Transcript File

WHY DO WE HAVE AN
IMMUNE SYSTEM?
Immune system
diseases
Non specific
immunity
Disease survival
mechanisms
Physical & chemical
barriers
Infectious
Disease
Inflammatory
Response
Non-specific Cellular
response
NK cells
phagocytes
Specific
immunity
Transmission
Epidemiology
Vaccination
Public Health
Immunological
surveillance
Clonal Selection
theory
B cells
T cells
BIG PICTURE
Cells of the Immune System – many cells we will look specifically at these …..
Bone graft
Macrophage
Mast cell
Eosinophil
Erythrocytes
Marrow
Basophil
Monocyte
Bone
Megakaryocyte
Hematopoietic
stem cell
Multipotential
stem cell
Myeloid
progenitor Neutrophil
cell
Platelets
Lymphoid progenitor cell
Dendritic cell
T lymphocyte
B lymphocyte
Natural killer cell
THE HUMAN BODY HAS THE CAPACITY TO
PROTECT ITSELF AGAINST PATHOGENS,
SOME TOXINS AND CANCER CELLS
THROUGH THE IMMUNE SYSTEM
GLOSSARY TERMS;
•PATHOGEN – DISEASE CAUSING ORGANISMS
•TOXINS – POISONS PRODUCED BY ORGANISMS
•IMMUNITY – BODY’S ABILITY TO RESIST INFECTION BY A PATHOGEN OR
DESTROY THE ORGANISM IF IT SUCCEEDS
LEARNING OUTCOMES
• DISTINGUISH BETWEEN THE NON-SPECIFIC
AND SPECIFIC IMMUNE SYSTEM
• IDENTIFY THE THREE LINES OF DEFENCE
• EXPLAIN THE NON-SPECIFIC DEFENCES
IMMUNE SYSTEM ORGANISATION
SPLIT INTO 2 AREAS –
NON SPECIFIC AND SPECIFIC
1.NON-SPECIFIC IMMUNITY WORKS AGAINST ANY
TYPE OF DISEASE-CAUSING AGENT
2.SPECIFIC IMMUNITY WORKS AGAINST A
PARTICULAR PATHOGEN
NON-SPECIFIC PHYSICAL BARRIERS
EPITHIAL CELLS
• THE FIRST LINE OF DEFENCE AGAINST INFECTION.
• LINE THE SURFACES AND CAVITIES OF THE ENTIRE BODY.
• FORM SHEETS/ LAYERS OF CLOSELY PACKED CELLS.
SECRETIONS
• SOME EPITHELIAL CELLS PRODUCE SECRETIONS SUCH AS ENZYMES,
HORMONES AND LUBRICATING FLUIDS THAT CAN DEFEND AGAINST
INFECTION.
• MUCUS TRAPS DIRT AND GERMS, PREVENTING THEM FROM ENTERING THE
BLOOD.
• VARIOUS GLANDS PRODUCE ANTIMICROBIAL SECRETIONS THAT HELP KILL
MICROBES.
OTHER PHYSICAL DEFENCES
• TINY HAIRS AT THE ENTRANCE TO THE NOSE.
• COUGH AND SNEEZE REFLEXES.
• ‘FRIENDLY’
BACTERIA.
NON-SPECIFIC IMMUNITY
• FIRST LINE OF DEFENCE ARE PHYSICAL AND CHEMICAL BARRIERS
Line of
defence
Specific (s) or
non-specific (ns)
Mechanism employed
Function
1st
NS
Skin barrier
Epithelial cells intact
1st
NS
Mucus
Traps microbes in respiratory and
gastrointestinal tract
Remove microbe by sweeping
Cilia
1st
NS
Acid
Contains hydrochloric acid at pH 1.5 2.5 which has a disinfecting action on
the stomach wall and contents.
1st
NS
Sweat and sebaceous
Low pH inhibits microbial growth
1st
NS
Saliva and tears
Enzymes lysozyme digests bacterial
walls so it destroys them
Remember lysozyme - ZZZZZ for
sleep in your eye!
