Professional Documents
Culture Documents
Created by:
1. Dhea Fany R.
(061411131171)
2. Aditya Wahyu V.
(061411131172)
3. Kevin
(061411131173)
4. Fladyan Armandito
(061411131174)
5. Alycius Noveno
(061411131175)
(061411131197)
6. Rizka Mulia A.
(061411131176)
(061411133001)
19.2016
20.
21. CHAPTER I
22. PREFACE
23.
24. 1.1 Background
25.
nature tends toward chaos, our lives tend to do the same. Houses become cluttered.
Litter gathers along the side of the road. It's a constant job just to keep things picked
up and tidy.Interestingly enough, a similar situation is happening inside our bodies all
the time. Cells are dying, bacteria are wandering in, and viruses are attempting mass
takeovers. Our immune system is constantly hard at work destroying these intruders
and cleaning up the mess. One cell in particular, the macrophage, is an integral part of
this cleanup process. In this lesson, we'll take a closer look at the work of a
macrophage and learn about its importance within the body.
26.
immune system. The word 'macrophage' literally means 'big eater.' It is an amoebalike organism and its job is to clean our body of microscopic debris and invaders. A
macrophage has the ability to locate and 'eat' particles such as bacteria, viruses, fungi,
and parasites.
27.
Macrophages are born from white blood cells called monocytes, which
are produced by stem cells in our bone marrow. Monocytes move through the
bloodstream and when they leave the blood, they mature into macrophages. They live
for months, patrolling our cells and organs and keeping them clean.
28.
29. 1.2 Aims
1. To know about the definition of macrophages
2. To know how macrophages work inside the bodies
30.
31.
32.
33.
34.
35. CHAPTER II
36. DISCUSSION
37.
38. 2.1 Macrophages Definition
39.
immune system. The word 'macrophage' literally means 'big eater.' It is an amoeba3
like organism and its job is to clean our body of microscopic debris and invaders. A
macrophage has the ability to locate and 'eat' particles such as bacteria, viruses, fungi,
and parasites.
40.
41. 2.2 Types of Macrophages
42.
patrolling for pathogens or eliminating dead cells. The table below describes the
location and function of a few different macrophage populations.
47. Anatomic
46. Cell Name
48. Function
al
Location
51. Protects
49. Adipose
tissue
macrophages
50. Adipose
tissue
against
54. Bone
53. Monocytes
marrow/bl
ood
58. Initiate
56. Kupffer cells
57. Liver
immune
60. Lymph
nodes
lipofuscin)
or
exogenous
pigments
reflecting
uptake
antigen
from
the
digestive tract
64. Phagocytosis of small
63. Pulmonar
62. Alveolar
macrophages (dust cells)
alveoli of
control of immunity
lungs
to
respiratory
pathogens
65. Tissue
macrophages (histiocytes
66. Connectiv
e tissue
mucosa
helps
in
the
development of skin
cells
71. Microglia
74. Hofbauer cells
nervous
system
nerves system
75. Placenta
77. Intraglomerular
78. Kidney
mesangial cells
80. Osteoclasts
83. Epithelioid cells
86. Splenic
72. Central
Metallophilic
82.
84. Granulom
85.
as
zone,
and
79.
81. Bone
macrophages
(marginal
76.
red
pulp macrophages)
89.
88. Red pulp
of spleen
87.
90. Peritoneal macrophages
91. Peritoneal
92.
cavity
93.
94.
97.
In bone marrow
of invertebrate, a hematopoietic
stem cell origins from a yolk sac.
Which process as a primitive
hematopoiesis
to
be
to
the
bone
marrow.
99.
100. Macrophages will not released from bone marrow if not differentiate
108.
On
Central
nervous
system,
Macrophages
named
function is
112.
environment,
apoptotic
cell
clearance,
prenatal
10
119.
Macrophages arise from monocytes that migrate into the tissues. Some
macrophages
macrophages),
are
freely
whereas
mobile
others
(free
(fixed
most important of these are interleukin-1 (IL-1), IL-6, IL-12, IL-18, and tumor
necrosis factor- (TNF) (Figure 5-6).
12
123.
