TUGAS IMUNOLOGI DASAR

TUGAS I :CELLS AND TISSUE IN THE IMMUNE SYSTEM

1. Sebutkan sel-sel yang terlibat dalam imunitas alami dan apa fungsi masing-masing sel tsb?
2. Sebutkan klas sel limfosit dan apa fungsi dasar masing-masing limfosit tersebut
3. Apa fungsi sumsum tulang, thymus dan lien dalam sistem imun?
4. Apa kepentingan sel dendritik?
5. Apa kepentingan sel T reg dalam sistem imun? Apa petanda permukaannya?

1. sel – sel yang terlibat dalam imunitas alami:

 epithelial barrier  epitel – epitel yang berada pada jalan masuk awal dari mikroba,
seperti kulit, GI track, serta respiratory track. Fungsinya adalah sebagai hambatan
secara fisik terhadap infeksi, mampu memproduksi substansi antimikroba lokal dan
mampu membunuh mikroba dan sebagai tempat datangnya limfosit intraepitel yang
mampu membunuh mikroba dan sel yang terinfeksi
 Fagosit  mengenali dan mencerna mikroba secara intraseluler
 Neutrofil  Neutrophils are the first cell type to respond to most
infections, particularly bacterial and fungal infections. They ingest
microbes in the circulation, and they rapidly enter extravascular tissues
at sites of infection where they also ingest microbes and die after a
few hours
 Monosit / Makrofag  They, too, ingest microbes in the blood and in
tissues. Unlike neutrophils, momcytes that enter exuavascular
tissues survive in these sites for long periods; in the tissues, these
monocyces differentiate into cells called macrophage If an infectious
microbe breaches an epithelium and enters the subepithelial tissue,
resident rnacrophages recognize the microbe and respond by
producing mluble proteins called cycokines
 Fungsi makrofag teraktivasi  membunuh mikroba, inflamasi, enhanced
adaptive immunity, remodelling tissue, merangsang presentasi antigen.
 Komplemen  Many complement proteins are proteolytic en-, and
complement activation involves the sequential activation of these enzymes,
sometimes called an enzymatic cascade.
 The complement system serves three functions in host defense. First, C3 b
coats microbes and promotes the brnding of these microbes to
phagocytes, by virrue of receptors for C3b that are expressed on the
phagocytes. Second, some breakdown products of complement proteins
are chemaattractants for neutrophils and monocytes and promote
inflammation at the site of complement activation. Third, comptement
activation culminates in the formation of a polymeric protein complex that
inserts into the microbial cell membrane, forming pores that lead to the
influx of water and ions and death of the microbe
 NK sel  Natural killer (NK)c ells are a c hlass of lyrnphocyta
that respond to intracelular microbes by killing infected cells and
 by producing the macrophage - activating cytocine, IF'N gamma.
When NK cells are activated, rhey respond in two ways (see Fig. 2-
9). First, activation triggers the discharge of proteins contained in the
NK cells' cytoplasmic granules toward the ifikcted cells. These NK cell
granule proteins include molecules that create holes in the plasma membrane
of the infected cells and other molecules that enter the infected cells and
activate enzymes that induce apoptotic death.
 ac tivated NK cells synthesize and secrete the cytokine, IFN-y. IFN-y
activates macrophages to become more &tive at killing phagocycod
microbes
 Sitokin  Cytokines are soluble proteins that mediate immune and intlammatory
reactions and are responsible for communications between leukocytes and
between leukocytes and other cells.
 cytokines involved in recruiting blood neuttophils and monocytes to
sites of infection
 aktivasi makrofag dan nk sel, merangsang inflamasi melalui perekrutan
neutrofil ke ekstravaskular
2. The majority of T lymphocytes remgnioe peptide antigens that am bound to
and displayed by the major h i s c o c omp t i c~o mplex (MHC) &ules of
ant+n-presenting cells (AF'Cs).
 CIass I and c b I1 MHC molecules are membrane proteins that each
contains a peptide-binding cleft at its aminwterminal end. Although the
subunit composition of class 1 and class I1 molecules is differ*ent, their
overall structure is very similar
 Class II MHC-assodatad presentation of extraselluler antigen
to helper T cell lewat cd4  t cell efector fuction  makrofag
activation yang mengarah pada penghancuran dan
fagositosis mikroba; selain itu juga merangsang sekresi
antibodi dari sel b untuk berikatan dengan mikroba
Class I MHC-assodatad presentation of cystolic antigen to cytolitik
t limfosit melalui cd8  merangsang kehancurn dari sel terinfeksi
yang mempresntasikan antigen
3. The events are common to B and T lymphocytes eventhougn B lymphocytes
maturn in the bone marrow and T lymphocytes mature in a specialized
organ called the thymus.
 Ptoliferarim of the earliest lymphocyte precmrs is stimulated mainly by
the growth factor, interleukin-7 (IL7), which is prcdud by stromal
cells in the bone mamw and the thymus
 The maturation of T lymphocytes in the thymus
4. Dendritic cells: initiation of T cell responses
  Dendritic cells capture protein antigens of microbes that enter through the
epithelia and transport the antigens to regional lymph nodes. Here the antigen-
bearing dendrit ic cells display portions of the antigens for recognition by T
lymphocytes
 Immature dendrihic cells in the epithetlium (skin, in the example sham.
where the dendritic cells are called Langerhans cells) capture microbial antigens
and leave the epithelium. The dendritic cells migrate to draining lymph nodes,
being attraCted there by chmkines produced in the mdes. During their
migration, and probably in response to the microk, the dendritic cells mature;
and in the lymph nodes, ftm dendritic cells pmnt antigens to naive T lymph-.
Dendritic cdls at difkrent stages d their maturatian may express diirent
mmbrane proteins. I W r e dendritb cells express surface mptars that capture
microbial antigens, whereas nature dendritic cells expregs high levels of MHC
molecules and cmtirnulators. which function to stimulate T cells
5. Regulatory T cells. A population of T cells that regulate the activation or effmor functions
of other T cells and may be necessary to maintain tolerance to self antigens. Regulatory
T cells express CD4 and CD25
1. aa
TUGAS II : INNATE AND ADAPTIVE IMUNE RESPONS

1. Jelaskan perbedaan karakteristik respon imun alami (innate) dan respon imun yang didapat
(adaptif)
2. Sebutkan komponen dari imunitas alami dan imunitas adaptif
3. Sebutkan efektor dari sistem imun humoral dan seluler
4. Sebutkan fase dari respon imun
5. Bagaimana cara mikroba bisa menghindar dari sistem imun?

