Basic immunology 2025.pptx microbiology immune system

microbiology

1. Basic Immunology MBCHB III 2025 Maemu Gededzha Department of Virology

2. Why do we need an immune system ? Fails to recognize a threat Activated without a threat Switched off after exposure Infection and other diseases Allergic reaction and autoimmune diseases Prevent or limit infection

3. Terminology Immunity - refers to the body’s ability to prevent the invasion of an antigen/pathogens Innate immunity- immunity that occurs naturally because of genetic factors or physiology, and is not specific to pathogen or vaccination Adaptive immunity- immunity that has memory and occurs after exposure to an antigen either from a pathogen or a vaccination Immune response- collective and coordinated response to the foreign substance in an individual mediated by the cells and molecules of the immune system Cytokines - chemical messenger that regulates cell differentiation, proliferation, gene expression, and cell trafficking to effect immune responses Major histocompatibility class (MHC) I/II molecule- protein found on the surface of all nucleated cells (I) or specifically on antigen-presenting cells (II) that signals to immune cells whether the cell is healthy/normal or is infected/cancerous Antibody ( immunoglobulin ) - protein that is produced by plasma cells after stimulation by an antigen

4. What is an antigen? Literally: Anti body gen erator This is any molecule which can stimulate an immunological response Often peptide but can be any molecular structure (lipid, carbohydrate, proteins, or nucleic acids ) Important: does not need to be derived from a pathogen (Toxins, pollen, chemicals) Antigen presentation The process by which antigen derived from a pathogen or from the host is introduced to the adaptive immune system Antigen presenting cell Any cell which can present antigen Professional antigen presenting cell Cells which express MHC II and which present to CD4+ T cells – classically includes monocytes/macrophages, B cells and myeloid dendritic cells

5. Immune system Adaptive immunity Innate immunity Second line of defence First line of defence Overview of the immune system Delayed Immediate

6. Innate Immunity Non-specific internal defenses Skin and mucosal membranes and barriers (Prevent entry) Physiological response E.g. Inflammation Fever Chemicals E.g. Interferon Complement Cytokines Cells E.g. Macrophages, NK cells

7. Adaptive Humoral immunity B lymphocytes Cellular immunity T lymphocytes Plasma cells Antibodies Cytotoxic T cells Helper T cells

8. Phagocytosis Degranulation 1-6% Degranulation 8-12 days 50% to 75% 6hrs-few days Eosinophil Neutrophil Migrates from blood vessels into tissues. First responders at the site of infection. Circulates in blood and migrates to tissues

9. Basophil <1% Degranulation Lifetime uncertain Inflammation Few hours-few days Mast cells 3% Inflammation- Histamine Up to a month Circulates in blood and migrates to tissues Connective tissues, mucous membranes

10. Dendritic cells Monocytes Macrophages Phagocytosis APC 10 to 14 days 1% Varies Phagocytosis APC Months-years Present in epithelial tissue, including skin, lung and tissues of the digestive tract Migrates to lymph nodes upon activation Stored in spleen, moves to infected tissues Migrates from blood vessels into tissues

11. 20-40% CD4-Immune response mediators Week to years CD8-Cell destruction Lymphocytes B produce antibodies B and T lymphocytes

12. Phagocytes Phagocytic cells consist of granulocytes (neutrophils, eosinophils, basophils, and mast cells), monocytes/macrophages, and dendritic cells Granulocytes are effector cells that predominate during the early or acute phase of the innate immune response The main function of these cells is to identify, ingest, and destroy microbial pathogens

13. Phagocytosis Residue is exocytosed Phagolysosome destroys infectious agent Phagosome Lysosome Macrophage Infectious agent engulfed Activation Chemotaxis Attachment Ingestion Destruction

14. Lymphoid organs

15. Primary Lymphoid Organs Secondary Lymphoid Organs Organs of the immune system where lymphocytes are formed and mature Organs of the immune system which maintain mature naïve lymphocytes and initiate an adaptive immune response Allow lymphoid stem cells to proliferate, differentiate and mature Allow lymphoid cells to become functional Contain either T cells or B cells Contain both T cells and B cells Have no contact with antigens Have contact with antigens Undergo atrophy with age Increase size with age

