Imunologi Infeksi Tropis

dr. Godeliva Maria Silvia M., MSc

FK UKDW Jogjakarta
2014

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Sejarah Imunologi Infeksi
Sejak 132 SM sudah menjadi pemikiran orang-orang untuk
memahami fenomena yang terjadi dalam tubuhnya
Sampai th 1700 an, percobaan para ahli mengarah pada
pembuatan vaksin
Pada 1845, Ellie Metchnikoff mencoba mengungkapkan
bagaimana mekanisme sel imun bekerja melawan benda asing,
dengan menusukkan sebatang duri bunga mawar ke dalam
larva bintang laut, dan tampaklah kerumunan sel di dekat duri
bunga. Metchnikoff berkesimpulan bahwa sel yang dapat
bergerak (mobile) itu terlibat dalam respon imun, dengan kata
lain, respon imun bersifat SELULER.
Hal serupa juga diamati oleh Koch dan Neiser
FAGOSITOSIS
Sejarah Imunologi Infeksi
Penelitian dilanjutkan Fodor, 1886 yang menentang teori
seluler karena ia mengamati pengaruh serum imun terhadap
mikroba tanpa campur tangan komponen seluler.
Behring dan Kitasato (1890) juga mengukuhkan pendapat
tersebut dengan percobaan yang menunjukkan bahwa serum
imun dapat menetralkan aktivitas tetanus dan difteri
Jules Bordet (1870-1961) ilmuwan muda mengemukakan
teori bahwa untuk melumpuhkan bakteri diperlukan 2
komponen yang masing-masing punya karateristik sendiri.
Dia juga menemukan komponen termostabil (antibodi) dan
termolabil (komplemen) HUMORAL
Konsep Dasar Imunologi Infeksi
Infeksi dapat terjadi karena interaksi unik
antara host dan agen infeksi:
Faktor virulensi agen
(antigenisitas/imunogenisitas)
Sistem imunitas host
Escape/evade mechanism agen
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ASPECT OF HOST PARASITE RELATIONSHIP
1. Entry of the parasite
2. Multiplication and spread
3. Pathology
4. Natural immunity
5. Adaptive immunity
6. Immunopathology
7. Parasite survival mechanism
8. Host-parasite balance
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1. Faktor Virulensi Agen
Faktor yang membuat suatu agen menjadi patogenik

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IMMUNOGENICITY / ANTIGENICITY
SURFACE STRUCTURES OF PATHOGENS
BACTERIA
Gram-positive
Gram-negative
Mycobacteria
Spirochaete
VIRUSES
Viral proteins
(virion, infected cell membrane)
PARASIT
Surface membrane
Excretory - Secretory (ES Ag) ,
Granules (Gra)
1.1 Route of Microbial entry
Site of entry Method of entry Examples

Skin
Wound, burns

Insect bites
Dog bites
Direct penetration
Staphylococcus, Streptococcus
Tetanus
Malaria, Trypanosome, Filaria
Rabies
Schistosome, Hookworm larvae
Nose and throat
Attach to cells
Attach to teeth
Adenoviruses
Strep. mutans
Respiratory tract
Receptor on epithelium
Mucus/ciliary defect
Influenza
B. pertusis
Gut
Attach & penetrate
Attach without penetration
Salmonella, Entamoeba, Polio
Cholera, Giardia, hookworms
Genito-urinary
Attach to epithelium gonococcus
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Cell surface receptor for parasites
Organism Receptor Cell Infected
Viruses :
EBV
HIV
Rhinovirus
Polio
Rabies

CR2 (C3d receptor)
CD4
ICAM-1
ICAM?
Acetylcholine receptor

B-Cells
T-cells, macrophages
Respiratory tract
Intestine
neurone
Bacteria : E. coli
V. cholerae
CR3 (CR3b1 receptor)
Manose-fucose recepptor
Intestine
intestine
Protozoa: Entamoeba
Giardia
malaria
Lieshmania
Asialo-fetum
Manose-D-phosphatase
Glycophorin
Fibronectin, CR3, manose-
fucose
Colon
Small intestine
Rbc
macrophages
Fungi : Histoplasma CR3, LFA1 macrophages
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1.2 Multiplication & spread
After entry microorganisms multiply in different
ways:
Virus, fungi, protozoa rapidly multiply
Staphylococcus : 3 division/hour
Mycobacterium : once in a week
Worms do not replicate
Worms: they may spread locally or
general via blood/lymph
They may produce pathology
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2. Sistem Imunitas Host


Bagaimana tubuh menanggapi invasi agen infeksi
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Sistem Imun Host
brief review
Natural/alami/innate/nave/native:
ada pada tubuh semua orang sehat, dipersiapkan untuk
mengeblok mikroba yang masuk (rapid response/first
line defense)
Adaptive/dapatan/acquired: distimulasi
oleh mikroba yang menginvasi jaringan, beradaptasi
dengan jenis mikroba yang masuk (second line defense)
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2.1 Natural Immune Response
Selular: fagosit, makrofag, NK sel
Humoral: komplemen, sitokin (TNF, IL-1, IFN)
Fisik: barier endotel, mukus, fili
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Figure 1-4 part 3 of 3
Video I.21
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Recognition
pengenalan antigen oleh sel
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Video I.23
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2.2 Adaptive Immune Response
dependent on antigen
recognition
Selular/cell mediated: sel limfosit T,
makrofag
Humoral: limfosit B (antibodi)
Kombinasi: ADCC (Antibody Dependent
Celular Toxicity)
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Specific Immune Responses
Selective attack aimed at "target" following prior exposure
Two classes of responses:
Humoral immunity - antibodies produced by B lymphocytes
Cell-mediated immunity - activated T lymphocytes

Lymphocytes:
Originate as stem cells in the
bone marrow
Some migrate to the thymus &
develop into T-cells
Others remain in the Bone
marrow & develop into B-
cells.
Both B- & T-cells then migrate
to lymphoid tissue.
B lymphocytes (or B cells)
most effective against bacteria & their toxins
a few viruses
T lymphocytes (or T cells)
recognize & destroy
body cells gone awry (non-self),
including virus-infected cells &
cancer cells.

