Lecture 23: Immunopathology

Question 1

Lymphoid folliclem

Answer 1

B cell monoclonal expansion site; splenic nodules in spleen. Primary follicle = no germinal center, secondary follicle = germinal center.

Question 2

Lymphoid follicle structure + cells

Answer 2

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

Question 3

Lymph fluid composition

Answer 3

• ECF from CT
• Immune cells (lymphocytes, DCs)
• Bound Igs
• Lipids
• Macromolecules, particulates

Question 4

Lymphatic vessels

Answer 4

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.

Question 5

GI lymphatic system

Answer 5

Peyer’s patches, organized GALT, M-cells

Question 6

Skin lymphatics

Answer 6

Papillary dermis, Langerhans cells in epidermis, SALT

Question 7

Lung lymphatics

Answer 7

BALT, alveolar mφ’s, systemic mφ’s

Question 8

Tonsils

Answer 8

Oral cavity MALT. Folded oral epithelium forming crypts with reticulated epithelia (leaky basement, reduced desmosomes)

Question 9

Head/neck lymph nodes

Answer 9

Superficial cervical nodes

Question 10

Lymph nodes of the arms

Answer 10

Axillary (armpit): lateral, apical, anterior, central - arm, upper quadrant breast, chest
Epitrochlear (elbow): distal arm

Question 11

Lymph nodes of the legs

Answer 11

Inguinal (upper inner leg/groin): proximal leg
Popliteal (kneecap): distal leg

Question 12

Central lymph nodes/lymph nodes of the abdomen/pelvis

Answer 12

• Abdominal
• Superficial inguinal (lower abd, genitalia)
• Deep inguinal
• Ext. iliac (legs/perineum)
• Int. iliac (pelvic organs)

Question 13

Cisterna chyli

Answer 13

Spinal, intestinal, hepatic branches lymph nodes which coalesce and drain to thoracic duct

Question 14

Lymph nodes of the thorax

Answer 14

• Hilar (lungs)
• Mediastinal (heart, esophagus, diaphragm)

Question 15

Lymphatic circulation compartment of lymph nodes

Answer 15

Afferent, subcapsular, peritrabecular, medullary sinus, efferent lymphatics

Question 16

CT compartment of lymph nodes

Answer 16

• Cortex
• Paracortex
• Medullary cords

Question 17

Systemic circulation of lymph nodes

Answer 17

• Systemic arteriole
• High Endothelial Venules (HEVs)
• Systemic venules

Question 18

High Endothelial Venules

Answer 18

HEVs are post-capillary venules in lymph nodes. Most common leukocyte extravasation site with highly active endothelium (metaplasia -> cuboidal, euchromatic)

Question 19

Features of lymph node capsule

Answer 19

Adventitial CT surrounding lymph nodes. Contains afferent lymphatics, capsular/trabecular CT, afferent sinuses.

Question 20

Features of lymph node cortex

Answer 20

Contains experienced peripheral B cells, naive systemic circulation B cells, site of B cell proliferation

Question 21

Features of lymph node paracortex

Answer 21

Contains experienced T cells/APCs from periphery, naive circulation T cells, T cell proliferation site. Does not contain lymphoid follicles or medullary cords.

Question 22

Features of lymph node medulla

Answer 22

Contains medullary cords (continuation of CT), systemic circulation w/ naive B/T cells entering, medullary sinuses, efferent lymphatics.

Question 23

Lymph node Ab response stages

Answer 23

1. Ag processing; APCs present to Th cells
2. Selection for appropriate B cells
3. Monoclonal expansion of selected cells with Th coactivation
4. Differentiation of expanded cellsinto plasma cells

Question 24

Methods to deal with environmental pathogens

Answer 24

1. Avoidance
2. Resistance
3. Tolerance

Question 25

Avoidance of environmental pathogens

Answer 25

- Behavioral avoidance - Skin/mucosal barriers, mucosal surface measures

Question 26

Resistance of environmental pathogens

Answer 26

- Innate + adaptive immune systems

Question 27

Tolerance of environmental pathogens

Answer 27

- 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)

Question 28

Types of hypersensitivity

Answer 28

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

Question 29

Autoimmunity

Answer 29

Lack of appropriate tolerance response results in B/T cell autoreactivity

Question 30

Placental immune exclusion

Answer 30

Syncytiotrophoblasts uniquely lack MHC-I, so they don't react with parental blood, Fetal immune development occurs with placental IgG diffusion and milk IgA

Question 31

Major functions of the spleen

Answer 31

1. Remove effete RBCs 2. Immune surveillance of blood (backwater white pulp w/ WBCs)

Question 32

Spleen mechanisms for removing effete RBCs

Answer 32

1. Mechanical deformation required for re-entry to splenic sinuses 2. Splenic mφ's recognize/remove senescent cells

Question 33

Spleen closed circulation

Answer 33

Blood flow from splenic artery through trabecular/central/radial/penicillar arteries, sheathed capillaries, splenic sinuses, trabecular/splenic vein(s)

Question 34

Spleen open circulation

Answer 34

Only part where blood normally leaves endothelial lined space and enters CT; creates marginal zone separating red/white pulp

Question 35

White pulp

Answer 35

Slower flow rate regions with WBCs (splenic nodules) allowing time/space for immune surveillance. Lowest flow region = peri-arterial lymphatic sheath (PALS)

Question 36

Red pulp

Answer 36

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).