Bacteria Virus

HUMAN
Fungal BODY Riketsial

Mycoplasm Chemical
 IMMUNE RESPONSE

RECOGNITION
ELIMINATION

Autoimmunity Immunodeffisiency

Hypersensitivity
 Foreign Antigent

Enter

Human
Elimination Elimination
body

Specific Non-specific

Pathologic
 Immunity to microbe

Infection procces involved sequence

interaction between the microbe and
the host :
- entry of microbe
- invasion & colonization
- evasion from the host immunity
- tissue injury or fuctional impair-
ment
 Immunity to microbe
1. Mediated by both natural and
acquired
immunity
2. Stimulate distinct lyphocyte response
and effector mechanism
3. Influenced by their ability to evade or
resist
4. Tissue injury & disase may be caused
by the host response to mirobe and its
 Extracelluler bacteria

- Replicating outside host cells :

- gram-positive pus-forming (Sta-
phylococcus & Streptococcus)
- gram-hegative cocci (meningo-
coccus & gonococcus)
- gram-negative bacilli (eanteric)
- gram positive bacilli (Clostridium)
Extracelluler bacteria cause disease by

1. Induce inflamation wich result

in tissue destruction

2. Produce toxins, wich have diverse

pathologic effect :
a. endotoxin ( bacterial cell wall)
b. exotoxin (actively secreted)
 Natural immunity to extracelluler
bacteria

-Phagocytosis by neutrophil , monocyt

and tissue macrophages
-Activation complement system in the
absent of antibody
-Inflamation
 Cytokine Adhesion
M
Chemokine neutrophil
.

Bacreial LPS monocyts

Activatin Migration &

Bacterial local accula-
of
elimination tiom of inflam-
inflam.cell
matory cells
 Phagocytic Cells
1. Professional phagocytes :
- PMN leukocytes
- Monocytes
- Macrophages
2. Paraprofessional
-Dendritic cells (DC) have selective
phagocyte activity
3. Non professional :
- fibroblast & ephithelial cells
 Macrophage function
1. Detection of microbial invasion
Opsonic and nonopsonic receptor fo
microbe and their product
2. Restriction of microbial spread
Phagocytosis
Granuloma formation
Intracelluler killing
3. Recruitment of immune cells
Cytokines & inflamatory mediators
4. Accessory cells in lymphocyte ac
-Ag processing & and presentation
-Costimulatory molecules : CD40
CD28 and CTLA4
-Cytokines
5. Effector cells in CMI
-Increase phagocytosis
-Increase intracelluler killing
-Clearence of apoptotic cells
6. Participation in humoral immunity
 Properties of Macrophages
1. Membrane receptor
-Scavenger receptor
-C receptor
-Fc- eceptor
-Macrosialine
-Cytokines receptor
-CD14 (LPS receptor)
2. Production of
cytokines
 - TNF
- IL-12
- IL-10
- IL-4
- FGF
3. Antigent processing and
presentation
4. Produce enzymes
- colagenase
- elastase
- lysozymes
- lysosomal enzymes
5. Production of bioactive lipid and

small radical
- Prostaglandin
- Platelet activatig factor
- reactive oxygen & nitrogen
interme-
diate
.
 Phagocytosis
1. Microbial recognition
- PRRs (pattern recognition reseptor
a. membrane bound
b. free in plasma
- Recognize wide variety of microbia
molecules
- As reeptors for binding & entry of
many intraclluler pathogens
2. Microbial uptake
- actin polymerization
- engulfment and internalization
3. Phagosomal maturtion
- depolymerization of actin
- fussion with endosome
- final step : fussion with lysosome
---> phagolysosome generating lo
pH and containig degradative hy
lases
4. Microbial killing
Accomplished by :
- low pH of phagosom
- limitation of nutrien (iron)
- generation of reactive oxygen and
nitrogen intermediates
- Nramp-1 : removal of iron and di-
valen cation from phagosom
- phox ---> reactive oxygen intermed
- inos ----> reactive nitrogen interme
Phox : phagocyte NADPH oxydase
phox

