Lecture notes Year 1 MBChB: Introduction to Medical Sciences (IMS)
Lecture notes Year 1 MBChB: Introduction to Medical Sciences (IMS)
Lecture notes Year 1 MBChB: Introduction to Medical Sciences (IMS)
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University of Leeds (UoL)
University of Leeds
Year 1 MBChB: IMS
All documents for this subject (12)
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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
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