IMMUNITY TO

MICROBE
SAKINAH NUR FADILLAH
CONETA WULANDARI
SUB POKOK BAHASAN

1. RESPON IMUN TERHADAP BAKTERI, VIRUS, JAMUR,

DAN PARASIT
2. IMUNO EVASION OLEH PATOGEN
3. VAKSINASI
INTRODUCTION

1. Defense against microbes is mediated by the effector mechanisms of

innate and adaptive immunity.

2. The immune system responds in distinct and specialized ways to

GENERAL FEATUREA OF different types of microbes to most effectively combat these infectious
IMMUNE RESPONSES agents.
TO MICROBES

3. The survival and pathogenicity of microbes in a host are critically

influenced by the ability of the microbes to evade or resist the effector
mechanisms of immunity.

4. In many infections, tissue injury and disease may be caused by the host
response to the microbe and its products rather than by the microbe itself
IMMUNITY TO MICROBES
(BACTERIA, FUNGI,VIRUSES, AND
PARASITE)
IMMUNITY TO
EXTRACELLULER BACTERIA
 IMMUNITY TO
EXTRACELLULER BACTERIA
Extracellular bacteria are capable of replicating outside host cells, for example, in the circulation, in
connective tissues, and in tissue spaces such as the lumens of the airways and gastrointestinal tract.
Many different species of extracellular bacteria are pathogenic, and disease is caused by two principal mechanisms.
First, these bacteria induce inflammation, which results in tissue destruction at the site of infection. This is how
pyogenic (pusforming) cocci cause a large number of suppurative infections in humans.
Second, many of these bacteria produce toxins, which have diverse pathologic effects.

INNATE IMMUNITY TO EXTRACELULER BACTERIA

ADACTIVE IMMUNITY TO EXTRACELLULER BACTERIA

 INNATE IMMUNITY TO EXTRACELLULER BACTERIA

THE PRINCIPAL MECHANISM OF INNATE IMMUNITY TO EXTREACELLULER BACTERIA

ARE COMPLEMENT ACTIVATION, PHAGOCYTOSIS, AND THE INFLAMMATORY RESPONE

Bacteria that express mannose on their surface may bind mannose-binding lectin, thereby leading to
complement activation by the lectin pathway.

In addition, activated phagocytes secrete cytokines, which induce leukocyte infiltration into sites of infection
(inflammation). Injury to normal tissue is a pathologic side effect of inflammation. Cytokines also induce the
systemic manifestations of infection, including fever and the synthesis of acute-phase proteins.
 ADACTIVE IMMUNITY TO EXTRACELLULER BACTERIA
HUMMORAL IMMUNITY IS THE PRINCIPAL PROTECTIVE RESPONSE AGAINTS
EXTRACELLLER BACTERIA, AND IT FUNCTIONS TO BLOCK INFECTION, ELIMINATE THE
MICROBES, AND NEUTRALIZE THEIR TOXINS

Antibody responses against extracellular bacteria are directed against cell wall antigens and secreted and
cell-associated toxins, which may be polysaccharides or proteins.

The effector mechanisms used by antibodies to combat these infections include neutralization,
opsonization and phagocytosis, and activation of complement by the classical pathway

Neutralization is mediated by high-affinity immunoglobulin G (IgG) and IgA isotypes, opsonization by some
subclasses of IgG, and complement activation by IgM and subclasses of IgG. The protein antigens of
extracellular bacteria also activate CD4+ helper T cells, which produce cytokines that stimulate antibody
production, induce local inflammation, and enhance the phagocytic and microbicidal activities of
macrophages and neutrophils
Figure 1. Addactive Immune Respones to Extracelluler Microbes
INJURIOUS EFFECTS OF IMMUNE RESPONSES

The principal injurious consequences of host responses to extracellular bacteria are inflammation and
septic shock

INFLAMMATION
tissue damage by local production of reactive oxygen species and lysosomal enzymes

SEPTIC SHOCK
severe pathologic consequence of disseminated infection by gram-negative and some gram-positive bacteria.
 IMMUNITY TO
INTRASELLULER BACTERIA
INNATE IMMUNITY TO INTRACELLULER BACTERIA