O2 O2-

NADPH NADPH+
O2 - + H2O H2O2 + OH*
Cl-
H2O2 HOCl -
+ OH *

MPO antibacterial
LPS Deaminasi
IL-1 INOS oxydative
TNF L-arginin
IFN-

NO NO
+ +
H2O2 Thiol
groups
peroxynitri nitrosothiol
t
5. Production of soluble mediator
- signal & recruit other cells to the
side of infect.
. Stimulate adaptive immune resp.
6. Antigen presentation
- Histocompatibility molecule(HLA)
- HLA-I --> CD8 cells
- HLA-II --> CD4 cellsa
- Costimulatory molecules
 Ag IL-1
Th1
HLA-II
M CD4 Th2
HLA-I IL-4 , IL-12
BCGF, BCPF, BCDF

CD8 IFN-

ADCC B
Ab P
IL-2
NK
 microbe CD 4

phagosom
lysosom

golgi

phagolysosom

Phox
Inos
Nram-1

RE
Specific imm. resp.to extracelluler bact.

- Polysaccharides capsules & cell walls

(as T-independent -antigent) directly
stimulate B cells antibody
- Respons of CD4+T cells to bacterial pro
teins in association with Class II MHC
- Antibody & T cells perform several
function that serve to eliminate bacteria
Three types effector mehanisms of
IgM and IgG antibodies

1. IgG opsonize bacteria & enhance phag

cytosis by binding to Fc rceptors
2. Both IgG & IgM neutralize bacterial tox
and prevent their binding to target cells
3. Both IgG & IgM activate omplement
microbicidal MAC and mediators acute
inflammatiom
 neutralization

bacteria B Ab Opsonizatiom
and phagocytosi
Polysacc-Ag
Complement
activation

Bacterial inflammation Phagocytosis of

lysis C3b-coated bacteri
 HLA-II
APC CD4+
bacteria

Various IFN TNF

cytokines

Antibody Nacrophage inflammation

response activation-->
phagocytosis
and Bacterial
killing
Immune evasion by extracelluler bact.

- Mechanism utilized by bacteria to

evade spedific immunity
- Produce surface atigent that favor tissu
invasion and colonization
Immune Evasion by Extacelluler bacteria
-
N.gonorrhoeae
Antigenic variation - E. coli
-
S.typhimurium
Inhibition of Compl. - Many bacteria
activation
Resistence to phago- - Pneumococcus
cytosis
Scavenging of reactive - Catalase positive
oxygen intermediates staphylococcus
Immune resp. to intracelluler bacteria

- Mycobacteria
- Listeria monocytogenes
- Legionella pneumophila
- Survive and replicate within host cells
- Resistent to degradation in macropha-
ges
- Tend to cause chronic infection that
may last years
Natural immunity to intracelluler bacteria

- Phagocytosis
quite ineffective in controlling coloniza-
tion and spread of this microorganism
- Activate NK cells --> IFN- --> activate
macrophage --> promote killing of
phagocytosed bacteria
- NK cells provide an early defense again
this microbe
 IFN-

Resting Phagocytosed CD4+ Klling of

macrophaqge icrobe phagocytosed
microbe

CD8
Resting Phagocytosed
macrophaqge icrobe

Lysis of macrophage
and dead of bacteria
Immune Evasion by intracelluler
bacteria

Inhibition of phagolysosom - M.tuberculosis

Formation - Legionella pneumophilla

Scavenging of reactive oxygen - M. leprae

Intermediates (phenolic glycolipid)

Disruption of phagosome - Listeria monocytogenes

membrane, escpae into (hemolysin protein)
cytoplasm
 Natural immunity to virus
1. Viral infection directly stimulate the
production of Interferon (IFN) -->
inhibit viral replication
2. NK cells lyse virally infected cells
IFN can also enhance ability of NK cell
to lyse infected target cells
3. Complement activation and phagocy-
tosis serve eliminate extracelluler
viruses & from the circulation
Specific immune response to virus
- Is mediated by combination of humoral
and celluler immune mechanism
- Neutralizing and opsoning antibodies
- The principal specific immunity to virus
is lysis cells cells by CD8 CTLs
 Immune Evasion by Viruses
1. Antigenic variation : - Influenza,

-rhinovirus,
- HIV
2. Inhibition of Antigen processing
- inhibition of proteasome activity : - EBV,

HCMV
- block in TAP transport - HSV

- block MHC synthesis - Adenovirus,

3. Production of reseptor cytokine
homologues : - Vaccinia, poxvirus
( IL-1 , IFN-
- CMV (chemokine)

4. Production of immunosupressive
cytokine - EBV (IL-10)

5. Infection of immunocompeten
cells - HIV

6, Interference with CTL recognition murine CMV