A rough guide to the immune system

Dr Adrian PalfreemanSenior Clinical Scientist MRC CTU

Stem cells

Stem cells –why they matter

Neutrophil (polymorph)

• Multi-lobed nucleus.• Commonest leucocyte (2500-7500/mm3 of

blood).• A short-lived phagocytic cell whose granules

contain numerous bactericidal substances.• leave the blood to go to tissues where

infection or inflammation is developing

Eosinophil

• A leucocyte whose large refractile granules contain a number of highly basic or ‘cationic’ proteins,

• possibly important in killing larger parasites including worms.

• Bind avidly to IgE-coated particles (i.e. Helminthic parasites) .

• Abundant at sites of allergic reactions.

Components of the immune system

• Monocyte– The largest nucleated cell of the blood (16-20μm– diameter), developing into a macrophage when it– migrates into the tissues.

• Macrophage (A professional antigen presenting cell)– The principal resident phagocyte of the tissues.– Strongly phagocytic of particles and microbes.– Has receptors for Ig and complement.– CNS – “microglia”– Liver – “Kupffer cells”– Lungs – “alveolar macrophages”– Bone – “osteoclasts”

T lymphocyte (T cell)

• A thymus-derived (or processed) lymphocyte.• 1500 - 4000/mm3 blood• 6-15μm diameter (red blood cell 7.2μm

diam.)• 2 main subdivisions – CD8 (cytotoxic T cells)- CD4 (helper T cells)

• B lymphocyte– A bone marrow- (or in birds, bursa-) derived

lymphocyte, the precursor of antibody-forming cells. In foetal life, the liver may play the role of ‘bursa’.

• NK (Natural Killer) cells– do not have to recognise a specific antigen

before acting against it– are effective against a wide range of infectious

microbes.

The 2 arms of the adaptiveimmune response

1. Humoral immunity (antibodies)2. Cellular immunity (T-cells)• Sub-divided into T helper cells (CD4+) and• Cytotoxic T cells (CD8+)

CD4 Lymphocytes (T helper cells)

• coordinate much of the immune response to micro-organisms

• help B-cells respond to foreign proteins• secrete substances that enable CD8 T-cells to

proliferate• activate macrophages so that they can kill

certain organisms, including some organisms associated HIV infection.

CD8 Lymphocytes (Cytotoxic T cells)

• kill cells in the body identified as abnormal or foreign

• tumour cells • cells that have been infected by viruses.

How does HIV reduce CD4 Cells?

• Increased turnover of cells in response to infection

• Trapping of HIV in lymph nodes• Shortened survival of CD4 cells• Reduced production of new cells• Reduction of T cell progenitor production

from bone marrow

Sites of theprincipal

lymphoid tissueswithin the human

body.

Primary lymphoidorgans

Secondary lymphoidorgans

Human lymphoid organs

Primary lymphoidorgans

Secondary lymphoid

organs

• Lymphoid tissues– Immune system compartmentalised into

organs/tissues.– Funtionally unified via blood and lymph systems.– Lymphocytes recirculate.– In total, equivalent in weight to brain or liver.

• Primary lymphoid organs– Bone marrow where T and B lymphocytes are made.– Thymus where T lymphocytes mature/are selected.

• Secondary lymphoid organs– e.g. spleen, lymph nodes and Peyer’s patches.– Contain T cells, B cells, antigen presenting cells (APCs)

T cell precursors(thymocytes) migrate

from the bone marrowto the thymus to mature.

Mature T cells leave thethymus and migrate tosecondary lymphoid tissueswhere they may encounterforeign antigen.

Thymus

Lobules show - a lymphocyte-dense outer cortex- an inner lighter-staining medulla.Stromal framework with specialised epithelial cells, DCsand macrophages (APCs).T cell precursors arrive from the bone marrow.Cortex and medulla ‘educate’ thymocytes into mature,competent T cells (1 to 3% of T cells survive education).Mature T cells are released into the peripheralcirculation.

THYMUSDevelopingthymocytesoccupy the

interstices ofan extensivenetwork of

epithelial cells

Clusters of Differentiation (CD)

• CD3 T cells• CD4 Helper T cells• CD8 Cytotoxic T cells• CD16 Macrophages• CD19 B cells

Maturation of T lymphocytes in the thymus

Circulatinglymphocytes

meetlymph-borne

pathogensin draining

lymph nodes.

Lymph node

Cytokines

• Il2 stimulates division of B and T cells and killing of HIV infected cells by NK cells

• IL2 levels reduced in HIV infection

IL2

• Does administration of IL2 help?• Raises CD4 numbers• Significant side effects• Injectable • Short term benefit in clinical trials• Does it reduce mortality and morbidity in the

long term?

Summary • B cells recognise antigens (antigenic epitopes) via their monomeric IgM

receptor• T cells recognise antigens (small peptides)via the T cell receptor (TCR) which

is always associated at the cell surface with CD3 11• The monomeric B cell receptor (and, in fact, all antibodies) recognise

antigens in solution – in their native (folded) state• The TCR does not recognise soluble antigens but only small antigenic

peptides associated with the Major Histocompatibility (MHC) molecules I & II

• For a T cell or B cell to be activated 2 appropriate signals are always required

• T cells need binding of the TCR to peptide/MHC plus specific cytokines from the APC (notably IL- 1 and IL-2) and interaction between B7 and CD28

• B cells need binding of mIgM surface receptor plus signals from TH cells (notably IL-4 and IL- 10) and interaction of CD40/CD40L.

• This process has evolved to prevent unwanted activation of immune cells which can lead to harmful responses such as allergies and autoimmunity