Humoral and cell mediated immunity, Educational Platform.pptx

Humoral and cell mediated immunity, Educational Platform

1. Humoral and cell mediated immunity By M. Zubair Lecturer kmu

2. IMMUNITY is the balanced state of multicellular organisms having adequate biological defenses to fight infection, disease, or other unwanted biological invasion, while having adequate tolerance to avoid allergy, and autoimmune diseases. a condition of being able to resist a particular disease especially through preventing development of a pathogenic microorganism or by counteracting the effects of its products

3. Immune Cells

4. Three Lines of Defenses

5. First Line of Defense It is nonspecific Defense: Intact Skin: Forms mechanical barrier that prevents entry of pathogens and other harmful substances into body. Intact mucous membranes: Form mechanical barrier that prevents entry of pathogens. Mucous: Traps pathogens in respiratory and digestive tracts. Nasal hair: Filter and trap microbes in nasal passage.

6. First Line cont… Gastric juice: Contains HCl that destroys pathogens in stomach. Lysozyme: Found in tears and saliva that Kills microbes. Urine: Flushes out lower urinary tract; and, its lower PH also inhibits some microbial growth.

7. Second Line of defense Nonspecific cellular and chemical defense Inflammatory response: Prevents spread of harmful agents to adjacent tissues; promotes tissue repair; release chemical mediators to attract phagocytes and stimulate third line of immune response. Fever: It is systemic response initiated by pyrogens (i.e. prostaglandin); elevetaed body temperature inhibits microbial proliferation.

8. Second Line cont… Phagocytes: Engulf pathogens and contribute immune response. Antimicrobial proteins: ► Interferon: Proteins released by virus infected cells that protect uninfected cells from viral overtake; mobilize immune system. ► Complement: Enhances phagocytosis by opsonization, Lyses microbes, and intensifies inflammatory and immune responses.

9. Third Line of defense It’s response is antigen specific, means differentiates pathogens. Third line of defense consists of humoral and cell mediated immune response. For each type of pathogen, the immune system produces cells and antibodies that are specific for that particular pathogen.   They fight off pathogens and provide long term immunity by keeping record of the antigen into its memory. Secondary response is thus relatively rapid and stronger than the primary response.

10. Nonspecific immune cells Phagocytes: Neutrophyles – bacteria Eosinophyles – enzymes that kills parasites Macrophages - "big eaters" Non phagocytic leukocytes : Basophiles – role in allergic response Mastocytes Natural killer lymphocytes – antiviral and anti-tumor activity

11. Nonspecific immune cells Macrophages have important functions in both innate and antigen-specific immune responses. As phagocytic cells with antigen nonspecific activity, they help to contain infectious agents until specific immunity can be marshaled. In addition, early in the host response, the macrophage functions as an accessory cell to ensure amplification of the inflammatory response and initiation of specific immunity. Macrophages are activated by the presence of antigen to engulf and digest foreign particles . Activated macrophages act as antigen presenting cells (APCs) that break down complex antigens into peptide fragments that can associate with class I or II Major Histocompatibility Complex (MHC) molecules. Macrophages can then present these complexes to the helper T cell so that nonself-self recognition and activation of the immune response can occur .

12. Presentation of antigen to helper T cell by an antigen-presenting cell (APC)

13. NK cells The NK cell is a nonspecific effector cell that can kill tumor cells and virus-infected cells. They are called natural killer cells because, unlike T cytotoxic cells, they do not need to recognize a specific antigen before being activated. NK cells kill after contact with a target cell. The NK cell is programmed automatically to kill foreign cells. Programmed killing is inhibited if the NK cell membrane molecules contact MHC self-molecules on normal host cells. The mechanism of NK cytotoxicity depends on production of pore-forming proteins ( i.e., NK perforins), enzymes, and toxic cytokines.

14. Specific Immunity Specific or acquired immunity develops during an individual’s lifetime. It distinguishes self from nonself, and responds specifically to different pathogens and foreign molecules. Components: Lymphocytes are key players in the specific or acquired immune response: Lymphocytes represent 20% to 40% of blood leukocytes; T lymphocytes (also called T cells), which participate in cell-mediated immunity (60-70%); B lymphocytes (also called B cells), which participate in humoral immunity (10-20%); Cell-mediated immunity involves the production of cytotoxic T cells, which have the ability to destroy antigen-bearing cells. Humoral immunity is characterized by the transformation of B cells into plasma cells, which secrete immunoglobulins (antibodies) that have specific activity against the inciting antigen.

15. T cells T cells are maturated in the thymus. There, they learn how to distinguish self from nonself. Only the T cells that ignore self antigen molecules are allowed to mature and leave the thymus. Without this training process, T cells could attack the body's cells and tissues. Mature T cells are stored in secondary lymphoid organs (lymph nodes, spleen, tonsils, appendix, and Peyer's patches in the small intestine). These cells circulate in the bloodstream and the lymphatic system. After they first encounter a foreign or abnormal cell, they are activated and search for those particular cells.

16. Immune Cells Pathway for Tcell differentiation

17. Types of T cells Helper T (CD4) cells help other immune cells. Some helper T cells help B cells produce antibodies against foreign antigens. Others help activate killer T cells to kill foreign or abnormal cells or help activate macrophages enabling them to ingest foreign or abnormal cells more efficiently. The Th1 response is characterized by the production of interferon - gamma, which activates the bactericidal activities of macrophages, and induces B-cells to make opsonizing (coating) antibodies, and leads to cell mediated immunity. The Th2 response is characterized by the release of interleukin 4, which results in the activation of B-cells to make neutralizing (killing) antibodies, leading to humoral immunity. Generally, Th1 responses are more effective against intracellular pathogens (viruses and bacteria that are inside host cells), while Th2 responses are more effective against extracellular bacteria, parasites and toxins.

