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MBBCh 2- HAEM2000A > F. Immunology (3) > Flashcards

F. Immunology (3) Flashcards

1
Q

What does ● An immunological synapse?

A

● An immunological synapse refers to the direct cell-to-cell contact between certain immune cells, such as T cells and dendritic cells, during immune responses. It plays a crucial role in the activation and coordination of the immune system.

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2
Q

● In the context of a naïve T cell and a mature dendritic cell, the immunological synapse occurs when….

A

the T cell receptor (TCR) on the T cell recognizes and binds to the major histocompatibility complex (MHC) molecule and the specific peptide presented on the surface of the activated mature dendritic cell. This interaction leads to the activation of the T cell, initiating an immune response.

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3
Q

● Additionally, an immunological ______ can form between effector CD8 T cells and infected cells. The TCRs on the CD8 T cells recognize _____ presented by MHC class I (MHCI) molecules on the surface of infected cells. This recognition triggers the killing of infected cells by the CD8 T cells, helping to eliminate the ______.

A

synapse
peptides
infection

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4
Q

● Furthermore, effector CD4 T cells can form an immunological synapse with antigen-presenting cells (APCs) like…

A

macrophages, B cells, or dendritic cells. The TCRs on the CD4 T cells recognize peptides presented by MHC class II (MHCII) molecules on the surface of these APCs. This interaction enhances the activation of CD8 T cells, promotes the development of more efficient macrophages, and facilitates the production of plasma cells.

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5
Q

● Furthermore, effector CD4 T cells can form an immunological synapse with antigen-presenting cells (APCs) like…

A

macrophages, B cells, or dendritic cells. The TCRs on the CD4 T cells recognize peptides presented by MHC class II (MHCII) molecules on the surface of these APCs. This interaction enhances the activation of CD8 T cells, promotes the development of more efficient macrophages, and facilitates the production of plasma cells.

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6
Q

Dendritic cell activation
● Dendritic cell activation involves several steps:

A
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7
Q

How do dendritic cells present peptides to activate naive T cells?

A
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8
Q

The immunological synapse between an effector CD8 T cell and an infected cell

● The immunological synapse between an effector CD8 T cell and an infected cell functions as follows: (4)

A
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9
Q

The immunological synapse between an effector CD8 T cell and an infected cell

● The immunological synapse between an effector CD8 T cell and an infected cell functions as follows: (4)

A
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10
Q

Immunological synapse between Effector CD4 TH1 cells and macrophage:

● The immunological synapse between effector TH1 CD4 T cells and macrophages functions as follows: (5)

A
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11
Q

Immunological synapse between Effector CD4 TH1 cells and macrophage:

● The immunological synapse between effector TH1 CD4 T cells and macrophages functions as follows: (5)

A
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12
Q

Immunological synapse between Effector TFH CD4 T cell and B cell:

● The immunological synapse between effector TFH CD4 T cells and B cells functions as follows: (5)

A
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13
Q

Immunological synapse between Effector TFH CD4 T cell and B cell:

● The immunological synapse between effector TFH CD4 T cells and B cells functions as follows: (5)

A
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14
Q

● NFκB =

A

nuclear factor kappa-light-chain-enhancer of activated B cells

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15
Q

● NFκB =

A

nuclear factor kappa-light-chain-enhancer of activated B cells

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16
Q

NFκB is a transcription factor:

What are transcription factors?

A

Transcription factors are proteins that bind to specific DNA sequences and regulate the transcription of genes.

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17
Q

NFκB

● In an inactive state, NFκB is typically found in the cytoplasm, but upon activation, it _______ into the nucleus where it binds to specific DNA sequences and controls gene transcription.

● When activated, NFκB promotes the production of various cytokines, acute phase proteins involved in the immune response, and regulators of ______ (programmed cell death).

A

translocates
apoptosis

17
Q

NFκB

● In an inactive state, NFκB is typically found in the cytoplasm, but upon activation, it _______ into the nucleus where it binds to specific DNA sequences and controls gene transcription.

● When activated, NFκB promotes the production of various cytokines, acute phase proteins involved in the immune response, and regulators of ______ (programmed cell death).

A

translocates
apoptosis

18
Q

● The NFκB family consists of five members, which typically function as heterodimers, meaning they pair up with different combinations of each other.

􏰁 The members of the NFκB family are:

A
  • NF-κB1 (also known as p105, which can be further processed into p50),
  • p100 (which can be further processed into p52),
  • RelA (also known as p65),
  • RelB
  • c-Rel.
19
Q

● The NFκB family consists of five members, which typically function as heterodimers, meaning they pair up with different combinations of each other.

􏰁 The members of the NFκB family are:

A
  • NF-κB1 (also known as p105, which can be further processed into p50),
  • p100 (which can be further processed into p52),
  • RelA (also known as p65),
  • RelB
  • c-Rel.
20
Q

● Each member of the NFκB family possesses an __-________ Rel homologous domain, which is responsible for binding to specific DNA sequences in the regulatory regions of target genes.

A

N-terminal

21
Q

● Each member of the NFκB family possesses an __-________ Rel homologous domain, which is responsible for binding to specific DNA sequences in the regulatory regions of target genes.

A

N-terminal

22
Q

● The NFκB family can be divided into two classes: (2)

A

􏰁 Class I members, such as p105 and p100, are synthesized as large precursors that undergo selective degradation of their C-terminal portions to produce mature proteins.

􏰁 Class II members, have a C-terminal transactivation domain (TAD), which allows them to activate gene expression.

23
Q

● The NFκB family can be divided into two classes: (2)

A

􏰁 Class I members, such as p105 and p100, are synthesized as large precursors that undergo selective degradation of their C-terminal portions to produce mature proteins.

