Immunology basics

Cells and Organs:Identify the different types of immune cells and where they originate and reside in the body.

– Neutrophils: the most common of the white blood cells in the body, they are attracted to foreign materials, inflammation and bacteria by a process called chemotaxis. Once they find a foreign particle, neutrophils will engulf it and release enzymes and hydrogen peroxide to kill the infected cells.

– Eosinophils and Basophils: E-phils are focused on parasites in the skin and lungs. Basophils carry histamines and are important in inflammatory responses.

– Myeloid and Lymphoid cells: Include NK cells, T cells and B cells. Monocytes become either a macrophage or a dendritic cell.

– Dendritic cells: Professional antigen presenting cells that capture antigens process them into peptides then move from the tissues to lymph nodes where they present them to T cells, the bridge the gap between the innate and adaptive immune system.

– NK cells: contain small cytotoxic granules that are released into cells to kill them. NK cells are part of the innate immune system because they have germ-line encoded receptors for recognizing pathogens and do not clonally expand.

– B cells are antibody-producing cells, they have unique B cell receptors that take the form of an immunoglobulin that binds directly to its matching antigen. Once this binding occurs the B cells divide rapidly and become plasma cells that secrete soluble forms of their receptor which are antibodies.

-T cells: coordinators of the immune system. The express a T cell receptor, but it is not secreted.

Understand how inflammation is triggered

-Triggers of inflammation can be endogenous or exogenous. Endogenous triggers are things like broken bones or tissue death. Exogenous triggers are infections or traumas. Binding of PAMPS (such as flagellin, peptidoglycans, dsRNA or unmethylated DNA) by PRRs and induction of cytokines and chemokines. Chemokines are a family of cytokines which work through receptors.

–TNF-alpha, IL-1beta, IL-6 and IL-8

Understand how T cells develop in the thymus.

The thymus plays an important rile in the development of T cells. T cell progenitors from the bone marrow and attracted to the thymus. The role of the thymus is to then educate the thymocytes about MHC and self antigens. Positive selection: thymocytes with a TCR that can bind an MHC class I or II molecule are retained. Negative selection: Thymocytes with a TCR that strongly recognises a self peptide in MHC are eliminated. CD4+ and CD8+ cells come out of the thymus.
Explain the signals required to fully activate a naïve T cell.

Naïve T cells need to meet antigen-presenting dendritic cells in secondary lymphoid tissues. Signal I of T cell activation depends on antigen specificity- this activates proliferation and cytokine production Signal 2: co-stimulation, additional receptors bind on T cells.

Understand the properties of effector T cells.

Activated t cells proliferate and produce a large number of effector T cells. These are antigen responsive cells that still express a TCR. Effector T cells then go where they are needed- where the antigen is. Helper T cells are recruited to B cell areas in secondary lymphoid tissue and the cytotoxic T cells are recruited to infected tissues via the blood.

Examine the function of cytotoxic T cells.

Cytotoxic T cells kill virus infected cells. These effector cytotoxic T cells scrutinize MHC class I molecules on infected cells. The infected cell is then killed by apoptosis and then removed by macrophages. Viral peptides are presented to CD8 T cells via MHC class I molecules. Cytotoxic T cells only require signal 1 to kill. Binding of FASL on cytotoxic T cells to FAS induces apoptosis pathway.
Identify the subtypes of effecter helper T cells and explain how they are generated.

Helper T cells make cytokines and help professional antigen presenting cells through CD40/CD40L binding and cytokine release. Effector T helper cells are found as 4 main subtypes: TH1 which release IFN-gamma and TFN-alpha. TH2 which release IL-4,IL-5 and IL-13. TH17 which release IL-17. Treg which release TGF-beta and IL-10. T helper subsets are driven by cytokines produces by dendritic cells. The dendritic cell cytokine is driven by the tissue environment and the type of pathogen. Also influenced by the nature of PAMPS.

Identify the basic molecular structure of antibodies (chains, bonds, regions)

-An antibody is a protein made by B cells that binds a specific antigen. Each B cell makes its own BCR and hence antibody. They consist of 4 protein chains that are joined by disulphide bonds. There are 2 identical light chains and 2 identical heavy chains. The ends of the N-terminus are the variable regions.

 Examine the nature of antigen binding by antibodies

-Immunoglobulin fold domains are made from beta-strands which form a barrel-like structure. Variable domains have 3 hyper-variable regions called complimentary determining regions (CDRs). The pairing of the H and L chains brings together their CDRs, creating the antigen binding site of the antibody.

 Identify the type of antibodies (Isotypes)

–There are 5 classes of antibodies based on their heavy chain c regions:

IgM, IgA, IgE, IgD, IgG. IgG is at highest concentration throughout the body and is found in serum and intra/extracellular spaces. IgM is the next most abundant and is found in the serum and intravascular spaces, this is also the B cell receptor. IgA is found in external fluids and IgE on basophils and mast cells.

Be introduced to antibody class switching

–Heavy chain constant regions of the gene segments can be switched after a mature B cell encounters an antigen. This requires T cell help. Class switching changes the function but not the specificity.

Understand the basic life-cycle of a B cell.

-In the bone marrow the B cells start out as stem cells. They then go to pre B cells and then immature B cells. These immature B cells then move to the lymphoid tissues such as lymph nodes, spleen and MALT: Here they become mature (naïve) B cells. Once activated they become plasma cells that secrete antibodies.

 Differentiate between thymus dependent and independent antibody responses

-Thymus dependent antibody responses involve naïve B cells, IgM, helper T cells, class switching and naïve T cells. Thymus independent antibodies are common with polymeric molecules and second signal can be provided by extensive cross-linking.




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