16. 1. Origin Both B and T lymphocyte precursors originate in the bone marrow. B cells mature in the bone marrow T cells mature in the thymus 2. Maturation (Education) During maturation lymphocytes develop immunocompetence and self-tolerance. 5. Proliferation and differentiation Activated lymphocytes proliferate (multiply) and then differentiate into effector cells and memory cells. Memory cells and effector T cells circulate continuously in the blood and lymph and throughout the secondary lymphoid organs. 4. Antigen encounter and activation When a lymphocyte’s antigen receptors bind its antigen, that lymphocyte can be activated. 3 . Seeding secondary lymphoid organs and circulation Immunocompetent but still naive lymphocytes leave the thymus and bone marrow. They “seed” the secondary lymphoid organs and circulate through blood and lymph. Antigen B or T lymphocytes Lymph node Blood

17. Structure of T-Cell Receptor Constant Region -anchor the receptor to the plasma membrane Variable Region -contact the antigen V regions contain hyper variable regions that determine the specificity for antigen

18. Major Histo c ompatibility ( MHC)/HLA MHC Class I Expressed on almost all cells Cytotoxic T-cells express the molecule CD8 with the T-cell receptor (TCR) CD8 facilitates the binding of MHC-I to the T cell receptors MHC Class II Expressed mainly on specialized APCs T-helper cells express CD4 which, facilitates the binding of MHC-II to the helper T cells receptors

19. T cells maturation: T cells mature in thymus under positive and negative selection ("tests") Immunocompetence - permits the survival of only those T cells whose TCRs are capable of recognizing self-MHC molecule Self-tolerance- eliminates T cells that react too strongly with self-MHC plus self-peptide

20. Types of T cells and functions T cells types Functions Helper T ( Th ) cells (CD4+) Th cells become activated when presented with antigens and have the ability to differentiate into cell subtypes. When activated, T helper cell assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages Cy totoxic T (Tc) cells (CD8+) CD8+ T cells destroy, Virus-infected cells, cells with intracellular bacteria or parasites, cancer cells and foreign cells (transfusions or transplants) CD8+ T cells releases perforins and granzymes by exocytosis Perforins create pores through which granzymes enter target cell Granzymes stimulate apoptosis

21. T cells types Functions Regulatory T cells ( Treg cells) Treg cells are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Prevent pathological self-reactivity, i.e. autoimmune disease. Types of T cells and functions

22. 15 min break

23. Humoral immunity Antibody mediated immune response B lymphocytes Active Passive Naturally acquired Infection such as Parasites Viruses Artificially acquired Vaccine -dead or Attenuated pathogens Naturally acquired Antibodies passed from mother to fetus via placenta To the infant in her milk Artificially acquired Injection of exogenous antibodies (gamma globulin)

24. Structure of Antibodies Antibody - protein that is produced by plasma cells after stimulation by an antigen; also known as an immunoglobulin Five classes IgG, IgM, IgA, IgD and IgE Structure of an antibody molecule ( Janesway Immunobiology)

25. IgM Secreted initially during primary infection Cannot cross the placenta Major functions Secreted first during primary exposure Activates the complement Used as a marker of recent infection

26. IgG Structure of an antibody molecule ( Janesway Immunobiology) 70-75% of total immunoglobulin Secreted in high quantities in secondary exposures Cross the placenta Major functions neutralize microbes and toxins opsonize antigens for phagocytosis activate the complement protect the newborn

27. IgA Monomeric in serum Dimeric with secretory component in the lumen of the gastro-intestinal tract and in the respiratory tract Major function Neutralizes microbes and toxins

28. IgE Monomeric Mediates type I hypersensitivity Major functions Associated with anaphylaxis Plays a role in immunity to helminthic parasites

29. Function of Antibodies

30. Overview of B and T lymphocytes B lymphocytes T lymphocytes Type of immune response Humoral Cellular Antibody secretion Yes No Primary targets Extracellular pathogens ( eg . Bacteria, Fungi, parasites) Intracellular pathogens ( eg . Viral infected cells) and cancer cells Site of maturation Bone marrow Thymus Effector cells Plasma cells Cytotoxic T (Tc) cells Helper T ( Th ) cells Regulatory T ( Treg ) cells Memory cells formation Yes Yes

