Transcript Document

Resistance of the body to infection:
Inflammation.
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Objectives
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Define Monocyte –Macrophage Cell System and
describe how monocytes are converted into
macrophages.
List the body tissues where this system is active.
Describe the functions of macrophages
Define Inflammation
Describe the stages of inflammation
 Recommended reading: Tortora & Derrickson. .
Principles of Anatomy and Physiology.12th edn. 2009
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The MPS (Mononucleur phagocytic
system) (RE System)
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Monocytes leave circulation to enter
tissue
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Enlarge in size as they move towards
site of inflammation/infection
(WANDERING MACROPHAGES)
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Some collect at specific sites in body
tissues
(FIXED MACROPHAGES)
Secrete Interleukins which stimulate
bone marrow
NO macrophages in the CNS: job done
by MICROGLIA
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Phagocytosis by macrophages
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1. Chemotaxis
2. Adherence
3. Ingestion
4. Digestion
5. Killing
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1 CHEMOTAXIS Microbe
Phagocyte
2 ADHERENCE
3 INGESTION
Pseudopod
Lysosome
Plasma
membrane
4 DIGESTION
5 KILLING
Digestive
enzymes
Digested microb
in phagolysosom
Residual body
(indigestible
material)
Phases of phagocytosis
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Inflammation: nonspecific response of the body
to tissue damage.
Caused by
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bacterial infection, trauma, chemicals, heat, hypoxia
Cardinal signs
 1. Redness
 2. Pain
 3. Heat
 4. Swelling
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Redness; Swelling; Heat
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vasodilatation
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increased capillary permeability to allow leakage
of fluid into interstitial spaces along withy WBCs
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(Emigration of WBCs)
As result of release of
Histamine from mast cells, basophils
Kinins (bradykinin) peptides : chemotaxis
Prostaglandin E from damaged tissues
Leukotriens from basophils and mast cells
- increase adherence of phagocytes
- increase permeability
- act as chemotactic agents
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Pain Kinins & PGs stimulate free nerve endings
Local edema produces pressure and pain
Release of clotting factors to localize the
bacteria
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Response of WBcs during inflammation:
1st line of defence: Locally present macrophages reach the
site of injury within a few minutes and start phagocytosis.
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2nd line of defence
i. neutrophils are attracted to the inflamed area by
CHEMOTAXIS.
ii. increase capillary permeability
iii. neutrophils stick to capillary walls at the site of
inflammation (Margination)
iv. stored neutrophils are brought into circulation
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All this takes a few hours . The neutrophils which are now plenty at site of injury
start their phagocytic action.
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3rd line of defence
More macrophages are recruited to come to the inflamed area. Takes about 8
hours before the newly formed monocytes and granulocytes come into the area.
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4th line of defence
Formation of these cells by bone marrow : stimulation by Interleukins, Tumour
Necrosis Factor, GM and M Colony Stimulating Factors secreted by activated
macrophages. Takes 3-4 days
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Macrophages also initiate immune process such as activation of T and B
lymphocytes
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Collection of all these cells with the necrotic tissue forms PUS
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Throbbing pulsating pain: presence of PUS
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Recap:
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Monocyte –Macrophage Cell System: The
Wandering & the Fixed macrophages.
Body tissues where this system is active.
Phagocytosis by macrophages
Inflammation
Stages of inflammation
Pus formation
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Innate and acquired immunity
Innate Immunity
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Objectives:
Define and classify Immunity into the two types:innate and acquired.
 Describe the process of innate immunity
 Define the term antigen
 Describe the two types of acquired immunity: cell
mediated and humoral.
 Understand that two types of lymphocytes, T and B,
are responsible for acquired immunity
 Appreciate that B lymphocytes produce antibodies
 List the types of antibodies.