Infla
mmation
Macrophages
recognize
tissue
damage,
promote
the
recruitment
of
neutrophils,
and regulate
the processes by which neutrophils recruit monocytes. As sentinel cells,
macrophages promote neutrophil emigration from blood vessels. The release
of high-mobility group band protein-1 (HMGB1) and other damageassociated molecular patterns (DAMPs) from damaged tissues stimulates
resident macrophages to produce TNF- and IL-6 as well as neutrophil
chemotactic chemokines, CXCL8, CCL3, and CCL4 and reactive oxygen
species. Exosomes are small cytoplasmic vesicles, about 50 to 100 nm in
diameter, that can transmit signals between cells. They are released by
stimulated macrophages, dendritic cells, and B cells. These exosomes carry
with them a mixture of immunostimulatory and proinflammatory molecules.
They can spread through the extracellular fluid, where they interact with
nearby cells. Thus exosomes from macrophages containing bacteria can
express bacterial cell wall components such as glycopeptidolipids and other
pathogen-associated molecular patterns (PAMPs) on their surfaces. As a
result, the exosomes can bind to PRRs on nearby neutrophils and
macrophages, leading to MyD88-dependent release of TNF-, CCL5, and
iNOS and promoting more inflammation.
13
14
15
is formed around it. Then, enzymes are released into the phagosome by an organelle
within the macrophage called a lysosome. Much like the enzymes in our own
stomach are released to digest our food, the enzymes released by the lysosome digest
the particle. The remaining debris, or what is left of the particle, exits the macrophage
to be absorbed back into the body.
132. The neutrophils are at first attracted to a site, where they proliferate,
before they are phagocytized by the macrophages. When at the site, the first wave of
neutrophils, after the process of aging and after the first 48 hours, stimulate the
appearance of the macrophages whereby these macrophages will then ingest the aged
neutrophils.
133. The removal of dying cells is, to a greater extent, handled by fixed
macrophages, which will stay at strategic locations such as the lungs, liver, neural
tissue, bone, spleen and connective tissue, ingesting foreign materials such as
pathogens and recruiting additional macrophages if needed.
134. When a macrophage ingests a pathogen, the pathogen becomes trapped
in a phagosome, which then fuses with a lysosome. Within the phagolysosome,
enzymes and toxic peroxides digest the pathogen. However, some bacteria, such as
Mycobacterium tuberculosis, have become resistant to these methods of digestion.
Typhoidal Salmonellae too induce their own phagocytosis by host macrophages in
vivo, and inhibit digestion by lysosomal action, thereby use macrophages to replicate
and cause macrophage apoptosis. Macrophages can digest more than 100 bacteria
before they finally die due to their own digestive compounds.
135. Macrophages do not distinguish between the different types of bacteria,
viruses, or other outsiders, they do recognize that those particles do not belong in the
body by detecting the different outer proteins. Macrophages even have the ability to
detect signals sent out by bacteria, allowing them to travel to the site of infection.
136.
16
137.
Parts:
138.
1. Pathogens
139.
2. Phagosome
140.
3. Lysosomes
141.
4. Waste material
142.
5. Cytoplasm
143.
6. Cell membrane
144.
145.
148.
Monocytes are recruited into tissues in response to a very
wide range of different stimuli. Where a pathogen is involved, they are commonly
preceded by neutrophils, which release a range of toxic agents designed to kill
extracellular pathogens. The macrophage then has the task of clearing both the dead
pathogens and the dead neutrophils. To enter a tissue, the monocyte in peripheral
blood must adhere to the vessel wall, cross the endothelial cell barrier, and then
migrate towards the stimulus; a process known as chemotaxis. The process of
recruitment of neutrophils and macrophages involves the resident macrophages which
act as sentinels. They responds to local stimuli by producing cytokines that make the
endothelial cells more sticky (through the increased expression of cell adhesion
molecules such as P-selectin) and so-called chemokines, that promote the directed
migration of inflammatory cells. Monocytes may also migrate towards increasing
concentrations of molecules that produced by microorganisms themselves, by
damaged tissues, or by the activation of the complement or clotting cascades which
release bioactive peptides such as C5a. One example of a microbial chemoattractant
is N-formyl-methionyl peptides; which are unique to bacteria because this is the
initiating amino acid at the N terminus of all bacterial proteins.
