F. Immunology (3)

Question 1

What does ● An immunological synapse?

Answer 1

● 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.

Question 2

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

Answer 2

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.

Question 3

● 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 ______.

Answer 3

synapse
peptides
infection

Question 4

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

Answer 4

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.

Question 5

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

Answer 5

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.

Question 6

Dendritic cell activation
● Dendritic cell activation involves several steps:

Answer 6

Question 7

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

Answer 7

Question 8

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)

Answer 8

Question 9

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)

Answer 9

Question 10

Immunological synapse between Effector CD4 TH1 cells and macrophage:

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

Answer 10

Question 11

Immunological synapse between Effector CD4 TH1 cells and macrophage:

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

Answer 11

Question 12

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)

Answer 12

Question 13

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)

Answer 13

Question 14

● NFκB =

Answer 14

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

Question 15

● NFκB =

Answer 15

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

Question 16

NFκB is a transcription factor:

What are transcription factors?

Answer 16

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

Question 17

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).

Answer 17

translocates
apoptosis

Question 17

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).

Answer 17

translocates
apoptosis

Question 18

● 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:

Answer 18

• 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.

Question 19

● 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:

Answer 19

• 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.

Question 20

● 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.

Answer 20

N-terminal

Question 21

● 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.

Answer 21

N-terminal

Question 22

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

Answer 22

􏰁 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.

Question 23

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

Answer 23

􏰁 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.

Question 24

● 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)

Answer 24

􏰁 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.

Question 25

● 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)

Answer 25

􏰁 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.

Question 26

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

Answer 26

􏰁 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)

Question 27

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

Answer 27

✔ 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.

Question 28

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

Answer 28

✔ 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.

Question 29

􏰁 IL1 via IL1R:

Answer 29

✔ 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.

Question 30

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

Answer 30

✔ 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.

Question 31

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

Answer 31

✔ 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.

Question 32

● Once the IKK complex is activated, it phosphorylates an inhibitor protein called IκB (inhibitor of NFκB), specifically IκBα. How does this process occur? (3)

Answer 32

Question 33

● Once the IKK complex is activated, it phosphorylates an inhibitor protein called IκB (inhibitor of NFκB), specifically IκBα. How does this process occur? (3)

Answer 33

Question 34

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

Answer 34

Question 34

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

Answer 34

Question 35

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

Answer 35

Question 35

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

Answer 35

Question 36

● NFκB and Disease: 􏰁 Viruses: (4)

Answer 36

✔ 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.

Question 37

● NFκB and Disease: 􏰁 Cancer: (3)

Answer 37

✔ 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.

Question 38

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

Answer 38

✔ 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.