 Describe the principal of vaccination
 List commonly used vaccinations
 Define allergy and describe the role of IgE in allergy
 List common allergic conditions
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Immunity is the body’s ability to resist organisms
and toxins which may cause damage
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INNATE : external physical, and chemical barriers
present in the body at birth
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ADAPTIVE /ACQUIRED: immunity is the ability to
defend against specific bacteria, toxins, viruses, toxins –
substances called ANTIGENs
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IMMUNITY
Innate
Acquired
-Salivary lysozomes
-Tears with lysozomes
-Acid in stomach
-Macrophages/
-Neutrophils
-Skin as a barrier
-NK Cells
Cell mediated
Humoral
Antibodies
: B lymphocytes
Ig G commonest
IgM
IgE allergy
IgG A milk
Ig D rare:
unknown function
T lymphocytes:
1. Helper T cells
2. Killer: Cytotoxic)
3. Memory
4. Suppressor
NATURAL KILLER CELLS
Resemble early large T cells
Found in blood and lymphoid tissue
Recognize and destroy
virally infected cells
& cancer cells
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ANTIGENS are proteins/
polysaccharides which excite
immune mechanisms.
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Haptens small molecules which
must combine with proteins to
excite antigenicity
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Characteristics of antigens:
i. Immunogenicity: provoke
formation of specific antibodies
ii. Reactivity The antigen reacts
with the antibody it generates
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Innate Immunity
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Present at birth
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Involves external physical, and chemical barriers
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Helps humans resist diseases such as
- Distemper ) ‫( سل الكالب‬
- Cattle plague ) ‫( طاعون الماشية‬
- Viral infections of animals
(Lower animals do not get many human diseases:
Polio, Mumps, Cholera, Syphilis, Measles)
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Interferons: (α, β, γ) :
proteins produced by viral infected
- lymphocytes
- macrophages
- fibroblasts
Mechanism of action:
-enter non-infected cells
-induce production of anti-viral proteins
- stop viral multiplication
CANNOT STOP VIRUSES FROM ENTERING
CELLS
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Complement system C1-C9:
- proteins which are normally lying inactive in
blood
Action: when activated by antibodies- increase
phagocytosis, promote inflammation
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Iron binding proteins
Action: deprive bacteria of iron by binding to it
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Antimicrobial proteins
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i. Defensins & Cathelicidins by Neutrophils and macrophages,
epitheila:
ii. Dermicidin by sweat glands
iii. Thrombocidin by platelets
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Natural Killer cells (NK Cells)
Lymphocytes Effective against tumour cells, viral
infected cells, any cells which have
abnormal proteins
Action by:
i. Release of proteins called PERFORINS_ dig holes in
to the cell membrane- cell gets flooded with H2O) from
ECF and cell bursts
CYTOLYSIS
ii. Release of GRANYZYME which promote cell
apoptosis
 Inflammation
 Phagocytosis by Macrophages and Neutrophils
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ACQUIRED IMMUNITY
(Adaptive immunity)
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Objectives: Innate and acquired immunity 2 & 3
Define Acquired immunity as CELL MEDIATED &
HUMORAL
 Describe the role of the thymus in processing of T
lymphocytes
 List the 4 types of T lymphocytes involved,
appreciate that AIDS is a disease caused by ineffective
 T lymphocyte functions .
Recognition of self
 Recognize that transplanted organs are likely to be
destroyed by cell mediated immune mechanisms.
 Define auto-immune disease
 Name important autoimmune disorders.
 Appreciate that stress and aging affect immune
mechanisms adversely
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Acquired (Adaptive) immunity is the ability to
defend against specific bacteria, toxins, viruses,
toxins – substances called ANTIGENs
i. Cell mediated immunity:
-by activated T Lymphocytes in the lymph nodes:
-active in tissues
ii. Humoral
-by activated B lymphocytes which develop
circulating antibodies.
