The document summarizes the immune system, including its two main responses - non-specific innate immunity involving physical barriers and phagocytes, and specific adaptive immunity involving lymphocytes and antibodies. It describes the skin and mucous membranes as the first line of defense, followed by phagocytes, inflammation, and antimicrobial proteins as the second line of innate defense. The third line of specific defense involves B and T lymphocytes that provide long-lasting adaptive immunity through immunological memory and humoral or cell-mediated responses.

1. IMMUNE SYSTEM

2. The Immune System Recall the components of blood Recall what is a pathogen Recall the function of the skin

3. Two types of immune response Non-specific External E.g. Skin, mucus, tears Internal Phagocytic cells, antimicrobial proteins, inflammatory response Specific E.g. lymphocytes, antibodies

4. Innate immunity Plants and animals have mechanisms that target a wide range of pathogens

6. Skin and the mucus membrane as the first line of defense Imagine a body without a skin First, it is gross Secondly, it is not protected against invading pathogens Epithelial lining makes a good barrier against pathogens Mucus membrane lines the digestive, respiratory and genitourinary tracts

7. The skin Not only function as a barrier Secretions from sebaceous(oil) and sweat glands make it acidic pH range of 3-5 Most bacteria cannot live in an acidic environment Normal flora are adapted to this kind of environment

8. Mucus and other substances Mucus, saliva, tears- washes pathogens that might enter the body Antimicrobial proteins are also present Lysozyme- destroys cell wall of bacteria Destroys bacteria that might enter through the respiratory tract or around the eyes

9. Mucus and other substances Mucus- traps some microbes Is moved by the beating cilia in the respiratory tract Bacteria in mucus that is swallowed is destroyed in the stomach Hepatitis A can live in acidic environment

10. Cilia

11. Phagocytic cells, inflammation, antimicrobial proteins When an opening occurs in the skin through abrasion or wound the second line of defense is activated Phagocytosis is the main mechanism employed by the body Phagocytosis- synergistic with inflammation and antimicrobial protein response

12. Phagocytic cells and natural killer cells Mostly made up of neutrophils (60-70%) Damaged cells release chemical signals that attract neutrophils Engulfs damaged cell (neutrophils are also destroyed) Monocytes 5% of WBC Become macrophages Long-lived cells Engulfs cell to form vacuoles that fuse with lysozymes (lysosomes)

13. Macrophage engulfing two RBC Two actions of macrophage: Through toxic forms of O2 -superoxide anion -nitric oxide Use of lysozyme

14. Resistant bacteria towards lysosomal destruction Mycobacterium tuberculosis Resistant to lysosomal destruction Can even proliferate inside the macrophage

15. Specific Macrophages Lung- alveolar macrophage Liver- Kupffer’s cells Kidney- mesengial cells Brain-microglial cells Connective tissue-histiocytes

16. Still on the types of leukocytes..... Eosinophil- make up 1.5 % of all WBC Action is on parasites (e.g. vermiform such as Schistosoma mansoni) discharge destructive enzyme from their cytoplasmic granules on the external wall of parasites Other non-specific defense Natural killers cells (NK cells)- do not attact pathogens directly Destroy infected cell as well as abnormal body cells do not engulf cells, rather lyse infected cells

17. Schistosoma mansoni

19. The lymphatic system

20. The inflammatory response Injured area: precapillary arteriole dilates; postcapillary venule constrict- WHY?

21. The inflammatory response To increase blood supply- so what? This in turn will lead to edema

22. The inflammatory response Inflammatory response may be caused by the following: From the pathogen itself Histamines released by the body (from basophils and mast cells) Prostaglandins (dilate/constrict BV or aggregate/disaggregate clotting factors)

23. Phagocytosis during inflammatory response Phagocytosis begins an hour after an injury occurred Phagocytic cells move in the area through the increased permeability of the BV Attracted to chemotactic factors released by the pathogens Chemokines released by endothelial cells, monocytes can also attract phagocytic cells

24. Chemokines Bind to receptors of different leukocytes E.g. Induce toxic form of oxygen in lysosome Release of histamine from basophil

