Fire Ant Stings and Other Mishaps: Immnology

1. Fire Ant Stings and Other Mishaps: Immnology Donna Sullivan, PhD

2. Host Defensive Systems • 1st line of defense - • intact skin • mucous membranes and their secretions • 2nd line of defense - • phagocytic white blood cells • inflammation -complement • fever -interferon • 3rd line of defense- • B and T lymphocytes • antibodies nonspecific specific

3. Physical or anatomical barriers • Outermost layer of skin is composed of epithelial cells compacted, cemented together and impregnated with keratin • Flushing effect of sweat glands • Damaged cells are rapidly replaced • Mucous coat impedes attachment and entry of bacteria • Blinking and tear production • Stomach acid • Nasal hair traps larger particles

4. Chemical Defenses • Sebaceous secretions • Lysozyme, an enzyme that hydrolyzes the cell wall of bacteria, in tears • High lactic acid and electrolyte concentration in sweat • Skin’s acidic pH • Hydrochloric acid in stomach • Digestive juices and bile of intestines • Semen contains antimicrobial chemical • Vagina has acidic pH

5. DIFFERENTIATION OF CELLS

6. Leucocytes • Granulated: granules, lobed nuclei • Neutrophils • Eosinophils • Basophils • Agranulated: un-lobed, round nuclei • Monocytes • Macrophages, dendritic cells • Lymphocytes • T cells, B cells

7. GRANULOCYTES • Neutrophils (PMNs) • Strongly phagocytic, important in controlling bacterial infections • Usually first cells to arrive at site • Eosinophils • Weakly phagocytic, main role in allergic reactions, destruction of parasites • Basophils • Non phagocytic • Cell surface receptors for IgE • Mediated allergic and antiparasitic responses due to release of histamine

8. NEUTROPHILS Rapid increase in production (and in blood) during acute phase of infection Only found in inflamed tissues Single mature form Rapidly form pus Short-lived; die after phagocytosis MACROPHAGES Only slight increase in blood during inflammation Found in healthy tissues Multiple mature forms Slowly form granulomas (with T cell help) Long-lived-survive after phagocytosis DIFFERENCES BETWEEN NEUTROPHILS AND MACROPHAGES

9. MONOCYTES/MACROPHAGES • Released from bone marrow • Circulate in blood and enter tissues where they mature into macrophage • Activated macrophage • Initiated by phagocytosis of particulate antigens

10. BRAIN - MICROGLIAL BLOOD - MONOCYTES LUNGS - ALVEOLAR LYMPH NODES -RESIDENT & RECIRCULATING MACROPHAGES SPLEEN - MACROPHAGES KIDNEY - MESANGIAL LIVER - KUPFFER CONNECTIVE TISSUE - HISTOCYTES BONE MARROW - PRECURSORS JOINTS - SYNOVIAL A CELLS OF THE MONOCYTE- MACROPHAGE SYSTEM

11. MACROPHAGES: FUNCTION • Stand guard • Initiate early innate immune response • Educate the specific immune system • Present antigen associated with Class II MHC to CD4 TH cells • Call in the troops • Secrete cytokines that promote immune responses • Join the battle • Phagocytoseand inactivate microbes • Secrete antibacterial substances, inflammatory mediators, and complement components

12. Phagocytosis

13. NATURAL KILLER CELLS • Primary targets of NK cell killing are virus infected and tumor cells • May depend on reduced expression of Class I MHC molecules, alterations in surface carbohydrates • Mechanism of killing • Direct cytotoxicity • Antibody dependent cellular cytotoxicity (ADCC)

14. Stages Of Inflammation • Blood vessels dilate in response to chemical mediators and cytokines • Edema swells tissues, helping prevent spread of infection • WBC’s, microbes, debris and fluid collect to form pus • Pyrogens may induce fever • Macrophages and neutrophils engage phagocytosis

15. Developmental Stages of Monocytes and Macrophages

16. INFLAMMATION • Tissue damage due to trauma, caustic agents, microbes • Mediated primarily by immune system cells, cytokines • Acute inflammation • Chronic inflammation

