F2 - Random Stuff We Gotta Know

Fibroblasts

secrete ground substance, fibers, MMPs, GFs

Myofibroblasts

fibroblasts containing contractile fibers (actin) that are the mechanism of wound contraction

Needed for secondary intention

Macrophages

Innate and Adaptive Immunity, phagocytize foreign stuff, present antigens,

If you see this in histology () then it is no longer acute babes.

Mast Cells

Have granules with histamine and heparin

Marked by tryptase activity, key in type I hypersensitivity -> allergen binds IGE antibodies expressed on cell surface

First cells to respond -> immediate; release histamine needed to activate weibel palade bodies for the upregulation of P selectins in neutrophil rolling

Natural Killer Cells

Kill cells expressing MIC ligands and no MHC-1 via release of lytic granules -> virally infected or tumor cells are killed

Can be activated by interferon cytokines

only innate immunity to be derived from common lymphoid progenitor cell

Dendritic Cell

Professional antigen presenting cell via MHC-II

travels to the lymph nodes to present

Often is used by HIV to get to other cells (langerhaans)

Neutrophil

Express membrane receptors (toll-like) respond to bacteria, engulf bacteria, kill with granules containing toxic substance; DOES NOT PRESENT ANTIGENS

Basophil

deal with parasites and allergens -> bind IgE

mediated by IL-4

Eosinophil

protect from fungi and parasites

Paneth Cells

Detect pathogens via TLRs and release defensins

found in the gut

Goblet Cell

Secretes Mucus in GI track.

In barret's esophagus metaplasia will turn esophageal ciliated cells into this due to GERD

CD8 T-Cell

Cytotoxic T-Cell; "Killer T-Cell"; kills target cells presenting pathogenic antigens

Very important for viral immunity and cancer cell destruction

CD4 T-Cell; th1

Helper T-Cell; ; release cytokines; activates macrophages to become microbicidal via IFN-gamma and IL-2 and CD40/40L interactions

CD4 T-Cel ; th2

Helper T-Cell; release cytokines; activates B-Cells via IL-4/5 and CD40/40L interactions

B Cells

binds to pathogens that respond to IgM antibody; C3d on pathogen activates CD19/CD2/CD81 complex on B cell to activate.

B-cell phagocytoses pathogens antigens and presents on MHC-II

Then a TH2 helper T-cell recognizes MHC-II on B-cell and binds and activates B-cell via IL-4/5 cytokines to make antibodies;

without activation can only make IgM -> activate classical complement pathway, NK cells, opsonization, virolysis

Gamma-delta T-Cell

Does not require MHC, traffics to inflammation via chemokines, bridge between innate and adaptive immunity

Memory T-Cells

Effector T-Cells that remain after infection acting as a memory allowing faster response

regulator T cell

used by tumor cells to inactivate adaptive immune response via IL-10

EGF

epidermal growth factor; Cell Proliferation; ErbB family, homolog with Her2/Neu; oncogene if mutated to be constitutively active; tyrosine kinase

FGF 1

angiogenesis & fibroblast proliferation/activity, involved in keratinocyte migration to cover wound with cells

FGF2

angiogenesis & fibroblast proliferation/activity, involved in keratinocyte migration to cover wound with cells,

FGF3

chondrocyte proliferation, if FGFR3 is mutated to be constitutively active achondroplasia

FGF7

epithelian cell proliferation re-epithelialization of the skin and regeneration of hepatocytes

PDGF

platelet derived growth factor; made by platelets and macrophages, Vascular remodeling via smooth muscle stimulation, fibroblast proliferation, production of type I and III collagen, formation of hypertrophic scars and keloids, tyrosine kinase

TGF-beta

produced by Platelets, leukocytes, macrophages, fibroblasts, keratinocytes; smad (serine threonine kinase);

angiogenesis, fibroblast proliferation, inhibits proliferation of other cells/inflammation -> also acts as anti-inflammatory cytokine

VEGF

Angiogenesis, negatively impacts embryo development and collateral circulation development

KGF

Keratinocyte Proliferation

TGF-alpha

Keratinocyte Proliferation; hepatic compensatory hyperplasia

HGF

Hepatic Compensatory Hyperplasia

TNF-α

Pro-Inflammation, pro-fibroblast actrivity -> increased collagen synthesis, cause fever; induces COX-2, induces NO in macrophage; over production systemically = septic shock; when produced by macrophages, it activates NK cells to produce IFNα/β which then activates NK cells

Interleukin-1 (IL-1)

Pro-Inflammation, pro-fibroblast actrivity -> increased collagen synthesis; induces COX-2, induces NO in macrophage, histamine release in mast cells, induces fever with IL-6

