CLS Revision L/16: How the Body Responds To Infection

Infectious Agents Fungi Protozoa and worms VirusesBacteria Need an immune system which can deal with all of them!

The Basics Antigen: any foreign material that can incite an immune response (specifically antibodies) Antibodies: secreted by plasma cells (from B lymphocytes) 2 categories of lymphocytes: B-cells and T- cells. T cells spend a period of their development in the thymus...hence the name vs B-cells which mature in the bone marrow.

Components of the Immune System Anti-microbial: Antibodies/immunoglobulins, Complement proteins, pentraxins (C-reactive protein), defensins, lytic enzymes, interferons, cytotoxins. Regulatory: cytokines (interleukins, Tumour Necrosis Factors (TNFs), prostaglandins, leukotrienes, histamines. Plus....lots lots more

The Lymphoid System: The Basics Lymphocytes develop in PRIMARY LYMPHOID ORGANS - consisting of BONE MARROW and THYROID. They circulate through LYMPH NODES, the SPLEEN and mucosa-associated lymphoid tissue (MALT). These are referred to as SECONDARY LYMPHOID ORGANS. It is at these various sites where lymphocytes come into contact with each other and with specialised ANTIGEN PRESENTING CELLS.

Lymphocyte Recirculation Lymphocytes leave the primary lymphoid organs once matured and continually cycle between the blood, body tissues and secondary lymphoid organs. Afferent lymphatics lead into a lymph node (one way in) but the majority of lymphocytes enter a lymph node directly in the blood supply, then cross a specialised region of HIGH ENDOTHELIAL CELLS (via binding with adhesion molecules. Lymphocytes exit via efferent lymphatics and enter the blood stream again via the thoracic duct The spleen has no lymphatic supply and so entry is gained via the splenic vein. ENABLES CONSTANT SURVEILLANCE!

Innate vs Adaptive INNATE Neutrophils, Eosinophils, Basophils, Mast Cells, Macrophages, Natural Killer Cells, Dendritic Cells. Acquired T lymphocytes, B lymphocytes

Innate Immunity Quickly activated but magnitude of response stays the same no matter how many times exposed to the same microbe. Can limit the spread and proliferation of a pathogen in the body in the early stages Based on recognition of PATHOGEN- ASSOCIATED MOLECULAR PATTERNS (PAMPs) by PATTERN RECOGNITION RECEPTORS on immune cells (e.g Toll-like receptors)

Adaptive/Acquired Immunity More slowly activated but highly efficient and improves with repeated exposure This is due to memory cells being formed during the initial immune response which can be quickly activated if exposed again. HIGHLY SPECIFIC recognition of antigens Microbial antigens are recognised by receptors on lymphocyte surface.

B lymphocyt e Microbe Antigen receptor Antigen: the part of the antigen recognised by a receptor is called the EPITOPE

If a B cell recognises an antigen (epitope): B-cells compete to interact with the antigen, and only that with the highest affinity is successful. It is this CLONAL SELECTION which ensures the immune response is specific for the invading pathogen. The activated B cells mature into plasma cells and secrete antibodies which recognise the same antigen as the B-cell surface receptor.

Stages of a Primary Immune Response The epithelial barrier is breached by a microbe There is an IMMEDIATE LOCAL RESPONSE (innate) with complement proteins and macrophages attracted to the area. Then there is an EARLY INDUCED RESPONSE (innate/inflammatory) with macrophages and mast cells releasing inflammatory mediators and subsequent attraction of leucocytes and more complement proteins.

Continued... There is then a LATER ADAPTIVE RESPONSE in which antigens are carried by antigen-presenting cells to secondary lymphoid organs, resulting in activation of the specific B and T lymphocytes which recognise the antigen. Plasma cells (a form of B cell), produce antibodies, which head to the site of infection. Once the infection is cleared, memory T and B cells remain, which give a faster, bigger response next time, if exposed to the same pathogen.

Different Categories of Infections Extra-cellular infection: complement proteins, phagocytes, antibodies Intra-cellular vesicular infection: Helper T cells Intra-cellular cytosolic infection: interferon proteins, natural killer cells, cytotoxic T cells.

Immunopathology Immunodeficiency Allergy Autoimmunity Transplant Rejection Lymphoproliferative Disease

Immunopathology y Severe combined immunodeficiency disease HIV/AIDS Eczema Allergic Rhinitis (hayfever) Allergy to house dust mite protein Anaphylaxis e.g insect venom Contact dermatitis Autoimmune thyroiditis Rheumatoid Arthritis SLE (Lupus) Transplant Rejection

Exam Tips: Immunology can seem confusing but work through the stages of a response logically and it will start to make sense! ‘Immunology’ by Ian Todd and Gordon Reeves is where all the diagrams in your lectures are taken from and is really good at explaining everything you’ll need to know for CLS (years 1 and 2) Learn the names of some immune-related illnesses - they come up in exams so you get easy marks just for recognising them!