-active in blood
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IMMUNITY
innate
acquired
humoral
Cell mediated
Salivary lysozomes
Tears
Acid in stomach
Neutrophils
Skin as a barrier
B lymphocytes
Become plasma
cells
Produce
antibodies
T lymphocytes:
1. Helper T cells
2. Killer: Cytotoxic)
3. Memory
4. Suppressor
Antibodies
:
Ig G commonest
IgM
IgE allergy
IgG A milk
Ig D rare:
unknown function
Antigen: foreign substance:
protein, which excites immune reaction
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The activation of Lymphocytes
Origin of lymphocytes:
Pluripotent stem cells in the embryo
Bone marrow
Develop in marrow: as - B lymphos
& Pre T lymphos
mature in the Thymus- T lymphos.
Reach
Immunocompetence by developing
antigen receptors on their surface
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Activation of lymphocytes so that they develop
IMMUNOCOMPETENCE
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T lymphocytes migrate to thymus before birth, and continue until
a few months post birth and B lymphocytes s go to the bone
marrow (& liver ?)
Rapid division
Specific reactivity to antigens and development of antigen
receptors
Non-reactive to “self”
T cells released from Thymus go to different lymphoid tissues as
Helper T cells (CD4 cells) and Cytotoxic T cells ( CD8 cells)
B lymphocytes: develop antibodies against the antigens and
become PLASMA cells
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The Helper T cells, Cytotoxic T cells and B cells are EFFECTOR
cells: die after taking part in immune activity
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Clone ) ‫ ( إستنساخ وطبيا النسيلة‬formation by lymphocytes
Both B and T cells are involved
Exposure to a particular antigen excites “cloning” of that type
of cell or make IDENTICAL cells by CLONAL
SELECTION (proliferation & differentiation)
Any time this antigen re-enters the body, these clones are
formed to destroy it
Role of MEMORY cells, both T and B
Are not associated with the initial response to antigen
They “REMEMBER” when an antigen enters body again,
and act by initiating formation of more clones of that type
of lymphocyte
They do not die: they have a long life.
Types of Memory cells: Helper, Killer, B
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T lymphocytes
i. Helper T cells
ii. Cytotoxic T cells
iii. Memory T cells
iv. Suppressor T cells
I & ii = Regulatory T cells?)
B lymphocytes
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Maturation and function of B lymphocytes
B lymphocyts are activated by HELPER T & B
cells
Formation of plasma cells: manufacture
ANTIBODIES against specific antigen
Antibodies
Ig G- commonest
IgM
IgE - allergy
IgA - milk
Ig D rare:
unknown function
Antigen-Antibody reactions
1.
2.
3.
4.
5.
6.
Agglutination ) ‫( متراصة‬
Enhance phagocytosis
Neutralizes antigen
Demobilizes bacteria
Activation of complement system
Precipitation of soluble antigens
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Physiological principles of
immunization
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Small dose of non virulent
antigen (bacteria/virus) is
given
Antibodies are formed
against this (type IgM).
