Overview Of The Immune System

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Overview Of The Immune System
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Immune System
a Defence System
b Extremely adaptable
c Generates a variety of cells and molecules
Immune Response
Two interrelated activities
1 Recognition
2 Response
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Recognition
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Response
Also known as effector function.
Eliminate or neutralize foreign organisms.
Later exposure to same foreign organism ? memory
response ? heightened immune reactivity.
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Immunity
State of protection from infectious diseases
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Nonspecific Immunity
Basic resistance to disease that a species
possesses
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Anatomic Barriers
Skin Sebaceous Glands ? secrete sebum ? low pH
(3-5) ? Inhibitory to growth of most
microorganisms.
Mucous membranes of the respiratory/GI/Urogenital
tracts
Secrete mucuc ? traps microorganisms and expels
them by movement of celia.
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Physiologic Barriers
Temperature
pH
Soluble factors Gastric juice acidic ? organisms
cant survive.
Newborns ? less acidic gastric juice ? more
susceptible to infections.
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Soluble factors Complement serum proteins that
are non active. when pathogen enters ?
activated ? membrane damaging reactions ? clear
infections
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Endocytic and Phagocytic Barriers
Endocytosis Macromolecules in the ECF
internalized by cells
Phagocytosis More specialised and involves
plasma membranes expanding around
macromolecules
Specialized phagocytic cells include monocytes,
macrophages and neutrophils.
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Inflammatory Response
Signs Redness (Ruber) Swelling (Tumor) Heat (Col
ar) Pain (Dolor)

• Three major events
• Vadodilation
• Increased capillary permeability
• Influx of phagocytic cells (chemotaxis)

