Lymphocytes and Immunity

1. Lymphocytes and Immunity Clinical Pathology Ms. Canga

2. Reading Assignment • A&P book: pp. 237 – 246 • Lab Pro book: pp. 45, & 48-49 • (There are some very helpful pictures on these pages as well!)

3. Lymphocytes… …are the predominant WBC in ___________ and ___________. …are the only WBC with no _________________ capabilities. …can constantly recirculate between ____________ and ____________. …may survive for _________ or even ____________. …cannot be differentiated __________________. …can cause __________________. …are predominantly found in _________ and other tissues. Only ~___% of population are in __________________.

4. Lymphocytes • Normal Ranges: 1,000 – 4,800/ in canines and 1,500 – 7,000/µL in felines • WBC originates from PPSCs in bone marrow • Immature lymphocytes are processed in the central ________________ organs: • _______________ • _____________________ • ____________ (gut-associated lymph tissue)

5. Lymphocytes • Mature lymphocytes live in the peripheral lymphoid organs • Lymph nodes • _____________ • Bone marrow • GALT • _____________ • _____________ Fact: The _______________ is the largest lymphoid organ in the body.

6. Lymphocytes in Circulation • The lymphocytes in circulation can be either: • _____________ lymphocytes • Large lymphocytes are thought to be less mature • Have more _________________ that is sky blue • Gradually develop into small lymphocytes • ______________ lymphocytes • _________________ lymphocytes • Very little sky blue cytoplasm usually on one side • May look like a _____________ with no cytoplasm at all!

7. Small Lymphocyte

8. Large Lymphocyte

10. “Reactive or “Atypical” Lymphocytes …may have ________________ granules in the cytoplasm …may have an abnormally shaped _____________. (It may look like a monocyte’s nucleus) …often have larger percentage of ______________ that is very __________________. …may be normal in some _____________ lymphocytes (granules present) …are often associated with chronic antigenic stimulation (common with Canine ____________________)

11. Lymphocytes at a Glance

12. Three Types of Lymphocytes • _____ – Lymphocytes • _____ – Lymphocytes • _____ Cells

13. T - Lymphocytes • Called T – Cells • Processed in __________ before going to periperal tissues. • In thymus, they are “pre-T cells” called __________________ • Multiply rapidly • Leave thymus and travel to specific zones in lymph nodes and spleen • Once they leave the thymus, they are functioning, adult T - cells • T-cells are involved in cellular _____________ and activation of ______-lymphocytes. • Most lymphocytes in circulation are ____ - Lymphocytes

14. B - Lymphocytes • Also called B – Cells • Processed in bone marrow and other lymph tissue referred to as “__________ equivalent” • _______________ producing lymphocytes, that are involved in ___________ immunity. (Antigen-Antibody complex) • We will discuss this in detail later

15. Bursa of Fabricius

16. B – Lymphocytes & Humoral Immunity • Use a “lock and key” type mechanism to fight foreign invaders. • Each B-lymphocyte is pre-programmed to produce only ______ specific ____________ against one specific ________________. • Cell surface has thousands of ________________ against that specific antigen. • Each antigen has a unique shape on it’s surface called an _______________. • When antigen binds with B-cell, __________ -_______________complex is formed.

17. Antigen – Antibody Complexes 1 2 3 4 Epitope

18. B- Lymphocytes & Humoral Immunity • Specific B-cells are _____-_______________ to recognize specific antigens. • ONLY these B-cells will undergo mitotic, _____________ transformation into ________ cells and begin producing antibodies against invaders. • All other B-cells are _______________. • Potential for over 100 trillion antibodies produced by the body!

19. Plasma Cells • Can ____________, store and ___________ antibodies known as immunoglobulins. (More on this with immunity) • Found in any ___________ of body • Most numerous in tissues constantly forming antibodies: spleen, lymph nodes • Rare in _______________ blood.

20. Natural Killer Cells • Called NK cells • Neither ___ nor ___ lymphocytes • Do not require _______________ by an antigen • Have the ability to kill some types of __________ cells and cells infected with various ___________. • Must come in ____________ contact with cells in order to destroy them.

21. Lymphocytosis • Physiologic: due to _______________ release. • Common in chronic __________________. • May be caused by ____________ stimulation. • Seen in later stages of resolving ____________. • Neoplastic lymphocytosis (___________ and lymphosarcoma) • Can be significant enough to cause ________________ .

22. Lymphopenia • One of the most ____________CBC abnormalities of sick dogs and cats. • Associated with __________. • Immunosuppressive therapy. • Immunodeficiency syndromes. • Acute _________ infections • Can be significant enough to cause ____________________, especially in _______________.

23. The Immune System • Function: To protect animal from damage/disease. • Recognize “______” from “_________________” • Destroy “______________” Mechanisms of Destruction • ___________________ • _________(cell membrane) • ___________________ • ___________________

24. 2 Types of Immunity • _________________ immunity • _______ and _______ lines of defense for the body. • _______________immunity • _______ line of defense for the body

25. Non-Specific Immunity • First Line of Defense: • _____________ barriers: _________, mucous membranes, etc… • Provide protection by ____________________ microorganisms from entering body. • ______________barriers: Hcl acid of gastric mucosa • Destroy microorganisms that may be ingested.

26. Non-Specific Immunity • Second Line of Defense • ______________________ Response • ______________________ (neutrophils, MPS) • ________Cells • __________________ • __________________

27. Nonspecific Immunity (2nd line of defense) • Inflammation • ____________ damage is caused when microorganisms enter the body. • Damage causes release of _______________ factors from cells • One example of chemotactic factor released is from mast cells. (_______________ of tissue) • What is released by mast cells/Basophils?