􏰁 Class II members, have a C-terminal transactivation domain (TAD), which allows them to activate gene expression.

24
Q

● The activation and nuclear translocation of NFκB are tightly regulated by a family of inhibitory proteins called IκB (inhibitor of NFκB).

What is the function of IkB? (2)

A

􏰁 IκB binds to the NFκB heterodimer in the cytoplasm, preventing it from entering the nucleus by masking the nuclear localization signal (NLS), a signal sequence that facilitates entry into the nucleus.

􏰁 When certain signalling pathways are activated, IκB is phosphorylated and degraded, allowing NFκB to translocate into the nucleus and initiate gene transcription.

25
Q

● The activation and nuclear translocation of NFκB are tightly regulated by a family of inhibitory proteins called IκB (inhibitor of NFκB).

What is the function of IkB? (2)

A

􏰁 IκB binds to the NFκB heterodimer in the cytoplasm, preventing it from entering the nucleus by masking the nuclear localization signal (NLS), a signal sequence that facilitates entry into the nucleus.

􏰁 When certain signalling pathways are activated, IκB is phosphorylated and degraded, allowing NFκB to translocate into the nucleus and initiate gene transcription.

26
Q

Signalling Pathways
● Here are some examples of signaling pathways that activate NFκB: (4)

A

􏰁 Tumor necrosis factor alpha (TNFα) via TNFR
􏰁 Pathogen-associated molecular patterns (PAMPs) on pathogens, e.g., lipopolysaccharide (LPS), via Toll-like receptor (TLR)
􏰁 IL1 via IL1R
􏰁 B cell receptor (BCR) and T cell receptor (TCR)

27
Q

􏰁 Tumor necrosis factor alpha (TNFα) via TNFR: (2)

A

✔ TNFα is a pro-inflammatory cytokine that binds to its receptor, TNFR. This binding triggers the recruitment of adaptor proteins, which ultimately lead to the activation of TAK1 (transforming growth factor-beta-activated kinase 1).

✔ TAK1 then phosphorylates and activates the IKK (inhibitor of NFκB kinase) complex.

28
Q

􏰁 Pathogen-associated molecular patterns (PAMPs) on pathogens, e.g., lipopolysaccharide (LPS), via Toll-like receptor (TLR):

A

✔ TLRs are receptors involved in recognizing specific components of pathogens. When TLRs bind to PAMPs, they activate adaptor proteins, leading to the activation of TAK1 and subsequent activation of the IKK complex.

29
Q

􏰁 IL1 via IL1R:

A

✔ IL1 is another pro-inflammatory cytokine that binds to its receptor, IL1R. This binding triggers a signaling cascade involving adaptor proteins and TAK1, ultimately leading to the activation of the IKK complex.

30
Q

􏰁 B cell receptor (BCR) and T cell receptor (TCR): (2)

A

✔ BCR and TCR are receptors found on B cells and T cells, respectively, involved in the immune response.
✔ Activation of BCR or TCR leads to intracellular signaling events that can activate NFκB.

31
Q

􏰁 B cell receptor (BCR) and T cell receptor (TCR): (2)

A

✔ BCR and TCR are receptors found on B cells and T cells, respectively, involved in the immune response.
✔ Activation of BCR or TCR leads to intracellular signaling events that can activate NFκB.

32
Q

● Once the IKK complex is activated, it phosphorylates an inhibitor protein called IκB (inhibitor of NFκB), specifically IκBα.

How does this process occur? (3)

A
33
Q

● Once the IKK complex is activated, it phosphorylates an inhibitor protein called IκB (inhibitor of NFκB), specifically IκBα.

How does this process occur? (3)

A
34
Q

T cell Receptor and B cell Receptor Signaling:
● T cell Receptor (TCR) Signaling: (3)

A
34
Q

T cell Receptor and B cell Receptor Signaling:
● T cell Receptor (TCR) Signaling: (3)

A
35
Q

T cell Receptor and B cell Receptor Signaling:
● B cell Receptor (BCR) Signaling: (3)

A
35
Q

T cell Receptor and B cell Receptor Signaling:
● B cell Receptor (BCR) Signaling: (3)

A
36
Q

● NFκB and Disease:
􏰁 Viruses: (4)

A

✔ NFκB is implicated in viral infections. For example, the HIV provirus contains binding sites for NFκB that control the expression of viral genes.
✔ NFκB’s activation can contribute to viral replication and pathogenicity.
✔ In the case of HIV, NFκB may be involved in activating the virus from a latent,
inactive state, leading to viral replication.
✔ Additionally, some pathogens, like Yersinia pestis (causes plague), secrete factors that interfere with the NFκB pathway, inhibiting the immune response of the infected individual.

37
Q

● NFκB and Disease:
􏰁 Cancer: (3)

A

✔ Aberrant activation of NFκB is frequently observed in various cancers, including leukemia, lymphoma, colon cancer, and ovarian cancer.
✔ The dysregulation of NFκB signaling can promote tumor growth, survival, and metastasis.
✔ Targeting NFκB signaling pathways is an area of research for potential therapeutic approaches in cancer treatment.

38
Q

● NFκB and Disease:
􏰁 Inflammatory Diseases: (3)

A

✔ NFκB plays a crucial role in many inflammatory diseases. Conditions like asthma, inflammatory bowel disease (such as Crohn’s disease and ulcerative colitis), and
autoimmune disorders like rheumatoid arthritis (RA) involve dysregulated NFκB signaling.

✔ NFκB contributes to the pathophysiology of these diseases by promoting inflammation and the production of pro-inflammatory cytokines.

✔ Therefore, inhibiting NFκB signaling pathways is being explored as a potential therapeutic strategy for cancer and inflammatory diseases.

MBBCh 2- HAEM2000A (30 decks)

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