Immunology Introductory course 2010 Series of lectures outlining - components of immune system, relevance to human disease.

ImmunologyIntroductory 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

• 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 - 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

T cell

B cell

lymphocytes

neutrophil 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 materialdigest 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 ofimmune system Alberts et al.

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

Alberts et al.

Resting lymphocyte ActivatedB 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

Innate Adaptive

work togetherclose collaboration

Specific immunity

• T and B lymphocytes

• Specific response to a single antigen

• Memory for that response