Learning Objectives Flashcards
1
Q
explain why there are four basic tissues
A
Epithelium – tissues that line external body surfaces, internal tubes, and form unicellular to multicellular glands
Connective Tissue – tissues that connect, bind, and give structural support
Muscle – tissue uniquely designed for contractility
Nervous – tissue designed to conduct, receive, transmit, integrate, and transduce information from both external and internal sources
2
Q
compare and contrast
Parenchyma/stroma
A
Parenchyma – functional tissue of an organ
Stroma – connective tissue framework supporting the organ parenchyma
3
Q
compare and contrast serosa and mucosa
A
Serosa – thin layer of simple squamous cells that form sheets which line the outer surfaces of organs when they are located in the body cavity
Mucosa – specialized epithelia and its associated connective tissue which line the luminal surfaces of body tubes, cavities, and canals with an external connection
4
Q
compare and contrast apical and basal layers
A
Apical – luminal border, away from the basement membrane
Basal – adjacent to the basement membrane
5
Q
Compare and contrast the four cell surface modifications based upon motility and size.
A
Microvilli – increase surface area, non-motile
Stereocilia – increase surface area, non-motile (long microvilli)
Cilia – highly motile, produce unidirectional transport of material
Flagella – similar to cilia, fewer in number and much longer
6
Q
what are the 5 kinds of simple epithelium
A
simple squamous, simple cuboidal, simple columnar, pseudostratified, transitional
7
Q
describe simple squamous epithelium location
A
Simple Squamous
Mesothelium: lines body cavities
Endothelium: lines vessels
8
Q
describe simple cuboidal epithelium location
A
Location: kidney tubules, respiratory tract, ducts
9
Q
describe simple columnar epithelium location
A
Location: stomach, intestines, parts of the respiratory tract, and glands
10
Q
describe pseudostratified epithelium (3)
A
All cells touch the basement membrane = simple
Ciliated or non-ciliated
Location: respiratory system
11
Q
describe transitional epithelium (3)
A
All cells contact the basement membrane = simple
Accommodates stretching
Location: urogenital tract
12
Q
list the 2 types of stratified epithelium
A
stratified squamous, stratified cuboidal/columnar
13
Q
describe stratified squamous epithelium (4)
A
Basal layer = cuboidal or columnar shape
Keratinized – external body surfaces, buccal cavity, forestomach (ruminants)
Non-keratinized – vestibular region of respiratory tract, esophagus, cornea, urogenital tract
Mixed – tongue, esophagus, non-glandular stomach
14
Q
describe stratified cuboidal/columnar epithelium (2)
A
Named by most apical layer
Location: genitourinary tracts, ducts of glands
15
Q
list the 4 basic categories of adult connective tissue
A
cartilage, bone, blood CT proper
16
Q
list the cells ad components of cartilage
A
cells: chondrocytes/blasts/clasts, fibroblasts
Matrix: fibers (collagenous or elastic) + ground substance (proteoglycans)
17
Q
distinguish between the 3 types of cartilage
A
hyaline: in bone forming sites and airways
elastic: ear, nose
fibrocartilage: regions of transitions, contains type I cartilage
18
Q
list the cells and matrix components of bone
A
cells: osteoblasts/clasts/cytes
Matrix – fibers, osteoid, ground substance, inorganic substance (washed out)
19
Q
Distinguish between woven and lamellar bone
A
lamellar: has osteons
woven: no osteons
20
Q
be able to label the parts of a haversian system of bones
A
Osteon
Canaliculi
Central Canal
Lamellae
Osteocyte
Volkmann’s Canal (communicating canal)
21
Q
distinguish between periosteum and endosteum
A
periosteum: covers and smooths outside of bone
endosteum: covers and smooths osteons
22
Q
distinguish between the 3 types of muscle tissue
A
skeletal: striated, voluntary movement, multinucleated and peripheral nuclei
cardiac: striated, involuntary, intercalated disks, centrally located nuclei maybe with halos, usually one nucleus per cell
smooth: nonstriated, involuntary, centrally located nuclei and usually one nucleus per cell
23
Q
define endomysium, perimysium, and epimysium
A
Endomysium – surrounds individual myofiber
Perimysium – surrounds fascicles (bundles of myofibers)
Epimysium – surrounds anatomically discrete muscles (groups of myofibers)
24
Q
list basic components of CNS and PNS
A
- Neurons – nerve cells
- Glial cells – supportive cells
