9/18 Flashcards

1
Q

Inflammation

A

Accumulation of fluid, plasma proteins, and WBCs that is initiated by physical injury, infection, or a local immune response

Attempts to remove harmful substances and initiate the healing process

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2
Q

Primary and Secondary Lymphoid Organs

A

Primary: bone marrow and thymus, where immune cells develop and mature

Secondary: where lymphocytes respond to invading pathogens, spleen, lymph nodes, tonsils

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3
Q

Innate vs. Adaptive Immunity

A
  1. Innate: respond rapidly and are not specific for a particular insult/infection

NK cell, neutrophil, mast cell, etc.

Inflammation

  1. Adaptive: immune response by B and T cells that recognize specific pathogens and generates memory immune responses
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4
Q

Inflammation in Sterile Injuries

A

Danger Associated Molecular Patterns (DAMPs): intracellular molecules released by damaged cells like HSPs, HMGB1, and DNA

Necrotic cardiomyocyte releases DAMPs after ischemic injury to result in endothelial cell activation, peripheral neutrophil activation, and mast cell degranulation

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5
Q

Two Types of T Cells

A

2 types of Glycoproteins expressed on the surface

CD4 T Cells: helper T cells, protect us by helping other immune cells work better

CD8 T Cells: cytotoxic T cells, protect us primarily by killing infected and malignant cells

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6
Q

Function of T Cells

A

Make contact with other cells and inducing them to change

CD8 T cell: kill virally infected cells after contact

CD4 TH1 cell: release cytokines to activate macrophages which can in turn release cytokines

CD4 TH2 cells: release cytokines to B cells to get plasma cell that releases antibodies

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7
Q

Lymphocyte Circulation

A

B and T cells travel through body in blood and lymph, leave blood through capillaries in lymph nodes

If encounter antigen recognized by its receptor in the lymph node it will stay and become activated

If not then leave lymphoid organ via efferent lymph vessel to the thoracic duct which empties into the left subclavian vein, returning the lymphocyte into circulation

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8
Q

Spleen Anatomy

A

Red pulp: old/damaged RBCs are removed from circulation

White pulp: where innate and immune cells reside, can respond to pathogens in the blood that is being filtered

Asplenia: lack a spleen, at increased risk of infection by encapsulated bacteria

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9
Q

Cyclin-Dependent Kinases Operation Pathway

A

Cdk start with ATP and are inactive until binding of phase-specific cyclins then get partially activated, get change in shape of the T loop

Cdk becomes fully activated by phosphorylation from CAK (Cdk activating kinase)

Additional phosphorylation by Wee1 kinase inactivates it, can be counteracted by Cdc25 phosphatase to return to being active

Cycling binding is the limiting event for the activation of CDKs, cycling expression levels vary with phases and kinase activity varies cyclically in turn

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10
Q

Mechanism of action of Cdk inhibitors (CKI)

A
  1. Cip/Kip proteins: inhibit the kinase activity of CDK/cyclin complexes

p21, p27, p57

  1. INK 4 proteins: inhibit the interaction between cyclins and CDKs

p15, p16, p18, p19

  1. Ubiquitin Ligase: SCF helps degrade p27 CKI
  2. Ubiquitin Ligase: APC (anaphase promoting complex) destroys M cycling and terminates M phase
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11
Q

Escape from G1 Phase

A

Mitogen binds to mitogen receptor to activate MAP kinase pathway and induce expression of Myc

Myc increases cyclin D expression to increase G1-Cdk activation, also raises SCF ubiquitin expression to increase p27 degradation and have higher G1/S-Cdk activity

G1-Cdk and G1/S-Cdk phosphorylates retinoblastoma (Rb) to prevent it from locking up E2F (powerful transcriptional activator of genes for S phase like G1/S-cyclin), get positive feedback since increase G1/S-cyclin expression

Cell active and mitogen depravation doesn’t impair proliferation

Alteration in E2F/Rb pathway are common in cancer

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12
Q

Regulation of S Phase

A

Need to ensure only copy DNA once

Pre-replicating complex: forms during G1 and gone by G2 and M phase, composed of origin replication complex (ORC) plus Cdc6 and MCM

S-Cdk triggers S phase, destroys Cdc6 via SCF/ubiquitin and phosphorylates MCM

S-Cdk high during G2 but reduced after M phase, M-Cdk phosphorylates Cdc6 and McM to prevent additional DNA replication during M phase

