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Lecture 13

front 1

Where do lymphocytes go after leaving the bone marrow or thymus?

back 1

They circulate through blood to lymph to secondary lymphoid tissues (lymph nodes, spleen, mucosal tissues) to search for antigen

front 2

How do lymphocytes (especially T cells) travel through the body?

back 2

Blood → enter lymph nodes via HEVs → scan for antigen → exit via efferent lymphatics → return to blood via thoracic duct

front 3

What is lymphocyte recirculation?

back 3

Continuous movement of lymphocytes through blood, lymph nodes, lymph, and back to blood

front 4

What is the general time course of the T cell response?

back 4

0–6 hr antigen capture → 6–24 hr APC migration → 1–2 days T cell activation → 2–4 days proliferation → 4–7 days effector cells exit

front 5

How does antigen travel to lymph nodes?

back 5

Free antigen via lymph or dendritic cells carrying antigen

front 6

Which method is most important for T cell activation?

back 6

Dendritic cells carrying antigen

front 7

How do lymphocytes enter lymph nodes?

back 7

Through HEVs via rolling, activation, adhesion, and diapedesis

front 8

Where are T cells located in the lymph node?

back 8

Paracortex

front 9

Where are B cells located in the lymph node?

back 9

Follicles (cortex)

front 10

Where do APCs go in the lymph node?

back 10

Paracortex (T cell zone)

front 11

What is the fibroblastic reticular cell (FRC) network?

back 11

Structural scaffold that guides T cells and dendritic cells and distributes chemokines

front 12

What is S1P?

back 12

Lipid signaling molecule high in blood and lymph

front 13

What is S1PR1?

back 13

Receptor for S1P on lymphocytes

front 14

What is the function of S1P

back 14

S1PR1? / Controls lymphocyte exit from lymph nodes

front 15

How does S1P signaling work?

back 15

Cells follow S1P gradient (low in node → high in blood) to exit

front 16

What are the 3 signals required for T cell activation?

back 16

Signal 1 (antigen), Signal 2 (costimulation), Signal 3 (cytokines)

front 17

What molecules are involved in signal 1?

back 17

TCR, MHC, CD4 or CD8, CD3

front 18

What molecules are involved in signal 2?

back 18

CD28 (T cell) and B7/CD80/CD86 (APC)

front 19

What happens if signal 1 occurs without signal 2?

back 19

Anergy or apoptosis (peripheral tolerance)

front 20

What molecules are involved in signal 3?

back 20

Cytokines (IL-12, IL-4, TGF-β, IL-6)

front 21

What is paracrine signaling in T cell activation?

back 21

Cytokines from nearby APCs influence T cell differentiation

front 22

What is autocrine signaling in T cell activation?

back 22

T cells produce IL-2 to stimulate their own proliferation

front 23

What is IL-2’s role?

back 23

Drives T cell proliferation (clonal expansion)

front 24

What is the role of PAMP

back 24

PRR interactions? / Determines cytokines released → determines helper T cell type

front 25

What is the cSMAC?

back 25

Central region of immunological synapse with TCR and signaling molecules

front 26

What is the pSMAC?

back 26

Peripheral ring with adhesion molecules for stability

front 27

What is the function of CD3?

back 27

Transmits TCR signal inside the cell

front 28

What is the function of CD4?

back 28

Binds MHC II and strengthens signaling

front 29

What is the function of CD8?

back 29

Binds MHC I and supports cytotoxic activation

front 30

What is the function of CD28?

back 30

Provides costimulatory signal for activation

front 31

What is the function of CD40?

back 31

Activates APCs and helps B cells via CD40L interaction

front 32

What is the role of ITAMs?

back 32

Become phosphorylated and initiate signaling cascade

front 33

What is the role of LCK?

back 33

Tyrosine kinase that phosphorylates ITAMs and starts signaling

front 34

What are the outcomes of CD3 signaling?

back 34

Cytokine production, proliferation, differentiation

front 35

What transcription factors are activated?

back 35

NFAT, NF-κB, AP-1

front 36

What is CTLA-4?

back 36

Inhibitory receptor that blocks T cell activation

front 37

How does CTLA-4 work?

back 37

Competes with CD28 for B7 and shuts down activation

front 38

What is a checkpoint inhibitor?

back 38

Drug that blocks inhibitory signals (CTLA-4, PD-1)

front 39

What is the effect of checkpoint inhibitors?

back 39

Enhances T cell response against cancer

front 40

What side effects occur with checkpoint inhibitors?

back 40

Autoimmune-like effects (rash, colitis, hepatitis, etc.)

front 41

What are intracellular signaling events of T cell polarization?

back 41

Cytokines → JAK-STAT → transcription factors → differentiation

front 42

What do Th1 cells do?

back 42

Activate macrophages and fight intracellular pathogens

front 43

What diseases are associated with Th1?

back 43

Autoimmunity and chronic inflammation

front 44

What do Th2 cells do?

back 44

Activate eosinophils, promote IgE, fight parasites

front 45

What diseases are associated with Th2?

back 45

Allergies and asthma

front 46

What do Th17 cells do?

back 46

Recruit neutrophils, fight extracellular bacteria/fungi

front 47

What diseases are associated with Th17?

back 47

Autoimmune and inflammatory disorders

front 48

What do Treg cells do?

back 48

Suppress immune responses and maintain tolerance

front 49

What happens if Tregs are too low or too high?

back 49

Low → autoimmunity, High → cancer immune suppression

front 50

What is a Treg?

back 50

CD4+ T cell that suppresses immune responses

front 51

What is the difference between central and peripheral Tregs?

back 51

Central = thymus-derived, Peripheral = induced in tissues

front 52

What is the phenotype of Tregs?

back 52

CD4+, CD25+, FOXP3+, CTLA-4

front 53

How do Tregs suppress immune responses?

back 53

IL-10, TGF-β, consume IL-2, inhibit APCs, suppress T cells

front 54

What defines a helper T cell subset?

back 54

Polarizing cytokines, master transcription factor, effector cytokines

front 55

What is T cell polarization?

back 55

Naïve T cell differentiates into specific helper subtype

front 56

What is reciprocal inhibition?

back 56

Helper T cell subsets suppress each other

front 57

What is T cell plasticity?

back 57

Ability of T cells to change phenotype

front 58

How do plasticity and reciprocal inhibition coexist?

back 58

Early flexibility, later commitment

front 59

What cells do helper T cells help?

back 59

Macrophages, B cells, CD8 T cells, other immune cells

front 60

How do T cells activate macrophages?

back 60

IFNγ secretion and CD40–CD40L interaction

front 61

What is the role of MHC class II?

back 61

Presents antigen to CD4 T cells

front 62

What is the role of IFNγ?

back 62

Activates macrophages and enhances killing

front 63

What is the role of CD40

back 63

CD40L? / Strengthens macrophage activation

front 64

What happens when macrophages are activated?

back 64

Increased killing, ROS production, cytokine release, better antigen presentation

front 65

What is macrophage polarization?

back 65

Differentiation into M1 or M2 states

front 66

What do M1 macrophages do?

back 66

Inflammation and pathogen killing

front 67

What do M2 macrophages do?

back 67

Tissue repair and anti-inflammatory functions

front 68

How do T cells influence macrophage polarization?

back 68

Th1 → M1, Th2 → M2

front 69

What is the relationship between T cells and macrophages?

back 69

Feedback loop where macrophages activate T cells and T cells activate macrophages