- Nuclei (CNS) or Ganglia (PNS) – clusters of nerve cell bodies
- Nerve Fiber – single axon
- Peripheral Nerve – bundle of nerve fibers
- Nerve (PNS) or Tract (CNS) – organized collection of axons
25
define white matter and grey matter
white matter: mainly myelinated axons
grey matter: mainly nerve cell bodies and unmyelinated axons
26
list the 3 anatomical classifications of axons
1. unipolar
2. bipolar
3. multipolar
27
list the 3 functional classifications of axons
1. sensory
2. motor
3. interneuron
28
describe basic function of immune system
Differentiate self from non-self, defense against pathogens
29
give the role of innate and adaptive immunity
Innate – non-specific, no memory, fast response
Adaptive – specific, memory, slower response
30
list the physical and physiological barriers of the innate immune system (4)
Epithelium
Mucus/tears/sebum
Flushing/peristalsis
Commensal flora
31
explain hematopoiesis to generate leukocytes
multipotential hematopoietic stem cell becomes either common myeloid progenitor or common lymphoid progenitor;
common myeloid progenitor gives rise to all granculocytes (neutrophils, eosinophils, basophils, monocytes (become macrophages and myeloid dendritic cells), erythrocytes, mast cells, and megakaryocytes (become thrombocytes); common lymphoid progenitors give rise to lymphocytes, natural killer cells, and lymphoid dendritic cells
32
Identify the major cells of the innate immune system, their features, functions, and significance in infiltrates or exudates
Myeloid Cells
Neutrophils – first responders (not in tissue)
Kill infecting microbes – NETs, phagocytosis, degranulation
Eosinophils – antihelminthic, degranulation
Basophils – migrate into tissues during multicellular parasitic infections
Monocytes – precursors to macrophages and DCs
Phagocytosis, cytokine production
Sentinel Cells
Macrophages – cytokine production, phagocytosis, antigen presentation
Dendritic Cells – antigen presentation, sentinel, phago/endocytosis
Reside in the tissues
Mast Cells – releases histamines in allergic reactions, vasodilation/vascular permeability, recruit other leukocytes
Natural Killer Cells – first line of defense against viruses, cytotoxic granules that drive apoptosis
33
name the 3 components of the innate immune response
In place at birth, fast response, non-specific
34
Describe in general terms how the innate immune system recognizes threats
PAMPs (pathogen-associated molecular patterns) bind to PRRs (pattern recognition receptors)
2. PRRs start a signaling cascade…
Toll-like receptors – membranous, wide variety
4 – LPS
5 – flagellum
NOD-like receptors – cytoplasmic, bacterial components
RIG-1-like receptors – cytoplasmic, viral dsRNA
3. Activation of transcription factor leads to transcription of genes: pro-inflammatory cytokines, adhesion molecules, co-stimulatory molecules
35
Explain the function and formation of the inflammasome
Recognition of both PAMPs and DAMPs leads to inflammasome production
The inflammasome can then activate IL-18 and IL-1β
36
List the consequences of sentinel cell exposure to PAMPs and DAMPs
Sentinel cells recognize and respond to PAMPs and DAMPs through PRRs
Results of PRR signaling:
1. Phagocyte activation
2. Cytokines/chemokines
3. Adhesion molecules
4. Lipid mediators
37
explain phagocytosis and degradation
Phagocytic Receptors on neutrophils, macrophages, dendritic cells
Opsonins = antibodies + complement proteins
More efficient phagocytosis than through PRRs alone
Antibodies bind to Fc receptor
Complement proteins (C3b) bind to CD3 receptor lead to phagocytosis:
1. Recognition & attachment
2. Engulfment of phagosome
Phagosome-lysosome fusion leads to phagolysosome
3. Destruction of pathogen via
Lysosomal enzymes
4. Decreased pH in phagosome
5. Respiratory burst (reactive oxygen species)
6. Reactive nitrogen intermediates
38
describe extracellular granule release of neutrophils and eosinophils
Neutrophils
Proteases, myeloperoxidases, NADPH oxidase, antimicrobial molecules (defensins, cathelicidins)
Neutrophil extracellular traps (NETs) – response to cytokines and PAMPs; composed of DNA, histones, and other antimicrobial molecules
Eosinophils – major basic protein (cytotoxic to helminths)
39
describe NK cell targeted cytotoxicity
Activation receptor – viral proteins, altered surface glycoproteins, antibody-coated cells
Inhibitory receptor – MHC Class I (marker of “self”)