During G1 Cdc6 accumulates and the pre-RC is formed but not active since low S-Cdk activity, in the next state S-Cdk is high but Cdc6 is inactivated so the pre-RC is active but not formed

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13
Q

DNA Regulation Checkpoint

A

M-cyclins stockpile during G2/M

Unfinished replication forks somehow send negative signal to M-Cdk, activates a kinase that inhibits the Cdc25 phosphatase and allows Wee1 to keep M-Cdk in inactive state

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14
Q

Start of M phase Regulation

A

Inactive M-Cdk becomes activated

M-Cdk activates Polo kinase which activates Cdc25, which activates M-Cdk and causes a positive feedback loop to further activate Polo kinase

M-Cdk also inhibits its own inhibitor (Wee1)

M-Cdk induces assembly of the mototic spindle, chromosome condensation, nuclear envelope breakdown, actin-myosin cytokinesis, and distribution of membranous organelles to daughter cells

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15
Q

Regulation of Sister Chromatid Separation

A

Anaphase-promoting complex (APC) ubiquitin Ligase activated by M-Cdk cohesin complex keeps chromatids bound at the centromere

At end of metaphase APC targets securin that inhibits securin, a protease that degrades the cohesin complex

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16
Q

Spindle-Attachment Checkpoint

A

Sensor that detects attachment of kinetochores to microtubules, failed attachment generates negative signal to block anaphase

Mad2 binds unattached kinetochores and blocks Cdc20-APC induced destruction of securin by sequestering Cdc20 away from APC

M-Cdk and Polo kinase release Cdc20 from Mad2 when all kinetochores become attached to the spindle

17
Q

DNA Damage Checkpoint

A

DNA damaged by X-rays induces phosphorylation of p53 to remove Mdm2 (the inhibitor for p53)

Active p53 increases transcription of p21 (a Cdk inhibitor protein), which then inactivates G1/S-Cdk and S-Cdk

18
Q

Basic Blood Vessels

A

Large arteries: aorta, elastic

Medium arteries: learn in anatomy, up to 8 layers of smooth muscle

Arterioles: one or two layers of smooth muscle, empty into capillaries, contract smooth muscle to control blood flow into capillaries which increases the vascular resistance

Capillaries: smallest vessels, gas and nutrient exchange in the tissues

Venules: move blood from capillaries into small veins, 0.1 mm diameter

Small veins: less than 1 mm diameter

Medium veins: most of what will learn in anatomy, diameter up to 10 mm

Large veins: diameter over 10 mm, hepatic portal vein and superior/inferior vena cava

19
Q

Basic Structure of Arteries and Veins

A
  1. Tunica Intima
    A: Endothelium- single cell layer of squamous epithelial cells, lines lumen
    B: Basal lamina- thin layer of extracellular tissue made of collagen, proteoglycans, and glycoproteins
    C: Subendothelial layer of LCT- in arteries/arterioles this layer contains the internal elastic membrane
  2. Tunica Media: circumferentially arranged smooth muscle cells, thicker in arteries than veins, goes from internal to external elastic membranes
  3. Tunica Adventitia: made of CT, longitudinally oriented collagen and some elastic fibers, thicker in veins than arteries

Vasa vasorum: Large veins/arteries have a network of blood vessels to supply blood to the cells of the vessel wall

Nervi vascularis: network of autonomic nerves that control the contraction of smooth muscle

20
Q

Three Types of Capillaries

A
  1. Continuous Capillaries: found in muscle, skin, brain, and spinal cord

Endothelial plasma membranes are continuous, tight junctions only allow passage of small molecules, pinocytosis transports larger molecules, have pericytes associated with it

  1. Fenestrated Capillaries: found in endocrine glands and sites of fluid/metabolite absorption (gallbladder, kidney, and GI tract)

Have pinocytotic vesicles, fenestrations may form when pinocytotic vesicles opens on each side of capillary

Fenestrations may have a thin nonmembranous diaphragm-like structure across its opening, GI tract changes wall thickness and fenestration number during absorption

  1. Discontinuous Capillaries (sinusoids): found in liver, spleen, bone marrow

Larger and more irregular in shape than other capillaries, larger gaps and more variable in size than fenestrae with discontinuous basement membrane

