LYMPHOCYTES & IMMUNOGLOBULINS. Dr Mere Kende, Lecturer SMHS

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1 LYMPHOCYTES & IMMUNOGLOBULINS Dr Mere Kende, Lecturer SMHS

2 Immunity Immune- protection against dangers of non-self/invader eg organism 3 components of immune system 1 st line: skin/mucosa/cilia/hair/saliva/fatty acid/stomach acid Non-specific 2 nd line: macrophages/neutrophils/complements Innate/Preformed/non-specific 3 rd Line: T-cells & B-cells/antibodies (humoural & cellmediated) Acquired/Highly specific

3 Two Basic Types of Acquired Immunities Humoral Immunity- antibody /B-cell mediated Cell-mediated immunity or T-cell immunity (because the activated lymphocytes are T lymphocytes). Both the antibodies and the activated lymphocytes are formed in the lymphoid tissues of the body. Antigens: Initiate Immune process

4 Lymphocytes Development

5 Antigens Antigen are high molecular weight molecules MW> 8000 (proteins & polysaccharides) Called Antigens = Antibody Generations Furthermore, the process of antigenicity usually depends on regularly recurring molecular groups, called epitopes, on the surface of the large molecule. This also explains why proteins and large polysaccharides are almost always antigenic, because both of these have this stereochemical characteristic

6 Lymphocytes Development: Bone Marrow, thymus Origin: Pleuripotential Stem Cell (BM) Types; T-cells & B-cells T-cells- cytotoxic (CD8), T-helper (CD4)/suppressor Responsible for acquired immunity Cell-mediated Immunity (T-cells)-thru thymus Humoral Immunity (B-cells)

7 T-cells Cytotoxic (CD8) T-helper- CD4 (Th1 & 2) T-suppressor cells- regulatory function, autoimmune, tolerance, (suppress function of)

8 CD4 cells Vs CD8 T-cells Recognise antigen when presented along with MHC protein complex II Active against bacteria & fungi Kills bacteria via interaction with other immune response elements Recognise antigen when presented with MHC protein complex I Active against viruses Kills viruses directly by punching holes in membrane

9 Location Lymph nodes Other locations: mucosa, spleen, thymus, BM Sites readily accessible on antigen exposure

10 Thymus Thymus preprocess T Lymphocytes. Develop specificity to diverse antigens. Then spread to reside in lymphoid organs Self -reacting T-cells are destroyed (self-tolerance) Development of Autoimmune Ds- loss of self tolerance.

11 B-lymphocytes Preprocessed in liver in utero & later BM Migrate to lymph nodes Activated to plasma cells secrete specific antibodies Lymph node contains highly specific B-cells and T-cells Once activated clones of specific sensitized lymphocytes are released & fill the entire body system

12 Genes & specificity Only few genes code for millions of specific T-cells and Antibodies Process of mixing and recombination of genes after encounter with antigen increases specificity Clone of B-cells & T-cells activated thru specific surface receptor [antibody for B-cells T-cell Receptor T-cells]

13 Antigen Presenting cells (APC) Examples APC include dendritic cells (myloid & lymphoid) Macrophages Tissues macrophages (langerhans, kuffer cells) -Activated B-cells Ingest, process, destroy & present antigens to and activate specific clone of lymphocytes Secrete interleukins (IL-1)- messenger/signal

14 Antigen Binding by APC

15 MCH protein/ peptide Bacteria

16 Antigen Presentation TCR +CD8- TCR+CD4 - recognize MHC I Ag complex co-receptor Recognize MHC II-Ag complex

17 Major Histocompatibility Complex (MHC) MHC class I Present in all cells Bind endogenous synthesized viral proteins MHC class II Present in APCs Bind exogenous peptides (bacteria antigen fragments)

18 Activate lymphocytes Activated T-cells (helper) Cooperation ensures B-cells secrete large quantities of Ig Activated B-cells-plasmablast-plasma cells=secrete Ig Ig production fast ~2000 molecules/sec for several weeks distribute to circulation, then plasma cells die Secrete lymphokines that assist activation of B-cells to secrete Ig

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21 Lymphokines Center of T-helper cell function Destroyed in HIV & Ig production impaired too. Among the important lymphokines secreted by the helper T cells are the following: Interleukin-2 (enhance CD8 action, helper cell ) Interleukin-3 Interleukin-4 (enhance B-cell action) Interleukin-5 (enhance B-cell action) Interleukin-6 (enhance B-cell action) Granulocyte-monocyte colony-stimulating factor (increase Macrophage action) Interferon-g

22 A number of cytokines have been used to potentiate the immune function of the host Cytokine IFN beta IFN-alpha IFN-alpha, beta IFN-gamma IL-2 Use Rx MS HBV rx Remission of hairy cell leukemia, Carcinoma of ovary Renal carcinoma and melanoma Anti-tumour Mechanism(s) Increased expression of class I MHC, possible cytostatic anti-tumor effect Increased MHC antigens; macrophage, Tc and NK cell activation T cell proliferation and activation of NK cells TNF-alpha Reduce malignant ascites Macrophages and lymphocyte activation

23 Cytotoxic T-cells Perforins-punch holes in infected cells

24 CD8 Activity

25 Cell-mediated Immune Response

26 Memory cells..immunity Some activated lymphocytes become memory cells (T/B-cells) Over population of specific clone of cells than original Subsequent reaction to infection is fast Primary exposure slow, less sustained Ig production Secondary exposure - fast, more potent & sustained Ig production Note: Concept of repeated injection on immunization

27 Antibodies 5 Classes: IgG, M, D, E, A ; (Subclasses: IgG1-4) Large protein Molecules: 160,00-790,000 20% of plasma protein IgG- most important; Accounts for 70% of total Ig quant IgM- 10 binding sites; very effective, initial released in bacterial infection IgE secreted in allergy ity

28 Antibody Concentrations

29 Immunoglobulin Structure

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31 Immunoglobulin 2 heavy & 2 light chains; Except IgM 10 each Light chain- specific/variable Heavy chain- constant (determines its chemical properties & class)

32 Mechanisms of Action of Antibodies Antibodies act mainly in two ways to protect the body against invading agents: (1) by direct attack on the invader and (2) by activation of the complement system that then has multiple means of its own for destroying the invader.

33 Antibody Antigen Binding highly specific =so many bonding sites antibody-antigen coupling is exceedingly strong, held together by (1) hydrophobic bonding, (2) hydrogen bonding, (3) ionic attractions, and 4) van der Waals forces.

34 Direct Action of Antibodies on Invading Agents. Antibodies can inactivate the invading agent in one of several ways, as follows: 1. Agglutination, in which multiple large particles with antigens on their surfaces, such as bacteria or red cells, are bound together into a clump 2. Precipitation, in which the molecular complex of soluble antigen (such as tetanus toxin) & Ig becomes so large that it is rendered insoluble and precipitates

35 Direct Action of Antibodies on Invading Agents 3. Neutralization, in which the antibodies cover the toxic sites of the antigenic agent 4. Lysis, in which some potent antibodies are occasionally capable of directly attacking membranes of cellular agents & thereby cause rupture of the agent

36 Complement system These direct actions of antibodies attacking the antigenic invaders often are not strong enough to play a major role in protecting the body against the invader. Most of the protection comes through the amplifying effects of the complement system described next

37 Complement system Amplify antibacterial Reaction Hundred fold

38 References Guyton. Text Book of Medical Physiology; 11 th Edition