Lecture: Connective Tissue derived from HSC

HSC and MSC

____ of CT come from the . . .

fibers of CT

collagen type I

collagen type III

elastic fibers

hydrated proteoglycans

ground substance of CT

electron microscopy

Specimens typically are stained with heavy metals (Pb, U). Uses an electron beam to detect electron-dense and electron-lucent regions

"scanning" (SEM)

beam bounces off surface giving a 3- D view of it

"transmission" (TEM)

beam passes through the thin- sectioned sample similar to LM slides

"freeze fracture" EM

a rapidly- frozen section is then cracked.

Separation of cell membranes tends to occur on the hydrophobic (inner) portion, allowing separate images of the E-face (extracellular) and P- face (protoplasmic, intracellular)

CT cells from MSC

fibroblast

myofibroblast

unilocular adipocyte

multilocular adipocyte

CT cells from HSC

mast cell

eosinophil

macrophage

neutrophil

lymphocyte

plasma cell

(basophil (!)

inflammation

function of mast cells and eosinofils

mast cell

pro-inflammatory HSC-derived cell

eosinophil

inflammatory modulation, allergy

innate immunity

macrophage, neutrophil

macrophage

phagocytic and APC

neutrophil

phagocytic and NETosis

adaptive immunity

lymphocyte, plasma cell

lymphocyte

pathogen recognition

plasma cell

antibody production

immune defenses other than cells

surface secretions

junctional complex

basement membrane

fiber matrix

proteoglycans

cytokines

cytokines

are molecules that communicate in a paracrine manner with other cells

interuleukins

type of cytokine

a large, diverse group of molecules that communicate between leukocytes.

type 1

pro-inflammaory cytokines

type 2

anti-inflammatory cytokines

calor

cardinal signs of inflammation (Celsus tetrad): heat

dolor

cardinal signs of inflammation (Celsus tetrad): pain

rubor

cardinal signs of inflammation (Celsus tetrad): redness

tumor

cardinal signs of inflammation (Celsus tetrad): swelling

increased blood flow

Inflammation:

vasodilation of arterioles

edema

inflammation:

increased fluid & cell movement out of vasculature

resident immune cells

inflammation:

cytokine signaling by . . .

diapedisis

the process by which leukocytes leave the circulation and enter the connective tissue

intravasation

leukocyte moves from CT to vessel

rare, generally limited to primary lymphoid organs

extravasation

leukocyte goes from the vessel into the connective tissue

paracellular diapedesis

migration between endothelial cells, requires breaking of endothelial tight junctions

transcellular dipedesis

migration through a pore in an individual endothelial cell

selectin

a (lectin-like) CAM that mediates "rolling adhesion", "the grass"

chemokines

(small MW cytokines) are secreted at the site of inflammation and form a gradient which cells can use for chemotaxis.

ligands

each leukocyte uses unique but overlapping constellation of ______, ensuring responses can be general or specific, local or widespread

stromal cells

chronic inflammation involves ___ ____

resolved

inflammation should get _____. off switch

apoptosis

resolution of inflammation:

leukocytes die by ____ and are cleared

macrophages

clear dead cells in inflammation resolution

lymphatics

resolution of inflammation:

lymphocytes migrate to

NETosis

resolution of inflammation:

granulocytes may die by

intravasate

resolution of inflammation

in some tissues (especially those that lack lymphatics), leukocytes may reverse migrate and _______ back to vasculature

remember

cells can _____ an infection- Breg, Treg

acute inflammation

cytokines produced by macrophages, neutrophils, lymphocytes

chronic inflammation

cytokines produced by stromal cells, e.g. fibroblasts

mast cell

has histamine and heparin granules

binds IgE antibodies

metachromatic granules

granule contents change color of stain- interact chemically with dye

compound exocytosis

secretory vesicles dock with each other

to speed degranulation

basophil

distinct from mast cell

mast cell for blood? has histamine and heparin granules, expresses IgE receptor

eosinophil

mediator of inflamation, anti-parasitic, mediator of allergic response

internum

eosinophil granules:

electron-dense crystalloid body containing major basic protein and

eosinophilic cationic protein and parasitic neurotoxins

externum

eosinophil granules:

aryl sulfatase, histaminase, acid phosphatase, ...