1. Jelaskan perbedaan karakteristik respon imun alami (innate) dan respon imun yang didapat
(adaptif)
 immunity. The mechanisms of innate immunity provide the initial defense against infections. Some
mechanisms (e.g., epithelial barriers) prevent infections, and other mechanisms (e.g., phagocytes,
natural killer [NK] cells, the complement system) eliminate microbes. Adaptive immune responses
develop later and are mediated by lymphocytes and their products. Antibodies block infections and
eliminate microbes, and T lymphocytes eradicate intracellular microbes. The kinetics of the innate
and adaptive immune responses are approximations and may vary in different infections.
 Adaptive immunity, also called specific immunity or acquired immunity, requires expansion and
differentiation of lymphocytes in response to microbes before it can provide effective defense; that
is, it adapts to the presence of microbial invaders. Innate immunity is phylogenetically older, and the
more specialized and powerful adaptive immune system evolved later.
 Innate immunity, also called natural immunity or native immunity, is always present in healthy
individuals (hence the term innate), prepared to block the entry of microbes and rapidly eliminate
microbes that do succeed in entering host tissues
 The first line of defense in innate immunity is provided by epithelial barriers and by cells and natural
antibiotics present in epithelia, all of which function to block the entry of microbes. If microbes do
breach epithelia and enter the tissues or circulation, they are attacked by phagocytes, specialized
lymphocytes called natural killer cells, and several plasma proteins, including the proteins of the
complement system. All these mechanisms of innate immunity specifically recognize and react
against microbes. In addition to providing early defense against infections, innate immune
responses enhance adaptive immune responses against the infectious agents
 The adaptive immune system consists of lymphocytes and their products, such as antibodies.
Whereas the mechanisms of innate immunity recognize structures shared by classes of microbes,
the cells of adaptive immunity (lymphocytes) express receptors that specifically recognize a much
wider variety of molecules produced by microbes as well as noninfectious substances. These
substances are called antigens. Adaptive immune responses often use the cells and molecules of the
innate immune system to eliminate microbes, and adaptiveimmunity functions to greatly enhance
these antimicrobial mechanisms of innate immunity.For example, antibodies (a component of
adaptive immunity) bind to microbes, and these coated microbes avidly bind to and activate
phagocytes (a component of innate immunity), which ingest and destroy the microbes.

2. Sebutkan komponen dari imunitas alami dan imunitas adaptif

o Komponen imunitas alami:
o Epithelial Barriers: The common portals of entry of microbes—the skin, gastrointestinal tract,
and respiratory tract—are protected by continuous epithelia that provide physical and
chemical barriers against infection
o Phagocytes: Neutrophils and Monocytes/Macrophages: The two types of circulating
phago� cytes, neutrophils and monocytes, are blood cells that are recruited to sites of
infection, where they recognize and ingest microbes for intracellular killing.
 o Dendritic Cells: Dendritic cells respond to microbes by producing numerous cytokines that
serve two main functions: they initiate inflammation and they stimulate adaptive immune
responses
o Mast Cells: Mast cells are bone marrow–derived cells with abundant cytoplasmic granules
that are present in the skin and mucosal epithelium
o Natural Killer Cells: Natural killer (NK) cells are a class of lymphocytes that recognize infected
and stressed cells and respond by killing these cells and by secreting the
macrophageactivating cytokine IFN-γ
o Complement System: The complement system is a collection of circulating and membrane-
associated proteins that are important in defense against microbes. Many complement
proteins are proteolytic enzymes, and complement activation involves the se� quential
activation of these enzymes, sometimes called an enzymatic cascade.
o Other Plasma Proteins of Innate Immunity: Several circulating proteins in addition to
complement proteins are involved in defense against infections. Plasma MBL recognizes
microbial carbohydrates and can coat microbes for phagocytosis or activate the complement
cascade by the lectin pathway, as discussed earlier. Surfactant proteins in the lung also
belong to the collectin family and protect the airways from infection. C-reactive protein (CRP)
is a pentraxin (five-headed molecule) that binds to phosphorylcholine on microbes and
opsonizes the microbes for phagocytosis by macrophages, which express a receptor for CRP
o Cytokines of Innate Immunity: In response to microbes, dendritic cells, macrophages, and
other cells secrete cytokines that mediate many of the cellular reactions of innate immunity
o Komponen imunitas adaptif:
o T lymphocytes in cell-mediated immunity (CMI), which provides defense against infections by
intracellular microbes. Two types of infections may lead to microbes finding a haven inside
cells, from where they must be eliminated by cell-mediated immune responses (Fig. 5–1).
o Humoral immunity is mediated by antibodies and is the arm of the adaptive immune
response that functions to neutralize and eliminate extracellular microbes and microbial
toxins. Humoral immunity is also the principal defense mechanism against microbes with
capsules rich in polysaccharides and lipids. This is because B cells respond to, and produce
antibodies specific for, many types of extracellular and cell surface molecules, including
polysaccharides, lipids, and proteins, but T cells, the mediators of cellular immunity,
recognize and respond only to protein antigens that are internalized into or synthesized in
cells.

3. Sebutkan efektor dari sistem imun humoral dan seluler

 Efektor sistem imun seluler:

o Two types of cell-mediated immune reactions are designed to eliminate different types of
microbes. CD4+ helper T cells secrete cytokines that recruit and activate other leukocytes
to phagocytose (ingest) and destroy microbes. CD8+ cytotoxic T lymphocytes (CTLs) kill any
infected cell containing microbial proteins in the cytosol or nucleus, eliminating cellular
reservoirs of infection
o EFFECTOR FUNCTIONS OF CD4+ HELPER T LYMPHOCYTES: CD4+ T lymphocytes of the TH1
subset enhance the ability of phagocytes to kill microbes, TH17 cells promote the
recruitment of leukocytes to the site of infection, and TH2 cells activate eosinophils to kill
helminthic parasites
o EFFECTOR FUNCTIONS OF CD8+ CYTOTOXIC T LYMPHOCYTES: CD8+ cytotoxic T lymphocytes
recognize class I MHC–associated peptides on infected cells and kill those cells, thereby
eliminating the reservoir of infection
 Efektor sistem imun humoral:
o NEUTRALIZATION OF MICROBES AND MICROBIAL TOXINS: Antibodies bind to and block, or
neutralize, the infectivity of microbes and the interactions of microbial toxins with host
cells
o OPSONIZATION AND PHAGOCYTOSIS: Antibodies coat microbes and promote their
ingestion by phagocytes (Fig. 8–4). The process of coating particles for subsequent
 phagocytosis is called opsonization, and the molecules that coat microbes and enhance
their phagocytosis are called opsonins.
o ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY: Natural killer (NK) cells and other
leukocytes may bind to antibody-coated cells and destroy these cells
o IMMUNOGLOBULIN E– AND EOSINOPHIL/ MAST CELL–MEDIATED REACTIONS:
Immunoglobulin E antibodies activate mast cell and eosinophil–mediated reactions that
provide defense against helminthic parasites and are involved in allergic diseases.
o complement refers to the ability of these proteins to assist, or complement, the
antimicrobial activity of antibodies.
o Mucosal Immunity: Immunoglobulin A is produced in mucosal lymphoid tissues,
transported across epithelia, and binds to and neutralizes microbes in the lumens of the
mucosal organs
o Neonatal Immunity: Maternal antibodies are actively transported across the placenta to the
fetus and across the gut epithelium of neonates, protecting the newborn from infections

