IMUNITAS TERHADAP

VIRUS, BAKTERI & FUNGI

Departemen Mikrobiologi
FK-Universitas Methodist
Indonesia
 Pathogens
 Microorganisms that are capable of
causing disease
Viruses

Bacteria

Fungi
 Extracellular microorganisms

Microorganism

Non-encapsulated microorganisms are easily

phagocytosed and killed within macrophages

Microorganism
encapsulated

Encapsulated microorganisms require the production

of antibody in order to be effectively phagocytosed.
Once engulfed, however, they are easily killed
 Intracellular microorganisms

Intracellular microorganisms elicit the production of

antibody, which allows effective phagocytosis. Once
engulfed, however, they survive within the
phagocyte and eventually kill it.

IFN
TNF

Intracellular microorganisms also activate specific

T-cells, which then release lymphokines (e.g. IFN,
TNF) that cause macrophage activation. Activated
("killer") macrophages are then very effective at
destroying the intracellular pathogens.
 The Viruses
• Dock with receptors on target
cell surface
• Insert viral DNA or RNA into
host cell
• Use host cell machinery to
replicate new viruses
• Lyse host cell and spread to
nearby cells
• Lytic vs. Lysogenic life cycles
• Examples: smallpox,
chickenpox, polio, HIV
 Siklus hidup virus secara umum
1. Virion diabsorpsi sel host melalui reseptor
2. Virus menembus sel dan melepaskan coat
3. Infeksi terjadi melalui beberapa fase 
bergantung jenis virus
4. Komponen virus dibentuk dalam sitoplasma
dan nukleus sel, komponen menyatu  virus
matang
5. Virus dilepas melalui budding membran sel
6. Virus dapat menyebar dari 1 sel ke sel lain
melalui kontak tanpa ada virus yg dilepas
keluar sel
 Siklus hidup virus secara umum
7. Beberapa virus tetap tinggal di dalam sel
dan dapat diaktifkan sewaktu-waktu
8. Beberapa virus mampu menyatukan
bahan genetiknya dengan genom sel
host dan tinggal bersifat latent  sel
menjadi produktif
9. Pada keadaan tertentu melalui
transformasi sel  neoplastik
10. Bbp infeksi virus bisa abortif, sel yg
mengandung virus akhirnya mati juga
 Respon Imun terhadap virus
 Akut
 Rekuren
 Laten  infeksi dorman (tdk terdeteksi tp
dapat menyebabkan penyakit)
 Sub-klinik  akut atau kronik dg infeksi
tanpa gejala walaupun virus dpt dideteksi
 Tidak ada respon  Kuru, Creutzfeld-Jacob
 Imunitas seumur hidup
 Imunopatologik kronik  hepatitis B
 Perjalanan infeksi virus
 Invasi setempat pada epitel
permukaan  masuk ke dalam
sirkulasi darah  viremia  invasi
hingga sel sasaran (kulit, susunan
saraf, dsb)  timbul pertahanan
tubuh terhadap infeksi virus
 Anti-Viral Immunity
Humoral immunity:

Virus neutralization
* In viraemic infections,
Antibodies neutralize virus, preventing its
attachment to receptor sites on susceptible
cells
e.g. Poliovirus, mumps, measles, rubella

* In superficial non-viraemic infections

(influenza)
Secretory IgA neutralizes virus infectivity at
the mucous surfaces
Netralisasi Virus

12
 Anti-Viral Immunity
Humoral immunity:

Antibodies destroy free virus particles directly

by:

i- Aggregation of virus and opsonization

ii- Complement mediated lysis

* Both mechanisms also act on virus infected

cells
Pada virus ber-envelop: MAC (Membran
Attack Complex) merusak envelop

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 Anti-Viral Immunity

Cell mediated immunity (CMI):

Cell mediated cytotoxicity, mediated by

- Cytotoxic T-cells (CTLs)

- NK cells

- Activated macrophages
 Anti-Viral Immunity
CMI acts on virus infected cells through:

1. CTLs kill virus infected cells directly after

recognition of viral antigens on cell surface in
association with MHC I
2. TH-cells stimulated by viral antigens release
cytokines. Cytokines attract and activate
macrophages to kill virus infected cells
3. NK-cells destroy virus infected cells early in
infection before appearance of antibodies
4. Antibody-dependent cell mediated cytotoxicity
(ADCC):
Antibody binds to virus infected cells such cells
are lysed by NK cells, macrophages and
polymorphs
 Cell-mediated: cytotoxic T cells
 Destroy cells infected by intracellular pathogens and cancer
cells
 Class I MHC molecules (nucleated body cells) expose foreign
proteins
 Activity enhanced by CD8 surface protein present on most
cytotoxic T cells (similar to CD4 and class II MHC)
 TC cell releases perforin, a protein that forms pores in the
target cell membrane; cell lysis and pathogen exposure to
circulating antibodies
 Anti-Viral Immunity
Anti-viral activity of interferons (IFNs)

1- Virus infected cells produce INF-α;