charcot-leyden crystal

The product of eosinophil degranulation has a characteristic pathological appearance (usually indicate hyper-eosinophilia)

mononuclear phagocyte system (MPS)

systemic macrophages

organ specific macrophages

professional phagocytes

the cells of the innate immune system are the " "

marrow

Neutrophils are born in

maringal pool in marrow

Neutrophils are stored in ____ ____ __ _____

usually adult form, also as pre-mature band cells

band cell

neutrophil is released in circulation, usually in adult form, but possibly as

rolling adhesion and diapedesis

neutrophil enters the connective tissue via

die

neutrophils get "activated" and ____ upon use

primary granules

types of neutrophil granules:

lysosomes, lysosomal enzymes digest bacteria

secondary (specific)

types of neutrophil granules:

antimicrobial

kill bacteria with enzymes and reactive oxygen compounds

tertiary (gelatinase)

types of neutrophil granules:

gelatinase, cathepsin, collagenase

facilitate migration to target

pus

Neutrophil dies; semidigested material and tissue fluid form _____

venules

Neutrophils can be stored in the vasculature by adhering to vessel walls, usually those of

phagocytosis, apoptosis

neutrophils have 2 strategies to kill

phagocytosis

neutrophils

up to 10-12 foreign bodies (bacteria) before neutrophil commits apoptotic cell death

apoptosis

neutrophils die en masse, releasing granules extracellularly which can kill larger invaders

NETosis

neutrophil extracellular traps

expulsion of stranded chromatin traps

bacteria, promotes clotting

chemokine signaling

Cells of the immune system trigger a migration of other appropriate cells via ____ ____. Basis of specificity of the immune system

marrow

macrophage is born in ___ as monocyte then released to circulation

spleen

there is a " reserve pool" of macrophages (stored as monocytes) in the . . .

macrophage

when a monocyte enters CT compartment, it becomes a . . .

resident macrophages

seed organs during fetal development

many "name" named cells are these

systemic macrophages

type of macrophages that circulate throughout life

macrophage functions

1. phagocytosis

2. antigen-presenting cell (way to communicate with adaptive immune system)

3. recruitment (cytokine production)

M1

type of macrophage responsible for phagocytosis

M2

type of macrophages involved in tissue modeling/ repair (resolution of inflammatory response)

macrophage syncytia

bunch of macrophages come together to form one big one

foreign body giant cell

macrophage syncytia with clumped nuclei

langhans cell

macrophage syncytia with horseshoe-ring nuclei

neutrophils

in response to infection/ damage, ____ peak around 24 hours (get called first)

local macrophages

in response to infection/ damage, ______ _______ release cytokines

36-48 hours

in response to infection/ damage, monocytes enter CT and become macrophages at ________ ______

B-lymphocyte

for extracellular pathogens

antigenic proteins -> antibodies (Ig)

T-lymphocyte

for intracellular pathogens

viruses -> MHC signaling

ILC

"innate lymphocyte cells" - a diverse

group not reliant on antibodies nor MHC

lymphoid follical

has a cortex of B cells and a germinal center of plasma cells then there are T-cells in the paracortex

marrow

B-lymphocyte is born in the . . .

marrow

T-lymphocyte is born in the . . .

marrow

innate lymphocyte is born in the . . .

marrow

B-lymphocyte matures in the _____. expresses Ig molecules

thymus

T-lymphocyte matures in the _____. expresses TCRs, MHCs

all lymphocytes

leaves circulation, enters connective tissue - potentially re-enters circulation via lymphatic system

plasma cell

mature for of B-lymphocyte, produces specific antibodies + secretes them

(there are also long lasting Bmem cells)

Tmem

T-lymphocyte that may last the entire lifetime