IMMUNE SYSTEM ORGANISATION
• SECOND LINE OF DEFENCE IS THE
INFLAMMATORY RESPONSE
• THIS OCCURS IF THE FIRST LINE ARE
BREACHED, BY A CUT/ PIERCING OR AN
INVASION OF AN INFECTIOUS
ORGANISMS
IMMUNE SYSTEM ORGANISATION
• SECOND LINE OF DEFENCE IS THE INFLAMMATORY RESPONSE
• THIS OCCURS IF THE FIRST LINE ARE BREACHED, BY A CUT/ PIERCING
OR AN INVASION OF AN INFECTIOUS ORGANISMS
• First line are breached, by a cut/piercing or an invasion of an
infectious organisms, bacteria, trauma, toxins, heat or any other cause
• Mast cells (type of white blood cell) in the connective tissue, releases
histamine
• Histamine causes blood vessels to become more permeable
• Vasodilation of blood vessels by injured site; causing swelling due to
stretchy capillary wall
• Cytokines (cell signalling molecules – many types like
TNF, IL 1-10 etc.) also released by damaged cells /
tissues
• Enhanced migration of phagocytes to the damaged
tissue by cytokines (phagocytes move to site) – next slide
• Cytokines also attract antimicrobial proteins to the
infected site which amplify immune response
• Cytokines attract blood clotting chemicals (complement)
to injury site thus preventing any blood loss / infection
to the wound and allows tissue repair to start
MAST CELLS HISTAMINE VASODILATION AND INCREASED CAPILLARY
PERMEABILITY  SECRETE CYTOKINES  PHAGOCYTOSIS  COMPLEMENT /
ANTIMICROBIAL PROTEINS  CLOTTING AND TISSUE REPAIR
PHAGOCYTOSIS
A phagocyte is motile (moves towards pathogen when chemicals
detected or antigens). It then engulfs pathogen (endocytosis) –
forming a phagocytic vesicle (vacuole) which merges with a lysosome.
Lysosomes contain digestive enzymes, which disposes of the pathogen
and released by exocytosis.
The phagocyte releases more cytokines – positive feedback
NATURAL KILLER CELLS
2
1. Protein from NK cell
inserts a pore into the
target cell membrane
1
3
3
2. Signal molecule
from NK enters cell
4
protease
vital cell protein
4. “suicide” proteins made
5. “suicide” protein function to make degradative enzymes
(protease / DNAase). Destroying vital proteins/DNA
4
Useless fragments of DNA
5
DNAase
DNA
5
Useless fragments
of protein
NATURAL KILLER (NK) CELLS
FINAL NON-SPECIFIC DEFENCE
• FOR VIRUS AND TUMOUR CELLS PREDOMINANTLY
• DISTINCT CLASS OF LYMPHOCYTES WHICH CAN WORK WITH
ANTIBODY-DEPENDENT CELLULAR CYTOTOXITY HOWEVER THEY
ARE NOT SPECIFIC – WILL ATTACK CELLS (DECIDE SELF/FOREIGN
BY LACK OF SELF ANTIGEN (MHC).
• A PORE RELEASED FROM NATURAL KILLER (NK) CELL
• NK CELL THEN RELEASES SIGNALLING MOLECULES
• THIS SIGNALS GENETIC CONTROL OF BOTH SELF DESTRUCTIVE
ENZYMES BEING RELEASED AND DNA / VITAL PROTEIN
BREAKDOWN
• PROCESS OF “CELL SUICIDE”, PROGRAMMED CELL DEATH IS
CALLED APOPTOSIS
NK CELLS
Perforin
Granzyme
Apoptosis
• Perforin released
forming a pore into
target cell membrane
• Granzymes enter the
cell, switch on genes
• Stimulating the cell to
produce enzymes
that degrade DNA –
inducing apoptosis
SECONDARY AFFECT WHICH LINKS TO THE SPECIFIC IMMUNE SYSTEM IS BOTH NK CELLS
AND PHAGOCYTES SECRETE CYTOKINES (INTERLEUKINS ) THAT SERVE TO STIMULATE THE
SPECIFIC IMMUNE RESPONSE THROUGH THE ACTIVATION OF T CELLS
NATURAL KILLER CELLS
2
1. Protein from NK cell
inserts a pore into the
target cell membrane
1
3
3
2. Signal molecule
from NK enters cell
4
protease
vital cell protein
4. “suicide” proteins made
5. “suicide” protein function to make degradative enzymes
(protease / DNAase). Destroying vital proteins/DNA
4
Useless fragments of DNA
5
DNAase
DNA
5
Useless fragments
of protein
COMPLEMENT SYSTEM
• THE PRESENCE OF BACTERIA AT THE
SITE OF INFECTION STIMULATES
ANTIMICROBIAL PROTEINS KNOWN
AS ‘COMPLEMENT’ TO ARRIVE AT THE
SITE OF INFECTION.