149.
17
150.
Necrosis is the death of body tissue. It occurs when too little blood
flows to the tissue. This can be from injury, radiation, or chemicals. Necrosis
cannot be reversed.There are some kinds of necrosis :
1. Coagulative
2. Liquefactive
3. Caseous
4. Fat necrosis
5. Gangrenous necrosis
151.
18
158.
159.
a Apoptosis
160.
Apoptosis is a physiological process and a type of
programmed cell death whi
ch is important for embryologic
development, maintenance of homeostasis and elimination of damaged cells.
This is a controlled, energy dependent process and involves a number of
different morphological changes. These changes are a result of the action of
efficient cysteinyl aspartate-specific proteases called caspases, and includes
reduced cell volume, chromatin condensation, nuclear fragmentation, and
membrane blebbing.
161.
Apoptotic death can be triggered by a wide variety of
different stimuli, which induce either the extrinsic or the intrinsic apoptotic
pathways. The extrinsic pathway is induced by the activation of proapoptotic
receptors on the cell surface. Specific molecules such as Apo2L/TRAIL and
Fas- Ligand, which are known as pro-apoptotic ligands, bind to the death
receptors (DR)4/DR5 and Fas, respectively, and thereby induce activation of
apoptosis.
162.
In contrast to the extrinsic pathway, the intrinsic pathway
is initiated from within the cell in response to stress signals, such as DNA
damage, hypoxia, or the loss of survival signals. Both pathways are however
interconnected with other signalling proteins, such as NK-B and p53MDM2, and also converge at the level of effector caspases. Caspases are
proteolytic enzymes that mediate apoptosis by cleavage of a number of
different substrates that are vital for cell survival.
19
163.
Apart from morphological changes during apoptosis,
changes on the apoptotic cell surface also occur. These changes are mainly
important to stimulate efficient removal of apoptotic cells by phagocytosis.
However, apoptosis is a dynamic process, during which cell surface molecules
are continuously changing. Phosphatidylserine (PS), a phospholipid that is
normally present on the inner leaflet of the plasma membrane, flips to the
outer leaflet early in the apoptotic process. Increased PS expression has been
found to stimulate phagocytosis.
164.
As a result of both oxidative and non-oxidative stressinduced apoptosis, expression of oxidized PS, in conjunction with the nonoxidized PS, serves as an important phagocytosisstimulatin signal. Other cell
surface changes are alterations in the pattern of 10 glycosylation of
glycoproteins and glycolipids, changed expression levels of specific
molecules, and non-specific changes such as surface charge possibly due to
changes in glycosyl groups. Alterations in sugar chains, surface charge and
oxidation result in the generation of sites resembling oxidised lipoprotein
particles, thrombospondin (TSP) binding sites, sites capable of binding lectins
or the complement proteins C1q and C3b, as well as various collectin-binding
sites. These surface alterations, resulting in new binding sites for receptors,
have important implications for the removal of the apoptotic cell.
165.
b Elimination of apoptotic cells an overview
166.
Elimination is accomplished by professional phagocytes
like macrophages and dendritic cells (DCs), but also by nonprofessional
phagocytes such as fibroblasts, epithelial and stromal cells to name a few cell
types (Fig.1). To recruit professional phagocytes, that are not always located
in immediate proximity, apoptotic cells have been found to secrete soluble
molecules that act as chemotactic factors, find me signals, to phagocytes.
Following recruitment of phagocytes, the elimination of apoptotic cells
consists of two central elements: 1) the apoptotic cell has to be tethered to the
phagocyte, and 2) induction of phagocytosis-stimulating signals upon cellcell
contact. These interactions between the apoptotic cell and the phagocyte are
key events for proper removal. Generally it is suggested that these interactions
induce phagocytosis stimulatory (eat me) or inhibitory (dont eat me)
signals and that the relative contribution of these signals determines whether
20
167.
168.
169.
