Lecture notes Year 1 MBChB: Introduction to Medical Sciences (IMS)

I MMUNOLOGY
INTRODUCTION


The immune system
 A complex orchestration of molecules, cells, tissues and organs to provide protection from:
o Microbial pathogens including bacteria, viruses, parasites, fungi
o Tumor cells

Innate immunity – first line of defense – non-specific response- neutrophils, cytokines, NK cells, T cells
Adaptive immunity - second line of defense – highly specific with memory – T cells, antibodies

Active immunity Passive immunity
 Antigens enter body and trigger innate and  Antibodies pass from mother to fetus across
adaptive immune systems placenta and to infant by breast milk
 Long-term protection  Short-term protection

Neutrophils - principal phagocytic cell of innate immunity
 Rapidly migrate to sites of infection, ingest microbes by phagocytosis, release oxygen free radicals, degranulate
releasing proteins with microbicidal properties e.g. lysozyme

Eosinophils: multicellular parasites; role in allergy and asthma
Basophils: inflammatory allergic reactions; releases the potent vasodilator, histamine

Monocytes
 Circulate in blood, bean (horse-shoe) shaped nuclei, precursors of tissue macrophages
 Effectors of the inflammatory response to microbes
 Kills pathogens via phagocytosis, free radical production, myeloperoxidase and inflammatory cytokines

Macrophages
 Participate in innate and adaptive immunity
 Phagocytosis, microbicidal mechanisms, antigen presentation to other cells

Dendritic cells: process and present antigens (APC) on their cell surface to T cells to initiate specific immune responses
Mast cells: Similarities with basophils, release histamine, close association with allergy and inflammation

Small lymphocytes
 B-lymphocyte: produce antibodies, present antigens, can produce memory cells
 T-lymphocyte: development and regulation of cell mediated immunity, influences other cells, kill virally infected and
tumour cells, produce memory cells

Large granular lymphocyte
 Natural killer cell – part of innate response
o Release perforins and granzymes and trigger apoptosis in target cell
o Kill infected cells which don’t express foreign surface antigen, respond rapidly, involved in tumour
immunosurveillance

Immunological sites in the body
 Primary lymphoid tissue – development and maturation of lymphocytes
o Bone marrow (B cells), Thymus gland (T cells)
 Secondary lymphoid tissue – mature lymphocytes encounter antigens/pathogens
o Lymph nodes, spleen
o Other sites – tonsils, appendix, adenoids, Peyer’s patches (ileum), bronchial associated
lymphoid tissue (BALT)




Lymph nodes

,  Virgin B- and T-lymphocytes home from bone marrow and thymus to specific sites in lymph nodes
 During infection, architecture and size of nodes change in response to activation and proliferation of lymphocytes




The spleen
 Lymphoid organ in the abdomen
 Removes damaged or old RBC’s
 Key site of activation of lymphocytes from blood born pathogens
 Architecture:
o Red pulp – RBC’s removed
o White pulp – lymphocytes stimulated


Components of the innate immune system
Mechanical barriers  Skin and mucous membranes, competition with normal flora, mucous entraps, and cilia
propel microbes out of body
Physiological  Stomach acid kills some pathogens
 Fever response inhibits pathogen growth
Chemical mediators  Lysozyme cleaves bacterial cell wall
 Interferon induces antiviral defences in uninfected cells
 Complement lyses microbes directly or facilitates phagocytosis
Phagocytic  Macrophages – reside in tissues, recruit neutrophils- release cytokines (TNF, IL1)
leukocytes  Neutrophils – enter infected tissues, - release cytokines (TNF), phagotose bacteria
Natural killer cell  Summoned from the blood
 Release cytokines (IFN-γ, IL2)
 Kill infected cells (trigger apoptosis)

Adaptive immune system
 Systems ‘adapts’ by activating, proliferating and creating specific
responses to eliminate the microbe
 Humoral immunity: mediated by antibodies
 Cell-mediated: effected by T lymphocytes

Non-infected tissue
 Resident macrophages: eating up dead and dying cells – ‘gardening’
duties
 Dendritic cells: on sentry duty waiting for the first sign of a pathogen
 Most monocytes and neutrophils in the blood-stream pass healthy
tissue

Infected tissue
1. Dendritic cells exit the infected tissue to inform lymphocytes in the lymph nodes about the invading pathogen;
neutrophils from the blood-stream into the infected tissue to kill the pathogen
2. Monocytes flood in from the blood-stream and become inflammatory macrophages
 Neutrophils have killed the pathogen but have destroyed themselves – pus
 Macrophages clear away the debris, while some may also migrate to lymph nodes to inform lymphocytes
 Inflammatory macrophages change properties as the infection resolves and help to repair damage to tissue

Macrophages
 Eat dying cells – membrane plasma lipid profile changes when a cell dies and macrophages can recognise this
 Eat opsonized cells and pathogens – surface is coated with complement proteins or with antibodies
 If the cell or pathogen is coated with antibodies, it can be efficiently taken up by the Fc receptor

Dendritic cells – present antigen to T-cell
 Has specialised receptors on its surface that allow it to recognise patterns of foreign molecules, e.g clusters of sugars,
that are present on the surface of many pathogens
 Can kick start the adaptive immune system
1. T-cell can proliferate and daughter T-cells can help B-cells
2. B cells proliferate and produce antibodies