Transcript Immunology Introductory course Series of lectures outlining

Immunology
Introductory course
2010
Series of lectures outlining components of immune system,
relevance to human disease
Immunology - an introduction
Conleth Feighery MD
John Jackson PhD
Derek Doherty PhD
Jacinta Kelly PhD*
Department of Immunology, Trinity College and St. James’s
Hospital
* Our Lady’s Hospital for Sick Children, Crumlin
Immunology
- purpose of course ?
• Learn some basic biology
• Learn about medical practice
• Learn to learn !
Immunology
What is it all about ?
• How the ‘immune system’ works
What does the immune system do ?
• 2 major functions • protects against infection
• causes ‘inflammation’
Major causes of ill-health
• Infection - 13 million die each year
• Inflammatory diseases - asthma
• Blood vessel disease - ‘atherosclerosis’ heart attacks, strokes
• Cancer
Immune system plays a significant role in all
these disorders.
Medical case history. 1
• 24 year old male
• Coughing and wheezing at night
• Examination - nasal speech, breathless;
wheezing
• DIAGNOSIS ?
Medical case history. 1
• DIAGNOSIS - asthma
• Mechanism - “inflammation” in lungs,
sinuses
• Cause - IgE, mast cells, white cells
Medical case history. 2
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3 year old boy
Serious lung infections x 5
Chest X-ray - “pneumonia”
Small size, weight
DIAGNOSIS ?
Medical case history. 2
• DIAGNOSIS - immune deficiency
• Mechanism - unable to produce antibodies
• Antibodies “fight” infection
Medical case history. 3
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7 year old girl
Widespread red rash, high temperature
Headache
DIAGNOSIS - measles
Cousin in same class, school - remains well
EXPLANATION ?
Medical case history. 3
EXPLANATION • Cousin was given measles vaccine!
• How do vaccines work?
• Antibodies to vaccine develop - e.g. to
measles vaccine
• “Educate” the immune system
• Real infection is rapidly eliminated
Immunology
An approach to study • lectures
• discussion !!
• textbooks
Immunology - terminology
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Difficult !
“immunobabble”
Learn some of the “language” - key terms
Abbreviations - useful, standard
Keep a list ?
Use it !
Immunology - reading
• Self-learning is an objective of the
University experience!
• Develop habit of seeking information - not
relying on ‘being taught’
• Internet offers endless opportunities for
information
Textbooks
A large variety exists - many too complex
• Few include full spectrum of this course
• B. Alberts - Molecular Biology of the Cell
• C.Janeway - Immunobiology
• H.Chapel, M.Haeney - Clinical Immunology
Immune system - components
Essential ‘nuts, bolts’
• white cells
• proteins
• organs
• circulatory system
• comprise - integral part biology
Immune system - components
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white cells - found in the blood, and tissues
proteins - also found in blood, and tissues
organs - such as the spleen, tonsils
circulatory system – blood, lymphatics
Circulatory systems
• arterial - blood
• venous - blood
• lymphatic - lymph
Blood circulation
Cells of blood include:
• red cells - 5000 x 103 per ml - carry oxygen
• platelets - 300 x103 per ml - help clotting
• white cells - 8 x 103 per ml - immune
system
Bone marrow
• Source of cells
Major cells of the immune
system
lymphocytes
T cell
neutrophil
B cell
monocyte
Multiple blood cell types
Fate of circulating blood cells
• Red cells - live 120 days; in blood vessels
• Platelets - live 10 days; in blood vessels
• Neutrophils - live ~ 1 day, migrate into
tissues
• Lymphocytes - majority short lived
- some live for years
- constantly circulate
2 types of lymphocytes
T
B
Mature in thymus - regulate, kill
Mature in the bursa - antibody
Lymphocytes
Resting lymphocyte
Neutrophils
ingest foreign material
digest it
“phagocytosis”
Neutrophils
Monocytes
monocyte
Macrophage in tissue
“present” antigen
Monocyte
Antigen
Definition
Any substance which • causes a lymphocyte reaction
• reaction is specific to that lymphocyte
• clone - single type of lymphocyte which
reacts to an individual antigen
Antigen
Example In the case of a B lymphocyte • Antibody is produced
Antigen
Examples • infectious agent - bacteria, virus
• tissue - from another person - transplant
• food !!
Antigen - immune response
Irradiation destroys bone marrow and cells of
Alberts et al.
immune system
Lymphocytes
• Importance discovered in 1950s
• 2 x 1012 in body = size of liver
• able to transfer “immune responses” to
irradiated animals
Lymphocytes - immune response
Alberts et al.
T lymphocytes
• Originate in bone marrow
• Mature in thymus
• Enter circulation
FUNCTION
• Control the immune system
• Eliminate infection - e.g. virus, fungus
Thymus - human
Importance of thymus
• Removal at birth - no T cells
• Absence in children - no T cells
Thymus in birds
Alberts et al.
Thymus absence in child
Smallpox vaccination - spread throughout body [live virus]
B lymphocytes
• Originate in bone marrow
• Mature in bursa (equivalent)
• Enter circulation
FUNCTION
• Become antibody producing “plasma” cells
• Absence - no antibody
B cells develop in bursa
Bursa in man unknown - may be the bone marrow
Alberts et al.
B cell identification
B cells have a specific receptor
for antigen
antibody molecule
B cell binding antigen
B cells have a specific receptor
for antigen
antigen
Antibody molecule
T and B cells - electron
microscope
Resting lymphocyte
Alberts et al.
Activated T cell
Activated
B cell
T cells - antigen receptor
alpha chain
beta chain
Monocytes
monocyte
Macrophage in tissue
“present” antigen
Macrophage - appearances
Monocyte
Macrophage - scanning
electron microscope
Monocytes
• Originate in bone marrow
• Enter circulation
• Migrate into tissues - change shape ---“macrophage”
• Phagocytic cell
• Present antigen to T cells
Dendritic cells
Antigen presenting cells - key role in
initiating T cell response to antigen
Macrophage/dendritic cell collaboration
T cell
B cell
- help
- suppress
- kill
antibody
Immune system
Non-specific
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Neutrophils
Macrophages
Complement
Mechanical
• “INNATE”
Specific
• Lymphocytes
• “ADAPTIVE”
Immune system
Innate
Adaptive
work together
close collaboration
Specific immunity
• T and B lymphocytes
• Specific response to a single antigen
• Memory for that response