PHAGOCYTES, INITIALLY NEUTROPHILS AND LATER MACROPHAGES, INGEST

AND ATTEMPT TO DESTROY THESE MICROBES,

THE INNATE IMMUNE RESPONSE TO INTRACELLULER BACTERIA IS MAINLY

MEDIATED BY OF PAGOCYTES AND NATURAL KILLER

Intracellular bacteria activate NK cells by inducing expression of NK cell-activating ligands on infected

cells or by stimulating dendritic cell and macrophage production of IL-12, a powerful NK cell-activating
cytokine. The NK cells produce IFN-γ, which in turn activates macrophages and promotes killing of the
phagocytosed bacteria. Thus, NK cells provide an early defense against these microbes, before the
development of adaptive immunity.
ADACTIVE IMMUNITY TO INTRACELLULER BACTERIA
Adaptive immunity against intracellular bacteria is principally cell mediated and consists of activation of
macrophages by CD4+ T cells (as in DTH) as well as killing of infected cells by CD8+ CTLs. The
characteristic pathologic response to infection by intracellular bacteria is granulomatous inflammation.
COOPERATION OF CD4+ AND CD8+ IN DEFENSE AGAINTS
INTRACELLULER BACTERIA
 IMMUNITY TO FUNGI

Protective responses to fungi consist of innate immunity, mediated by neutrophils and

macrophages, and adaptive cell-mediated and humoral immunity. Fungi are usually readily
eliminated by phagocytes and a competent immune system, because of which disseminated
fungal infections are seen mostly in immunodeficient persons.

INNATE IMMUNITY TO FUNGI

ADDACTIVE IMMUNITY TO FUNGI

 INNATE IMMUNITY TO FUNGI

The principal mediators of innate immunity against fungi are neutrophils and macrophages

Neutrophils presumably liberate fungicidal substances, such as reactive oxygen intermediates

and lysosomal enzymes, and phagocytose fungi for intracellular killing.

Virulent strains of Cryptococcus neoformans inhibit the production of cytokines such as TNF and
IL-12 by macrophages and stimulate production of IL-10, thus inhibiting macrophage activation. .

Neutrophils
Neutrophils (also called polymorphonuclear leukocytes [PMNs]) are the most abundant leukocytes in
the blood, numbering 4000 to 10,000 per μL.
Production of neutrophils from the bone marrow increases rapidly, and their number may rise to
20,000 per μL of blood.
Production of neutrophils is stimulated by cytokines,
Neutrophils are the first cell type to respond to most infections, particularly bacterial and fungal
infections
Ingest microbes in the circulation
Rapidly enter extravascular tissues at sites of infection, where they also ingest microbes and die after
a few hours.
ADAPTIVE IMMUNITY TO FUNGI

Cell-mediated immunity is the major mechanism of adaptive immunity against fungal infections.

Histoplasma capsulatum, is eliminated by the same celluler mechanisms that are effective againt
intracelluler bacteria.

CD4+ and CD8+ T cells cooperate to eliminate the yeast forms of C. neoformans, which tend to
colonize the lungs and brain in immunodeficient hosts. Candida infections often start at mucosal
surfaces, and cell-mediated immunity is believed to prevent spread of the fungi into tissues .

In many of these situations, TH1 responses are protective and TH2 responses are detrimental to the
host.
IMMUNITY TO VIRUSES
VIRUSES

Viruses are obligatory intracellular microorganisms that replicate within cells

using normal cell surface molecules as receptors to enter the cells

viruses can cause tissue injury and disease by any of several mechanisms.
Viral replication interferes with normal cellular protein synthesis and function and leads to injury and
ultimately death of the infected cell.
Viruses may also cause latent infections, during which viral DNA persists in host cells and produces
proteins that may or may not alter cellular functions.
IMMUNITY TO VIRUSES
INNATE IMMUNITY TO VIRUSES
THE PRINCIPAL MECHANISMS OF INNATE IMMUNITY AGAINST VIRUSES ARE INHIBITION OF
INFECTION BY TYPE I IFNS AND NK CELL-MEDIATED KILLING OF INFECTED CELLS.