28. Inflammatory Response

29. Inflammation continued

30. Nonspecific Immunity: Phagocytosis • Usually involves ________________, _______________ and tissue ____________________. • __________________ initiates the WBC’s death. • Accumulation of dead WBCs around site forms ________.

31. Nonspecific Immunity: NK Cells …are not __-Lymphocytes or __-Lymphocytes. …do not have to be ___________ by a specific antigen. …can kill some types of __________ and tumor cells. …can kill some cells infected with particular __________. …must come in ___________ contact with cell before destroying it.

32. Nonspecific Immunity: Interferon …is a _____________ produced by a cell after it has been infected by a virus. That cell then dies. …responds rapidly, entering other cells to inhibit further development and spread of the virus.

33. Overview of Interferon Production

34. Nonspecific Immunity: Complement …refers to a group of inactive ______________ in plasma. …are activated by attachment of antibody to antigen. …activated enzymes adhere to complement ______________ sites on antigens. -Each plasma enzyme that attaches, causes the activation of another and another, creating a chain reaction until all attachment sites are full. _______________________ fixation - process by which complement enzymes arrange into doughnut formation on antigen surface, create a hole, allowing sodium and water to enter cell and cause it to swell and burst.

35. Complement Fixation • As each binding site is filled, fragments break off and attach to the membrane causing the perforations that eventually lyse the cell.

36. Specific Immunity • The _______ line of defense • Primarily involves lymphocytes (__ and __ cells). • Includes _____________ and ___________ Immunity • Properties of all specific immune responses: • Response will be initiated only ________ the antigen enters the body. • Response will be aimed specifically against the _______________ present • If the antigen enters the body a second time, there will be a ______________ of the antigen and the immune response will occur more quickly.

37. Cell-Mediated, Specific Immunity • A function of __-cell that attaches to the antigen site. • Tissue __________________ MUST have ingested antigen and presented its ____________ on its own membrane. • T-cell attaches and becomes a _____________T-cell. • Sensitized T-cell divides many times, _________ itself, and forms either ____________T-cell (Tc), a ____________T-cell (Th), or a ______________T-cell (Ts) • _____________________ like lymphotoxin are secreted at the site of infection and quickly kill any cell it attacks.

38. The 3 T-Cells • After sensitization by the macrophage, the lymphocyte can become either a _____________ T-cell, a __________T-cell, or a _______________T-cell. • 1) Cytotoxic T-cells (Tc): Are known as __________ T cells. They attach to antigenic cells and destroy them but are not _________________ themselves.

39. The 3 T-cells • 2) __________ T-cells (Th): Are the most numerous of the T cells. They help the immune response by secreting additional _________________ into surrounding tissue. • Cytokines can increase activation of ___-cells, ____ cells, or _____ cells. • ___________________ is a cytokine that stimulates activity of all other T cells • ________________________________________: is a cytokine that attracts tissue macrophages to the area via _______________________ and increases the rate of phagocytosis. (This then, presents more epitopes to the Tc cells!)

40. The 3 T-cells • 3) _________________ T cells (Ts): Operate by ______________ feedback • They ___________ helper T-cells and cytotoxic T-cells. • They ______________ B-cells from transforming into plasma cells. • Help to control cell-mediated and humoral immune responses as infection _______________.

41. Additional info on Cell-Mediated Immunity • T-cells leave the lymphoid tissue and _______________ through blood and lymph. • B-cells usually stay in _______________ tissue and send out antibodies found in blood. • Because of this, most lymphocytes in peripheral blood are __-cells. • If a blood smear is made and both B and T cells are present, they will appear ______________.

42. Humoral Immunity • Is a function of __-Lymphocytes • B-cells, activated by an _____________-______________ complex (lock and key system), produce ___________ cells that secrete _________________ into the plasma. • B-cells and _____________ cells usually stay in lymphoid tissue. • _________________________ (antibodies) circulate in bloodstream (in the ____________), destroying antigens instead of adhering to cells’ membranes.

43. Antibodies: aka - Immunoglobulins • _______ types of antibodies (immunoglobulins) have been identified: • IgG, IgM, IgA, IgE and IgD • When an antibody attaches to an antigen: • Antigens may be _________________ into harmless substances. • Antigens may be _______________________ and then phagocytized by macrophages. • _______________________ system may be activated Fact: IgG is present in the greatest quantity of all the immunoglobulins

44. The 5 Immunoglobulins • 1) _______ : Is made during the bodies __________ exposure to an antigen. • Is the first immunoglobulin made by _____________. • Production is relatively _________, so illness may result before production of IgG is complete. • 2) ________: Is made when the animal has been exposed to an antigen for an _____________ period of time • Is made upon ________ exposure to an antigen. • Production is __________ than IgG, so illness is less likely.

45. The 5 Immunoglobulins • 3) ________: Plays an important role in preventing disease entering through ____________ or GI tract. • Can leave the __________ and enter tissue fluids. • 4) ________: Is associated with _____________ responses. • 5) ________: Function is ____________

46. Memory Cells • Both ___-cells and ___-cells are capable of becoming Memory Cells • Not all activated lymphocytes become immediately involved in the immune response. • Memory cells wait for a ___________ infection of the same ____________ that triggered their formation. • May ____________ in blood or wait in ________nodes. • Some can live for a few _______; others for several ___________. • Second exposure = more ________ & greater degree of response to antigen than the __________ exposure.