Adopted figure from Molecular Cell, Vol 14, 277-287, May 7, 2004. Lauber K.
et. Al. Clearance of apoptotic cells: Getting rid of the corpses
170.
21
174.
Dentritic cells
180.
DCs are professional antigen presenting cells with the
ability to activate T cells and thereby exert immune-regulatory functions.
Immature DCs are present in most tissues and have a high endocytic capacity
to capture a number of different antigens, such as peptides, bacteria, viruses,
and dying cells.
22
181.
In their mature state, DCs activate T cells and thereby
stimulate T cell immunity. Similar to macrophages, DCs also have the ability
to eliminate apoptotic cells with beneficial immunological effects, where DC
uptake is important for peripheral tolerance. Central tolerance is achieved in
the thymus where autoreactive T cells are eliminated.
182.
However, all self-antigens are not represented in the
thymus since many proteins dont have access to the thymus during
development (e.g. growth of new tissues such as breast during puberty),
making it possible that some self-reactive T cells escape selection in the
thymus.
183.
DCs phagocytose apoptotic cells, degrade them, and cross
present the digested self peptides from apoptotic cells on MHC class I on their
surface. By migrating to secondary lymphoid organs and presenting the
engulfed self-antigens to T cells, self-reactive T cells will become deleted or
anergic to achieve peripheral tolerance.
184.
Both non-professional and professional phagocytes can
eliminate apoptotic cells. Immature monocyte-derived DCs (iMoDC),
granulocyte-macrophage colony-stimulating factor (GMCSF)- driven
macrophages (M1s), and IL-10-producing M-CSF-driven macrophages
(M2s), are three professional phagocytes derived from the same monocyte
population.
185.
In a situation of apoptotic overload, other subsets of
phagocytes, such as the pro-inflammatory M1, might act as backups.
186.
Infections
187. By their position at sites of initial infection (e.g., the respiratory tract)
and their wide distribution in major organs of the body (e.g., the liver), macrophages
may be decisive in determining the susceptibility or resistance of an animal to virus
infections. The uptake or clearance of a virus particle from the circulation or
extracellular fluids has been shown first of all to depend on the particle size, as is the
case with inert particles, larger particles being cleared more rapidly than smaller ones.
However, other factors, such as the presence of virus specific receptor sites on
macrophages and the presence of opsonizing antibody, are also important. By uptake
and digestion of virus particles, macrophages may delay or even prevent the spread of
the infection to susceptible cells. However, if the virus can replicate in macrophages,
the infection may go further, and widespread destruction of organs and tissues may
occur. Furthermore, infected monocytes in the circulation can, provided they support
virus replication, be a source of dissemination of the infection by their migration
through the body. It thus seems clear that virus-macrophage interactions may be of
23
crucial importance for the outcome of the infection. Much information on the
importance of macrophages in resistance to virus infections has been gained by
studying experimental infections in which differences exist between the interactions
of macrophages with different strains or types of the same virus. Likewise, models in
which differences in handling a certain virus are found among macrophages from
animals of different ages or different strains of the same species have been
extensively studied.
188.
189. Besides constituting an immediate, "ready to function" barrier to virus
penetration and dissemination in the body, macrophages participate in the defenses
mounted by an infected host and directed against the invading pathogen. During the
courses of many infections, macrophages become hyperactive and activated with
increased microbicidal capacity. This process is immunologically mediated by
specifically sensitized T lymphocytes, presumably via the secretion of soluble
lymphokines, and macrophages are now recognized as important ultimate effectors of
both antiviral and antibacterial cell-mediated immunity. The increased antimicrobial
activity is at least partly nonspecific in that activated macrophages arising during an
infection with one microorganism show increased activity against other, unrelated
agents as well. In addition to increased microbicidal capacity, activated macrophages
have been shown to exhibit a number of other distinctive features: increased
phagocytic ability, accelerated "spreading" on glass surfaces, increased lysosomal
enzyme content, augmented metabolic functions, and antitumor activity. Many of
these properties are shared by nonspecifically stimulated macrophages elicited in vivo
or in vitro by various irritants, such as mineral oil, glycogen, proteose-peptone,
thioglycolate, etc., and it has been speculated that activated and stimulated
macrophages are fundamentally alike. It is well documented that specific macrophage
recruitment and activation occurring in the course of a virus infection are of crucial
importance for recovery. Much more open questions are the significance of
nonspecific macrophage activation and stimulation in the natural resistance of the
host to virus infections and the prospects of nonspecific macrophage activating
immunomodulation in the prophylaxis and treatment of virus infections. In vitro, both
stimulated and immunologically activated macrophages have shown great antiviral
potentials. Thus, Hirsch et al demonstrated by an infectious center assay that
proteose-peptone-stimulated peritoneal macrophages from adult mice were
considerably more restrictive in the replication of HSV-1 than were unstimulated
cells. Suckling mice, on the other hand, did not respond to proteose-peptone
stimulation with the production of a macrophage population with these
characteristics, a fact that might partly explain the inefficiency of suckling mouse
macrophages to restrict replication of viruses in vivo and in vitro.
