IMMUNITY TO MICROBES

Prof. Dr. dr. Djoni Djunaedi, SpPD, KPTI

General feature of immune response to microbes:

Defense against microbes is mediated by the effector mechanisms of
innate and adaptive immunity

The immune system respons in distinct and specialized ways to

different types of microbes to most effectively combat these infectious
agents
The survival and pathogenicity to microbes in a host are critically
influenced by the ability of the microbes to evade or resist the effector
mechanisms of immunity
In many infections, tissue injury and diseases may be caused by the
host response to the microbe and its products rather than by the
microbe itself

Immunity to extracellular bacteria

Microbe

Exam.of human diseases

Mechanisms of pathogenicity

Staphylococcus
aureus

Skin and soft tissue infections, lung

abscess; systemic: toxic shock
syndrome, food poisoning

Skin infections; acute inflammation induced by

toxins; cell death caused by pore-forming toxins
Systemic: enterotoxin (superantigen)-induced
cytokine production by T cell causing skin
necrosis, shock, diarrhea

Streptococcus
pyogenes (grA)

Pharyngitis
Skin infections: impetigo, erysipelas;
cellulitis
Systemic: scarlet fever

Acute inflammation induced by various toxins,

e.g., streptolysin O damages cell membranes
(antiphagocytic action of capsular
polysaccharides)

Streptococcus
pyogenes
(pneumococcus)

Pneumonia,meningitis

Acute inflammation induced by cell wall

constituents; pneumolysin is similar to
streptolysin O

Escherichia coli

Urinary tract infections,

gastroenteritis,septic shock

Toxins act on intestinal epithelium and cause

increased chloride and water secretion;
endotoxin (LPS) stimulats cytokine secretion by
macrophages

Vibrio cholerae

Diarrhea (cholera)

Cholera toxin ADP ribosylates G protein subunit,

which leads to increases cyclic AMP in intestinal
epithelial cells and results in chloride secretion
and water loss

 The principal mechanisms of innate immunity to extracellular bacteria

are complement activation, phagocytosis and the inflammatory
response
Humoral immunity is the principal protective immune response
against ectracellular bacteria, and it functions to block infection,
eliminate the microbes, and neutralize their toxins
The principal injurious consequences of host responses to
extracellular bacteria are inflammation and septic shock

Adaptive immune responses to extracellular microbes

Adaptive immune responses to extracellular microbes, such as bacteria, and their toxins consist of
antibody production and the activation of CD4+ helper T cells. Antibodies neutralize and eliminate
microbes and toxins by several mechanisms. Helper T cells produce cytokines that stimulate B cell
responses, macrophage activation, and inflammation.

Immunity to intracelullar bacteria

Microbe

Examples of human diseases

Mechanisms of pathogenicity

Mycobacterium

Tuberculosis, leprosy

Macrphage activation resulting in

granulomatous inflammation and tissue
destruction

Listeria
monocytogenes

Listeriosis

Listeriolysin damages cell membranes

Legionella
pneumophila

Legionnaires disease

Cytotoxin lyses cells and causes lung

injury and inflammation

 The innate immune response to intracellular bacteria is mainly

mediated by of phagocytes and natural killer (NK) cells
The major protective immune response against intracellular
bacteria is T cell-mediated immunity

Innate and adaptive immunity to intracellular bacteria

The innate immune response to intracellular bacteria consists of phagocytes and NK cells,
interactions among which are mediated by cytokines (IL-12 and IFN-). The typical adaptive
immune response to these microbes is cell-mediated immunity, in which T cells activate
phagocytes to eliminate the microbes. Innate immunity may control bacterial growth, but
elimination of the bacteria requires adaptive immunity.

Immunity to fungi
Microbe

Examples of human diseases

Mechanisms of pathogenicity

Candida albicans

Candidiasis

Unknown; binds complement proteins

Aspergillus
fumigatus

Aspergillosis

Invasion and thrombosis of blood vessels

causing ischemic necrosis and cell injury

Histoplasma
capsulatum

Histoplasmosis

Lung infection caused by granulomatous

infalmmtion

Immunity to viruses
Microbe

Examples of human diseases

Mechanisms of pathogenicity

Influenza

Influenza pneumonia

Inhibits host cell protein synthesis (tropism

for ciliated epithelial cells)

Herpes simplex

Various herpes infections (skin, systemic)

Inhibits host cell protein synthesis;

functional impairment of immune cells

Hepatitis B

Viral hepatitis

Host CTL response to infected hepatocytes

Epstein-Barr
virus

Infectious mononucleosis; B cell

proliferation, lymphomas

Acute infection: cell lysis (tropism for B

lymphocytes)
Latent infection: stimulates B cell
proliferation

Human immunodeficiency virus

(HIV)

Acquired immunodeficiency syndrome

(AIDS)

Multiple: killing of CD4+ T cells, functional

impairment of immune cells

 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 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

Innate and adaptive immune response against viruses

Immunity against viruses functions to prevent infection and to eradicate established infection.
Innate immunity is mediated by type I IFNs, which prevent infection, and NK cells, which
eliminate infected cells. Adaptive immunity is mediated by antibodies and CTLs, which also
block infection and kill infected cells, respectively

IMMUNE RESPONSE

Ag

IL-12/1L-1

IL-6
IL-4
Th-2
IL-2, IFN-

CTL

MHCI

AP
C

IL-5

B-lymph

MHC-II
IL-16

TNF-, IFN-

Abnormal
cell

FAST
Th-1
IL-2

IFN-

NK
cell

FC-R

Lysis
cell

Activated NK
cellCYTOKINE

Abnormal cell

Memory
cell

RESPONS IMUN PADA INFEKSI VIRUS DENGUE

Dengue virus infection of human
monocyte

TH
CD
8

D
Mo V
T cell
activation

TH
CD
4

Mo
IFN

T
CD
4

IL-2, other lymphokines

Endotheli
al cells
Plasma
leakage

Mo
Shock

T
CD
8

D
Mo V

IL-1 TNF
Tissue factor
Chemical mediators

D
D
V
D V
D D
Complement
V
V V
activation
Dengue virusantibody complex

C3a, C5a

Hemostatic
system

Hemorrhag
e