Module 5a

Question 1

After activation of the T-lymphocyte in a lymph organ, they migrate to peripheral areas and may become? (two types)

Answer 1

Effector cells: sensing through chemokines to go to tissues
Memory cells: ready for encounter with the same antigen in the future. prepared for attack.

Question 2

Cell-mediated immunity involves of which effector T-cells? and humoral immunity T-cells are?

Answer 2

Cytotoxic CD8 T cell and Th1 cell. Th2/Th1 cells

Question 3

What do Cytotoxic CD8 cells take action for?

Answer 3

Killing of infected cell.

Question 4

What do Th1 cells take action for?

Answer 4

Activation of infected macrophages. Pathogens live in vesicles of macrophage and need to be activated to eliminate.

Question 5

What do Th2/Th1 cells take action for?

Answer 5

Activation of specific B cell to make antibody.

Question 6

Where are macrophages located primarily and what form are they when transiting to blood?

Answer 6

Mainly in tissue. They are in form of monocytes going to blood.

Question 7

What type of antigens do B-lymphocytes present?

Answer 7

Soluble type

Question 8

Where are dendritic cells typically localised to?

Answer 8

In lymph nodes, and will only travel to when there is a T-cell to expose the antigen to.

Question 9

Can you find macrophages everywhere?

Answer 9

Yes indeed

Question 10

What’s Razacs favourite subject?

Answer 10

Neuro

Question 11

Where can you find B-cells? Are they everywhere or localised?

Answer 11

Very localised, in areas called germinal centres. They specialise and grow there. They acquire capability of producing antibodies

Question 12

What is macropinocytosis?

Answer 12

Cells taking up a large volume of extracellular fluid, nutrients or soluble compounds.

Question 13

Properties of dendritic cells as APC’s?

Answer 13

• Do macropinocytosis and phagocytosis
• Low MHC expression in tissue like skin (focusing on collecting antigens). High MHC expression in lymphoid tissue as they have to present antigen here
• Once dendritic cells mature and are in lymph nodes, they always express co-stimulatory molecules to activate naive T-cells, as well as the antigen on MHC.
• Peptides, viral antigens, allergens are presented
• Found in lymphoid tissue, connective tissue, epithelia

Question 14

Properties of macrophages as APC’s?

Answer 14

• Do phagocytosis
• Dont always express co-stimulatory molecules right away. Only induced by bacterial components (like LPS) and/or ytokines from other immune cells (like IFN-γ).
• macrophages can present antigens, but they’re not great at activating naïve T cells.
• Macrophages present fragments of things they’ve phagocytosed:
  Intracellular pathogens and extracellular pathogens.
• MHC levels low in tissue like skin (still collecting antigens). Once they migrate to lymph nodes and mature, they dramatically upregulate MHC class I and II to present.

Question 15

Properties of B cells as APC’s?

Answer 15

• Antigen-specific receptor (IgA, IgD., etc)
• B cells only express co-stimulatory molecules when they bind their specific antigen with their B-cell receptor (Ig), and get activated by a helper T cell.
• B cells always express MHC class II — even at rest — because they are ready to present antigens they specifically bind.
• Soluble antigens, toxins and viruses.

Question 16

How do B-cells present antigens to T-cells? (process)

Answer 16

1. B-cells use surface IG to specifically bind to their Ig.
2. these antigens are internalised by endocytosis.
3. These antigens are processed in endocytic compartments and loaded into MHC class II.
4. B-cells present a high density of specific antigen fragments on MHC II.
5. After activation (eg, via LPS), B-cells upregulate B7 co-stimulatory molecules to activate helper T-cells.

Question 17

How do dendritic cells mature and become effective APC’s?

Answer 17

Immature DC’s in peripheral tissues express high levels of certain molecules helping in efficient antigen capture. Upon encountering danger signals (pathogens) they migrate to lymphoid tissue and differentiate into mature dendritic cells.

Mature dendritic cells express high levels of MHC I and II for antigen presentation. Costimulatory molecules like B7.1 and B7.2 activate T-cells. ICAM-1 and ICAM-2 to form stable interactions in synapses with T-cells.

Question 18

What is a danger signal and how do these activate dendritic cells to become mature?

Answer 18

Dendritic cells recognize danger signals through pattern recognition receptors such as Toll-like receptors (TLRs), which detect microbial components like LPS (endotoxin), CpG DNA, and double-stranded RNA. Upon activation, dendritic cells mature and upregulate MHC molecules for antigen presentation and co-stimulatory molecules like B7, enabling them to effectively activate naïve T cells.

Question 19

How do Toll-like receptors (TLRs) regulate dendritic cell activation?

Answer 19

Dendritic cells detect pathogen-associated molecular patterns (PAMPs) such as DNA, RNA, and other degradation products through extracellular and intracellular Toll-like receptors (TLRs). These signals activate intracellular signaling cascades involving adaptor proteins and intermediate messengers. This ultimately leads to the transcription of genes that encode cytokines and co-stimulatory molecules. The resulting gene expression enhances dendritic cell maturation, antigen presentation, and the ability to activate T cells against specific infections.

Question 20

Where do dendritic cells originate and where do they travel to live predominantly in?

Answer 20

Originate in bone marrow and move around the blood and go and live in the tissue (skin). They will reside there as immature DC’s.

Question 21

What is the role of langerhans cells in antigen presentation and T cell activation?