If absent, NK cells release lytic granules
1. Perforin – makes a hole in the membrane
2. Granzyme – triggers apoptosis
40
explain which effector actions are most effective for which type of infection
Phagocytosis & Degradation – extracellular and intracellular infections
Granule Release – extracellular and helminth infections
NK Cells – viral infections and cancer
41
describe phagosomal maturation and how microbes are destroyed in this process
1. pH goes from neutral to acidic
2. Fusion with lysosome yields phagolysosome
3. Oxidative burst (free radicals, reactive nitrogen intermediates, etc.)
42
explain how the adaptive response augments the innate immune response
Natural Killer Cells (NK Cells) can be activated by antibody-coated cells and can be inhibited by MHC Class I (bridge between innate and adaptive immunity)
43
recognize location, structure, and function of primary lymphoid organs
bone marrow: in the medulla of long bones, spongy bone, hematopoiesis
thymus: in the neck, lobulated with cortex and medulla, T cell maturation via interaction with thymic epithelial cells
44
Describe the process of cell maturation from the site of origin to the site of activation for T cells
Immature cells travel from bone marrow to the thymus then exit thymus as mature, naïve T cells 🡪 and are presented linear peptides by antigen presenting cells (APCs) leading to clonal expansion
45
Describe the process of cell maturation from the site of origin to the site of activation of B cells
Mature in the bone marrow
enter bloodstream as mature, naïve cells then travel to secondary lymphoid organs where they bind antigens (in native form), differentiate into lymphocytes/plasma cells and clonal expansion occurs
46
Describe the organization and function of the lymphatics
Lymphatics– screen lymph/peripheral tissues
Brings in fluid from interstitial space (driven by Starlings’ forces)
to blood
Absorbs lipids from the GI tract
Extremities/GI Tract/Liver 🡪 cisterna chyli to the left subclavian vein
Right arm goes through the right subclavian vein
In the lymph node mixing of lymph fluid with dendritic, B, and T cells
Dendritic cells present antigens to T cells in paracortical region and B cells in the cortex
Differentiation of B cells
47
Describe the organization and function of the secondary lymphoid organs
Spleen – screens blood
Resident macrophages – help recycle senescent RBCs
Mounts immune response to blood-borne pathogens
Red pulp – RBCs and macrophages
White pulp – lymphoid tissue
MALT – monitors mucosal tissues
Nasopharyngeal, gut, bronchus, etc.
Specialized lymphoid aggregates with varying degrees of organization
48
Be able to define and distinguish antigen, epitope, immunogen, and hapten
Antigen – molecule that binds specifically to an antigen receptor
Epitope – part of the antigen that is recognized by the lymphocyte
Immunogen – antigens that an induce an immune response
Hapten – antigens that are unable to induce an immune response on their own
49
Understand the properties that make a molecule antigenic
1. complex
2. degradable
3. large
4. foreign (context)
5. organic
50
Understand the roles of MHC Class I and II in the process of processing and presenting antigen to T cells
MHC I
Proteosome acts as a garbage disposal
TAP – transporter associated with antigen processing
MHC I can present peptides from self or non-self
The CD8+ T cell can discriminate
MHC II
Extracellular protein endocytosed by professional APCs (dendritic cells, macrophages, B cells)
Invariant chain blocks binding groove to prevent MHC II from acting on self-antigens like MHC I
51
Understand how antigen presenting cells (APCs) process and present antigens to T cells
Professional APCs
Dendritic Cells
Always expressed
Can present to both MHC I and II (intra- and extracellular)
B Cells
Always expressed
Extracellular (MHC II)
Macrophages
Expressed in low levels
Extracellular (MHC II)
*Note: all professional APCs are capable of normal MHC I processing and presentation
52
Know which cells express MHC I and II what T cells are activated
CD4: Class II; professional APCs
CD8: Class I; all nucleated cells
53
Understand basics of MHC restriction, alloreactivity, and superantigens (these are all intertwined)
MHC restriction refers to the fact that TCRs can only recognize their antigen in the context of self-MHC so MHC restricts/determines the antigens that T cells will get to see and respond to;
