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 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 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 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 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 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 x 10 3 per ml - carry oxygen platelets x10 3 per ml - help clotting white cells - 8 x 10 3 per ml - immune system

Bone marrow Source of cells

Major cells of the immune system T cell B cell lymphocytes neutrophilmonocyte

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 Macrophage in tissue “present” antigen monocyte

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 immune system Alberts et al.

Lymphocytes Importance discovered in 1950s 2 x 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 Alberts et al. Resting lymphocyteActivated B cell Activated T cell

T cells - antigen receptor alpha chain beta chain

Monocytes Macrophage in tissue “present” antigen monocyte

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 - help - suppress - kill B cell antibody

Immune system Non-specific Neutrophils Macrophages Complement Mechanical “INNATE” Specific Lymphocytes “ADAPTIVE”

Immune system InnateAdaptive work together close collaboration

Specific immunity T and B lymphocytes Specific response to a single antigen Memory for that response