Overview of the immune system PDF

Preview

Summary

Overview of the immune system Immune system is essential in an environment where many harmful disease-causing microorganisms are present.  Evolved to protect the body against these pathogens.  Control malignancies through protective immune surveillance.  Pathogens – viruses (10-1000nm) – intrace...

Description

Overview of the immune system    

Immune system is essential in an environment where many harmful disease-causing microorganisms are present. Evolved to protect the body against these pathogens. Control malignancies through protective immune surveillance. Pathogens – viruses (10-1000nm) – intracellular infection, bacteria (0.1-5um) – largely extracellular, protozoa (5-200um) – intracellular and extracellular and fungi (3um-1mm) - extracellular.



Innate immune system – first line of defence consisting of physical barriers to prevent entry of pathogens, phagocytes to digest microorganism and chemical mediators to trigger recruitment and activation of immune cells (inflammation). During inflammation – increased blood flow, increased vascular permeability and chemotaxis and cell migration.



Adaptive system – formed principally by lymphocytes (T and B cells) which contain specific receptors to recognise specific antigens associated with pathogens – also retains memory of previous encounter with the pathogen.

Non-specific (innate) barrier to infection  Skin – important barrier and impermeable to most infectious agents. Acidic skin secretions inhibit bacterial growth.  Desquamation of skin cells removes potential pathogens.  Mucus secreted by membranes lining the inner surfaces of the body block the attachment of microbes to epithelial cells.  Washing action of tears saliva and urine also limit attachment.  Many secreted body fluids contain antibacterial components. Phagocytosis  If microorganisms penetrate the body they can be destroyed by phagocytosis.  Phagocytes – neutrophils (predominate white cell in the bloodstream – can migrate into tissues during inflammation), macrophages (differentiate from blood monocytes) and polymorphonuclear. 1. Phagocytes arrive at the site of inflammation by chemotaxis. 2. Attach to the microorganisms via surface receptors – they’re internalized and destroyed. 



Complement system – activation begins with recognition proteins which recognizing a wide range of strictures – pathogens – activation leads to coordinated cascade of enzymatic cleavage events generating complement protein fragments that carry out effector functions – cytolysis via membrane attack complex formation, inflammation mediated by C3a and C5a and opsonisation leading to phagocyte clearance via Cb3 deposition. Natural killer (NK) cells – T cells or B cells – specialised to kill virally infected cells and tumour cells.

Specific (adaptive) immune responses  Microorganisms develop strategies to evade our innate defence mechanisms – specific immunity provided by lymphocytes.  Lymphocytes – responsible for recognising molecules of infecting pathogens, have antigen receptors that recognise particular pathogens – two classes (T and B cells).  B cell use cell surface antibodies Ab as Ag receptors. T cells use specialised T cell receptors. B cell response  Recognise antigen through an antibody receptor on their surface – following encounter with Ag, B cells transform into plasma cells – formation of memory B cells provides an enhanced response on repeat exposure.  B-lymphocyte – develop in foetal liver and in bone marrow in adults.  Ag receptor = surface immunoglobulin.  Found in spleen and lymph nodes. o AB are tetrameric polypeptide structures, comprise of 2 identical heavy chains and 2 identical light chains, variable (Fab – confers Ag recognition) and constant (Fc- interacts with cell surface receptors and activates complement) domains. o They bind to pathogens, preventing them from entering or damaging body cells, activates complements and facilitate phagocytosis by opsonisation. o 5 different classes – IgG, IgA, IgM, IgD and IgE. o IgG – major serum Ig, crosses the placenta. o IgM – pentamer of basic 4 polypeptide structures, activates complement effectively. o IgD – cell surface receptor on B cells. o IgA – dimer of basic structure, most abundant Ig in external secretions. o IgE – Fc receptor binds to mast cells and basophils, important in allergy.  Initial Ab response following a primary antigenic involves IgM – as IgM levels fall, IgG levels increase .  T cell response  Recognise Ag as peptide fragments that come from inside the cells – cells present antigenic fragments on their surfaces for review by T –cells – MHC involved.  Major histocompatibility complex – Ag are cell surface glycoproteins: o Class I – gene products found on all nucleated cells and participate in Ag presentation to cytotoxic T cells – destroy virally infected or tumour cells and express CD8 cell surface receptor. o Class II gene products found on Ag presenting cells and participate in Ag presentation to T helper cells – express CD4 receptor on cell surface and secretes cytokines (produced by leukocytes and control the differentiation and division of haemopoetic stem cells – interleukin family, interferon and tumour necrosis factors).  T-lymphocyte – develop in the thymus.

  

TH- 1 – secrete cytokine – promote macrophage activation and cytotoxic reactions – important in protection against viruses and intracellular organisms. TH-2 – cells activate B-cells – important in humoral defence mechanism.

Cells of immune system  Originate from pluripotent haemopoetic stem cells in the bone marrow – stem cells differentiate into myeloid (neutrophils, eosinophils, basophils) and lymphoid (B and T lymphocytes) linages. Myeloid cells 1. Neutrophils – phagocytosis. 2. Eosinophils – defence against parasites. 3. Basophils and mast cells – regulate vascular tone and permeability. 4. Monocytes and macrophages – phagocytosis. 5. Dendritic cells – differentiated macrophages – act as Ag presenting cells. Lymphoid cells 1. B cells – differentiate into plasm cells and produce Ab. 2. T cells – for cell mediated immunity – T helper and T-cytotoxic cells. 3. Natural killer cells – kill tumour cells and virally infected cells. Antigen presenting cells – dendritic cells, macrophages and B-cells. Lymphoid tissue – secondary lymphoid organs provide an environment where lymphocytes respond to pathogens and foreign antigens. Centralised antigen recognition within secondary lymphoid tissue provides the most efficient means of rapid response – includes lymph nodes, spleen and MALT. Thymus – pre-T cells mature into functional T cells – as they mature they acquire TCR and CD4 and CD8 receptor. Lymph nodes – filter for lymph draining the tissues. Composed of capsule, cortex (contains aggregates of B-cells in lymphoid follicles) and paracortex (contains mainly T-cells) and medulla (contains T and B cells). Dendritic cells trap antigens which enter the lymph node through afferent lymphatics. Following stimulation by antigen, lymphoid follicles transform into secondary follicles which contain germinal centre....