Lecture 9

Lymphoid Anatomy

• Three tiers (levels) of Lymphoid Structures

  • Primary Lymphoid Tissues – Generate lymphoid cells

  • Secondary Lymphoid Tissues – Facilitate antigen sampling from tissues and organs in the body. Facilitates the activation of antigen specific responses

  • Tertiary Lymphoid Tissues – Specialized immune responses in inflamed tissues

  • Primary: RED ; Secondary: BLUE ; Tertiary: ?

    

Primary Lymphoid Tissues: Bone Marrow and Thymus

*Specialized structures to facilitate the differentiation of antigen-specific lymphocytes

Bone Marrow

• Primary site of hematopoiesis in adults

• Produces both myeloid and lymphoid cells

• Houses Hematopoietic Stem Cells (HSCs) in the perivascular niche, HSCs divide to become progenitor cells

  • Progenitor Cells:

    • Myeloid Progenitors → innate immune cells

    • Lymphoid Progenitors → adaptive immune cells

• Some mature and effector cells return to the bone marrow for long-term survival

Thymus

• Specialized for T cell development

Secondary Lymphoid Tissues (2° LTs)

* Specialized structures to educate and activate antigen-specific lymphoid cells, they’re organized to facilitate this process.

• Facilitate antigen recognition and lymphocyte activation

• T cells (T cell zone) and B cells (follicles) have separate zones in these structures

• Connected with the local environment/tissue in order to sample antigens.

Spleen

*Largest of the secondary Lymphoid tissues and it’s integrated into the circulation.

• Red Pulp – Open sinusoids with no endothelium, slow moving blood, filters blood, old RBCs specially.

• White Pulp – contains T cell zones and B cell follicles. Ideally placed to sample Antigens in the blood. Antigens enters via marginal zone

• Marginal Zone – antigen entry point. part of the white pulp

  

Lymph Nodes

• Composed by the lymphatic system and lymphatic vessels

• Embedded in most tissues and organs

• One main function is to return extracellular interstitial fluid to the circulation

• Lymphatic vessels collect and transport antigens to nodes

• Lymph nodes are located in junctions where they can effectively filter lymph and initiate immune responses.

  • Afferent lymphatics (Lymph goes in)

  • Efferent lymphatics (Lymph goes out)

• Antigens and some immune cells enter lymph nodes through afferent lymphatic vessels

• High Endothelial Venules (HEV) allow T and B cell entry to lymph nodes. These venules allow immune cells to move from the bloodstream into the lymph nodes.

Mucosal-Associated Lymphoid Tissues (MALT / GALT)

• Located in mucosal surfaces (intestines, airways, reproductive tract)

• M cells capture and transport antigens for immune activation

• Important for microbiota regulation

Tertiary Lymphoid Tissues (3° LTs)

• Form in chronically inflamed tissues

• Can be organized (follicles, T cell zones) or disorganized clusters

• Key Questions:

  • Do they worsen or improve inflammation?

  • Are they a result of tissue remodeling?

Lymphoid Lineage and Cell Types

Lymphoid Lineage Development

• Begins in the bone marrow

• Common Lymphoid Progenitor → Differentiate into immune cells

• Covered in Lectures 10-11, 14, and 15

Innate Lymphoid Cells (ILCs)

• Do not have antigen-specific receptors

• Act similar to myeloid cells but belong to the lymphoid lineage

• Key example: Natural Killer (NK) Cells

Natural Killer (NK) Cells

Target Recognition

• Identify stressed or infected self-cells

• Balance between activating (kill) and inhibitory (don’t kill) signals

“Missing Self” Hypothesis

• Some viruses and tumors reduce MHC expression to evade detection

• NK cells detect this loss and trigger killing

Important NK Cell Receptors

• NKG2D (activating receptor) – detects stress-induced molecules

• KIR / Ly49 family (inhibitory receptors) – recognize MHC class I

Effector Mechanisms

• Kill infected/tumor cells by inducing apoptosis

  • FasL pathway

  • Perforin/Granzyme B pathway

• Cytokine production:

  • TNF-α

  • IFN-γ

Lymphoid Cells and Anatomy Summary

• Innate Lymphoid Cells function like myeloid cells and distribute widely

• Adaptive Lymphoid Cells (B and T cells) require specialized lymphoid structures

• Lymphoid structures integrate into tissues to detect antigens

Lecture 9 Outline

1. Lymphoid Cells

   • T and B cells (antigen-specific)

   • NK cells & innate lymphocytes

   • Target recognition & effector functions

2. Lymphoid Tissues

   • Primary (Bone Marrow, Thymus)

   • Secondary (Spleen, Lymph Nodes, MALT)

   • Organization & antigen access