- IFN-α inhibit intracellular replication of viruses

- IFN-α activate NK-cells to kill virus infected cells

- IFNs have no direct effect on extracellular virus

- IFNs act early in viral diseases before antibody

- IFNs activity is not specific

Destruksi Sel Terinfeksi Virus
oleh Sel NK Melalui ADCC

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Destruksi Sel Terinfeksi Virus
oleh Sel NK Melalui ADCC

3 20
 The Bacteria

• Reproduce rapidly
• Secrete exotoxins or
contain endotoxins as
part of cell wall
• Examples: Escherichia
coli, Clostridium
botulinum, Salmonella

Figure from Holt Biosources

 Imunitas terhadap bakteri
 Terdiri dari non spesifik & spesifik
 Epitel permukaan (berfungsi

proteksi)  jika dapat dilewati 

patogenisitas bergantung pada
dinding sel bakteri
 Klasifikasi bakteri berdasarkan ddg

sel:
Gram negatif, Gram positif, basil
tahan asam, spirochaeta
Antibacterial Immunity

Immunity to extracellular bacteria:

1- The innate immunity:

a- Complement activation

b- Phagocytosis

c- The inflammatory response

 Immunity To Extracellular Bacteria
The acquired immune responses:
i-The humoral mechanisms (antibodies) “main role”
ii- Cell mediated immune response “less role”

Antibodies induce immunity through:

a- Neutralization of bacterial toxins
b- Antibodies attach to the surface of bacteria and;
- Act as opsonins, enhance phagocytosis (Opsonization)
- Prevent adherence of bacteria to their target cells
e.g. IgA on mucosal surfaces
- Activation the complement leading to bacterial lysis
- Agglutinate bacteria, preventing their spread and
facilitating phagocytosis
 Opsonisasi

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Step-1 Step-2
 Immunity To Extracellular Bacteria
Cell mediated immune mechanisms:

* Microbes are internalized by APCs and presented to TH

* TH cells are activated and release cytokines which;

- activate phagocytosis their microbicidal functions

- Stimulate antibody production

- Induce local inflammation

 Immunity To Intracellular Bacteria
1) Innate immunity
It is mainly by natural killer (NK) cells
- They kill infected cells and secrete IFN-γ
- IFN-γ activate phagocytosis to kill intracellular
microbe
E.g. tuberculosis, leprosy, listeriosos

2) Acquired immunity is mainly by CMI

- Activation of macrophages to kill intracellular
microbes
- Lysis of infected cells by cytotoxic cells (CTLs)
- Most of these organisms are resistant to
phagocytosis, cause chronic infection and
granuloma formation
Sitolisis Bakteri Gram-Negatif

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 Mechanisms of adhesion
• fimbrae
• flagella
• adhesive slimes or
capsules
• cilia
• suckers
• hooks
• barbs
 Virulence factors
 Exoenzymes – digest epithelial tissues &
permit invasion of pathogens
 Toxigenicity – capacity to produce toxins
at the site of multiplication
• endotoxins – lipid A of LPS of gram-negative
bacteria
• exotoxins – proteins secreted by gram-positive
and gram-negative bacteria
 Antiphagocytic factors – help them to kill
or avoid phagocytes, include leukocidins
and capsules
 Struktur dinding sel bakteri
 Kebanyakan bakteri mempunyai membran
lapisan dalam & peptidoglikan
 Gram negatif mempunyai lapisan luar dari lipid
 mengandung LPS
 Peptidoglikan dihancurkan oleh lisozim
 Lipid bakteri dihancurkan oleh komplemen
 Dinding bakteri mycobacterium sangat
kompleks, bahkan pada dinding selnya
mempunyai sifat ajuvan
 Beberapa bakteri mempunyai fimbriae atau
flagellamempunyai Ag
 Beberapa bakteri memiliki kapsul luar 
resisten fagositosis
 Respon imun yang umum terjadi pada infeksi
bakteri yang penting
Infection Pathogenesis Major defense
C. diphteriae Non-invasive Imunoglobulin
pharyngitis. Toxin menetralisir
V. cholerae Non-invasive Imunoglobulin
enteritis. Toxin menetralisir & cegah
adhesi
N. meningitidis Nasopharynx Opsonisasi, dibunuh
bacteraemia oleh Ig dan
meningitis komplemen lisis
S. aureus Locally invasive & Opsonisasi, dibunuh
toxic in skin, etc oleh Ig & komplemen
dgn fagosit
M. tbc Invasive, locally toxic Aktivasi makrofag
M leprae Invasive, space oleh sel T
occupying
 The Fungi
• Similar to bacteria-
• reproduce rapidly
• Damage cells directly or
indirectly by secreting
enzymes
• Examples: Athlete’s Foot,
Pneumocystis carinii
(fungal pneumonia)

http://www.ces.ncsu.edu/depts/pp/bluemold/
 Imunitas terhadap fungi
 Biasanya hanya bagian luar tubuh
 Penyakit jamur sistemik  spora

