1. Lec 4 Basic immunology Romana Siddique The Lymphocytes and it’s role in Adaptive immunity

2. Evasion of Innate Immunity by Pathogens Some pathogens avoid destruction by modifying their surface to prevent recognition or by resisting breakdown following phagocytosis Tuberculosis (TB) is one such disease and kills more than a million people a year

3. In adaptive immunity, receptors provide pathogen-specific recognition The adaptive response relies on two types of lymphocytes, or white blood cells Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells

6. Lymphocytes

7. B Cells T Cells NK Cells Lymphocytes

8. Stimulation of adaptive immunity by innate immune responses.

11. Two types of T cells

12. Classes of Lymphocytes

13. B Cell CD19+ T Helper CD4+ T Cytotoxic CD8+ Phenotypic Markers to Distinguish Lymphocyte Subsets

14. Stages of lymphocyte activation Naïve lymphocytes –Mature lymphocytes that have not previously encountered antigen; function -- antigen recognition –Preferential migration to peripheral lymphoid organs (lymph nodes), the sites where immune responses start Effector lymphocytes –Activated lymphocytes capable of performing the functions required to eliminate microbes (‘effector functions”) –Effector T lymphocytes: cytokine secretion (helper cells), killing of infected cells (CTLs) –B lymphocytes: antibody-secreting cells (e.g. plasma cells) Memory lymphocytes –Long-lived, functionally silent cells; mount rapid responses to antigen challenge (recall, or secondary, responses)

15. NaiveActivatedEffector Phases of Lymphocyte Activation

17. In adaptive immunity, receptors provide pathogen-specific recognition The adaptive response relies on two types of lymphocytes, or white blood cells Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells

18. Antigens are substances that can elicit a response from a B or T cell Exposure to the pathogen activates B and T cells with antigen receptors specific for parts of that pathogen The small accessible part of an antigen that binds to an antigen receptor is called an epitope © 2011 Pearson Education, Inc.

19. Figure 43.UN01 Antigen receptors Mature B cell Mature T cell

20. B cells and T cells have receptor proteins that can bind to foreign molecules Each individual lymphocyte is specialized to recognize a specific type of molecule © 2011 Pearson Education, Inc.

21. Pathogen recognition by adaptive immunity: great variety, selectivity

22. The B-cell receptor is a transmembrane receptor protein located on the outer surface of B-cells.transmembranereceptor proteinouter surfaceB-cells The receptor's binding moiety is composed of a membrane-bound antibody that, has a unique and randomly-determined antigen-binding site.moiety antibodyantigen When a B-cell is activated by its first encounter with an antigen that binds to its receptor (its "cognate antigen"), the cell proliferates and differentiates to generate a population of antibody-secreting plasma B cells and memory B cells.plasma B cellsmemory B cells B cell recptor 22

23. Antigen Recognition by B Cells and Antibodies Each B cell antigen receptor is a Y-shaped molecule with two identical heavy chains and two identical light chains The constant regions of the chains vary little among B cells, whereas the variable regions differ greatly The variable regions provide antigen specificity

24. Cytoplasm of B cell Antigen- binding site B cell antigen receptor B cell Light chain Disulfide bridge Antigen- binding site Variable regions Constant regions Transmembrane region Heavy chains Plasma membrane C C C C V V V V

25. Binding of a B cell antigen receptor to an antigen is an early step in B cell activation This gives rise to cells that secrete a soluble form of the protein called an antibody or immunoglobulin (Ig) Secreted antibodies are similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane © 2011 Pearson Education, Inc.

26. Directly by free Ag which bunds to receptor Ab called B cell receptor (BCR) B cell activated by T cell as T cells release cytokines.these activated b cells are called effector/ plasma B cells PLASMA CELL-these produce lots of antibodies Some activated B cells  MEMORY CELLS Memory cells divide rapidly as soon as the antigen is reintroduced. Function of B cell 26

27. Function of B cell 27

28. Each T cell receptor ( TCR) consists of two different polypeptide chains (called  and  ) The tips of the chain form a variable (V) region; the rest is a constant (C) region T cell and B cell antigen receptors are functionally different There are two types of TCR  CR-found in 95% of T cells  TCR-found in 5% of T cells © 2011 Pearson Education, Inc. Antigen Recognition by T Cells

29. T cell antigen receptor T cell Cytoplasm of T cell Plasma membrane  chain  chain Disulfide bridge Antigen- binding site Variable regions Constant regions Transmembrane region V V C C The structure of a T cell antigen receptor

30. CD3 &  chain

31. CD3 TCRs occur as either of two distinct heterodimers,  or , both of which are expressed with the non- polymorphic CD3 polypeptides  and  The CD3 polypeptides, especially  and its variants, are critical for intracellular signaling.

32.  TCR The  TCR are a second type of TCR. Their function remains largely unresolved. They do not recognize MHC-associated peptides and are not MHC restricted. In mice and chickens they are found in the small bowel mucosa and termed intraepithelial lymphocytes. In humans they are found in the tongue, uterus and vagina.

33. Proliferation of B Cells and T Cells(Clonal selection) In the body there are few lymphocytes with antigen receptors for any particular epitope In the lymph nodes, an antigen is exposed to a steady stream of lymphocytes until a match is made This binding of a mature lymphocyte to an antigen initiates events that activate the lymphocyte

34. Once activated, a B or T cell undergoes multiple cell divisions This proliferation of lymphocytes is called clonal selection Two types of clones are produced: short-lived activated effector cells that act immediately against the antigen and long-lived memory cells that can give rise to effector cells if the same antigen is encountered again © 2011 Pearson Education, Inc.

35. Antigen Antigen receptor Antibody Plasma cells Memory cells B cells that differ in antigen specificity Figure 43.14

36. Immunological memory is responsible for long-term protections against diseases, due to either a prior infection or vaccination The first exposure to a specific antigen represents the primary immune response During this time, selected B and T cells give rise to their effector forms In the secondary immune response, memory cells facilitate a faster, more efficient response Immunological Memory

37. Antibody Response After Exposure to Antigen (first and subsequent exposure ) 37