alloreactivity refers to how foreign MHC can still present peptides and potentially activate T cells, and thanks to MHC polymorphism, the MHC may contain non-self peptides, leading to indirect alloreactivity as the T cells may not have seen those non-self peptides and will react to self as if it is foreign;
superantigens are toxins and viral proteins that cause excessive activation of the immune system and bind outside the peptide-binding groove and cause nonspecific activation of large numbers of T cells resulting in polyclonal T cell activation and a massive cytokine release
54
Understand the structure and function of the TCR complex
Structure:
CD3 – transmembrane polypeptides that transduce signals to activate T cells
αβ chains (more common) or γδ chains
CD4 or CD8 associated with TCR in αβ cells
Extracellular “variable” regions contain the antigen binding region
55
Understand how the T cell diversity, specificity, and tolerance are generated in the thymus
Gene Rearrangement – how the variable (antigen binding) region is generated
Not germline encoded – random rearrangement of germline segments of the genes encoding TCRs
Occurs independently of antigens
α-chain genes random joining of V/J segments 🡪 new VJ segment (combinational diversity)
If this process fails twice (once for each chromatid), the cell dies
β-chain genes random joining of D/J segments linked with a new V segment 🡪 new VDJ segment (combinational diversity)
Meanwhile, random nucleotides are removed or added between segments to produce more diversity (junctional diversity)
Lymphocyte Maturation
Negative selection: self-reactive TCRs = bad
Positive selection: non-self reactive TCRs
After selection: double positive T cells (contains both CD4 and CD8) 🡪 single positive after further testing
Thymic Cortex Positive Selection – determines what type of T cell and eliminates non-functional TCRs
Immature thymocytes interact with cortical thymic epithelial cells that express MHC I and II
Cells that interact with MHC-peptide complexes are given survival signals
Cells that do not interact undergo apoptosis (96%)
Bind with MHC I 🡪 lose CD4 expression 🡪 CD8+ T Cells (cytotoxic)
Bind with MHC II 🡪 lose CD8 expression 🡪 CD4+ T Cells (helper)
Thymic Medulla Negative Selection – eliminates self-reactive TCRs
Medullary thymic epithelial cells express proteins found in other tissues of the body
Medullary APCs present peptides from those proteins
If the thymocyte binds too well 🡪 negative selection 🡪 apoptosis (central tolerance)
56
Understand the three signals necessary for T cell activation
Antigen – activated by an APC (usually dendritic cell) presenting a specific antigen
CD4+ T cells – extracellular (endocytosed) presented on MHC II
CD8+ T cells – intracellular (cytosolic proteins) on MHC I
Dendritic cells an take up extracellular antigens 🡪 cross-presentation to CD8+ T cells
Co-stimulation – CD80/86 molecules on APC interact with CD28 molecules on the T cell
No co-stimulation 🡪 apoptosis or anergy (non-responsiveness)
Cytokines – environmental or produced by APC 🡪 determine the fate of the T cell by providing context aka differentiation
After antigen and co-stimulation, T cells have high affinity for interleukin 2 (IL-2) receptor and secrete IL-2
Binding of IL-2 to its receptor 🡪 clonal expansion
57
Understand how Th cell differentiation is accomplished and describe the 5 most common T cells
Different cytokines released by APCs induce differentiation of T helper (Th) cells
The innate immune response determines which cytokines are secreted 🡪 which T cells are generated
Th1 – intracellular pathogens
IFN-γ (activate macrophages, enhances B cell proliferation/differentiation) and TNF-β (kills chronically infected cells, induces macrophages)
Th2 – parasites, extracellular pathogens, allergy/asthma
IL-4 – B cell differentiation
IL-5 – eosinophil activation
Th17 – inflammation (bacteria, fungi, parasites)
IL-17 – attracts neutrophils and macrophages 🡪 ROS 🡪 inflammation
Tfh – activates B cells
Closely associated with germinal center reactions in lymph nodes
Help B cells differentiate 🡪 plasma cells
58
Understand the differences between naïve, effector, and memory T cells
Naïve: mature, but haven’t been introduced to antibodies yet