4. Sebutkan fase dari respon imun

 Early Innate Immune Response to Microbes: The principal barriers between the host and the
environment are the epithelia of the skin and the gastrointestinal and respiratory tracts.
Infectious microbes usually enter through these routes and attempt to colonize the host. The
two major cellular reactions of innate immunity are inflammation, which is induced by cytokines
and other molecules and serves to bring leukocytes and plasma proteins to the site of infection
or injury, and antiviral defense, which is mediated by type I interferons (a particular family of
cytokines) and NK cells
 Phases of adaptive immune response. An adaptive immune response consists of distinct phases;
the first three are recognition of antigen, activation of lymphocytes, and elimination of antigen
(effector phase). The response declines as antigen-stimulated lymphocytes die by apoptosis,
restoring the baseline steady state called homeostasis, and the antigen-specific cells that survive
are responsible for memory. The duration of each phase may vary in different immune
responses. These principles apply to both humoral immunity (mediated by B lymphocytes) and
cell-mediated immunity (mediated by T lymphocytes)
5. Bagaimana cara mikroba bisa menghindar dari sistem imun?
 MICROBIAL EVASION OF INNATE IMMUNITY: Pathogenic microbes have evolved to resist the
mechanisms of innate immunity and are thus cells, where it is no longer susceptible to ROS or
NO (which are produced mainly in phagolysosomes). The cell walls of mycobacteria contain a
lipid that inhibits fusion of vesicles containing ingested bacteria with lysosomes. Other microbes
have cell walls that are resistant to the actions of complement proteins. As discussed in Chapters
6 and 8, these mechanisms also enable microbes to resist the effector mechanisms of cell-
mediated and humoral immunity, the two arms of adaptive immunity
 Many pathogenic microbes have evolved mechanisms to resist cell-mediated immunity. These
mechanisms include inhibiting phagolysosome fusion, escaping from the vesicles of phagocytes,
inhibiting the assembly of class I MHC–peptide complexes, and producing inhibitory cytokines or
decoy cytokine receptors.
 EVASION OF HUMORAL IMMUNITY BY MICROBES: Microbes have evolved numerous
mechanisms to evade humoral immunity (Fig. 8–12). Many bacteria and viruses mutate their
antigenic surface molecules so that they can no longer be recognized by antibodies produced in
response to previous infections. Antigenic variation typically is seen in viruses, such as influenza
virus, human immunodeficiency virus (HIV), and rhinovirus.
TUGAS III: THE MHC

1. Apa yang dimaksud dengan molekul MHC? Ada berapa macam molekul MHC ?
2. Apa kepentingan dari molekul MHC dalam sistem imun?
3. Apa perbedaan antigen yang diikat oleh MHC klas I dan klas II?
4. Sel-sel apa saja yang mengekspresikan molekul MHC?
5. Bagaimana peran molekul MHC dalam seleksi klonal ?

1. Apa yang dimaksud dengan molekul MHC? Ada berapa macam molekul MHC ?
 MHC molecules are membrane proteins on APCs that display peptide antigens for recognition by
T lymphocytes. We now know that the physiologic role of MHC molecules is to display peptides
derived from microbial protein antigens to antigen-specific T lymphocytes as a first step in
protective T cell–mediated immune responses to microbes.
 class I MHC molecule consists of an α chain nonÂ� covalently associated with a protein called
β2-microglobulin that is encoded by a gene outside the MHC.
o Therefore, CD8+ T cells can only respond to peptides displayed by class I MHC
molecules, the MHC molecules to which the CD8 coreceptor binds.
 class II MHC molecule consists of two chains, called α and β. The amino-terminal regions of both
chains, called the α1 and β1 domains, contain polymorphic residues and form a cleft that is large
enough to accommodate peptides of 10 to 30 residues.
o CD4+ T cells can only respond to peptides presented by class II MHC molecules.
 Class I molecules are expressed on all nucleated cells, but class II molecules are expressed mainly
on dendritic cells, macrophages, and B lymphocytes.

2. Apa kepentingan dari molekul MHC dalam sistem imun?

 MHC genes are codominantly expressed, meaning that the alleles inherited from both parents
are expressed equally.
 The function of MHC molecules is to bind peptide fragments derived from pathogens and display
them on the cell surface for recognition by the appropriate T cells.
 Each T cell responds to a single peptide bound to an MHC molecule
 MHC molecules bind only peptides and not other types of antigens
 MHC molecules acquire their peptide cargo during their biosynthesis, assembly, and transport
inside cells
 Only peptide-loaded MHC molecules are stably expressed on cell surfaces
 In each individual, the MHC molecules can display peptides derived from the individual’s own
proteins, as well as peptides from foreign (i.e., microbial) proteins

3. Apa perbedaan antigen yang diikat oleh MHC klas I dan klas II?
 Extracellular proteins that are internalized by specialized APCs (dendritic cells,
macrophages, B cells) are processed in endocytic vesicles and displayed by class II MHC
molecules, whereas proteins in the cytosol of any nucleated cell are processed by
cytoplasmic organelles and displayed by class I MHC molecules.
 Source of protein antigens:
 o Class II MHC  Endosomal/lysosomal proteins (mostly internalized from
extracellular environment.
o Class I MHC  Cytosolic proteins (mostly synthesized in the cell; may enter
cytosol from phagosomes
4. Sel-sel apa saja yang mengekspresikan molekul MHC?
 MHC clas II Dendritic cells, mononuclear phagocytes, B lymphocytes; endothelial cells, thymic
epithelium
 MHC Clas I  All nucleated cells

5. Bagaimana peran molekul MHC dalam seleksi klonal ?

 Prelymphocytes and immature lymphocytes that fail to express antigen receptors die by
apoptosis (see Fig. 4–9). Immature T cells are also selected to recognize self MHC molecules in
the thymus. This process, called positive selection, ensures the cells that complete maturation
will be capable of recognizing antigens displayed by the same MHC molecules on APCs (which
are the only MHC molecules these cells can normally encounter). Strongly self-reactive B or T
cells are eliminated to prevent the development of autoimmune responses; this process is called
negative selection.
 Klo kurang cek hal 102
TUGAS IV : ANTIGEN CAPTURE AND PRESENTATION TO LYMPHOCYTE

1. Apa perbedaan tipe antigen yang dikenali oleh antibodI dan TCR?
2. Apa yang dimaksud dengan trimolekuler kompleks?
3. Molekul asesori (costimulator) apa saja yang diperlukan untuk aktivasi limfosit T
4. Organ apa yang terlibat dalam maturasi limfosit T dan limfosit B?
5. Apa yang dimaksud dengan fenomena seleksi positif dan seleksi negatif dalam proses
maturasi limfosit ?
6. Apa kepentingan dari fenomena tersebut?