Liver: Kupffer cells are macrophages, Ito cells store Vitamin A

21
Q

Two important underlying concepts of capillaries

A
  1. Vasomotion
    Capillary blood flow, vasodilating factors like NO or low oxygen cause smooth muscle in wall of arteries to relax to get increased blood flow/pressure to the capillaries and some plasma fluid is driven into the surrounding tissue, occurs in peripheral edema

Vasoconstriction of arteriole smooth muscle from norepinephrine or ANS can result in decreased capillary blood flow/pressure, might prevent hypovolemic shock during blood loss

  1. Density of Capillary Network:
    Determines total SA for exchange between blood/tissue and is related to metabolic activity

Liver, kidney, and skeletal/cardiac muscle have extensive capillary networks

22
Q

Arteriovenous Shunt (AV anastomoses)

A

Skin, nose, lips, fingertips, penis/clit

Specialized arterioles supply the AV shunt: coiled, thick muscle layer, rich innervation

AV shunt arteriole contraction sends blood to a capillary bed while relaxation sends blood to venule and bypassing the capillary bed

Skin: opening the shunt reduces blood flow to Capillaries and conserves heat

Penis: close AV shunt to direct flow into corpora cavernosa to start erection

23
Q

Postcapillary venules

A

Collect blood from Capillaries, characterized by pericytes

Endothelium is the main site of action for vasoactive agents like histamine and serotonin, cause extravasation

Specialized in lymph nodes called high endothelial venules, prominent cuboidal morphology

24
Q

Lymphatic Capillaries

A

Numerous in LCT under skin and mucus membranes

Endothelial tubes that lack continuous basal lamina so permeable, open nature supported by anchoring filaments

As lymphatic channels become larger the vessel wall becomes thicker due to the presence of smooth muscle and CT

25
Q

Vascular Endothelium

A

Simple squamous epithelium, long axis in direction of blood flow, adhesion molecules and receptors on luminal surface

Activated by bacterial/viral antigens, cytotoxins, complement products, lipids, hypoxia

Release: cytokines, lymphokines, GFs, coagulation factors, vasoconstrictor/dilator

26
Q

Endothelial Cell Functions

A
  1. Selective Permeability: hydrophobic molecules do transcellular transport, hydrophilic molecules need active/facilitated transport or do paracellular transport across tight junctions

Transcellular transport involves pinocytosis (no clathrin) or receptor-mediated endocytosis (use clathrin)

  1. Prevent thrombosis: have anticoagulant factors like thrombomodulin to prevent coagulation of liquid to solid, have antithrombigenic factors like prostacyclin/tissue plasminogen activator to impair platelet aggregation

Normal Endothelium prevents platelet adherence but damaged Endothelium causes platelets to release prothrombogenic factors like von Wilebrand and plasminogen-activator inhibitor

  1. Mediates vasoconstriction: endothelins act as autocrine/paracrine activators on endothelial/smooth muscle cells, increased levels of Endothelin-1 (ET-1) does hypertension, atherosclerosis, heart failure, and other more

Endothelins, ACE, prostaglandin H2, thromboxane

  1. Mediates Vasodilation: NO and prostacyclin

Shear stress of flowing blood along surface causes endothelial cells to release NO that diffuses into tunica media to relax smooth muscle

27
Q

3 Types of Leukocytes

A
  1. Lymphocytes: B cells, T cells, NK
  2. Granulocytes: neutrophils, eosinophil, basophils
  3. Monocytes: dendritic cells, macrophages
28
Q

Hematopoietic Stem Cell

A

Gives rise to all blood cells in the bone marrow, pluripotent, CD34 (cluster of differentiation) is a surface marker for identification

Become: common lymphoid, myeloid, and erythroid megakaryocyte progenitor

29
Q

Erythropoiesis

A

Generation of red blood cells, occurs primarily in bone marrow

Early fetal development: occurs in mesodermal cells of the yolk sac then liver/spleen

Erythropoietin promotes generation of erythrocytes from erythroid megakaryocyte progenitor, given to anemic patients, cytokine in fibroblasts in kidney

30
Q

Cytokines

A

Help with differentiation of immune cells, affect behavior of other cells and allow communication

31
Q

Thrombopoietin

A

Cytokine that promotes development of megakaryocyte sand then platelets (thrombocytes)