24
190.
191. Aspects of the importance of the mononuclear phagocyte system as a
barrier to the establishment and dissemination of virus infection in the body have
been presented. From an anatomical point of view, cells of the mononuclear
phagocyte system are well suited for this function. They are strategically placed at the
portals of entry of many viruses and are widely distributed in close contact with the
circulating blood in most organs of the body, thus encountering the virus early in the
infection. From a functional point of view, the ability of macrophages to take up and
destroy invading virus particles may be of the utmost importance in the race between
the destructive growth of thevirus and the induction of a specific immune response.
If, on the other hand, the virus is able to multiply more or less freely in macrophages,
the "viral burden" and the destruction may have proceeded beyond the limit of the
capacities of the specific immune responses, when they eventually turn up.
Polymorphonuclear leukocytes do not constitute a fixed barrier system in the body,
and they are generally not a very conspicuous feature in the pathological lesions
produced by viruses. Although they are capable of taking up virus particles, there is
no evidence that they play a very prominent role, if any, in the antiviral defense
mechanisms of the body. The collaboration of macrophages with other host defense
mechanisms against virus infections is a subject of current interest. For example,
macrophages have been shown to be of importance in the production by specifically
sensitized lymphocytes ofimmune (type II) interferon. However, the role of
macrophages seems more important in the immune response. Thus, macrophages are
recognized as important ultimate effectors of antiviral cell-mediated immunity.
Probably, macrophages also play a role in the inductive phase of the immune
response by capturing the virus and by processing the viral antigens and presenting
them to lymphocytes for immune recognition. As previously stated, the basic nature
of the capacity of macrophages to restrict the replication of viruses is at present
unknown. A better understanding of this question, together with more insight into the
collaboration of macrophages with other host defense mechanisms, might open new
fields of specific immunomodulation. This could be of importance in the prophylaxis
and treatment of virus infections in persons with increased susceptibility, for example,
premature infants and persons with genetically determined or induced immune
deficiencies.
192.
193.
194.
Hemodynamic
is
the fluid
dynamics of blood
flow.
circuits are
controlled
by control
systems. Hemodynamic
25
response continuously monitors and adjusts to conditions in the body and its
environment. Thus hemodynamic explains the physical laws that govern the
flow of blood in the blood vessels. The relationships can be challenging
because blood vessels are complex, with many ways for blood to enter and
exit under changing conditions. Hemodynamic disorder such as : edema,
hyperemia, congestion, hemorrhage, hemostasis, thrombosis, embolism,
infark, and shock.
195.
1. EDEMA
196.
Edema is condition when the bodies tissue (interseluler tissue) and body
cavity swelled by fluid from blood plasma. Without any vascular damage
2. HYPEREMIA
197.
Hyperemia is an active process resulting from augmented tissue inflow
because of arteriolar dilation, as in skeletal muscle during exercise or at sites
of inflammation. The affected tissue is redder because of the engorgement of
vessels with oxygenated blood.
3. CONGESTION
198.
Congestion is a passive process resulting from impaired outflow from a
tissue. It may occur systemically, as in cardiac failure, or it may be local,
resulting from an isolated venous obstruction. The tissue has a blue-red color
(cyanosis), particularly as worsening congestion leads to accumulation of
deoxygenated hemoglobin in the affected tissues
4. HEMOSTASIS
199.
to vascular
200.
damage and provides a mechanism to seal an injured vessel to prevent
blood loss.
