8: Lymphoid tissues Flashcards
Primary lymphoid tissues
Sites where new lymphocytes are made - Lymphopoesis
Bone marrow and Thymus
Cells of lymphoid lineage
T cells, B cells and NK cells
What are the precursors of cells of lymphoid lineage ?
All derived from common lymphoid progenitor cells, which themselves derive from multipotent hematopoietic stem cells (HSCs) that give rise to all blood cells
Where do precursors for B and T cells originate in
Bone marrow
but because B cells compete most for their development in the bone marrow, precursors of T cells migrate to the thymus to complete development - become mature naive lymphocytes
Characteristics of bone marrow
Fat in centre (appears yellow)
Surrounded by red marrow - site of haematopoiesis
List the anatomical sites of haematopoiesis in a foetus and in an adult
Foetus - all bones, liver and spleen
Adult - mostly flat bones, Iliac bones, ribs, ends of long limb bones
Other name for T cells
Thymocytes
Two checks during T cell maturity
Positive selection - does the T cell recognise foreign antibodies
Negative selection- does it react against self cells
How does the thymic output and the thymus itself change with age?
In mature individuals, thymic output declines with age - thymus atrophied significantly
Thymic involution also occurs (shrinking and structural change of thymus with age) and functional tissue gets replaced with fat
How does the number of peripheral T cells change with age?
Remains the same
Peripheral T cell numbers maintained by division of mature T cells outside central Lymphoid organs
So less variety (fewer cells from new lineages) - reason why older people are more vulnerable to new strains of pathogen
What happens to the thymus during infection
No change
What happens to the bone marrow during infection
Increased white cell production
Secondary lymphoid organs
Sites where Lymphocytes interact with antigens and other lymphocytes
5 secondary lymphoid tissues
Spleen
Lymph nodes
Epithelial barriers
Gut associated lymphoid tissue
Tonsils
- areas where T cell is likely to encounter antigen
Why do we have a lymphatic system?
More fluid filtered than reabsorbed during tissue perfusion
Fluid needs to be returned to the systemic circulation
Achieved via lymphatic system
What are lymph nodes
Highly organised, encapsulated structures at points of convergence of lymph vessels
- interrupt vessels along their course
Describe the structure of a lymph node
Lymph enters via afferent vessels and leaves via efferent vessels
B and T cells enter and leave via systemic circulation
Consists of outermost cortex and inner medulla
Cortex - outer cortex of B cells organised into lymphoid follicles, adjacent or paracortical areas made up of T cells
Some B cell follicles include germinal centres, where activated B cells are undergoing intense proliferation and differentiation (during immune response)
Where are B and T cells located within a lymph node
B cells - outside of lymph nodes
T cells - found more on the inside, nearer to artery and vein
Immunological function of the spleen?
Collects antigen from blood (where RBCs die)
Involved in immune responses to blood-borne pathogens
Lymphocytes enter and leave spleen via blood vessels
Structure of the spleen
Bulk of spleen composed of red pulp - site of RBC disposal
Lymphocytes surround arterioles running through spleen, forming isolated areas of white pulp
Sheath of lymphocytes around arteriolar = periarteriolar lymphoid sheath (PALS), contains many T cells
Lymphoid follicles occur at intervals along the spleen, contain mainly B cells
What tissue forms the first line of defence against infection? How is it protected by the immune system?
Epithelial tissue / mucosal surfaces
Forms a physical barrier to pathogens
Protected by extensive system of lymphoid tissues known as mucosa-associated lymphoid tissues (MALT)
Give an example of a MALT, list it’s locations in the body
Gut-associated lymphoid tissues (GALT)
Tonsils, adenoids, appendix and Peyers patches in small intestine
Describe the structure and function of Peyer’s patches
Contain numerous B-cell follicles with germinal centres - areas between follicles occupied by T cells
Antigen collected (directly from gut) by M cells (specialised epithelial cells)
Dendritic cells resident within Peyers patch present antigen to T lymphocytes
Effector lymphocytes generated in Peyers patches travel through lymphatic system and into blood -disseminated back into mucosal tissues to carry out effector actions
Germinal centre or Peyers patches
Anatomically restricted site where B cells undergo mutation and selection to generate high affinity antibodies
Organisation of tonsils
Pharyngeal, tubular, palatine and lingual tonsils encircle oral and nasal cavity - form Waldeyers ring
Cells in Cutaneous immune system
Langerhans cells ( dendritic cell)
Keratinocytes
Tissue resident macrophages
T lymphocytes
Intraepidermal lymphocytes
Summarise principle by which secondary lymphoid tissues operate ?
Trapping antigens and antigen-presenting cells from sites of infection in order to present antigen to migratory small lymphocytes, thus inducing adaptive immune responses
Are the secondary lymphoid tissues “static”?
No, structures very in size and appearance depending on presence of infection
Where do mature naive lymphocytes go after they are produced?
Enter bloodstream, migrate and populate, continuously circulate through peripheral lymphoid tissues
Such as : lymph nodes, spleen, mucosal lymphoid tissue of gut, nasal and respiratory tract, urogenital tract and other mucosa
How do B and T cells enter lymph nodes
T and B cells enter lymph nodes via high endothelial venues (HEVs) [ specialised blood vessels found in T cell zones]
Stages of lymphocytes entering lymph nodes
- initial rolling of lymphocytes along endothelial surface - selections
- activation of integrity- chemokines
- firm adhesion- integrins
- diapedesis across endothelial layer into paracortical areas = T cell zones -chemokines
Regulated by a coordinated interplay of adhesion molecules and chemokines
How do antigens go from site of infection to peripheral lymphoid organs to activate lymphocytes?
T cell activation occurs via encounters with dendritic cells that obtain antigens at sites of infection and migrated to secondary lymphoid organs
Free antigens stimulate antigen receptors of B cells- most B cells require Th cells for optimal antibody response
Dendritic cells - antigen presenting cells - range of migratory and tissue resident variety
Describe how dendritic cells pick up antigens from site of infection
Activation of dendritic cells’ PRRs by PAMPs at site of infection, stimulates dendritic cells in tissues to engulf pathogen and degrade it intracellularly
Also take up Extracellular material - virus particles, bacteria- by receptor independent macropinocytosis
These processes lead to the display of peptide antigens on MHC molecules of dendritic cells
Describe the transport of lymphocytes and antigens in lymphatics and blood stream
free antigen and antigen-bearing dendritic cells travel from site of infection through afferent lymphatic vessels into draining lymph nodes
activated lymphocytes undergo proliferation and differentiation, leave lymph nodes as effector cells via efferent lymphatic vessel
eventually return to bloodstream and carried to tissues where they act
A patient has an upper respiratory tract infection, what will happen to their submandibular lymph nodes
increase in size
suggest where immune cells may have encountered the antigens in the vaccine
Lymph node
Lymphokinetic motion
Blood cappilaries > interstitial fluid > lymph capillaries > lymph veins > lymph ducts > lymph ducts > large veins