1. Apa perbedaan tipe antigen yang dikenali oleh antibodI dan TCR?
 The T cell receptor (TCR) recognizes some residues of peptide antigen and
simultaneously also recognizes residues of the MHC molecule that is displaying that
peptide.
 The plasma membrane antibodies that function as antigen receptors of B lymphocytes
can recognize a much broader range of chemical structures than the antigen receptors
of T cells
 Membranebound antibodies on B cells recognize antigens to initiate the responses, and
secreted antibodies neutralize and eliminate microbes and their toxins in the effector
phase of humoral immunity. In cell-mediated immunity, the effector function of
microbe elimination is performed by T lymphocytes themselves and by other leukocytes
responding to the T cells. The antigen receptors of T cells are involved only in antigen
recognition and T cell activation, and these proteins are not secreted and do not
mediate effector functions
 Antibodies can bind many different types of chemical structures, often with high
affinities, which is why antibodies can bind to and neutralize many different microbes
and toxins that may be present at low concentrations in the circulation. TCRs only
recognize peptide- MHC complexes and bind these with relatively low affinity, which
may be why the binding of T cells to APCs has to be strengthened by additional cell
surface adhesion molecules

2. Apa yang dimaksud dengan trimolekuler kompleks?

 Trimolekuler kompleks adalah ikatan yang terjadi antara 3 molekul yang merangsang
suatu signaling untuk mengaktivasi sel T sebagai respon imun. Ketiga molekul ini adalah
T-Cell Receptor, antigen, dan MHC yang mempresentasikan antigen.
 When antigen molecules bind to antigen receptors of lymphocytes, the associated
signaling proteins of the receptor complexes are brought into proximity. As a result,
enzymes attached to the cytoplasmic portions of the signaling proteins catalyze the
phosphorylation of other proteins. Phosphorylation triggers complex signaling cascades
that culminate in the transcriptional activation of many genes and the production of
numerous proteins that mediate the responses of the lymphocytes
  Dalam merangsang aktivasi sel limfosit T, tidak hanya dibutuhkan trimolekuler kompleks
saja, namun juga dibutuhkan signal kedua dari ikatan costimulator juga. Saat salah satu
ikatan costimulator tidak terjadi, maka sel T tidak dapat teraktivasi.

3. Molekul asesori (costimulator) apa saja yang diperlukan untuk aktivasi limfosit T
 The best-defined costimulators for T cells are two related proteins called B7-1 (CD80) and B7-2
(CD86), both of which are expressed on APCs and whose expression is increased when the APCs
encounter microbes. These B7 proteins are recognized by a receptor called CD28, which is
expressed on virtually all T cells. The binding of CD28 on T cells to B7 on the APCs generates
signals in the T cells that work together with signals generated by TCR recognition of antigen
presented by MHC proteins on the same APCs. CD28-mediated signaling is essential for the
responses of naive T cells; in the absence of CD28-B7 interactions, antigen recognition by the
TCR is insufficient for T cell activation. The requirement for costimulation ensures that naïve T
lymphocytes are activated fully by microbial antigens, and not by harmless foreign substances
(or by self antigens), because, as stated previously, microbes stimulate the expression of B7
costimulators on APCs.
 Another set of molecules that participate in T cell responses are CD40 ligand (CD40L, or CD154)
on activated T cells and CD40 on APCs. These molecules do not directly enhance T cell activation.
Instead, CD40L expressed on an antigen-stimulated T cell binds to CD40 on APCs and activates
the APCs to express more B7 costim� ulators and to secrete cytokines (e.g., IL-12) that
enhance T cell differentiation. Thus, the CD40L-CD40 interaction promotes T cell activation by
making APCs better at stimulating T cells.

4. Organ apa yang terlibat dalam maturasi limfosit T dan limfosit B?

 The maturation of B lymphocytes occurs mainly in the bone marrow
 The IgM-expressing B lymphocyte is the immature B cell. Its further maturation may occur in the
bone marrow or after it leaves the bone marrow and enters the spleen
 T cell progenitors migrate from the bone marrow to the thymus, where the entire process of
maturation occurs
 Sel T imatur mengalami semua pembelajaran dan seleksidi timus.


5. Apa yang dimaksud dengan fenomena seleksi positif dan seleksi negatif dalam proses
maturasi limfosit ?
 Different clones of double-positive T cells express different αβ TCRs. If the TCR of a T cell
recognizes an MHC molecule in the thymus, which must be a self MHC molecule displaying a self
peptide, and if the interaction is of low or moderate affinity, this T cell is selected to survive. T
cells that do not recognize an MHC molecule in the thymus die by apoptosis; these T cells would
not be useful because they would be incapable of seeing MHC-displayed cellassociated antigens
in that individual. This preservation of self MHC–restricted (i.e., useful) T cells is the process of
positive selection.
 During this process, T cells whose TCRs recognize class I MHC–peptide complexes preserve the
expression of CD8, the coreceptor that binds to class I MHC, and lose expression of CD4, the
coreceptor specific for class II MHC molecules. Conversely, if a T cell recognizes class II MHC–
peptide complexes, this cell maintains expression of CD4 and loses expression of CD8. Thus, what
emerges are single-positive T cells (or singlepositive thymocytes), which are either CD8+ class I
MHC restricted or CD4+ class II MHC restricted.
 Immature, double-positive T cells whose receptors strongly recognize MHC-peptide complexes in
the thymus undergo apoptosis. This is the process of negative selection, and it serves to eliminate
T lymphocytes that could react in a harmful way against self proteins that are expressed in the
thymus
 6. Apa kepentingan dari fenomena tersebut?
 if the antigen receptor of a T cell recognizes a self MHC–self peptide complex with low avidity,
the result is positive selection, whereas high-avidity recognition leads to negative selection. High-
avidity recognition occurs if the T cell expresses a TCR that has a high affinity for that self peptide,
and if the self peptide is present in the thymus at a higher concentration than positively selecting
peptides. If such a T cell were allowed to mature, antigen recognition could lead to harmful
immune responses against the self antigen, so the T cell must be eliminated

TUGAS V : CYTOKINE

1. Apa yang dimaksud dengan sitokin? Jelaskan nomenklaturnya

2. Jelaskan perbedaan sitokin innate dan adaptif
3. Apa yang anda ketahui tentang reseptor sitokin?
4. Apa yang dimaksud dengan Tumor Nekrosis Faktor, diproduksi oleh sel apa dan jelaskan
biologic action nya
5. Apa yang dimaksud dengan interferon, diproduksi oleh sel apa dan apa fungsinya?
6. Jelaskan tentang Septic Shock Syndrome dan sitokin apa yang terlibat ?

