Transcript 1. immune_team_,_natural_immunity.ppt

Immune team
Cell injury can result from :
Hypoxia
Physical & chemical agents .
Microbial agents. (defective immunity).
Immune reactions. (abnormal responses)
Genetic factors .
Nutritional imbalances.
These Various stimuli cause cell injury & induce a complex
vascular & cellular response called :
Inflammation
Inflammation
There are 2 types of infections : 1 – sub clinical infections (MCQ) : we have it all the time so it is common , it
have no symptoms or signs because it get controled before produce
symptoms
2 – clinical infections : they are quite rare , they produce symptoms and
usually indicate failure to control infections
All defense mechanisms are collectively called immunity
Immunity is divided into
:(MCQ)
Natural ( innate ) :
is non-specific
Adaptive ( acquired ) :
Specific
1 – the to divisions are well integrated
2 – the 2 division are connected through a cytokine network ( inflammatory pathway )
The immune system has to main functions :
Recoginition
Response
1- the immune system is able to
recognize and distinguish one
pathogen from another through
chemical differences
The response is divided to :
2- and able to discriminate
between foreign molecules and
the body own cells
Memory response :
Effector response :
this mechanism usually accure in natural
immunity , once a foreign body has been
recognized , the immune system will call and
recrutis all his warriors army ( effecror cells ) to
defeat that organism
this mechanism usually accure in
acquired immunity , later
exposure to the same foreign
body induce a response that call
and recrutis a special unit of the
big army ( maybe Marine
)
that have an effecte on that
organism , so this mechanism is
specific and contain memory for
different pathogens
Differences between the natural and acquired immunity
Natural immunity
Mechanism of
recognition of microb
Very limited
Cell surface receptors
acquired immunity
diverse cell surface
receptors
(Fewer than 100 receptor)
Effecror mechanism
( response )
Non specific
specific
Immunologic memory
No memory retention
there is immunologic
Because the cells half
Life is short
memory
Natural immunity serve as :
A warning
signal that a
microbe is
invading the
tissues
A critical early
defense , ( mobilized
within minutes after
invasion by
microbes )

Stimulate &
influence adaptive
immunity
( secrete cytokines &
activate cells )

