CH14 - The Immune Response in Space and Time

Where do naïve lymphocytes go after entering blood?

~50% spleen, ~40% lymph nodes, ~10% barrier tissues

How long do naïve lymphocytes stay in tissues?

Spleen ~5 hrs, lymph nodes ~12-18 hrs

Why is constant recirculation important?

Very few lymphocytes (~1 in 100,000) recognize a specific antigen

What structure allows lymphocytes to enter lymph nodes?

High-endothelial venules (HEVs)

What is the role of CD62L (L-selectin)?

Binds GlyCAM → rolling

What is the role of CCR7?

Responds to chemokines → activates integrins → arrest

What are addressins?

Adhesion molecules that control tissue-specific homing

What are the 4 steps of leukocyte extravasation?

Rolling → selectins (CD62L), Activation → chemokines (CCR7), Arrest → integrins (LFA-1), Transmigration → PE-CAM1

Where do T cells go in lymph nodes?

Paracortex (T cell zone)

Where do B cells go in lymph nodes?

Follicles

What guides T cell movement?

Fibroblast reticular cell (FRC) network

What guides B cell movement?

Follicular dendritic cell (FDC) network

Why are FRC and FDC networks important?

Increase chance of antigen encounter

How do T cells find antigen?

Scan APCs along FRC network

How do B cells find antigen?

Scan FDCs in follicles

What happens if lymphocytes don't find antigen?

Exit via S1P1 signaling through lymphatics

What is the first step in innate immunity?

PRRs detect pathogen → cytokines/chemokines released

What are the 2 main goals of innate immunity?

Kill pathogens + activate adaptive immunity

Which cells arrive first at infection site?

Neutrophils

Outline early immune response to viral lung infection.

PRRs detect virus, Cytokines recruit innate cells, Neutrophils + monocytes respond, DCs process antigen, DCs migrate to lymph nodes (CCR7), Activate T and B cells, Effector + memory cells generated

How does processed antigen reach T cells?

APCs (DCs) → lymph node → present via MHC

How does unprocessed antigen reach B cells?

Direct entry → follicles OR via macrophages → FDCs

How fast do antigens reach lymph nodes?

Unprocessed = minutes, processed = hours

What happens after B cells bind antigen?

Upregulate CCR7 → move to T cell border

Where do B cells get T cell help?

Follicle-paracortex border

How do T cells help B cells?

CD40L-CD40 interaction + cytokines

What are outcomes of B cell activation?

Plasma cells OR germinal center formation

What happens in the dark zone?

B cell proliferation + mutation

What happens in the light zone?

Antigen testing + T cell help

What determines dominant B cell clones?

Highest antigen affinity

How are CD8 T cells fully activated?

Require CD4 T cell help

How does CD4 help CD8 if they don't directly interact?

Through APC (tricellular interaction)

What happens when T cells encounter antigen?

Arrest + form stable APC interactions (1-24 hrs)

How much do lymphocytes expand?

Up to ~1000-fold

When does peak response occur?

~7-14 days

What happens after peak immune response?

Contraction phase (95% cells die)

What percentage becomes memory cells?

~5-10%

What causes contraction?

Loss of antigen signals + apoptosis + regulatory signals

Where are central memory T cells (TCM)?

Secondary lymphoid organs

Where are effector memory T cells (TEM)?

Peripheral tissues

Where are resident memory T cells (TRM)?

Stay in tissues (skin, lungs, gut)

How do effector cells leave lymph nodes?

Upregulate S1P1

What do effector cells downregulate?

CD62L (to avoid returning to lymph nodes)

What controls tissue-specific homing?

Adhesion molecules + chemokines

Where do effector T cells go?

Tissue where antigen originated

Where do plasma cells go?

Bone marrow or lymphoid tissues

What is the full immune response timeline?

Minutes: innate detection (PRRs), Hours: APC migration to lymph node, Days 1-7: T/B activation + expansion, Days 7-14: peak response, Weeks 2-4: contraction, Long-term: memory cells remain

What is the antigen flow to lymph node?

Pathogen enters tissue, APCs process antigen → migrate (CCR7), Processed antigen → T cells, Unprocessed antigen → B cells, B + T interaction → activation

What is the B cell activation process?

Bind antigen in follicle, Upregulate CCR7, Move to T cell border, Receive help (CD40 + cytokines), Differentiate → plasma or GC

What is the effector cell homing process?

Activated in lymph node, Upregulate homing receptors, Exit via S1P1, Travel via blood, Enter infected tissue

What is the contraction process?

Antigen cleared, Cytokine signals decrease, Apoptosis triggered, ~95% cells die, Memory cells remain

What is the main purpose of lymphocyte trafficking?

Maximize chance of antigen encounter

What molecule keeps naïve cells in lymph nodes?

CCR7

What molecule lets cells exit lymph nodes?

S1P1

Why are memory cells important?

Faster, stronger response upon reinfection