1. Apa yang dimaksud dengan sitokin? Jelaskan nomenklaturnya

 In response to microbes, dendritic cells, macrophages, and other cells secrete cytokines
that mediate many of the cellular reactions of innate immunity (Fig. 2–14). As
mentioned earlier, cytokines are soluble proteins that mediate immune and
inflammatory reactions and are responsible for communications between leukocytes
and between leukocytes and other cells. Most of the molecularly defined cytokines are
called interleukins, by convention, implying that these molecules are produced by
leukocytes and act on leukocytes. (In reality, this is too limited a definition, because
many cytokines are produced by or act on cells other than leukocytes, and many
cytokines that do mediate communications between leukocytes are given other names
for historical reasons

2. Jelaskan perbedaan sitokin innate dan adaptif

 In innate immunity, the principal sources of cytokines are dendritic cells and
macrophages activated by recognition of microbes, although epithelial cells and other
cell types may also secrete cytokines. Recognition of bacterial components such as LPS
or of viral molecules such as dsRNA by TLRs and other microbial sensors is powerful
stimuli for cytokine secretion by dendritic cells and macrophages. In adaptive immunity,
a major source of cytokines is helper T lymphocytes
 The cytokines of innate immunity serve various functions in host defense. Tumor
necrosis factor (TNF), interleukin-1 (IL-1), and chemokines (chemoattractant cytokines)
 are the principal cytokines in innate immunity. Sedangkan IL-2, IL-4, IL-5, IFN-gamma, IL-
17 dan TGF Beta adalah sitokin yang berperan dalam adaptive immunity

3. Apa yang anda ketahui tentang reseptor sitokin?

 Reseptor sitokin adalah reseptor yang terdapat dalam sel-sel imun yang akan
menangkap sitokin sebagai bagian dari signaling dalam respon imun. Kebanyakan
pathway yang dijalani oleh reseptor sitokin dalam menjalankan signaling adalah dengan
jak-stat pathway.
 Dalam aktivasi sel T, Activation also rapidly enhances the ability of T cells to bind and
respond to IL-2, by increasing the expression of , the high-affinity IL-2 receptor, which is
a three-chain molecule.
 Naive T cells express two signaling chains but do not express the chain that enables the
receptor to bind IL-2 with high affinity. Within hours after activation by antigens and
costimulators, the T cells produce the third chain of the receptor, and now the complete
IL-2 receptor is able to bind IL-2 strongly. Thus, IL-2 produced by antigenstimulated T
cells preferentially binds to and acts

4. Apa yang dimaksud dengan Tumor Nekrosis Faktor, diproduksi oleh sel apa dan jelaskan
biologic action nya
 Tumor necrosis factor (TNF), interleukin-1 (IL-1), and chemokines (chemoattractant
cytokines) are the principal cytokines involved in recruiting blood neutrophils and
monocytes to sites of infection (described later). TNF and IL-1 also have systemic affects,
including inducing fever by acting on the hypothalmus
 At high concentrations, TNF promotes thrombus formation on the endoÂ� thelium and
reduces blood pressure by a combination of reduced myocardial contractility and
vascular dilation and leakiness. Severe, disseminated bacterial infections sometimes lead
to a potentially lethal clinical syndrome called septic shock, which is characterized by
low blood pressure (the defining feature of shock), disseminated intravascular
coagulation, and metabolic disturbances. The early clinical and pathologic
manifestations of septic shock are caused by high levels of TNF, which is produced in
response to the bacteria

5. Apa yang dimaksud dengan interferon, diproduksi oleh sel apa dan apa fungsinya?
 IFN-γ, whose function as a macrophage-activating cytokine was also described earlier. Because
IFN-γ is produced by T cells as well, it is considered a cytokine of both innate immunity and
adaptive immunity. In viral infections, a subset of dendritic cells, and, to a lesser extent, other
infected cells, produce type I IFNs, which inhibit viral replication and prevent spread of the
infection to uninfected cells.
 Type I interferons induce resistance to viral infection and replication, called an antiviral state.
Type I IFNs, which include several forms of IFN-α and one IFN-β, are secreted by many cell types
infected by viruses. A major source of these cytokines is a type of dendritic cell called the
plasmacytoid dendritic cell (see Chapter 3). When type I IFNs secreted from dendritic cells or
other infected cells bind to the IFN receptor on adjacent uninfected cells, signaling pathways are
activated that inhibit viral replication and destroy viral genomes (Fig. 2–18). This action is the
basis for the use of IFN-α to treat some forms of chronic viral hepatitis.
  Virus-infected cells may be destroyed by NK cells, as described earlier. Type I IFNs enhance the
ability of NK cells to kill infected cells. In addition, part of the innate response to viral infections
includes enhanced apoptosis of infected cells. Death of the infected cells eliminates the reservoir
of infection.

6. Jelaskan tentang Septic Shock Syndrome dan sitokin apa yang terlibat ?
 Septic shock╇ Severe complication of bacterial infections that spread to the
bloodstream (sepsis), and is characterized by vascular collapse, disseminated
intravascular coagulation, and metabolic disturbances. This syndrome is due to the
effects of bacterial cell wall components, such as LPS or peptidoglycan, which bind to
TLRs on various cell types and induce expression of inflammatory cytokines, including
TNF and IL-12.
 syndrome called septic shock, which is characterized by low blood pressure (the defining
feature of shock), disseminated intravascular coagulation, and metabolic disturbances.
The early clinical and pathologic manifestations of septic shock are caused by high levels
of TNF, which is produced in response to the bacteria

TUGAS VI : CELL MEDIATED IMMUNE RESPONSES

1. Sebutkan sel-sel yang terlibat dalam CMI

2. Bagaimana tanda-tanda dari makrofag yang teraktifasi pada CMI?
3. Apa fungsi limfosit T CD4 efektor?
4. Apa fungsi limfosit T CD8 efektor?
5. Bagaimana cara limfosit T efektor melisiskan sel target?
6. Jelaskan bagaimana mekanisme mikroba intraseluler dapat terhindar dari mekanisme
efektor imunitas seluler

1. Sebutkan sel-sel yang terlibat dalam CMI

 Two types of cell-mediated immune reactions are designed to eliminate different types
of microbes. CD4+ helper T cells secrete cytokines that recruit and activate other
leukocytes to phagocytose (ingest) and destroy microbes. CD8+ cytotoxic T lymphocytes
(CTLs) kill any infected cell containing microbial proteins in the cytosol or nucleus,
eliminating cellular reservoirs of infection

2. Bagaimana tanda-tanda dari makrofag yang teraktifasi pada CMI?

 Activation of macrophages by TH1 lymphocytes. Effector T lymphocytes of the TH1
subset recognize the antigens of ingested microbes on macrophages. In response to this
recognition, the T lymphocytes express CD40L, which engages CD40 on the
macrophages, and the T cells secrete interferon-γ (IFN-γ), which binds to IFN-γ receptors
on the macrophages. This combination of signals activates the macrophages to produce
microbicidal substances that kill the ingested microbes. Activated macrophages also
secrete cytokines that induce inflammation—tumor necrosis factor (TNF), interleukin-1
(IL-1), and chemokines—and activate T cells (IL-12), and they express more major
histocompatibility complex (MHC) molecules and costimulators, which enhance T cell
 responses. A, Illustration shows a CD4+ T cell recognizing class II MHC–associated
peptides and activating the macrophage. B, The table summarizes macrophage
responses and their roles in cell-mediated immunity
 Production of reactive oxygen species, nitric oxide, increased lysosomal enzymes 
Killing of microbes in phagolysosomes (effector function of macrophages)
 Secretion of cytokines (TNF, IL-1, IL-12) and chemokines  TNF, IL-1, chemokines:
leukocyte recruitment (inflammation
 Increased expression of MHC molecules and costimulators  Increased T cell activation
(amplification of T cell response)
 activated macrophages produce IL-12, and this cytokine drives the differentiation of
naïve CD4+ T cells to TH1 cells, thus amplifying the response.