5. HEMORRHAGE
201.
26
202.
Hemostasis
hemorrhage
with other blood elements on the wall of a blood or lymphatic vessel or heart
or free in their lumen [thrombo-emboli].
206.
Hemorrhage
Trhrombus
7. EMBOLISM
207.
8. INFARK
208.
Necrosis of tissue cause lack of oxygen, and make tissue become lot of
27
209.
215.
216.
217.
218.
219.
220.
221.
222. Acute inflammation is a rapid response to an injurious agent that serves
to deliver mediators of host defense leukocytes and plasma proteins to the site of
injury. Acute inflammation has three major components: (1) alterations in vascular
caliber that lead to an increase in blood flow; (2) structural changes in the
microvasculature that permit plasma proteins and leukocytes to leave thecirculation;
and (3) emigration of the leukocytes from the microcirculation, their accumulation in
the focus of injury, and their activation to eliminate the offending agent.
28
secreting
the
cytokines
TNF,
IL-1,
andchemokines
(chemoattractant
cytokines).TNF and IL-1 act on the endothelial cells of postcapillary venules adjacent
to theinfection and induce the expression of several adhesion molecules.
224. Phagocytosis and the release of enzymes by neutrophils and
macrophages are responsible foreliminating the injurious agents and thus constitute
two of the major benefits derived from theaccumulation of leukocytes at the
inflammatory focus.
225.
226.
227.
Inflamation
228.
29
229.
230.
231.
232.
233.
234.
235.
236.
237.
238.
239.
240.
241.
242.
243.
30
31
32
of neutrophils influences macrophage phenotype, causing a switch from proinflammatory to a growth promoting, reparative phenotype.
251. Macrophages influence wound healing through the generation of growth
factors that promote cell proliferation and protein synthesis, as well as by the
production of proteases and their inhibitors that influence ECM content and
remodeling. A multitude of factors that are known to be present in healing wounds
have been shown to be produced by macrophages.
252. During this final phase, capillary regression and collagen remodeling
are dominant features. Macrophages can produce factors that are anti-angiogenic
(such as thrombospondin-1 and IP-10), and others, including CXCR3 ligands, that
direct the termination of the repair response in multiple ways. Other cells within the
wound may also produce these concluding signals,but since macrophages can
theoretically be a major source of these types of factors, these cells may play an
active role in the termination of the wound healing process.
253.
255.
256.
257.
258.
259.
260.
261.
262.
263.
264.
265.
266.
254.
267.
34
278.
279.
CHAPTER III
280.
CONCLUSION
281.
3.1 Macrophage is a large white blood cell that is an important part of our immune
system
3.2 Macrophage plays a lot of roles in immune system. But mostly, macrophage
recognizes the foreign agents that invade the bodies and secreting several types of
chemical mediator to destroy the foreign agent, then finally, eliminating the debris
of foreign agents by phagocytosis.
282.
283.
284.
285.
286.
287.
288.
289.
290.
291.
292.
293.
294.
295.
296.
297.
298.
299.
300.
301.
35
302.
303.
304.
305.
REFERENCES
306.
307.
308.
https://en.m.wikipedia.org/wiki/Macrophage
309.
http://www.news-medical.net/life-sciences/Macrophage-Function.aspx
310.
www.ncbi.nlm.nih.gov/pmc/articles/PMC3596046
311.
https://www.diva-portal.org/smash/get/diva2:278362/FULLTEXT01.pdf
312.
https://en.wikipedia.org/wiki/Macrophage
313.
http://study.com/academy/lesson/macrophages-definition-function-
types.html
314.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC281459
315.
316. Yohnston RB. Monocytes and macrophages. Dalam: Lachman PJ, Keith DP, Rosen FS,
Walprot MJ, penyunting. Clinical aspects of immunology, vol 1; edisi ke-5, Oxford:
Blackwell Scientific, 1993. Veterinary Immunology 9t, Ian Tizard
36