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Specific Immunity
Reflecting the presence of a specific and
functional immune system
Properties of self immunity
SPECIFICITY
DIVERSITY
MEMORY
SELF/NONSELF RECOGNITION
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Cells and Organs of The Immune System
Cells of The Immune System
WBC or leukocytes ? development of immune
response.
LYMPHOCYTES are CORE cells of the immune system.
WHY?
SPECIFICITY
DIVERSITY
MEMORY
SELF/NONSELF RECOGNITION
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Remaining WBC _at_ Activate lymphocytes
_at_ Increase effectiveness of antigen
clearance _at_ Secrete immune
effector molecules
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Cells of The Immune System
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Haematopoiesis
Formation and development of white blood cells
and red blood cells from stem cells
Begins in the yolk sac in the first few weeks of
embryonic developments
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Stem Cells
1/104 bone marrow (BM) cells
Pluripotent (Differentiate along a number of
pathways).
Two main lineages from stem cells
Lymphoid stem cells
Myeloid stem cells
These further differentiate into committed
progenitor cells.
Progenitor cells respond to particular growth
factors ? differentiation to mature RBCs and
WBCs.
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Lymphoid Cells
Lymphocytes are WBC responsible for immune
response.
Based on function and cell membrane components
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Effector cells B cells Plasma cells T cells
T helper cells (TH) and cytotoxic T cells (CTL)
Lymphocytes express glycoprotein as membrane
cluster of differentiation (CD)
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B Cells
Mature in the BM.
Mature B cells have antibodies (Ab) on their
surface (? 1.5x105 molecules/cells).
All antibodies on a single B cell have identical
binding sites for antigen (Ag).
B cells express CD45
B cells also express MHCII ? functions as
antigen presenting cell (APC).
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B Cells
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T Cells
Produced in BM. Matures in thymus.
Recognise Ag ONLY if presented on MHC complex.
Possess distinctive membrane molecules.
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T Cell Subtypes
T Helper Cells (TH)
Express CD4 and are class II restricted.
Secrete lymphokines ? activation of B cells,
cytotoxic T cells and other immune cells.
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Cytotoxic T Cells (TC)
Express CD8 and are class I restricted.
Ratio of THTC is 21 in normal blood.
Altered in autoimmune diseases and
immunodeficiency.
Suppressor T Cells (TS)
Not isolated yet.
May suppress humoral and cell-mediated immunity.
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Null Cells
Lack CD4 and CD8.
Lack specificity and memory.
Natural killer cells (NK).
5 - 10 of lymphocyte population.
Display cytotoxicity towards a variety of
tumours, in absence of previous immunisation
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Natural Killer Cells
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Mononuclear Cells
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Macrophages
Either fixed or free.
Motility by amoeboid movement.
Nomenclature depends on location KidneyMesangial
cells Liver Kupffer cells Connective tissue
Histiocytes Lung Alveolar macrophages Brain
microglial cells.
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Macrophages
Activation by IFN? from TH cells.
Activated Macrophages
a) Secrete more inflammatory mediators.
b) Increased microbicidal activity
c) Increased activation of T cells
d) Increased expression of MHCII ? better as APC.
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Phagocytosis
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Neutrophil
Granulocytes
Eosinophil
Basophil
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Neutrophils
Stain with both acidic and basic dyes.
Increased number indicated infection.
First arrival at site of inflammation.
Possess phagocytic properties
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Eosinophils
Stain with Eosin Y (acidic dye).
Less phagocytic than neutrophils
Important in fighting parasitic infections.
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Basophils
Stain with methylene blue (basic dye).
Non phagocytic
Major role in allergic reactions
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Mast Cells
Skin and connective tissues of organs.
Granules containing histamine ? development of
allergies.
Dendritic Cells
Express high levels of MHCII ? good APC.
Capture Ag in tissue then travel to lymphoid
organs where they present it to T cells.
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Organs Of The Immune System
Primary Organs
Sites of maturation of lymphocytes.
Thymus T cell maturation Bone marrow B cell
maturation
Lymphocytes then become IMMUNOCOMPETENT
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Secondary Organs
Trap antigens
Sites of interaction between immunocompetent
cells and the antigen.
Lymph nodes Trap antigen from intracellular
fluids
Spleen Trap antigens from blood
Mucosal-Associated Lymphoid Tissue (MALT) Trap
antigens entering from several mucous membrane
surfaces.
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Thymus
Cortex Densely packed with thymocytes ?
maturation begins.
Medulla Sparsely populated with thymocytes ?
fully mature.
Exit thymus via postcapillary venules.
T cell receptor diversity generated by a series
of random gene rearrangements.
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Positive Selection
T cells recognizing self MHC molecules are
released from thymus.
Negative Selection
Self-reactive thymocytes (i.e. recognise MHC
self antigen) are eliminated.
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Secondary Lymphoid Organs
Lymph is produced from plasma seeping through
thin capillary walls.
Lymph Nodes
Contain Lymphocytes, macrophages and dendritic
cells.
Cortex, paracortex and inner medulla.
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Cortex B lymphocytes and macrophages B
cells differentiate into plasma and memory cells.
Paracortex T lymphocytes and dendritic cells.
Medulla Plasma cells secreting antibody.
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Humoral and Cell-Mediated Immunity
Humoral Immunity
Immunity conferred on a nonimmune individual by
administration of serum antibodies from an immune
individual
Antibodies produced interact with antigens and
the antigen is then eliminated.
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Cell-Mediated Immunity
Immunity only transferred on by T cells
Cytokines secreted by TH cells ? activate
phagocytic cells B cells.
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Recognition Of Antigen by B and T
Lymphocytes
Lymphocytes recognise DISCRETE sites on the
antigen called EPITOPES.
B cells recognise epitopes alone. T cells
recognise epitopes in association with MHC
molecule on the surface of a self cell.
Humoral branch Recognise enormous variety of
epitopes on bacteria, viruses and soluble
proteins from invading pathogens.
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Cell-Mediated branch Recognise altered self
cells such as a virus-infected self cell and a
cancerous cells.
Generation of Lymphocyte Specificity and
Diversity
Mature immunocompetent humans contain large
numbers of antigen-reactive clones of B and T
cells.
Specificity of each clone is determined by random
rearrangements in the bone marrow during
maturation of the lymphocytes.
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Antigen processing and Presentation
Processing Conversion of proteins into
MHC-associated peptide
fragments
Presentation of antigen with MHCI or MHCII
molecules is determined by route of entry of
antigen into the cell.
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Exogenous Antigens
Produced outside host cell.
Enters cell by endocytosis or phagocytosis.
Associated with MHCII on APC.
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Endogenous Antigens
Produced within the host cell.
Degraded endogenously into peptide fragments.
Associated with class MHCI molecule.
Examples are viral proteins within cells and
unique proteins synthesized by cancerous cells.
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Clonal Selection
Role of antigen is to SELECT for and EXPAND
population of lymphocytes with a given genetic
specificity.
Humoral and Cell-Mediated Responses
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Reading
Immunology. Janis Kuby. W.H.Freeman and
Company Chapters 1 and 3