3. Apa fungsi limfosit T CD4 efektor?

 CD4+ T lymphocytes of the TH1 subset enhance the ability of phagocytes to kill
microbes, TH17 cells promote the recruitment of leukocytes to the site of infection, and
TH2 cells activate eosinophils to kill helminthic parasites.
 The major function of TH1 cells is the activation of macrophages, which is critical for
efficient elimination of ingested microbes
 Effector T lymphocytes of the TH1 subset that recognize macrophage-associated
antigens activate the macrophages by CD40 ligand–CD40 interactions and by secreting
the cytokine interferon-γ (IFN-γ)


4. Apa fungsi limfosit T CD8 efektor?

 CD8+ cytotoxic T lymphocytes recognize class I MHC–associated peptides on infected
cells and kill those cells, thereby eliminating the reservoir of infection
 CTLs kill target cells mainly as a result of delivery of granule proteins into the target cells.
Two types of granule proteins critical for killing are granzymes (granule enzymes) and
perforin.
 Activated CTLs also express a membrane protein called Fas ligand, which binds to a
deathinducing receptor, called Fas (CD95), on target cells. Engagement of Fas activates
caspases and induces target cell apoptosis; this pathway does not require granule
exocytosis and probably plays only a minor role in killing by CD8+ CTLs

5. Bagaimana cara limfosit T efektor melisiskan sel target?

 CTLs kill target cells mainly as a result of delivery of granule proteins into the target cells.
Two types of granule proteins critical for killing are granzymes (granule enzymes) and
perforin. Granzyme B cleaves and thereby activates enzymes called caspases (cysteine
proteases that cleave proteins after aspartic acid residues) that are present in the
cytosol of target cells and whose major function is to induce apoptosis. Perforin disrupts
the integrity of the target cell plasma membrane and endosomal membranes, thereby
facilitating the delivery of granzymes into the cytosol and the initiation of apoptosis.
 6. Jelaskan bagaimana mekanisme mikroba intraseluler dapat terhindar dari mekanisme
efektor imunitas seluler

TUGAS VII : HUMORAL IMMUNE RESPONSES

1. Sebutkan perangkat dari Imunitas Humoral

2. Sebutkan klas antibodi dan apa fungsi khusus dari masing masing antibodi tersebut
3. Bagaimana cara efektor imunitas humoral (antibody) mengeliminasi antigen
4. Jelaskan bagaimana mekanisme mikroba ekstraselluler dapat menghindar dari mekanisme
efektor humoral?

1. Sebutkan perangkat dari Imunitas Humoral

 Naive B lymphocytes express two classes of membrane-bound antibodies,
immunoglobulins M and D (IgM and IgD), that function as receptors for antigens. These
naive B cells are activated by antigens binding to membrane Ig and by other signals
discussed later in the chapter
 plasma cells, which actively secrete antibodies and are thus the effector cells of humoral
immunity
 Antibody╇ Type of glycoprotein molecule, also called immunoglobulin (Ig), produced
by B lymphocytes that binds antigens, often with a high degree of specificity and affinity.
The basic structural unit of an antibody is composed of two identical heavy chains and
two identical light chains
 B lymphocyte╇ The only cell type capable of producing antibody molecules and
therefore the mediator of humoral immune responses. B lymphocytes, or B cells,
develop in the bone marrow, and mature B cells are found mainly in lymphoid follicles in
secondary lymphoid tissues, in bone marrow, and in low numbers in the circulation.
 Mature B cell╇ IgM- and IgD-expressing, functionally competent naive B cells that
represent the final stage of B cell maturation in the bone marrow and that populate
peripheral lymphoid organs.


2. Sebutkan klas antibodi dan apa fungsi khusus dari masing masing antibodi tersebut
3. Bagaimana cara efektor imunitas humoral (antibody) mengeliminasi antigen
 Antibodies bind to and block, or neutralize, the infectivity of microbes and the
interactions of microbial toxins with host cells (Fig. 8–3). Most microbes use
molecules in their envelopes or cell walls to bind to and gain entry into host cells.
Antibodies may attach to these microbial surface molecules, thereby preventing the
microbes from infecting the host. Antibodies can neutralize the microbes during
their transit from cell to cell and thus limit the spread of infection.
 Antibodies coat microbes and promote their ingestion by phagocytes (Fig. 8–4). The
process of coating particles for subsequent phagocytosis is called opsonization, and
the molecules that coat microbes and enhance their phagocytosis are called
opsonins. When several antibody molecules bind to a microbe, an array of Fc regions
is formed projecting away from the microbial surface. which can expressed on
 neutrophils and macrophages. The phagocyte extends its plasma membrane around
the attached microbe and ingests the microbe into a vesicle.
 ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY: Natural killer (NK) cells and other
leukocytes may bind to antibody-coated cells and destroy these cells (Fig. 8–5). NK
cells express an Fcγ receptor called FcγRIII (CD16), which is one of several kinds of
NK cell– activating receptors (see Chapter 2). FcγRIII binds to arrays of IgG antibodies
attached to the surface of a cell, generating signals that cause the NK cell to
discharge its granule proteins, which kill the opsonized cell. Cells infected with
enveloped viruses typically express viral glycoproteins on their surface that can be
recognized by specific antibodies and this may facilitate ADCCmediated destruction
of the infected cells.
 IMMUNOGLOBULIN E– AND EOSINOPHIL/ MAST CELL–MEDIATED REACTIONS
Immunoglobulin E antibodies activate mast cell and eosinophil–mediated reactions
that provide defense against helminthic parasites and are involved in allergic
diseases. The humoral immune response to helminths is dominated by IgE
antibodies. The IgE antibody binds to the worms and promotes the attachment of
eosinophils through the high-affinity Fc receptor for IgE, FcεRI, expressed on
eosinophils and mast cells. Engagement of FcεRI, together with the cytokine
interleukin-5 (IL-5) produced by TH2 helper T cells reacting against the helminths,
leads to activation of the eosinophils, which release their granule contents, including
proteins that can kill the worms (Fig. 8–6). IgE antibodies may also bind to and
activate mast cells, which secrete cytokines, including chemokines, that attract more
leukocytes that function to destroy the helminthes.
 The late steps of complement activation are initiated by the binding of C5 to the C5
convertase and subsequent proteolysis of C5, generating C5b (Fig. 8–8). The
remaining components, C6, C7, C8, and C9, bind sequentially to a complex nucleated
by C5b. The final protein in the pathway, C9, polymerizes to form a pore in the cell
membrane through which water and ions can enter, causing death of the microbe.
This poly-C9 is the key component of the membrane attack complex (MAC), and its
formation is the end result of complement activation.
 Mucosal Immunity: Immunoglobulin A is produced in mucosal lymphoid tissues,
transported across epithelia, and binds to and neutralizes microbes in the lumens of
the mucosal organs (Fig. 8–11). Microbes often are inhaled or ingested, and
antibodies that are secreted into the lumens of the respiratory or gastrointestinal
tract bind to these microbes and prevent them from colonizing the host.
 Neonatal Immunity : Maternal antibodies are actively transported across the
placenta to the fetus and across the gut epithelium of neonates, protecting the
newborn from infections. During pregnancy, some classes of maternal IgG bind to
FcRn expressed in the placenta, and the IgG is actively transported into the fetal
circulation. After birth, neonates ingest maternal antibodies in their mothers’
colostrum and milk. Ingested IgA antibodies provide mucosal immune protection to
the neonate. The neonate’s intestinal epithelial cells also express FcRn, which binds
ingested IgG antibody and carries it across the epithelium. Thus, neonates acquire
the IgG antibody profiles of their mothers and are protected from infectious
microbes to which the mothers were exposed or vaccinated.
 4. Jelaskan bagaimana mekanisme mikroba ekstraselluler dapat menghindar dari mekanisme
efektor humoral?
 Microbes have evolved numerous mechanisms to evade humoral immunity (Fig. 8–
12). Many bacteria and viruses mutate their antigenic surface molecules so that they
can no longer be recognized by antibodies produced in response to previous
infections. Antigenic variation typically is seen in viruses, such as influenza virus,
human immunodeficiency virus (HIV), and rhinovirus. There are so many variants of
the major antigenic surface glycoprotein of HIV, called gp120, that antibodies
against one HIV isolate may not protect against other HIV isolates. This is one reason
why gp120 vaccines are not effective in protecting people from HIV infection.
Bacteria such as Escherichia coli vary the antigens contained in their pili and thus
evade antibodymediated defense. The trypanosome parasite, which causes sleeping
sickness, expresses new surface glycoproteins whenever it encounters antibodies
against the original glycoprotein. As a result, infection with this protozoan parasite is
characterized by waves of parasitemia, each wave consisting of an antigenically new
parasite that is not recognized by antibodies produced against the parasites in the
preceding wave. Other microbes inhibit complement activation or resist
phagocytosis