18. Types of T cells Th1 cells: secrete IL-2, IL-12, IFN gamma, TNF-beta; activate macrophages, amplifying their cytokine secretion capacity and potential for presentation of antigens; activate synthesis of IgG but not IgE; are involved in delayed hypersensitivity reactions; are activated by signals from intracellular bacteria and viruses; Th2 cells: secrete IL-4, IL-5, IL-6, IL-10; activate the synthesis of IgE; stimulate proliferation and activation of eosinophils; are stimulated by allergens or parasite components .

19. Types of T cells Killer (cytotoxic) T cells (CD8) attach to particular foreign or abnormal (for example infected) cells because they have encountered them before. Killer T cells may kill these cells by making holes in their cell membrane and injecting enzymes into the cells or by binding with certain sites on their surface called death receptors. Suppressor (regulatory) T cells produce substances that help end the immune response or sometimes prevent certain harmful responses from occurring. Sometimes T cells—for reasons that are not completely understood - do not distinguish self from nonself. This malfunction can result in an autoimmune disorder, in which the body attacks its own tissues.

20. Types of T cells Γδ T cells (gamma delta T cells) represent a small subset of T cells, which possess a different receptor on the surface (TCR). Most T cells receptor consists of two chains α-and β-gp. Unlike T cells, γδ cells have a TCR composed of gamma and a delta chains. This group is more poorly represented than beta alpha cells. They are abundant in the intestinal mucosa. Natural killer T cells (NKT) are a heterogeneous group of T cells, which have properties of both NK cells and T cells and represents only 0.2% of all circulating T lymphocytes in the blood.

21. The central role of T helper cells (CD4)

22. B cells B cells are formed in the bone marrow. B cells have particular sites (receptors) on their surface where antigens can attach. B cells are the major cells involved in the creation of antibodies that circulate in blood plasma and lymph, known as humoral immunity. In mammals there are five types of antibody IgA, IgD, IgE, IgG, and IgM, differing in biological properties. Each has evolved to handle different kinds of antigens. Upon activation, B cells produce antibodies, each of which recognizes a unique antigen, and neutralize specific pathogens .

23. B cells The B-cell response to antigens has two stages: Primary immune response: When B cells first encounter an antigen, the antigen attaches to a receptor, stimulating the B cells. Some B cells change into memory cells, which remember that specific antigen, and others change into plasma cells. Helper T cells help B cells in this process. Plasma cells produce antibodies that are specific to the antigen that stimulated their production. After the first encounter with an antigen, production of enough of the specific antibody takes several days. Thus, the primary immune response is slow. Secondary immune response Whenever B cells encounter the antigen again, memory B cells very rapidly recognize the antigen, multiply, change into plasma cells, and produce antibodies. This response is quick and very effective.

24. B cells

25. Primary and secondary phases of the humoral immune response to the same antigen.

26. Immunity Non specific Physical barrier (skin, mucous membrane) Inflammation Phagocytes (neutrophils, macrophages), Chemical barrier (lysozyme, HCl, interferon) Specific Humoral Immunity Cell-mediate Immunity

27. Nonspecific Defense/immunity body’s primary defense. intact skin & healthy mucous membranes lysozyme (in saliva and tears) destroys bacteria stomach acid destroys ingested bacteria phagocytes engulf bacteria entering the body inflammatory response including fever Complement proteins in plasma Specific Defense/immunity directed against antigens, or molecules recognized as foreign bodies. produces antibodies to destroy invader. memory cells develop and remain in circulation. Two main types of cells: B cells and T cells

28. Nonspecific cellular components Natural killer cells (NK cells): Lymphocytes that can destroy other cells, especially tumor cells and other infected cells. Macrophages (phagocytes) often act as antigen presenting cells (APCs). This is then identified by T cells.

29. Humoral and Cell-mediated Humoral immunity (or antibody mediated): involves the production of antibodies. It is governed by B-lymphocytes. Cell mediated immunity: is governed by T-lymphocytes which involve different types of T-cells

30. Cell mediated Immunity Cell mediated immunity Involves T-lymphocytes that act against infected cell or foreign cell or tissue. T cells are produced in bone marrow but mature in the thymus gland. Also regulate the activation and proliferation of other immune system cells Cell mediated immune response is directed against bacteria and viruses inside phagocytic cells or infected host cells. This also causes rejection of implanted tissue. T lymphocytes proliferate into different types of cells

31. Types of T cells Helper T-Cells: which activate macrophages and help B cells. Helper T cell also produce chemicals called cytokines such as interlukin and interferon. Cytotoxic T-Cells: destroy target cells on contact by producing toxin ( perforin) that lyses infected cells. Suppressor T-Cells: (also called regulatory T cells) are involved in stopping the reaction once the danger is finished. Memory T-Cells: are long-lived cells which give long term immunity against that pathogen.

32. Humoral immunity B cells or B lymphocytes are responsible for antibodies production. This provides resistance to bacteria and viruses and bacterial toxins Antibodies or immunoglobulins that recognize different types of antigens.

33. B cells cont… B cells are produced and matured in stem cells of bone marrow. Mature B cells are found in lymphoid tissues like spleen and lymph nodes. B cells Recognize antigen by antigen receptors on cell surface. We make 100 million lymphocytes a day, so equal number must die. This death of cells is known as ‘ Apoptosis’ or ‘programmed cell death’

34. Activation of B cells Each B cell produces an antibody against a particular antigen. When antigen comes in contact with B cells they form plasma cells and B memory cells . Plasma cells start the production of antibodies while Memory cells give long term immunity against that pathogen by keeping its record. Antibodies start binding to antigen and thus inactivate the antigens. Secondary response of immune system is quicker and stronger than the primary one.