Answer 21

Langerhans cells in the skin capture antigens through phagocytosis or macropinocytosis. After Ag uptake they leave the epidermis and enter lymphatic system. They migrate to the lymph node where they mature to become dendritic cells and express B7. The B7-positive cells stimulate naive T-cells.

Question 22

How do dendritic cells activate T-cells after migrating to peripheral tissues?

Answer 22

1. Immature DC’s reside in peripheral tissues and take up antigen via macropinocytosis
2. Upon detecting pathogen they migrate via lymphatics to the regional lymph node.
3. During migration they mature - upregating MHC and costimulatory molecules.
4. In the deep cortex of lymph node, mature DC’s present Ag to naive T-cell
5. T-cell scan for their specific antigen. Essential for adaptive immune response.

Question 23

What are the steps involved in the extravasation of naive T-lymphocyte into lymphoid tissue?

Answer 23

1. rolling: t-cells express L-selectin, which loosely binds to ligands (CD34) on endothelial cells which slows down T-cell.
2. Activation: chemokines presented by the epithelial cell bind to chemokine-R on the T-cell.
3. Adhesion/arrest: activated integrins (LFA-1) on the T-cell bind strongly to ICAM-1 on the endothelium causing T-cell to stop firmly.
4. Transendothelial migration: the T cell squeezes through the endothelium into the lymph node, where it can scan for antigens presented by dendritic cells.

Question 24

What happens to T-cells in the lymph node during antigen surveillance? And what kind of cells will t-cells turn to after recognising antigen.

Answer 24

1. t-cells enter lymph nodes through HEVs and scan APC’s in the cortex.
2. They assess whether these APC’s re presenting their specific antigen via MHC.
3. If no antigen recognised, t-cells leave the lymph node via efferent lymphatics.
4. If antigen recognised, T-cells interact more efficiently with DC’s (due to B7 costimulation). T-cell becomes activated, proliferate, and differentiate into effector T-cells

Question 25

What are the two signals required for T cell activation at the APC-T synpase?

Answer 25

Signal 1 - Antigen specific signal. The TCR on the T-cell binds to a specific peptide-MHC complex on APC. CD4 or CD8 coreceptor stabilises interaction Signal 2 - Co-stimulatory signal. CD28 on the T-cell binds to B7 molecules (B71 or B72) on the APC. The second signal essential for full T-cell activation & prevents anergy.

Question 26

What is the immunological synapse and what molecules are involved?

Answer 26

Structured interface where a T-cell and an APC make contact. TCR binds to MHC-peptide complex. CD4/CD8 help stabilise the TCR-MHC interaction. LFA-1 (T-cell) and ICAM-1 (APC) provide strong adhesion and keeps cells in contact.

Question 27

How does resting T-cell turn into effector Tcell?

Answer 27

1. Signal 1: TCR binds to peptide presented by MHC by mature APC. Signal 2: co-stimulatory interaction of CD28 on T-cell binds to B7 on APC. 2. T-cell becomes activated and starts expressing IL-2 and the IL-2 receptor. 3. IL-2 binds to its own receptor in an autocrine loop triggering proliferation. 4. The activated T-cell proliferates and differentiates into effector T-cells.

Question 28

What role does IL-2 play in T cell activation & proliferation?

Answer 28

Resting T cells express low affinity IL-2 receptors. Upon activation and C28 costimulation, T-cells produce IL-2 and express the IL-2 receptor a-chain (IL-2Ra), forming a high-affinity receptor. IL-2 binds to this receptor in autocrine loop triggering entry into cell cycle and proliferation.

Question 29

Why do macrophages need to recognise bacteria over non-bacteria?

Answer 29

They express B7 which interacts with CD28 therefore activate T-cells. Non-bacterial proteins not getting B7 and C28 second signal therefore become anergic.

Question 30

What is the trick for immunisations?

Answer 30

Bacterial products used together with non-bacterial proteins so macrophage gets activated, and express B7 on APC and T-cell gets activated to recognise this non-bacterial protein.

Question 31

How can dendritic cells activate CD8 T-cells without CD4 T-cell help?

Answer 31

Virus-infected dendritic cells can express high levels of B7, allowing them to directly activate naive CD8 T-cells. CD8 T cells receive signal 1 and signal 2. The CD8 T-cell produces IL-2 which binds to its own receptor, driving proliferation without CD4 assistance.

Question 32

How does CD4 help contribute to CD8 T cell activation?

Answer 32

CD4 cells interact with APC via MHC class II activating them to upregulate CD40 and 4-1BBL. The activated APC can then stimulate CD8 T-cells via MHC I and co-stimulatory molecules like CD40L and 4-1BBL

Question 33

In absence of B7 cells become what?

Answer 33

anergic

Question 34

What is T cell anergy and why is it important?

Answer 34

If a T-cell receives signal 1 without signal 2 it becomes anergic. Anergic t-cells do not respond even if later re-exposed to antigen. This maintains peripheral tolerance.

Question 35

What is CTLA-4 and how does it regulate T-cell activation?

Answer 35

CTLA-4 is upregulated on activated T-cells. It binds B7 on APC's more strongly than CD28, blocking co-stimulation. This delivers an inhibitory signal to t-cell reducing activation. This prevents overactivation and maintain tolerance once infection is controlled.

Question 36

Whats the difference between naive and memory CD8+ T cell activation?

Answer 36

Naive CTL-Ps require signal 1 and signal 2, and help from CD4+ Th1 cells which help produce IL-2 to support activation. Memory CTL-Ps can activate with just MHC I + B7-CD28 without CD4 help. produce their own IL-2.