ADAPTIVE IMMUNITY TO VIRUSES

ADAPTIVE IMMUNITY AGAINST VIRAL INFECTIONS IS MEDIATED BY ANTIBODIES, WHICH BLOCK VIRUS
BINDING AND ENTRY INTO HOST CELLS, AND BY CTLS, WHICH ELIMINATE THE INFECTION BY KILLING
INFECTED CELLS
Antiviral antibodies function mainly as neutralizing antibodies to prevent virus attachment and entry into
host cells
Secreted antibodies of the IgA isotype are important for neutralizing viruses that enter through the
respiratory and intestinal mucosa
Antibodies may opsonize viral particles and promote their clearance by phagocytes.

Induced by either infection or vaccination

Virus-specific CTLs are CD8+ T cells that recognize cytosolic, usually endogenously synthesized,
viral antigens in association with class I MHC molecules on any nucleated cell.
IMMUNITY TO PARASITES
INNATE IMMUNITY TO PARASITE

PROTOZOA
The principal innate immune response to protozoa is phagocytosis, but many of these parasites are resistant to
phagocytic killing and may even replicate within macrophages .
Some protozoa may express surface molecules that are recognized by TLRs and activate phagocytes.

HELMINTH
Phagocytes also attack helminthic parasites and secrete microbicidal substances to kill organisms that are
too large to be phagocytosed. .
Some helminths may also activate the alternative pathway of complement
ADAPTIVE IMMUNITY TO PARASITE
PROTOZOA

The principal defense mechanism against protozoa that survive within macrophages is cell-mediated
immunity, particularly macrophage activation by TH1 cell-derived cytokines

PRINCIPAL MECHANISMS OF PROTECTIVE

PROTOZOA DISEASES
IMMUNITY
Plasmodium species MALARIA ANTIBODIES AND CD8 CTLS

CD4 Th1 CELL ACTIVATE MACROPHAGES TO

Leishmania donovani LEISHMANIASIS
KILL PHAGOCYTOSED PARASITES
AFRICAN
Trypnasoma brucei ANTIBODIES
TRYPANOSOMASIS
Entamoeba histolytica AMEBIASIS ANTIBODIES< PHAGOCYTOSIS
ADAPTIVE IMMUNITY TO PARASITE

HELMINTH
Defense against many helminthic infections is mediated by the activation of TH2 cells, which results in production
of IgE antibodies and activation of eosinophils

IgE antibodies that bind to the surface of the helminths may activate mast cells

METAZOA DIASES PRINCIPAL MECHANISMS OF PROTECTIVE IMMUNITY

Schistosoma species SCHISTOSOMIASIS ADCC MEDIATED BY EOSINOPHILS, MACROPHAGES

Filaria FILARIASIS CELL-MEDIATED IMMUNITY

IMMUNE EVASION BY PHATOGEN
IMMUNE EVASION BY EXTRACELLULER BACTERIA
Mechanism of immune evasion Examples

Extracellular bacteria

Neisseria gonorrhoeae, Escherichia coli,

Antigenic variation
Salmonella typhimurium

Inhibition of complement activation Many bacteria

Resistance to phagocytosis Pneumococcus

Scavenging of reactive oxygen intermediates Catalase-positive staphylococci

IMMUNE EVASION BY INTRACELLULER BACTERIA

Mechanism of immune evasion Examples

Intracellular bacteria

Mycobacterium tuberculosis, Legionella

Inhibition of phagolysosome formation
pneumophila

Mycobacterium leprae (phenolic

Inactivation of reactive oxygen and nitrogen species
glycolipid)

Disruption of phagosome membrane, escape into Listeria monocytogenes (hemolysin

cytoplasm protein)
IMMUNE EVASION BY VIRUSES

Mechanism of immune evasion Examples

Antigenic variation Influenza, rhinovirus, HIV

Inhibition of antigen processing

Blockade of TAP transporter Herpes simplex

Cytomegalovirus

Removal of class I molecules from the ER

Cytomegalovirus (chemokine)

Production of immunosuppressive cytokine Epstein-Barr virus (IL-10)

Infection of immunocompetent cells HIV
IMMUNE EVASION BY PARASITES

Mechanism of immune evasion Examples

Antigenic variation Trypanosomes, Plasmodium

Acquired resistance to complement, CTLs Schistosomes

Filaria (secondary to lymphatic obstruction),

Inhibition of host immune responses
trypanosomes

Antigen shedding Entamoeba