A progressing infection that pass natural defense mechanisms will be stoped by
adaptive ( antibody mediated response called humoral immunity ) if it was
extracellular infection , but if it was intracellular infection it will be stoped by
adaptive ( cell mediated response called cell mediated immunity )
Defense mechanisms of natural immunity : -
♥ anatomic barriers ♥
1- skin : is a mechanical barrier that work as a shaled preventing microbes from entering
It has an acidic enviroment that retards grouth of microbes
2- The mucus membranes : Normal flora compete ( fight ) with microbes for attachment
sites and nutrients
3- Mucus secreted by goblet cells entraps foreign bodies & microbes
4- Cilia propel microorganisms out of the body by coughing and sneezing ( smooking
cause damage to cilia so smookers are expoused to lung infections )
disruptions of anatomic barriers :
1- burns , cut wounds , skin diseases (eczema)
2- Aseptic techniques ( taking a blood sample or I / V catheters )
3- Disruption of the mucus membrane ( oral cavity ) by dental procedures
♥ Physiologic barrier ♥
Temperature: Normal body temperature inhibits growth of some pathogens ( fever
inhibits growth of pathogens)
Low pH Acidity : of stomach contents kills most ingested microbes
Chemical mediators : Lysozyme cleaves bacterial cell wall , and Collectins wich stick
to the pathogen so it get phagocytosed
Natural antibiotics : like defensins , cryptidins in stomach
Physiologic functions :
Coughing , sneezing , voiding urine , tears , saliva in oral cavity etc
when Physiologic functions are absent like in ( Inability to cough or Urine retention )
predispose to infections is likely to be
Circulating effector cells
1- Neutrophils ( most important )
2- Macrophages
3- Natural killer (NK) cells (viral immunity)
4- Eosinophils (parasitic and allergic immunity)
5- Mast cells (mediator of inflammation )
6- Platelets ( coagulation and mediator of inflammation)
7- B-1 cells found in fetus & neonates respond to bacterial antigens (
polyssacharides )
The Phagocytic cells have two hands on its surface that use them to shake the two
hands found on pathogen surface so it can recognize it
The first hand of Phagocytic cells called Toll - like receptor (TLRs) that shake
lipopolysaccaride (LPS) hand found on pathogen surface (gram negative bacteria )
The second hand of Phagocytic cells called Pattern-recognition receptors (PRR) that
shake Pathogen - associated molecular patterns hand (PAMPs ) found on pathogen
Neutrophils :
Mediate the early phase of inflammation
They are recruited to the site of infections by a process called
chemotaxis
comprise ( 60 -70 percent) Of the WBC
Short - lived cells
work in extra - cellular infections
Contain enzymes
Perform killing by :
1- Oxygen - dependent mechanisms
2- Oxygen - independent mechanisms
It is a polymorphonuclear cell
Chemotaxis of phagocytic cells involve the following steps :
1- Rolling ( loose adherence ) to endothelium
2- Activation of cells
3- Stable adherence to endothelium
4- Transmigration into tissue spaces
Mononuclear cells
Monocytes & Macrophages
Long - lived cells
Contain enzymes & secrete many cytokines
work in intra-cellular infections
Professional phagocytic cells
Antigen – presenting cells
important in both natural & adaptive immunity
Circulating monocytes enter tissues & become resident macrophages , e.g of tissues:
1- Sub - epithelial connective tissue
2- Interstitia of organs
3- Vascular sinusoids of the liver & spleen
4- Lymph nodes
Macrophages are strategically located at sites where Microbes enter the
tissues
They recognize microbes first by their receptors (PRR ) Become activated
,secrete cytokines and attract Neutrophils
Macrophages are activated by
Bacterial products.
LPS.
(gram neg. bacteria)
Bacterial DNA
Secrete cytokines, attract neutrophils
Induce
local
inflammation.
Macrophages produce many cytokines :
1. IL-1.
2. TNF
3. IL-6
4. IL-8
5. IL-12
Act on various
tissues & cells .
macrophges perform multiple functions :
1. Induce local inflammation.
2. Perform phagocytosis.
3. Activate coagulation .
4. Enhance
antigen presentation.
5. Initiate tissue
repair .
Functions of macrophages :
Invading agent
Macrophage
Antigen presentation
Macrophage
Activated macrophage
Macrophage
Th
cell
Cytokines
Cytokines
Lymphokines
Anti-microbial functions
Anti-tumor function
Mechanism of intracellular killing by phagocytic cells
1- Lysosomal enzymes
2- Production of reactive oxygen intermediates
3- Production of nitric oxide
4- circulating effecter proteins
Natural killer cells
A class of larg granular cytotoxic lymphocytes that do not have T or B cell
receptors
They are antibody – independent killers of tumors cells and also participate in
antibody – dependent cell mediated cytotoxicity
NK-cells are activated by :
IL-12 and IL-15
Which are Produced by macrophages
Functions of NK cell :
1- anti - viral activity
2- anti – tumor activity
Circulating effector proteins :
1 - The complement proteins
2 - Mannose- binding lectin
3 - C – reactive proteins
4 - Coagulation factors
5 - Cytokines
The complement proteins
The complement system is a biochemical cascad that’s help to clear pathogens
from the body
it consists of a number of small proteins found in the blood and synthesized by the
liver
Normaly they are inactive [ zymogens ]
Activation of the complement system lead to initiation of important effects which
include :
1- Release of chemotactic factors (C3a and C5a )
2- Opsonisation of microbes (C3b )
3- Lysis of target cells (C8 & C9 )
The complement proteins
The complement system is activated by 3 pathways :
1 - classical pathway , require antigen - antibody interaction
2 - alternative pathway , activated by bacterial products (LPS ,DNA )
3 - lectin pathway , activated by mannan-binding lectin
MEMBRANE ATTACK COMPLEX
C
C6
C7
CC
9 9C
C
9 C
9 9
b
Cytokines of natural immunity
1- interferons ( anti - viral )
2 – IL-1 , TNF and Chemokines ( mediate inflamation )
3 – IL-12 and IL-15 ( NK – cells )
4 – interferon – gamma ( act on macrophages )
5 – IL-6 ( act on bone marrow )
6 – IL-10 and TGF-B ( limit local inflammation )
Other functions of Cytokines
The Cytokines IL-1 and IL-6 and TNF-alpha coordinate body responses
to infections by acting on :
1 – liver , they induce the synthesis of acute phase proteins
2 – bone marrow , by stimulating the mobilization of neutrophils
3 – Hypothalamus , they induce it to increase body temperature (induce
fever )
4 - Fat & muscle , to supply proteins & energy
5 - T and B Lymphocytes , to become activated and produce adaptive
immune responses
Summary .
1. Natural Immunity is
the first
of defense.
line
2. It influence & stimulate subsequent
adaptive immune responses .
3. The immune response is a :
* Protective.
* Sub clinical .
* Localized reaction
5 - All are fearures of NK cells EXCEPT :
.a)phagocytic
.b)anti-tumor activity
.c)stimulated by activity
.c)stimulated by IL-12
.d)activated by interferons
e)anti-viral activity
6 - Regarding cytokines all of the following are
true EXCEPT :
.a) they are low MW proteins
.b) they act with surface receptors
.c) are long acting mediators
d) regulate inflammation
7 - Regarding CD molecules :
.a) CD3 is found on all B calls,not T cells
.b) CD1 is found on mature T cells
.c) CD19+CD20 are found on T cells
.d) CD4 is called cytotoxic
e) CD56 found on NK cells
8 - All are features of complement system
EXCEPT :
.a) lysis of damaged cells
.b) opsonization of microbes
.c) chemoattractants for neutrophils
.d) participates in inflammation
e) inhibits cytokines