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

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

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

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

What is lymphocyte recirculation?

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

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

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

How does antigen travel to lymph nodes?

Free antigen via lymph or dendritic cells carrying antigen

Which method is most important for T cell activation?

Dendritic cells carrying antigen

How do lymphocytes enter lymph nodes?

Through HEVs via rolling, activation, adhesion, and diapedesis

Where are T cells located in the lymph node?

Paracortex

Where are B cells located in the lymph node?

Follicles (cortex)

Where do APCs go in the lymph node?

Paracortex (T cell zone)

What is the fibroblastic reticular cell (FRC) network?

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

What is S1P?

Lipid signaling molecule high in blood and lymph

What is S1PR1?

Receptor for S1P on lymphocytes

What is the function of S1P

S1PR1? / Controls lymphocyte exit from lymph nodes

How does S1P signaling work?

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

What are the 3 signals required for T cell activation?

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

What molecules are involved in signal 1?

TCR, MHC, CD4 or CD8, CD3

What molecules are involved in signal 2?

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

What happens if signal 1 occurs without signal 2?

Anergy or apoptosis (peripheral tolerance)

What molecules are involved in signal 3?

Cytokines (IL-12, IL-4, TGF-β, IL-6)

What is paracrine signaling in T cell activation?

Cytokines from nearby APCs influence T cell differentiation

What is autocrine signaling in T cell activation?

T cells produce IL-2 to stimulate their own proliferation

What is IL-2’s role?

Drives T cell proliferation (clonal expansion)

What is the role of PAMP

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

What is the cSMAC?

Central region of immunological synapse with TCR and signaling molecules

What is the pSMAC?

Peripheral ring with adhesion molecules for stability

What is the function of CD3?

Transmits TCR signal inside the cell

What is the function of CD4?

Binds MHC II and strengthens signaling

What is the function of CD8?

Binds MHC I and supports cytotoxic activation

What is the function of CD28?

Provides costimulatory signal for activation

What is the function of CD40?

Activates APCs and helps B cells via CD40L interaction

What is the role of ITAMs?

Become phosphorylated and initiate signaling cascade

What is the role of LCK?

Tyrosine kinase that phosphorylates ITAMs and starts signaling

What are the outcomes of CD3 signaling?

Cytokine production, proliferation, differentiation

What transcription factors are activated?

NFAT, NF-κB, AP-1

What is CTLA-4?

Inhibitory receptor that blocks T cell activation

How does CTLA-4 work?

Competes with CD28 for B7 and shuts down activation

What is a checkpoint inhibitor?

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

What is the effect of checkpoint inhibitors?

Enhances T cell response against cancer

What side effects occur with checkpoint inhibitors?

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

What are intracellular signaling events of T cell polarization?

Cytokines → JAK-STAT → transcription factors → differentiation

What do Th1 cells do?

Activate macrophages and fight intracellular pathogens

What diseases are associated with Th1?

Autoimmunity and chronic inflammation

What do Th2 cells do?

Activate eosinophils, promote IgE, fight parasites

What diseases are associated with Th2?

Allergies and asthma

What do Th17 cells do?

Recruit neutrophils, fight extracellular bacteria/fungi

What diseases are associated with Th17?

Autoimmune and inflammatory disorders

What do Treg cells do?

Suppress immune responses and maintain tolerance

What happens if Tregs are too low or too high?

Low → autoimmunity, High → cancer immune suppression

What is a Treg?

CD4+ T cell that suppresses immune responses

What is the difference between central and peripheral Tregs?

Central = thymus-derived, Peripheral = induced in tissues

What is the phenotype of Tregs?

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

How do Tregs suppress immune responses?

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

What defines a helper T cell subset?

Polarizing cytokines, master transcription factor, effector cytokines

What is T cell polarization?

Naïve T cell differentiates into specific helper subtype

What is reciprocal inhibition?

Helper T cell subsets suppress each other

What is T cell plasticity?

Ability of T cells to change phenotype

How do plasticity and reciprocal inhibition coexist?

Early flexibility, later commitment

What cells do helper T cells help?

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

How do T cells activate macrophages?

IFNγ secretion and CD40–CD40L interaction

What is the role of MHC class II?

Presents antigen to CD4 T cells

What is the role of IFNγ?

Activates macrophages and enhances killing

What is the role of CD40

CD40L? / Strengthens macrophage activation

What happens when macrophages are activated?

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

What is macrophage polarization?

Differentiation into M1 or M2 states

What do M1 macrophages do?

Inflammation and pathogen killing

What do M2 macrophages do?

Tissue repair and anti-inflammatory functions

How do T cells influence macrophage polarization?

Th1 → M1, Th2 → M2

What is the relationship between T cells and macrophages?

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