 Tergantung derajat & jenis respon

imun  infeksi saluran napas ringan

 hipersensitivitas
 kematian
 Mekanisme pertahanan fungi
 Kapsul yang sulit dimakan 
Cryptococcus
 Resistensi terhadap fagositosis 

Histoplasma
 Destruksi sel polimorfonuklier 

Coccidioidosis
 Alveolitis alergik
 Manifestasi penyakit akibat jamur di
saluran napas
 Kadar spora yg tinggi  Ab presipitin

 Rx hipersensitivitas oleh Ab ini 

komplex tipe 3 berupa pneumonitis

pulmoner difus atau alveolitis alergik
 Efek ditimbulkan oleh inhalasi
spora jamur
 Rangsangan IgA pd membran
mukosa
 Rangsangan IgE  anafilaksis tipe I

pada dinding saluran napas

 Rangsangan IgG (Ab presipitin

dijumpai)
 Reaksi kompleks toksik dgn Ag

jamur dalam sirkulasi

 Anti-Fungal Immunity
Immune response to fungi consist mainly of :

1) Innate immunity is mediated by:

- Neutrophils and macrophages
- Fungi are readily eliminated by phagocytes

2) Acquired immunity (cell mediated immunity)

- CMI acts in a manner similar to its action
against intracellular bacteria

* Disseminated fungal infection are seen in:

immunodeficiency persons
Immune Response- Step by Step
1. Pathogen (carrying foreign antigens) enters and
survives the inflammatory response

2. Some pathogens remain exposed in tissues

where their antigens may be recognized by
circulating B cells
OR
3. Macrophages engulf pathogens and display their
antigens on MHC (major histocompatibility
complex) receptors. Macrophage has now
become an Antigen Presenting Cell (APC)
 Humoral Immunity
B cell response
• If a circulating B cell’s receptors bind to foreign
antigens, the B cell becomes activated
• Activated B cells divide into Memory B cells and
Plasma B cells
• Plasma B cells rapidly produce and secrete
antibodies (immunoglobulins)
• Clonal selection amplifies the production of cells
that produce effective antibodies
 Humoral response: B cells
 Stimulated by T-dependent
antigens (help from Th
cells)
 Macrophage (APCs) with
class II MHC proteins
 Helper T cell (CD4 protein)
 Activated T cell secretes IL-
2 (cytokines) that activate
B cell
 B cell differentiates into
memory and plasma cells
(antibodies)
 Clonal Selection

Figure from AccessExcellence.org

 Mechanism of Antibody Function
 Antibodies bind to
antigens and aggregate
pathogens for removal by
macrophages
 Antibodies disrupt
function of pathogen’s
surface proteins
 Antibody-antigen
complexes trigger the
Complement system, a
a series of enzymes
carried in the
bloodstream that lyse
invaders Figure from AccessExcellence.org
 Cell-Mediated Immunity
T cell Response
 Helper T cells (TH or CD-4 T cells)
constantly interact with macrophages
 When TH cell finds a macrophage that is
presenting antigen (APC) it becomes
activated
 Activated TH cells secrete cytokines,
chemicals that stimulate both T and B cells
 Stimulated cytotoxic T cells (killer or
CD-8 T cells) divide rapidly, bind directly
to pathogen infected cells and secrete
enzymes that lyse infected cells
 Helper T lymphocytes
 Function in both humoral & cell-mediated immunity
 Stimulated by antigen presenting cells (APCs)
 T cell surface protein CD4 enhances activation
 Cytokines secreted (stimulate other lymphocytes):
 a) interleukin-2 (IL-2): activates B cells and cytotoxic
T cells
 b) interleukin-1 (IL-1): activates helper T cell to
produce IL-2
The Immune Response - Overview
Respon Imun Primer dan Sekunder

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 Induction of Immune Responses
 Primary immune response: lymphocyte
proliferation and differentiation the 1st time the body is
exposed to an antigen
 Plasma cells: antibody-producing effector B-cells
 Secondary immune response: immune response if
the individual is exposed to the same antigen at some
later time~ Immunological memory
 Immunity
 Immune system primed to eliminate antigen after a
previous exposure (active immunity)
 Passive immunity: antibodies administered to
individual (Medical treatment or mother-fetus
across placenta)
 tetanus, snake venoms, hepatitis, botulism,

rabies, etc.
 Vaccination: Artificially acquired immunity
• weakened pathogen, recombinant DNA produced
vaccines (artificial pathogen proteins)
• irradicated small pox, polio, whooping cough,
etc.
 Immunity in Health & Disease
 Active immunity/natural: conferred
immunity by recovering from
disease
 Active immunity/artificial:
immunization and vaccination;
produces a primary response
 Passive immunity: transfer of
immunity from one individual to
another
- natural: mother to fetus; breast
milk •--
artificial: rabies antibodies
 ABO blood groups (antigen
presence)
 Rh factor (blood cell antigen); Rh-
mother vs. an Rh+ fetus (inherited
from father)