How B & T cells recognize
unwanted cells & other material?
Antigen = foreign protein (e.g., an antigenic protein from the outer
surface of bacterium or parasites)
Each B & T cell has receptors on surface for binding with a particular
antigen.

B-cells: Antibody-mediated immunity
B-cells that bind with an antigen will subsequently differentiate into
Plasma cells & Memory cells
Plasma cells - begin to produce antibodies (up to 2,000 per
second)
Memory cells - remain dormant until a person is again exposed
to the same antigen
Mekanisme sel B memproduksi Antibodi
The B cell uses its receptor to bind a
matching antigen, which it proceeds to
engulf and process.

Then it combines a fragment of antigen with
its special marker, the class II protein (on
surface of cell membrane)

This combination of antigen and marker is
recognized and bound by a T cell carrying a
matching receptor.

The binding activates the T cell, which then
releases lymphokines interleukins B cell
transform to plasma cell produce antibody
Hummoral immunity
Antibodies
Grouped into 5 subclasses:
1. IgM - B cell surface receptor for antigen attachment;
secreted early in an immune response
2. IgG - most abundant antibody; produced in large numbers
3. IgE - mediator for common allergic responses (hay fever,
asthma, & hives)
4. IgA - found in secretions of digestive, respiratory, urinary,
& reproductive systems, as well as in breast milk and in
tears
5. IgD - found on the surface of many B cells; function is
unknown
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Video 10.IV 1
Respon Imun mengeradikasi agen infeksi
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Memory cells:
remain dormant but respond quickly if exposed to the antigen a
second time
responsible for SECONDARY RESPONSE, a response so fast &
effective that infection is typically prevented.
form the basis for long-term immunity

Primary and Secondary antibody responses
Active ('natural') = production of antibodies as a
result of exposure to an antigen (immunization)
Passive = direct transfer of antibodies formed by
another person (or animal), e.g., transfer of IgG
antibodies from mother to fetus across placenta
or in colostrum ('first milk') OR treatment for
rabies or poisonous snake venom

Vaccine
As long ago as the 5th century B.C., Greek physicians noted
that people who had recovered from the plague would never
get it again - they had acquired immunity.
This is because, whenever T cells and B cells are activated,
some of the cells become "memory" cells. The next time that
an individual encounters that same antigen, the immune
system is primed to destroy it quickly.
The degree and duration of immunity depend on the kind of
antigen, its amount, and how it enters the body.
An immune response is also dictated by heredity; some
individuals respond strongly to a given antigen, others weakly,
and some not at all.


Development of memory B cells and effector B cells (plasma cells) occurs in two
phases.
Short-lived plasma cells that make mostly IgM (but some IgG) are generated
during the primary response and occupy sites, such as lymph nodes.
The second phase involves the formation of the memory B-cell pool and
seeding of long-lived plasma cells to the bone marrow.
Pasive immunity
Infants are born with relatively weak immune responses. They
have, a natural "passive" immunity; which protect them during the
first months of life by antibodies they receive from their mothers.
The IgG which travels across the placenta, makes them immune to
the same microbes to which their mothers are immune.
Children who are nursed also receive IgA from breast milk; it
protects the digestive tract.
Passive immunity can also be conveyed by antibody-containing
serum obtained from individuals who are immune to a specific
infectious agent. Immune serum globulin or "gamma globulin" is
sometimes given to protect travelers to countries where hepatitis is
widespread.
Passive immunity typically lasts only a few weeks
Active" immunity can be triggered by both infection and
vaccination.
Vaccines contain altered microorganisms will produce an
immune responses.
Some vaccines are made of
killed microbes.
microbes that have been changed slightly so they can no
longer produce infection or unable to multiply.
Some vaccines are made from a live virus that has been
weakened, or attenuated, by growing it for many cycles in
animals or cell cultures.

2.3 Imunopatologi
Adaptive immunity are potentially dangerous
to the host for 2 reasons:
1. effector mechanism may pasively damage
uninfected host tissue (hypersensitivity)
2. antigenic similarity between host and
parasites (mimicry) response originally
directed to parasite may also targetted to host
tissue (autoimmunity)

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3. Ecsape/evade Mechanism
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EVADE MECHANISMS AGAINST PHAGOCYTE-
MEDIATED KILLING
secret repellents / toxins inhibit chemotaxis
bear capsules / outer coats inhibit attachment
releases molecules (M. tuberculosis) interfere phagolysosome
fusion
secret catalase break down hydrogen peroxide
possess a phenolic glycolipid (M.leprae) scavenges free
radicals
release lipoarabinomannan (Mycobacteria) block the ability of
M in respond to IFN- stimulus
others : anatomic sequestration, antigenic mimicry,
antigenic variation (parasites)
PARASITE ESCAPE MECHANISM
Type Effector mechanism
concealment Intracellular
Capsule
Cysts
Mimicry of host
Host antigen coating
variation Mutation, recombination,
Gene switching
supression Non-specific
Specific tolerance by
macrophages
T suppressor cells
Parasite products
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Immunology is
fun fun fun!