This is the PRIMAY
response
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IgG
IgM
Few weeks later same
antigen dose is repeated:
much bigger antibody
response: Secondary
response- IgG )
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Common vaccinations:
Bacterial
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DPT
Typhoid
Cholera
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Viral
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Polio
Measles
Influenza
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Use of immunity for protection
1. Active immunity:
vaccinations
2. Passive immunity
a. Mother to fetus : IgG antibodies via placenta
Ig A in milk
b. Injection of Immunoglobulins
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Aging & Immunity
- Old people get infections/cancers more easily
- Response to vaccines is decreased
- They produce more auto-antibodies to own tissues
- T cells respond less to antigens
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Stress and Immunity
- Decreases in stress: effect of main stress
hormone: corticosteroids
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MHCs Major Histocompatibility Complexes (MHCs)
Human Leucocyte Antigen (HLA)
MHC I : present on all body cells (NOT RBC)
MHC II : on Antigen presenting cells
(Macrophages, Dendritic cells, B cells)
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Process of antigen presentation: Exogenous antigens:
outside cells (bacteria, toxins, pollens, viruses)
1. Ingestion and digestion of antigen
to form peptide fragments
4. Peptide s and MHC II then fuse
To form a complex
5. Complex inserted in to
plasma membrane
2. Synthesis of MHC II molecule
in the ER and their packaging
3. Peptide fragments +
MHC II mols Vesicles fuse
6.APC then migrates to lymphoid tissue
To meet lymphocytes through receptors
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Key:
1 Phagocytosis or
endocytosis of
antigen
Exogenous
antigen
5 Vesicles containing antigen
peptide fragments and
MHC-II molecules fuse
6 Antigen peptide
fragments bind to
MHC-II molecules
Antigen
peptide
fragments
MHC-II
self-antigen
Phagosome
or endosome
Antigenpresenting
cell (APC)
2 Digestion of
antigen into
peptide fragments
4 Packaging of MHC-II
molecules into a vesicle
7 Vesicle undergoes
exocytosis and
antigen–MHC-II
complexes are inserted
into plasma membrane
Endoplasmic
reticulum
3 Synthesis of MHC-II molecules
APCs present exogenous antigens in association with MHC-II molecules
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Endogenous antigens : INSIDE body cells (toxins,
viral proteins, abnormal proteins by cancer cells)
Digestion of these proteins
Peptide s and MHC I then fuse
To form a complex
Complex inserted in to
plasma membrane
Formation of MHC I
Peptide fragments +
MHC I mols Vesicles fuse
APC then migrates to lymphoid tissue
To meet lymphocytes through receptors
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Endogenous Antigens
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Recognition of SELF
T cells must know own MHC s :SELF RECOGINITION
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T cells must NOT react to own peptide fragments : TOLERANCE
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Positive selection
Immature T cells (before activation) form receptors that react with self
MHCs & form a self antigen-MHC binding & recognize the MHC
T cells that don’t form and recognize this complex under go cell death
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Negative selection
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i. Deletion: self reactive T cells undergo natural cell death (apoptosis)
ii. Anergy : Unresponsive to antigen stimulation
Tolerance to SELF (own tissue) develops during embryonic life
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Abnormal immune reactions:
Basically categorized as HYPERSENSITIVITY:
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Allergy: Harmful effects of hypersensitivity to
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environmental (exogenous) antigen
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Autoimmune disease: when the body defence
mechanisms act against the self.
When immune mechanisms of one individual produces
reactions in another person, it is know as ALLO
IMMUNITY.
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AUTOIMMUNE disorders
Non recognition of SELF causes this reaction.
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Sequestered antigens: tissue not drained by body lymphatics,
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have never been exposed to body immune mechanisms. Eg.
Cornea of the eye. That is why anybodies cornea can be grafted on to
anyone else’s eye. But if accidentally such tissue enters the body, it will excite a
severe immune response.
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Neo(new) antigens a chemical binds to a body tissue, forms a
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Infectious disease may induce formation of a substance which is
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Rheumatic heartdisease; glomerulonephritis
Supressor cell dysfunction the negative feed back control is not
new antigen which is now new to immune mechanisms of the
host.
similar to one of the host tissues. This then excites a reaction. Egs.
there.
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ALLOIMMUNITY: Immune system of one individual
reacts against antigens of another individual: classically
mismatched blood transfusion reactions, and Hemolytic
disease of the new born (Rh factor deficiency)
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CONGENITAL immune deficiency:
Agammaglobulinemia
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HIV as a immune disorder. This is an ACQUIRED
immune deficiency syndrome
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HIV is a RETRO virus. It carries a RNA which enters the host
cell by combining with a cell surface receptor and then converts
into a DNA. Once inside it may increase in number.
CD4 lies on surface of Helper T cells. HIV attaches to it, enters
Helper T cells, and then destroys them.
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Some autoimmune diseases
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Hashimoto’s Thyroiditis (Hypothyroid disease)
Graves Disease (Hyperthryroidism)
Myasthenia Gravis
Multiple Sclerosis
Atrophic gastritis
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