IL-4

Increased Collagen Synthesis, inflammatory in allergy response when released by basophils via IgE crosslinking; inhibits COX-2 in anti-inflammatory pathway; B-cell proliferation and differentiation (released by TH2-cell)

IL-13

Increased Collagen Synthesis

Erythropoetin (EPO)

promotes development of erythrocytes

thrombopoeitin (TPO)

promotes development of megakaryocytes

GM/M/G-CSF

promote myelopoisis

G-CSF

granulocyte colony-stimulating factor--promotes neutrophil production

IL-3

promote myelopoisis (specifically monocytes)

IL-2

Induces T-Cell proliferation by activating proto-oncogenes and cyclins (Jak-stat)

Released by T-cells to make macrophages microbicidal along IFN-gamma

All cytokines that are not chemokines use

Jak-Stat

Chemokines use

GCPR

IFN-γ

regulates antiviral/tumor and inflammatory responses by enhancing MHC expression for T-cell response, enhancing signaling for T-Cell differentiation, inducing isotype switching in B cells for antibody production (Jak-Stat)made by immune cells; induces NO in macrophage

Released by TH1-cells to make macrophages microbicidal alongside IL-2

IL-8

CXCL8; Produced by macrophages, directs neutrophils to infections (GCPR), histamine release in mast cells

IL-6

Inflammatory -> fever and acute phase protein production in liver; Hepatic Compensatory Hyperplasia

IFN-α

Type I, made by virally infected cells, protects other cells from infection; activates NK cells

IFN-β

Type I, made by virally infected cells, protects other cells from infection; activates NK cells

IL-12

produced by macrophages, it activates NK cells to produce IFNα/β which then activates NK cells

IL-7

T-cell differentiation; B-cell differentiation; if IL-7 or IL-7R is mutated -> SCID

CCL19

chemokine for T/B cell chemotaxis

CCL21

chemokine for T/B cell chemotaxis

IL-10

Anti-inflammatory - made by macrophages; made by T-regs to inactivate

be nice to yourself

or else

IL-5

Th2 releases to activate B cells alongside IL-4

Collagen

Synthesized by fibroblasts

Triple Helix, Gly-X-Y usually with proline or lysine and hydroxyproline and hydroxylysine (vitamin C required)

1: Bone, late wound healing, cornea 2: cartilage 3: blood vessels, early wound healing, 4: basement membrane, Lens, involved in goodpastures syndrome

Nucleus: transcription of preprocollagen, ER: translation, hydroxylation w vit C, glycosylation, formation of procollagen triple helix, ECM: cleavage of terminus to form tropocollagen, lysine-hydroxylysine cross linking via lysyl oxidase to form collagen fibrils with Copper

Associated with Scurvy (vit C), Osteogenesis Imperfecta, Ehlers-Danlos Syndrome, Good pastures Disease, Aging

Elastin

Produced by fibroblasts as tropo-elastin

Insoluble, desmosine, isodesmosine crosslinks

Flexibility in structure due to crosslinking

associated with Alpha-1 Antitrypsin Deficiency and Emphysema

Ground Substance

produced by fibroblasts

Proteoglycans (core protein + GAGS) and adhesive glycoproteins

Associated with Hurler and Hunter Syndrome

Fibrillin-1

produced by Fibroblast associated with FBN1 gene

It offers scaffolding for elastin

associated with Marfan Syndrome

Broken down by Elastase; binds and sequesters TGF-beta

Fibronectin

Cell adhesion to ECM, Binds to integrins, type IV collagen, heparin and fibrin

Adhesive Glycoprotein

Laminin

Attaches cell to basal membrane, Binds to integrins, type IV collagen, heparin and fibrin

Adhesive Glycoprotein

Tenascin

Modulates cell adhesion in ECM; Binds to fibronectin, integrins, CAMs, heparin and growth factors

Osteopontin

Binds to osteocytes and integrin receptor on osteoclasts; Binds calcium and hydroxyapatite

Reticular Fibers

Heavily Glycosylated Collagen I

Support vasculature

Defensins

antimicrobial peptides

Cox-1

Cyclooxygenase-1; constitutively expressed; functions in platelet aggregation via thromboxane, GI protection, Renal Protection

Cox-2

upregulated in inflammation; via IL-1, TNF-alpha,

Inhibited by IL-4

substance P

A neurotransmitter that is involved in the transmission of pain messages to the brain.

