD28 binds CD80 on APC

leads to AP-1 activation and IL-2 secretion= cytokine

50
Q

What are the 6 classes of cytokines

A 
IL1
Hematopoietin
IFN
TNF
IL17
Chemokine
51
Q

THe IL-1 Family (general characteristics)

A

secreted very early in the immune response by DC’s monocytes and macrophages

stimulated by micrbes binding to PRRs

  • > proinflammatory
  • > induction of acute phase proteins (Type 1 IFNa/b, IL-6 and CXCL8)

Activates T and B cells and leads to the destruction of viral RNA and a general high fever to silimate temp sensitive bacteria

52
Q

Members of the IL-1 family

A 
IL-1a/b
IFNa/b
IL-6
IL-18
IL-33
53
Q

IL-33

A

induction of Th2 cytokines that promote T lymphocyte interactions with B cells

54
Q

Members of the Hematopoietin family (class 1 cytokines)

A 
IL-2
IL-6
IL-4
IL12
GM-CSF, G-CSF
55
Q

IL-2

A

leads to T and B cell proliferation

56
Q

IL-6

A

B-cell differentation to plasma cells

57
Q

IL-4 and IL12

A

Th cell singnalling

58
Q

The JAK-STAT pathway

A 
JAK = tyrosine kinase
STAT = TF that can translocate to the nucleus

ALLOWS:
Immune specificity to cytokines

BY:

  • > exquisite specificity of a given cytokine to a receptor
  • > Particular cytokine receptors are bound to specific JAKs with unique STATS
  • > ew Specific STAT homo/heterodimers will only interact with specific promoters
  • > those promoters need to be available (not hidden in the heterochromatin)

Can be turned off by STAT inhibitors ( PIAS & SOCS)

59
Q

TNFb / Lymphotoxin a

A

produced by activated lymphocytes

-> when binds to a neutrophil it induces adhesion and an increase in the expression of MHC

60
Q

Cytokine mimicry

A

Epstein-Barr Virus produces an IL-10-like moleule that binds to the IL-10 receptors
-> suppresses the Th1-type cell-mediated response`

61
Q

Septic shock

A

overproduction of TNFa and IL-1b from PRR activation -> lowers blood pressure form leaky capillaries as a result of the inflammatory response
-> cytokines that are secreted raise the body temp super high
also increases the WBC count as well as a change in respiration rate as well as blood clots and organ failure

62
Q

Anti-microbial peptides

A

Amphipathic and net +ve

-> this allows them to interact with the acidic phospholipids of microbial membranes

63
Q

C-reactive protien

A

an oposonin that recognizes phophocholine and carbohydrates on microbes
-> is then bound to FcR and phagocytosis is enchanced

Immunology (23 decks)

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