Virus

Bacteria

Fungal

Mycoplasm

HUMAN
BODY

Riketsial

Chemical

IMMUNE RESPONSE
RECOGNITION
ELIMINATION

Autoimmunity

Immunodeffisiency

Hypersensitivity

Foreign Antigent
Enter
Elimination

Human
body

Elimination

Non-specific

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 impairment

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 (Staphylococcus & Streptococcus)
- gram-hegative cocci (meningococcus & 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
Chemokine

monocyts

Bacreial LPS

Bacterial
elimination

Adhesion
neutrophil

Activatin
of
inflam.cell

Migration &
local acculatiom of inflammatory 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
intermediate
.

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 divalen 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*
HOCl
+
OH
H2O2
MPO

antibacterial

LPS
IL-1
TNF
IFN-

NO
+
H2O2
peroxynitri
t

INOS

Deaminasi
oxydative
L-arginin

NO
+

Thiol
groups
nitrosothiol

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 cells
- Costimulatory molecules

Ag

IL-1
M

HLA-II

Th1
CD4

IL-4 , IL-12

HLA-I
CD8
ADCC

Th2
BCGF, BCPF, BCDF

IFN-

Ab

B
IL-2

NK

CD 4

microbe

phagosom

lysosom

golgi
phagolysosom

RE

Phox
Inos
Nram-1

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 complement
microbicidal MAC and mediators acute
inflammatiom

neutralization
bacteria

B
Polysacc-Ag

Bacterial
lysis

Ab

Opsonizatiom
and phagocytosi
Complement
activation

inflammation Phagocytosis of
C3b-coated bacteri

APC

HLA-II

CD4+

bacteria
Various
cytokines

IFN

Antibody
response

Nacrophage
activation-->
phagocytosis
and Bacterial
killing

TNF

inflammation

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 macrophages
- Tend to cause chronic infection that
may last years

Natural immunity to intracelluler bacteria

- Phagocytosis
quite ineffective in controlling colonization 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
macrophaqge

Resting
macrophaqge

Phagocytosed
icrobe

CD4+

Phagocytosed
icrobe

Lysis of macrophage
and dead of bacteria

Klling of
phagocytosed
microbe

CD8

Immune Evasion by intracelluler

bacteria
Inhibition of phagolysosom
Formation

- M.tuberculosis
- Legionella pneumophilla

Scavenging of reactive oxygen

Intermediates

- M. leprae
(phenolic glycolipid)

Disruption of phagosome
membrane, escpae into
cytoplasm

- Listeria monocytogenes
(hemolysin protein)

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 phagocytosis 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,
- block in TAP transport
- block MHC synthesis
CMV

HCMV
- HS
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