TUGAS VIII : THE COMPLEMENT SYSTEM

1. Apa yang dimaksud dengan komplemen? Apa fungsi komplemen?

2. Ada berapa jalur aktivasi komplemen ? sebutkan
3. Bagian (pecahan) komponen komplemen mana yang berfungsi sebagai
Khemotaxin ?
Opsonin ?
4. Bagaimana regulasi dari system komplemen ?

1. Apa yang dimaksud dengan komplemen? Apa fungsi komplemen?

 The complement system is a collection of circulating and membrane-associated proteins that are
important in defense against microbes. Many complement proteins are proteolytic enzymes,and
complement activation involves the se� quential activation of these enzymes, sometimes called
an enzymatic cascade.
 The term complement refers to the ability of these proteins to assist, or complement,
the antimicrobial activity of antibodies. The complement system may be activated by
microbes in the absence of antibody, as part of the innate immune response to
infection, and by antibodies attached to microbes, as part of adaptive immunity
 The complement system serves three functions in host defense. First, C3b coats
microbes and promotes the binding of these microbes to phagocytes, by virtue of
receptors for C3b that are expressed on the phagocytes. Thus, microbes that are coated
with complement proteins are rapidly ingested and destroyed by phagocytes. This
process of coating a microbe with molecules that are recognized by receptors on
phagocytes is called opsonization. Second, some proteolytic fragments of complement
proteins, especially C5a and C3a, are chemoattractants for leukocytes (mainly
 neutrophils and monocytes), so they promote leukocyte recruitment (inflammation) at
the site of complement activation. Third, complement activation culminates in the
formation of a polymeric protein complex that inserts into the microbial cell membrane,
disturbing the permeability barrier and causing either osmotic lysis or apoptosis of the
microbe. A more detailed discussion of the activation and functions of complement is
presented in Chapter 8, where we consider the effector mechanisms of humoral
immunity.

2. Ada berapa jalur aktivasi komplemen ? sebutkan

 The complement cascade may be activated by any of three pathways (Fig. 2–13). The
alternative pathway is triggered when some complement proteins are activated on
microbial surfaces and cannot be controlled, because complement regulatory proteins
are not present on microbes (but are present on host cells). The alternative pathway is a
component of innate immunity. The classical pathway is most often triggered after
antibodies bind to microbes or other antigens and is thus a component of the humoral
arm of adaptive immunity.
 The lectin pathway is activated when a carbohydrate-binding plasma protein,
mannosebinding lectin (MBL), binds to terminal mannose residues on the surface
glycoproteins of microbes This lectin activates proteins of the classical pathway, but
because it is initiated by a microbial product in the absence of antibody, it is a
component of innate immunity. Activated complement proteins function as proteolytic
enzymes to cleave other complement proteins, in an enzymatic cascade that can be
rapidly amplified. The central component of complement is a plasma protein called C3,
which is cleaved by enzymes generated in the early steps. The major proteolytic
fragment of C3, called C3b, becomes covalently attached to microbes and is able to
activate downstream complement proteins on the microbial surface. The three
pathways of complement activation differ in how they are initiated, but they share the
late steps and perform the same effector functions.

3. Bagian (pecahan) komponen komplemen mana yang berfungsi sebagai

Khemotaxin ?
Opsonin ?

4. Bagaimana regulasi dari system komplemen ?

 Mammalian cells express regulatory proteins that inhibit complement activation, thus
preventing complement-mediated damage to host cells (Fig. 8–10). Many such
regulatory proteins have been described. Decayaccelerating factor (DAF) is a lipid-linked
cell surface protein that disrupts the binding of Bb to C3b and the binding of C4b to C2a,
 thus blocking C3 convertase formation and terminating complement activation by both
the alternative and the classical pathways
 Membrane cofactor protein (MCP) serves as a cofactor for the proteolysis of C3b into
inactive fragments, a process mediated by a plasma enzyme called factor I. CR1 may
displace C3b and promote its degradation. A regulatory protein called C1 inhibitor (C1
INH) stops complement activation early, at the stage of C1 activation. Additional
regulatory proteins limit complement activation at the late steps, such as MAC
formation.
 and readily enter the blood, from where they may go anywhere. Antibodies also serve
protective functions at two special anatomic sites, the mucosal organs and the fetus.
There are special mechanisms for transporting antibodies across epithelia and across
the placenta, and antibodies play vital roles in defense in these locations

TUGAS IX: IMMUNOLOGIC TOLERANCE

1. Apa yang dimaksud dengan toleransi imunologik?

2. Bagaimana mekanisme induksi toleransi sentral pada sel T dan sel B?
3. Bagaimana mekanisme terjadinya anergi pada sel T di perifer?
4. Apa penyebab hilangnya toleransi self dan apa akibatnya?

