ࡱ> M bjbj== EWWltttt D /////|D 00000!!!!!!$V vE _Ett00sZ(t20 0A:,  0z0 ٞ0D "/ ü p0ͼR# ttttImmunology Greg Tucker E-mail:  HYPERLINK "mailto:Gregory.tucker@nottingham.ac.uk" Gregory.tucker@nottingham.ac.uk Texts: Instant notes in immunology Lydyard, Whelan and Fanger Immunology Roitt, Brostoff and Male Outline of immune system (2) Production and properties of antibodies The Nature of Immunity Infective organisms Virus Bacteria Fungi Protozoa Worms Mechanisms of Infection Invasion Viruses and Bacteria can infect cells (Polio) Excessive Bacterial growth in body tissues (Pneumonia) Toxins Endotoxins such as in food poisoning by Salmonella, released on death (cooking) Exotoxins such as the neurotoxin secreted by Clostridium botulinum. Healthy tissues are devoid of bacteria and viruses. There are Immune systems in operation. Barriers to Infection Physical/Chemical Barriers Skin Mucosal secretions Lysozyme in secretions Acid in gastric juices Cellular and Molecular Mediated Immunity Innate: non-specific present from birth first line of defence Acquired : specific adaptive late development Cell mediated immunity Leucocytes- derived from haemopoitic stem cells Phagocytes Auxiliary cells Lymphocytes Cells of the Immune System (Leucocytes)  Cells of the Innate System Phagocytes Monocytes circulate in blood. Migrate into tissues and enlarge to become Macrophages. Long lived. Neutrophils Major circulatory cell (90%). Small short lived cells (2-3 days). Circulate in blood but can cross capillary wall. Eosinophils Small number in blood (5%). Some phagocytic activity. Can degranulate and release toxic chemicals. Thought to have a specialised role in combating large parasites. Natural Killer cells Large granular lymphocytes. Binds self cells but normally prevented from killing them. Infected cells can loose their protection. Auxiliary cells Mast Cells. Associated with blood vessels. Secrete soluble mediators of immunity (e.g. histamine). Release soluble mediators of immunity upon destruction. Basophils Similar to Mast cells but circulatory Dendritic cells Major antigen presenting cell (APC) Deposit fragments of antigens in cell membrane and interact with cells of the acquired system Cells of the Acquired Immune System Lymphocytes T-Cells Differentiate in the thymus Cell mediated response Two major types T(helper) and T (cytotoxic) B-Cells Differentiate in the bone marrow Antibody production T-cell functions Tc Bind to infected self cells and kill them Th Bind to Antigen Presenting Cells (dentritic cells, B-cells) and then secrete cytokines to activate immune system. Simple overview of immune response  Antibody Production B cells have surface receptors which are specific for epitopes on an antigen. Clonal Selection and Expansion Each individual B-Cell (or T-Cell) receptor has a unique shape  When this receptor binds to an epitope on an antigen then that cell is activated (clonal selection) and undergoes rapid expansion in numbers Antigen may have several epitopes. Thus several B or T cells are activated result is a Polyclonal response. Clonal Expansion of B-Cells B-Cells differentiate into a mixture of Plasma Cells and Memory Cells. Plasma cells secrete antibodies- these have the same receptor structure as the original B-cell receptor - so will bind to the antigen. Plasma cells are relatively short lived. Memory cells remain in the circulation for a long time. Antibody Structure Major antibody in blood is Immunoglobulin G (IgG) Made from 4 polypeptides: 2 Identical light chains 2 Identical heavy chains  Fc = fragment crystallisable this is a region which is the same in all IgG molecules Fab = fragment antigen binding. This is the variable region between IgG molecules. Types of Antibodies IgG; IgD and IgE all similar structures :  IgA:  IgM: A B-cell only secrete one type. That all have the same Fab region but differ in the Fc region of the heavy chain. Antibody Action Blocking an important site on the antigen e.g. docking protein on a virus Precipitate Antigen (if a small molecule such as a toxin)  Large precipitate inactivates antigen. Allows digestion by phagocytes in particular Neutrophiles. 3. Opsonisation  4. Chemical response complement Antibody Antigen interactions Nature of antigenic determinant (epitope) Protein 3 to 6 amino acids. Carbohydrate- 5 to 6 sugars. Must be part of larger antigen (whole protein). Individual units- hapten will not initiate a response. Weak and strong antigenic determinants. Interaction Hydrogen bonds Electrostatic bonds Van der Waals bonds Hydrophobic bonds Affinity  Ag + Ab AgAb K = [AgAb] [Ag].[Ab] Range of affinities, not a normal distribution Valency IgG has 2 Fab sites thus valency of 2 Avidity Multiple binding sites on antigen and antibody Avidity >>>>> sum of affinities Haemopoietic Stem Cell Common Lymhoid Progenitor Monocyte T Cells B-Cells Basophil Common Myeloid Progenitor Antibody forming Cell Macrophage Auxiliary Cells TC TH Antigen Epitopes Stem Cell B-Cells Antigen Activated B-Cell Memory Cell Plasma Cells Antibodies Fc region Fab region Heavy chain Light chain Lymphocytes Mast Cell Neutrophile Eosinophil Phagocytes Cell mediated immunity Antibodies Tc Th Plasma cell T-cells B-cell Antigen Presenting Cells Phagocytes Invader (Antigen)  $%YZ[z{ABV$&B2I' B C N !".  9:=FY/Copz}jCJUmHnHsH u 5CJ,\"j5CJU\mHnHsH u 5CJ$\CJ,0JCJ4jCJ4U jCJ4UCJ4CJHG  #$|}ABVW_j$^a$$ & Fa$$a$$`a$jr}lm $&BCJ_x$a$^ 02IJz{& ' B  $^`a$$^a$$^a$ p^p` ^`B C N O [ \ p  6 7 C D ` z  X ^` 5 6 @ A g h x y !"./8Um^`m !$a$$^a$ $^`a$$`a$^   9:[\  EFYZ)*+,-./CDn$a$noqrstyz~ IJjk#$&'()*+`8^8h^h & F$%Tv &./8Tjkv)*6OZg~ 5CJ \CJ H*CJ 5>*CJ$\"j5CJU\mHnHsH u 5CJ$\C+,-./0123TUuvwMuvp^p KLMNVWp^p%&./89STjkvw)*67ABNOZ[ffg~p^p,1h. 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