31. How does t hese 2 categories of immune system work together

32. Regulation of lymphocyte activation Transfer of peptide-MHC complexes from APCs to lymphocytes Directing secretion of cytokines granules Function of Immunological synapse

33. An MHC molecule Peptide bound to the MHC A T-cell receptor which fits the peptide CD4 or CD8 to stabilise the TCR-MHC interaction A second signal Cytokines The following things are required for a good synapse

34. Cytokines Cytokines are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells Their major functions are to mediate and regulate immune response and inflammatory reactions Classification of cytokines Interleukin, IL Interferon , IFN Tumor necrosis factor, TNF Colony stimulating factor  Transforming growth factor Cell growth Cell differentiation Cell death Induce non-responsiveness to other cytokines/cells Induce responsiveness to other cytokines/cells Induce secretion of other cytokines

35. Cytokines secretions and biological activities of T cells

36. T helper cell and a B cell ( eg. infection by parasites)

37. T helper cell and antigen presenting cell ( eg. intracellular infection Th1 functions to empower macrophages so that they can destroy intravesicular pathogens.

38. Cytotoxic T cell and antigen presenting cell ( eg. intracellular infection) Th1 functions to empower macrophages so that they can destroy intravesicular pathogens.

39. How does the immune system respond Primary immune response - occurs when an antigen comes in contact to the immune system for the first time During this time the immune system has to learn to recognize antigen and how to make antibody against it and eventually produce memory lymphocytes Secondary immune response- occurs when the second time (3rd, 4th, etc.) the person is exposed to the same antigen At this point immunological memory has been established and the immune system can start making antibodies immediately

40. Primary and Secondary response

41. Primary Immune Response Secondary Immune Response This occurs as a result of primary contact with an antigen This occurs as a result of second and subsequent exposure of the same antigen Responding cell is naïve B-cell and T-cell Responding cell is memory cell Lag phase (latent period) is often longer (4-7 days), sometimes as long as weeks or months Lag phase (latent period) is shorter (1-4 days) due to the presence of memory cell Level of antibody reaches peak in 7 to 10 days Level of antibody reaches peak in 3 to 5 days It takes longer time to establish immunity Takes shorter time to establish immunity First antibody produced is mainly IgM. Although small amount of IgG are also produced Mainly IgG antibody is produced. Although sometimes small amount of IgM are produced Amount of antibody produced depends on nature of antigen. Usually produced in low amount Usually higher levels (100-1000) times more antibodies are produced Antibody level declines rapidly Antibody levels remain high for longer period Affinity of antibody is lower for its antigen Antibodies have greater affinity for its antigen Primary response appears mainly in the lymph nodes and spleen Secondary response appears mainly in the bone marrow, followed by the spleen and lymph nodes Both Thymus dependent and Thymus independent antigen gives primary immune response Only Thymus-dependent antigen gives secondary immune response

42. How do we detect immune response Immunoassay These biochemical and serological techniques are based on the detection and quantitation of antibodies generated against an infectious agent, a microbe, or non-microbial antigen Because antibodies can be produced against any type of macromolecule, antibody-based techniques are useful in identifying molecules in solution or in cells Most assays rely on the formation of large immune complexes when an antibody binds to a specific antigen which can be detected Antigen – antibody reactions are performed to determine the presence of either the antigen or antibody-serological tests Either the antigen or the antibody have to be known

43. Primary binding tests Primary binding tests are tests that directly measure the binding of antigen and antibody (i.e.; directly measure or visualize the immune complex) Performed by allowing antigen and antibody to combine and then measuring or visualizing the amount of immune complex formed Use radioisotopes, fluorescent dyes, or enzymes as labels to identify one of the reactants

44. Secondary binding tests Secondary binding tests are tests that detect and measure the consequences (secondary effect) of antigen-antibody interaction

45. Tertiary binding tests Tertiary binding tests measure the consequences of immune responses in vivo These tests are much more complex than primary and secondary tests, but their results reflect the practical significance of the immune response. E.g. measurement of the protective effects of antibody A common example is ELISPOT assay for the detection of the frequency of cytokine producing cells eg effector CD4 cells