1. Apa yang dimaksud dengan toleransi imunologik?

 that it can react to an enormous variety of microbes but does not react against the
individual’s own (self) antigens. This unresponsiveness to self antigens, also called
immunological tolerance
 maintained despite the fact that the molecular mechanisms by which lymphocyte
receptor specificities are generated are not biased to exclude receptors
 Immunological tolerance is a lack of response to antigens that is induced by exposure of
lymphocytes to these antigens.
 Immunological tolerance to different self antigens may be induced when developing
lymphocytes encounter these antigens in the generative (central) lymphoid organs, a
process called central tolerance, or when mature lymphocytes encounter self antigens
in secondary lymphoid organs or peripheral tissues, called peripheral tolerance

2. Bagaimana mekanisme induksi toleransi sentral pada sel T dan sel B?

 Sel T:
 The principal mechanisms of central tolerance in T cells are cell death and the
generation of CD4+ regulatory T cells
 The lymphocytes that develop in the thymus consist of cells with receptors capable of
recognizing many antigens, both self and foreign. If an immature lymphocyte interacts
strongly with a self antigen, displayed as a peptide bound to a self major
histocompatibility complex (MHC) molecule, that lymphocyte receives signals that
 trigger apoptosis, and the cell dies before it can complete its maturation (negative
selection), is a major mechanism of central tolerance. The process of negative selection
affects self reactive CD4+ T cells and CD8+ T cells
 Immature lymphocytes may interact strongly with an antigen if the antigen is present at
high concentrations in the thymus, and if the lymphocytes express receptors that
recognize the antigen with high affinity. Antigens that induce negative selection may
include proteins that are abundant throughout the body, such as plasma proteins and
common cellular proteins.
 Some immature CD4+ T cells that recognize self antigens in the thymus with high
affinity do not die but develop into regulatory T cells and enter peripheral tissues
 Sel B:
 Self polysaccharides, lipids, and nucleic acids are T-independent antigens that are not
recognized by T cells. These antigens must induce tolerance in B lymphocytes to prevent
autoantibody production. Self proteins may fail to elicit autoantibody responses
because of tolerance in helper T cells and in B cells
 When immature B lymphocytes interact strongly with self antigens in the bone marrow,
antigens in the bone marrow may reexpress RAG genes, resume immunoglobulin (Ig)
lightchain gene recombination, and express a new Ig light chain (see Chapter 4). This
new light chain associates with the previously expressed Ig heavy chain to produce a
new antigen receptor that is no longer specific for the self antigen. This process of
changing receptor specificity, called receptor editing
 If editing fails, immature B cells that recognize self antigens with high avidity receive
death signals and die by apoptosis
 If antigens, such as soluble proteins, are recognized in the bone marrow with low
avidity, the B cells survive but antigen receptor expression is reduced, and the cells
become functionally unresponsive

3. Bagaimana mekanisme terjadinya anergi pada sel T di perifer?

 Anergy in T cells refers to long-lived functional inactivation that occurs when these cells
recognize antigens without adequate levels of the costimulators that are needed for full
T cell activation
 Anergic cells survive but are incapable of responding to the antigen. The two best-
defined mechanisms of cell-intrinsic unresponsiveness are a block in signaling by the
TCR complex and the delivery of inhibitory signals from receptors other than the TCR
complex
 When T cells recognize antigens without costimulation, the TCR complex may lose its
ability to transmit activating signals. In some cases, this is related to the activation of
enzymes (ubiquitin ligases) that modify signaling proteins and target them for
intracellular destruction by proteases
 On recognition of self antigens, T cells also may preferentially engage one of the
inhibitory receptors of the CD28 family, cytotoxic T lymphocyte–associated antigen 4
(CTLA-4, or CD152) or programmed death protein 1 (PD-1), both of which function to
terminate T cell activation (see Chapter 5). The net result is longlasting T cell anergy
  CTLA-4 works by blocking and removing B7 molecules from the surface of APCs, thus
further reducing costimulation and preventing the activation of T cells; CTLA-4 might
also deliver inhibitory signals to T cells. This is an interesting example of how the level of
available costimulation (in this case, B7 molecules) influences the balance of T cell
activation or tolerance. As discussed below, CTLA-4 also is used by regulatory T cells to
suppress immune responses.

4. Apa penyebab hilangnya toleransi self dan apa akibatnya?

 Aa
 Autoimmunity is defined as an immune response against self (autologous) antigens.
 The principal factors in the development of autoimmunity are the inheritance of
susceptibility genes and environmental triggers, such as infections
 that susceptibility genes interfere with pathways of self-tolerance and lead to the
persistence of self-reactive T and B lymphocytes. Environmental stimuli may cause cell
and tissue injury and inflammation, resulting in the entry and activation of these self-
reactive lymphocytes. The activated lymphocytes injure the tissues and cause the
disease.
 Inherited risk for most autoimmune diseases is attributable to multiple gene loci, of
which the largest contribution is made by MHC genes
 Many autoimmune diseases in humans and inbred animals are linked to particular MHC
alleles. Some hypotheses are that particular MHC alleles may contribute to the
development of autoimmunity because they are required to present pathogenic self
peptides to autoreactive T cells, or they are inefficient at displaying certain self
antigens in the thymus, leading to defective negative selection of T cells, or because
peptide antigens presented by these MHC alleles may fail to stimulate regulatory T cells.
 Infections may contribute to autoimmunity in several ways (Fig. 9–13). An infection of a
tissue may induce a local innate immune response, which may lead to increased
production of costimulators and cytokines by tissue APCs. These activated tissue APCs
may be able to stimulate self-reactive T cells that encounter self antigens in the tissue.
 Some infectious microbes may produce peptide antigens that are similar to, and cross-
react with, self antigens. Immune responses to these microbial peptides may result in
an immune attack against self antigens. Such cross-reactions between microbial and self
antigens are termed molecular mimicry
 Several other environmental and host factors may contribute to autoimmunity. Many
autoimmune diseases are more common in women than in men, but how gender might
affect immunological tolerance or lymphocyte activation remains unknown.

TUGAS X : REGULATION OF IMMUNE RESPONSES

1. Apa kepetingan regulasi dalam system imun?

2. Sebutkan ada berapa macam cara regulasi dari system imun
3. Bagaimana mekanisme apoptosis dari sel T?
4. Bagaimana mekanisme regulasi idiotipik?
5. Bagaimana mekanisme regulasi antibody feedback?
6. Apa yang dimaksud dengan sitokin regulator?

1. Apa kepetingan regulasi dalam system imun?



2. Sebutkan ada berapa macam cara regulasi dari system imun

3. Bagaimana mekanisme apoptosis dari sel T?
4. Bagaimana mekanisme regulasi idiotipik?
5. Bagaimana mekanisme regulasi antibody feedback?
6. Apa yang dimaksud dengan sitokin regulator?