INTRODUCTION TO IMMUNOLOGY

Dr Lynda Partridge

Dept. Molecular Biology & Biotechnology

(l.partridge@sheffield.ac.uk)

Introduction

Overview of Immunology

Innate and adaptive immunity

Adaptive Immunity

Humoral (Antibody) Immunity

Cell-mediated (T cell) immunity

Reading: Lodish et al “Molecular Cell Biology”

Roitt “Essential Immunology”

British Society for Immunology http://bitesized.immunology.org/

IMMUNOLOGY is the study of the IMMUNE SYSTEM

• Integrated system of cells and molecules that defends

against disease

reacts against infectious pathogens

Pathogens

Bacteria (1-5m) Staphlyococcus aureus (MRSA) Boils, septicaemia

Myocbacterium tuberculosis TB

Viruses (20-400nm) HIV AIDS

Influenza virus Flu

Fungi (2-20m)

Candida albicans Thrush

Epidermophyton flocosum Ringworm

Parasites (1m – 10m)

Schistosoma mansoni Schistosomiasis

Trypanasoma brucei Sleeping sickness

• Medical importance

vaccination

malfunctions

immunodeficiency

allergy

autoimmune disease

graft rejection

• Immunological reagents (antibodies) are useful

research

diagnostics and therapeutics

IMMUNE SYSTEM

INNATE ADAPTIVE

Broad specificity Highly specific

Resistance not improved by Resistance improved by

repeat infection. repeat infection.

Rapid response (hrs) Slower response (days-

weeks)

Leucocytes

phagocytes, B lymphocytes

natural killer T lymphocytes

(NK) cells

Soluble factors

lysosyme, antibody

complement,

interferons etc.

KEY CONCEPTS

•Immune system reacts against NON-SELF molecules

(ANTIGENS) or recognises DANGER.

•Following primary contact with antigen there are

INNATE and weak adaptive responses. Secondary

contact with antigen results in enhanced ADAPTIVE

responses.

•The immune system is TOLERANT of the body’s

own cells and molecules.

EXTERNAL BARRIERS TO INFECTION

Keratinized skin

Secretions

Mucous

Low pH

Commensals

PHAGOCYTES

Neutrophils

Mononuclear phagocytes

monocyte macrophage

(blood) (tissues)

Main phagocyte in blood

Short-lived, fast-moving

lysosomes release enzymes, H2O2 etc.

Long-lived (months- years)

Help initiate adaptive

responses

Elie Metchnikoff 1883

INNATE IMMUNE MECHANISMS

LEUCOCYTES (white blood cells). Originate in bone marrow

NATURAL KILLER (NK) CELLS

type of lymphocyte - recognise “altered self”

- kill virally infected cells

- may kill cancer cells

- induce apoptosis (cell suicide)

PATHOGEN RECOGNITION BY INNATE CELLS

Phagocytes – have general pathogen-recognition receptors

(PRRs) that recognise pathogen-associated molecular

patterns (PAMPs)

e.g. Toll-like receptor 4 recognises lipopolysacchride (LPS)

Natural killer cells - kill targets unless they recognise a

self-protein (MHCI)

e.g. COMPLEMENT SYSTEM

• 20 proteins in blood, activated on infection

• inflammation, cell lysis, phagocytosis

e.g. DEFENSINS

• Positively charged peptides made by neutrophils

• Disrupt bacterial membranes

e.g. INTERFERONS

Produced by virally infected cells

• protect uninfected cells

• activate macrophages and NK cells

SOLUBLE FACTORS

INFLAMMATION

• Localised response to infection/damage

• dilation of blood vessels

• increased capillary permeability

• phagocytes migrate into tissues

Integrated responses to infection/injury

Induced by the production of CYTOKINES

ADAPTIVE (SPECIFIC) IMMUNITY

Adaptive immune responses are initially slower to

develop than innate response, but show SPECIFICITY

and MEMORY.

Foreign material (ANTIGEN) is recognised by specific

receptors on T and B LYMPHOCYTES

Receptor: Antibody T cell receptor

ADAPTIVE IMMUNITY

B LYMPHOCYTES T

Mature: Bone marrow Thymus

Stem cell precursor

(bone marrow)

Central lymphoid tissue

(antigen independent differentiation)

Peripheral lymphoid tissue

(antigen-dependent differentiation)

Lymph nodes,

spleen etc.

antigen antigen

Lymphocyte receptors are specific and diverse

Lymph nodes,

spleen etc.

antigen antigen

Response: secrete antibody kill infected host cells; make

cytokines

Immunity: Humoral Cell-mediated

Infections: extracellular bacterial, viral, intracellular bacterial,

2ndry viral intracellular parasitic

ANTIGEN

ANTIBODIES (anti-foreign bodies) are produced in

response to ANTIGEN (antibody generating material)

Bacterium

Antigen

2

1

3

2

2

2 2 2 2

2 2 2 2 2 2 2 2

Plasma cells

Production of antibody 2

Clonal selection

Memory

cells

Clonal Selection Hypothesis

Lymphocytes that

recognise “self” are

deleted early in

development Macfarlane Burnett 1957

CELL-MEDIATED (T CELL) IMMUNE RESPONSES

Clonal expansion, differentiation, memory

NOTE: T cells can only recognise antigen bound to host

cells

Organization of lymphoid tissue

Primary lymphoid tissue: lymphocytes reach maturity

Secondary lymphoid tissue: mature lymphocytes stimulated by

antigen

IMMUNE SYSTEM

INNATE ADAPTIVE

HUMORAL (B) CELL-MEDIATED (T)

PHAGOCYTES T HELPER CELLS

NATURAL KILLER T CYTOXIC CELLS

CELLS

COMPLEMENT ANTIBODY CYTOKINES