Effector: exposed to antibodies, defined by cytokines, target other cells to initiate an immune response (CD4+) or kill target cells (CD8+)
CD4+: Th1 🡪 macrophages, Th2 🡪 eosinophils, Th17 🡪 neutrophils, Tfh 🡪 B Cells
CD8+: activated by dendritic cells + CD4+ cells
Memory: certain amount of T cells kept around after an immune response is over to be able to quickly respond to the same pathogen down the road
59
Understand the functions of T helper and T cytotoxic cells
T Helper Cells (CD4+)
Th1: produce INF-γ (major) and TNF-β 🡪 activates macrophages
Th2: produces IL-4 (B cell differentiation) and IL-5 (eosinophil activation)
Th17: IL-17 attracts neutrophils and macrophages 🡪 inflammation
Tfh: CXCR5 🡪 B cell differentiation into plasma cells
T Cytotoxic Cells (CD8+)
Kill target cells via release of cytotoxic granules
Perforin – forms a pore in the target cell
Granzyme – induces apoptosis
60
Understand the difference between alpha-beta and gamma-delta T cells
αβ cells
Majority of T cells in mammals
Express both CD4 and CD8 prior to selection (double positive)
Junctional? diversity allows for more diversity
γδ cells
Small fraction of T cells in most mammals
Do not express CD4 or CD8 (double negative)
Do not require MHC:antigen interaction but can recognize unprocessed antigen (without MHC)
Less diverse repertoire
Cytotoxic function (similar to CD8+ cells)
61
Where are B cells made? Where do they mature?
B cells are made and mature in the bone marrow
62
What stimuli are required to cause maturation? What events cause a B cell to undergo apoptosis?
Maturation occurs after exposure to antigens in the lymphoid follicles; see notes for apoptosis events
63
What “product” do mature B cells produce?`
Antibodies
64
know basic structure of immunoglobiuns, Name the different classes of antibody.
Identify basic differences in structure for each antibody class.
see notes
65
Know the signals required for activating B cells to make antibody.
see notes (without T cell (2 ways) or with T cell)
66
Understand the clinical consequences of class- switching
Heavy chain determines the Ig class
Class switching: deletion of portions of the heavy chain gene
The cytokine profile of the T helper cell determines the antibody class that is produced
Know the order in which antibody classes are produced (and why this matters)
Present on naïve B cells: IgD and IgM
Require stimulation and class switching: IgE, IgG, and IgA
67
Know the anatomical location in which antibody classes predominate (serum, mucosa)
see notes from immunology
68
Know the main functions of antibodies.
Classical pathway of complement activation
Blocking membrane receptors
Activating natural killer cells
Eosinophil degranulation
Mast Cell degranulation
see notes for each antibody role
69
Understand the arrangement of a biochemical cascade such as the complement system (CS)
1. Inactive precursors while healthy
2. Activation by an upstream complement protein/enzyme
3. Active complement protease leads to activation downstream
4. Amplification!
70
Know the three different mechanisms of complement activation
Alternative Pathway – direct pathogen activation (most common)
Classical Pathway – antibody-initiated (crosstalk with adaptive)
Lectin Pathway – binding to mannose on pathogen surfaces (similar to classical)
70
Understand the role of the CS in the innate and adaptive immune system
Major part of the innate (protection against infections, regulation of inflammation, removal of damaged cells)
Regulatory role in the adaptive
71
Know the role of major complement proteins and their consequences in innate (C3 convertase, C3b, C3a, C5a, C5-9) and adaptive (C3) immunity
C3 convertase – key effector protein that activates the rest
C3a, C5a – recruitment of inflammatory cells
C3b – opsonization of the pathogen for phagocytosis
C5-9, MAC – direct killing of the pathogen
72
Understand control mechanisms of complement activation
Factor H – similar function to CD55 in the alternative pathway
CD59 – inhibits assembly of the MAC
Complement receptors – ensure removal of the antigen-antibody-complement complexes
73
Describe the divisions of the autonomic nervous system.
sympathetic: fight or flight; thoracolumbar
parasympathetic: rest and digest; craniosacral; repsonsible for defecation and urination
both innervate the heart
74
Explain the preganglionic and postganglionic neurons and what the primary neurotransmitters and receptors are.