17. Rubor, Calor, Tumor, Dolor • Rubor: Redness caused by increase circulation and vasodilation in injured tissues • Calor: Warmth, heat given off by increased flow of blood • Tumor: Swelling, caused by increased fluid escaping into the tissues • Dolor: Pain, causes by stimulation of nerve endings

18. TRAUMA AND INFLAMMATION

19. TRAUMA AND INFLAMMATION

20. TRAUMA AND INFLAMMATION

21. TRAUMA AND INFLAMMATION

22. TRAUMA AND INFLAMMATION

23. Activities Of Phagocytes • Stand guard • To survey tissue compartments and discover microbes, particulate matter and dead or injured cells • Join the Battle • To infest and eliminate these materials • Educate Specific Immune System • To extract immunogenic information from foreign matter

24. Chemical Mediators

25. Complement • Consists of 26 blood proteins that work in concert to destroy bacteria and viruses • Complement proteins are activated by cleavage • Classical pathway • Alternative pathway

26. Complement

27. Specific immunities • B and T lymphocytes • Specificity and memory

29. Lymphocyte Development and Differentiation

30. Antigen Presentation Challenge of B and T Cells B Cell Antibody Production T Cell Responses

31. Preliminary concepts • Cell receptors or markers confer specificity and identity • Major functions of receptors are • To perceive and attach to nonself or foreign molecules • To promote the recognition of self molecules • To receive and transmit chemical messages among other cells of the system • To aid in cellular development.

32. How Are Receptors Formed? • As a cell matures, certain genes that encode cell receptors are transcribed and translated into protein products with a distinctive shape, specificity and function. • Receptor is modified and packaged by the endoplasmic reticulum and Golgi complex. • It is ultimately inserted into the cell membrane, accessible to antigens, other cells, and chemical mediators.

33. Receptor Formation in a Developing Cell

34. Major Histocompatibility Complex (MHC) • Receptors found on all cells except RBCs • Also known as human leukocyte antigen (HLA) • Plays a role in recognition of self by the immune system and in rejection of foreign tissue • Genes for MHC are located on chromosome 6, clustered in a multigene complex of classes I, II, III

35. MHC Receptors

36. Functions of MHC • Class I – markers that display unique characteristics of self molecules and regulation of immune reactions • Required for T lymphocytes • Class II – receptors that recognize and react with foreign antigens. Located primarily on macrophages and B cells • Involved in presenting antigen to T cells • Class III – secreted complement components, C2 and C4

37. Clonal Selection Theory • Lymphocytes use 500 genes to produce a tremendous variety of specific receptors • Undifferentiated lymphocytes undergo genetic mutations and recombinations while they proliferate in the embryo forming a billion different clones with the ability to react with a tremendous variety of antigens.

38. Ability to React to Every Antigen Is Pre-Programmed • Lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the system. • Each genetically different type of lymphocyte expresses a single specificity. • First introduction of each type of antigen into the immune system selects a genetically distinct lymphocyte and causes it to expand into a clone of cells that can react to that antigen.

40. Structure of Antibodies

41. Immunoglobulins • Immunoglobulin genes lie on 3 different chromosomes • Undifferentiated lymphocyte has 150 different genes for the variable region of light chains and 250 for the variable region and diversity region of the heavy chain • During development, recombination causes only the selected V and D genes to be active in the mature cell.

42. Gene Segments of Immunoglobulins • Heavy chains • Variable (V) • Diversity (D) • Joining (J) • Constant (C) • Light chains • Variable (V) • Joining (J) • Constant (C)

44. HYPERSENSITIVITY REACTIONS • Type I (immediate) hypersensitivity: IgE-mediated atopic (allergic) and anaphylactic reactions • Type II hypersensitivity: Ab-dependent cytotoxicity • Type III hypersensitivity: Immune complex induced tissue damaging inflammation • Type IV (delayed) hypersensitivity:Cell-mediated cytotoxicity

46. TYPE II REACTIONS: Blood Typing and Transfusion Reactions

48. TYPE IV (DTH) REACTION: TB Skin Test

50. IMMUNE REACTIONS DUE TO MATERNAL ANTIBODIES