Neuropeptide, makes mast cells release histamine

C-reactive protein

Acute Phase Liver Protein released due to IL-6 interactions with hepatocytes

General inflammatory biomarker

Activates classical complement system

transudate

clear low protein fluid accumulation due to inflammation

exudate

cloudy, fibrin rich, purulent, fluid accumulation due to inflammation

NF-kB

transcription factor

activated to make shit for fever and inflammation

Makes IL-1, IL-6, TNFa, and IFNγ which then activate PGE2 which activates EP3 receptors in hypothalamus to increase set point

PAMPS

(pathogen-associated molecular patterns) Molecules associated with groups of pathogens, that are recognized by cells of the innate immune system via TLRs

DAMPS

Damage-associated molecular patterns: TLRs react with these non self antigens on damaged tissue, --> then release proinflammatory cytokines and chemokines

Derived from: plasma membrane, nucleus, ER, mitochondria, cytosol

CD40L/CD40

interaction through which helper T-Cells activate B-cells alongside cytokines; when occurs with macrophages in presence of IFN gamma (from Th1) makes macrophages microbicidal

CD28 - B7 (CD80/86)

interaction through which APCs activate T-cells alongside MHC2-TCR activation; stronger activation step

MHC2-TCR

interaction through which APCs activate T-cells alongside CD28 - B7 (CD80/86) activation; weaker first activation step

CTLA-4- B7 (CD80/86)

Interaction through which T-cells deactivate.

Activated T-cells express CTLA-4 which responds more strongly to B7 allowing for inactivation. Loss of CTLA-4 may lead to lymphoproliferative disease and autoimmunity

T-independent antigens

Stimulate the B cell without the help of T cells

Provoke a weak immune response, usually producing IgM

No memory cells generated

PD1L

upregulated by cancer to avoid immune detection acts as an off switch for T-cells via PD1 receptor

IgG

most abundant high affinity antibody; found in blood and tissues; crosses placenta

IgM

first made low affinity, pentameric antibody; primarily found in blood

IgA

monomeric in tissues/blood dimeric in mucosa/breast milk

IgE

low abundance in circulation, binds to FcεRI on the surface of mast cells. Cross-linking IgE on mast cells caused production of inflammatory mediators (IL-4) associated with allergies; found in connective tissues below epithelia associated with mast cells

XII/XIIa

XII: Inactive form of the Hageman factor, activates when exposed to negative charges (inflamation, platelets, basement membrane, etc.)

XIIa: active form of Hageman factor, activates prekallikrein to Kallikrein (kinin pathway); clotting factors leading to thrombin (clotting cascade);

Kallikrein

Converts HWMK to bradykinin (Kinin cascade), and plasminogen into plasmin (fibrinolytic cascade)

Bradykinin

Increases vascular permeability, dialation, bronchoconstriction and uterine contraction (smooth muscle contraction), pain, excess can cause chronic cough and angioedema;

binds to GPCRs -> B1 induced by cytokines IL-1/TNF-alpha/IFN-gamma; B2 constitutively expressed

Plasmin

Lyses fibrin clots, increases vascular permeability (fibrin split products and by activating C3a)

Thrombin

converts fibrinogen into fibrin making clots, promotes production of inflammatory mediators in endothelial cells

Fibrin

makes up clots

protein C

anticoagulant and anti-inflammatory

prostacyclin/PGI2

inhibits platelets

tPA

thrombolytic

Pro-Angiogenic Mediators

VEGF bFGF FGF-2 PDGF IL-8 HGF PIGF Inflammation Hypoxia Inducible Factor (HIF)

Anti-angiogenic Mediators

Thrombospondin Interferon a/b Angiostatin Endostatin Collagen IV fragments

vasoactive amines

histamine and serotonin

C3a

trigger release of histamine from mast cells, increases vascular permeability and vasodialation

recruits phagocyte, increases vascular permeability, anaphylactoxin

C5a

trigger release of histamine from mast cells; activates lipo-oxygenase pathway; strong role in chemotaxis!!; increases vascular permeability and vasodialation

recruits phagocyte, increases vascular permeability, anaphylactoxin

C4a

trigger release of histamine from mast cells

Arachidonic Acid

Normally esterified to membrane lipids, inflammatory mediators activate PLC to form DAG and IP3 (activates PKC and MAPK -> PLA2) ultimately releasing AA from the membrane so it can be converted into eicosanoids which bind GPCRs

Prostaglandins

Eicosanoid that activates GPCRs mediating inflammation -> vascular and systemic inflammation; made by cyclooxygenase (COX) in mast cells, macrophages, and endothelial cells

Leukotrines

Eicosanoid that activates GPCRs mediating inflammation; made by lipoxygenase, secreted by leukocytes; chemoattractants for leukocytes; inverse relationship with lipoxins