parasymapthetic: preganglionic in CNS; Ach acts on muscarinic receptors
sympathetic: preganglionic neuron in CNS; Ach acts on nicotinic receptors and muscarinic receptors
Ach leads to release of norepinephrine which acts on alpha and beta adrenergic receptors
75
Describe the effect of activation of individual components of the autonomic nervous system on the tissues and organs they innervate.
parasympathetically: long preganglionic; ach on nicotinic receptors at synapse and short postganglionic with ach on muscarinic receptors
sympathetically: short preganglionic with ach on nicotonic receptors and long postganglionic with norepineprhine on alpha and beta adrenergic receptors
76
Predict the action of cholinergic and adrenergic drugs on tissues and organs innervated by the ANS.
atropine is anticholinergic so it blocks parasympathetic; cholinergic drugs increase (activate parasympathetics) Ach levels, encouraging muscles to contract (heart faster, vessel constriction to increase BP, clearing of bowels, salivation, sweating, etc.)
adrenergic drugs either increase or inhibit sympathetic response by influencing norepinephrine release; will have different effects based on whether bind beta (dilation) or alpha (constriction) adrenoreceptors
77
Recognize that neurons in the ANS have a basal level of activity and why this is important.
inhibition of parasympathetic is similar to increasing sympathetic and vice versa because they are always active and opposite actions
78
Predict what would happen if a single component of the ANS was removed from an organ (e.g., What happens to heart function if the parasympathetic innervation is removed?).
effects of removal of parasympathetic/increase of sympathetic
pupil: no effect on radial muscle, would effect contraction of circular and ciliary muscles
heart: would lead to an increase in HR, conduction, contractility, velocity
arterioles: little to no effect as parasympathetic not really innervate them
lungs: would inhibit contraction and mucus secretion, making it easier to breather
stomach: decrease motility and tone, contract sphincters, inhibit secretion
intestines: same as stomach
gallbladder: same as stomach
spleen capsule and liver: not really innervated by parasympathetic
pancreas: decrease secretion
urination: relax destrusor and contract sphincters (no pee, hold it)
rectum: relax wall of rectum and contract internal anal sphincter (no shit, hold it)
skin: not much parasympathetic control
salivary glands: thick viscous secretion and amylase secretion
lacrimal glands: mostly parasympathetic, so would decrease secretion
juxtaglomerular and pineal gland: little parasympathetic innervation
removal of sympathetic of stimulation of parasympathetic would be opposite
79
Describe what happens during fear and submission behaviors.
literally no clue; if anyone knows pls text me
80
Describe the baroreflex and explain what happens when blood pressure goes up or down.
the baroreflex is governed by barometric receptors in the carotid sinus and ateriolar contriction alpha 1 receptors;
if blood pressure increases, the body will act to decrease heart rate and inhibit peripheral alpha receptors to decrease afterload by activating sympathetic and inhibiting parasympathetic systems
if blood pressure drops, the body will act to increase heart rate and activate peripheral alpha receptors to increase afterload bring blood pressure back up (the renin-angiotensin-aldosterone system also helps increase blood pressure)
81
Describe the pupillary light reflex and explain what happens when light levels increase or decrease
1. light hits the afferent pupillary fibers start at the retinal ganglion cell layer and then travels through the optic nerve, optic chiasm, and optic tract
2. the path then joins the brachium of the superior colliculus and travels to the pretectal nucleus, which send fibers bilaterally to the efferent EW nuclei of the oculomotor complex
3. efferent parasympathetic fibers travel on the oculomotor nerve to synapse in the ciliary ganglion, sending parasympathetic impulses to the iris sphincter smooth muscle via muscarinic receptors and constricts the pupil (meiosis) in response to light
the motor nucleus is cranial nerve 3
pupil dilation is a different pathway
82
Describe the diving response.
not clear cut fight/flight sympathetic activation
sensory stimulus from cranial nerve 5 (trigeminal nerve) and 10 (glossopharyngeal nerve)
motor response is characterized by: apnea, bradycardia, peripheral vasoconstriction, and decreased metabolic rate
this is elicited by immersion in cold water, and the blood flow to the brain stays constant as it is very metabolically active and MUST always be fed
lactate increases in the rest of the body; is a good indicator of a slow metabolic rate
83
Describe the enteric nervous system and its function.
composed of the mesenteric plexus and submucosal plexus; facilitates motor, sensory, secretory, and absorptive functions of the gastrointestinal system
