Lecture 23: Immunopathology Flashcards
Lymphoid folliclem
B cell monoclonal expansion site; splenic nodules in spleen. Primary follicle = no germinal center, secondary follicle = germinal center.
Lymphoid follicle structure + cells
Mantle = mostly monoclonal B cells
Germinal center = mostly plasma blasts
Additional cells: follicular mφ’s, follicular DCs, Tfh cells, Tfreg cells.
Outside follicle: T cells
Lymph fluid composition
- ECF from CT
- Immune cells (lymphocytes, DCs)
- Bound Igs
- Lipids
- Macromolecules, particulates
Lymphatic vessels
Sprout from existing veins in development (angiogenesis, not vasculogenesis). Carry lymph from CT thru lymph nodes to venous circulation. Require active ligand binding for cell entry.
GI lymphatic system
Peyer’s patches, organized GALT, M-cells
Skin lymphatics
Papillary dermis, Langerhans cells in epidermis, SALT
Lung lymphatics
BALT, alveolar mφ’s, systemic mφ’s
Tonsils
Oral cavity MALT. Folded oral epithelium forming crypts with reticulated epithelia (leaky basement, reduced desmosomes)
Head/neck lymph nodes
Superficial cervical nodes
Lymph nodes of the arms
Axillary (armpit): lateral, apical, anterior, central - arm, upper quadrant breast, chest
Epitrochlear (elbow): distal arm
Lymph nodes of the legs
Inguinal (upper inner leg/groin): proximal leg
Popliteal (kneecap): distal leg
Central lymph nodes/lymph nodes of the abdomen/pelvis
- Abdominal
- Superficial inguinal (lower abd, genitalia)
- Deep inguinal
- Ext. iliac (legs/perineum)
- Int. iliac (pelvic organs)
Cisterna chyli
Spinal, intestinal, hepatic branches lymph nodes which coalesce and drain to thoracic duct
Lymph nodes of the thorax
- Hilar (lungs)
- Mediastinal (heart, esophagus, diaphragm)
Lymphatic circulation compartment of lymph nodes
Afferent, subcapsular, peritrabecular, medullary sinus, efferent lymphatics
CT compartment of lymph nodes
- Cortex
- Paracortex
- Medullary cords
Systemic circulation of lymph nodes
- Systemic arteriole
- High Endothelial Venules (HEVs)
- Systemic venules
High Endothelial Venules
HEVs are post-capillary venules in lymph nodes. Most common leukocyte extravasation site with highly active endothelium (metaplasia -> cuboidal, euchromatic)
Features of lymph node capsule
Adventitial CT surrounding lymph nodes. Contains afferent lymphatics, capsular/trabecular CT, afferent sinuses.
Features of lymph node cortex
Contains experienced peripheral B cells, naive systemic circulation B cells, site of B cell proliferation
Features of lymph node paracortex
Contains experienced T cells/APCs from periphery, naive circulation T cells, T cell proliferation site. Does not contain lymphoid follicles or medullary cords.
Features of lymph node medulla
Contains medullary cords (continuation of CT), systemic circulation w/ naive B/T cells entering, medullary sinuses, efferent lymphatics.
Lymph node Ab response stages
- Ag processing; APCs present to Th cells
- Selection for appropriate B cells
- Monoclonal expansion of selected cells with Th coactivation
- Differentiation of expanded cellsinto plasma cells
Methods to deal with environmental pathogens
- Avoidance
- Resistance
- Tolerance
Avoidance of environmental pathogens
- Behavioral avoidance
- Skin/mucosal barriers, mucosal surface measures
Resistance of environmental pathogens
- Innate + adaptive immune systems
Tolerance of environmental pathogens
- B cell class switching
- Abs by high -> low immunogenicity: E > G > M > A
- Central tolerance: thymus/marrow (T/B)
- Peripheral tolerance: activation control via Treg/T cell involve., Ag density, Ab class switch (T/B)
Types of hypersensitivity
Type 1: IgE; mast cell allergy
Type 2: IgM, IgG; Ab produced
Type 3: Ag sequestration -> Ab immune complex
Type 4: T cell involvement, e.g. autoimmunity
Autoimmunity
Lack of appropriate tolerance response results in B/T cell autoreactivity
Placental immune exclusion
Syncytiotrophoblasts uniquely lack MHC-I, so they don’t react with parental blood, Fetal immune development occurs with placental IgG diffusion and milk IgA
Major functions of the spleen
- Remove effete RBCs
- Immune surveillance of blood (backwater white pulp w/ WBCs)
Spleen mechanisms for removing effete RBCs
- Mechanical deformation required for re-entry to splenic sinuses
- Splenic mφ’s recognize/remove senescent cells
Spleen closed circulation
Blood flow from splenic artery through trabecular/central/radial/penicillar arteries, sheathed capillaries, splenic sinuses, trabecular/splenic vein(s)
Spleen open circulation
Only part where blood normally leaves endothelial lined space and enters CT; creates marginal zone separating red/white pulp
White pulp
Slower flow rate regions with WBCs (splenic nodules) allowing time/space for immune surveillance. Lowest flow region = peri-arterial lymphatic sheath (PALS)
Red pulp
Splenic cords of Billroth; higher flow CT regions (cords + sinuses). Re-entry to endothelial vascular outflow at splenic sinuses requires passing through splenic mφ’s and tight endothelial spacing/reticular fibers (mechanical filter).