• THE COMPLEMENT SYSTEM HELPS THE
BODY TO RID ITSELF OF INFECTION BY
AMPLIFYING THE IMMUNE
RESPONSE.
CYTOKINES ....
• MADE BY DAMAGED TISSUE / WHITE BLOOD CELLS
• ENHANCE MIGRATION OF PHAGOCYTES (CHEMOTAXINS CHEMOATTRACTANTS) WHICH ENGULF/DIGEST
PATHOGEN AND RELEASE MORE CYTOKINES
• DELIVER ANTIMICROBIAL PROTEINS FASTER WHICH
AMPLIFIES IMMUNE RESPONSE
• DELIVER BLOOD CLOTTING CHEMICALS (COMPLEMENT)
WHICH SEALS THE WOUND AND HELPS TISSUE REPAIR
• HAVE A DUAL PURPOSE; NOT ONLY IN THE NON-SPECIFIC
DEFENCE BUT ALSO SPECIFIC DEFENCE SYSTEM BY
TRIGGERING LYMPHOCYTES (NEXT LESSON)
CLOTTING SYSTEM
• THE FINAL STAGE OF INFLAMMATION IS TISSUE REPAIR.
• WHAT DO YOU REMEMBER FROM UNIT 2?
• WHAT MOLECULES INVOLVED?
• WHAT IS PROTHROMBIN / FIBRINOGEN?
NON-SPECIFIC IMMUNITY
• SECOND LINE OF DEFENCE ARE INFLAMMATION CASCADE AND
CELLULAR RESPONSES
Line of
defence
Specific (s) or nonspecific (ns)
Mechanism employed
Function
2nd
NS
Inflammatory response
Inflammatory response initiated by
histamine and serotonin release from
basophils/mast cells attracts
phagocytes to infected region. Reduces
spread of infection throughout organism.
2nd
NS
Cellular response of phagocytes
(phagocytosis)
Ingestion and digestion of foreign
particles/microbes by neutrophils,
eosinophils, monocytes and macrophages.
2nd
NS
Cellular response of natural killer cells
(NK cells)
Attack virus and cancer cells by releasing
molecule which forms a pore in target
cells membrane which signals apoptosis
by self destroying enzymes
SUMMARY SLIDE
NON-SPECIFIC DEFENCES
PHYSICAL DEFENCES
• EPITHELIAL CELLS ON THE BODY SURFACE AND CAVITY LININGS FORM
A PHYSICAL BARRIER (SKIN/TRACHEA/OESOPHAGUS ETC.)
CHEMICAL DEFENCES
• MUCUS MEMBRANES SECRETE STICKY MUCUS TRAPPING
MICROORGANISMS
• ACID FROM EPITHELIAL CELLS IN STOMACH DESTROY INGESTED
MICROORGANISMS
• SKIN SEBACEOUS/SWEAT GLANDS PRODUCE LOW PH SECRETIONS
THAT ARE TOO LOW FOR MOST MICROBES TO SURVIVE
SUMMARY SLIDE
NON-SPECIFIC DEFENCES
INFLAMMATORY RESPONSE
• RELEASE OF HISTAMINE BY MAST CELLS CAUSES VASODILATION AND
INCREASED CAPILLARY PERMEABILITY.
• THE INCREASED BLOOD FLOW AND THE SECRETION OF CYTOKINES
RESULTS IN THE ACCUMULATION OF PHAGOCYTES AND THE DELIVERY
OF ANTIMICROBIAL PROTEINS AND CLOTTING ELEMENTS TO THE SITE
OF INFECTION.
SUMMARY SLIDE
NON-SPECIFIC DEFENCES
CELLULAR MECHANISMS
• A VARIETY OF SPECIALISED WHITE BLOOD CELLS PROVIDE PROTECTION
AGAINST PATHOGENS.
• PHAGOCYTES RECOGNISE SURFACE ANTIGEN MOLECULES ON
PATHOGENS AND DESTROY THEM BY PHAGOCYTOSIS.
• NATURAL KILLER (NK) CELLS INDUCE THE PATHOGEN TO PRODUCE SELF
DESTRUCTIVE ENZYMES IN APOPTOSIS.
• BOTH PHAGOCYTES AND NK CELLS RELEASE CYTOKINES WHICH
STIMULATE THE SPECIFIC IMMUNE RESPONSE.
• COMPLEMENT SYSTEM AMPLIFIES THIS IMMUNE RESPONSE.