25. Sequence of events.... After inflammation, phagocytic cells arrive on the scene Neutrophils arrive first, followed by macrophages Macrophage- engulfs pathogens and other debris Pus- made up of dead phagocytic cells, fluid and proteins that leaked from the BV

26. Severe infection Fever is an immune response to severe infection Can be caused by the pathogens May be due to pyrogens released by some leukocytes Can facilitate phagocytosis Septic shock- high fever, hypotension

27. Antimicrobial proteins Proteins that attack microbes or stall reproduction of microbes Lysozyme is an example Also, presence of the complement system Made up of 20 serum proteins Action: lysis or attraction of phagocytic cells Is also part of specific immune response

28. Antimicrobial proteins Interferons Secreted by virus-infected cells Neighboring cells are stimulated to produce chemicals that can inhibit viral infection Not virus-specific A specific type of interferon activates phagocytes

29. Self vs Non-self Self recognition is important in an immune response Presence of receptors/markers in pathogens that enter the body Very efficient, even undigested proteins are considered as antigens

30. Self vs Non-self Lymphocytes react on special surface glycoproteins encoded by genes called Major Histocompatibilty Complex (MHC) In Humans, Human Leukocyte Antigens (HLA) Class I MHC- Almost all nucleated cells Class II MHC- macrophages, B cells, activated T cells, cell in the interior of the thymus Varies from one person to another

31. Invertebrate immunity Self and non-self is also exhibited by invertebrates starting from sponges Cells of different sponge species if mixed sort themselves and reaggregate Coelomocytes- phagocytic cells in sea stars Cytokines are also present E.g. Coelomocytes produce interleukin-1 that enables proliferation of coelomocytes

32. coelomocytes Sea urchin coelomocyte Coelomocytes from Placobdella

33. More on invertebrate immunity Makes use of innate, non-specific rather than active Exception is the hemolin protein in the hemolymph of insects Hemolin acts like vertebrate lymphocyte Hemolin belongs to the immunoglobulin superfamily

34. Absence of immunological memory Memory cells of vertebrates increase the immunological response of the body towards a pathogen Coelomocytes do not possess this trait Another exception: the earthworms First graft is rejected for two weeks Second graft is rejected in about a week

35. Active immunity vs Passive immunity Active immunity- immunity through recovery from a disease Natural or artificial Passive immunity- immunity passed by another individual short-lived

36. Specific immunity: the third line of defense Lymphocytes- cells responsible for the specific immune response There are two types: B cells and T cells Antigen- molecules that elicit specific response from lymphocyte E.g. Molecules from bacteria, fungi, virus, parasitic worms Antigens activate B cell in producing antibodies

38. Recognition of antigens by B cells and T cells Specificity is possible because membrane-bound antigen receptor B cell antigen receptor- transmembrane version of antibodies Also called membrane antibodies T cell antigen receptor- called T cell receptor Structurally related to membrane antibodies T cell receptor never released in secreted form

39. Clonal selection Antigen binds to a specific antigen receptor (B cell) B cell produce its clone Some B cells become plasma cells (short-lived) that can secrete antibodies to the specific antigen Plasma cells- also called effector cells Some B cells become memory cells (long-lived) for re-exposure to the antigen

40. Immunological memory Primary immune response- selective proliferation and differentiation of lymphocytes upon first exposure 10-17 days to develop maximum effector cells Selected B cells and T cells produce their respective effector cells

41. Immunological memory Secondary immune response- re-exposure to the same antigen response is faster, greater magnitude, more prolonged Also, more antibodies are produced Antibodies have greater affinity to the antigens Secondary response is called immunological memory

42. Graph showing immunological memory

43. Lymphocyte development All blood cells develop from pluripotent cells Lymphocytes also develop from pluripotent cells T cells- mature in the thymus B cells- mature in the bone marrow

44. Immune tolerance for self Maturing lymphocytes’ antigen receptors are rendered non-functional If antigen receptors cannot be switched off, lymphocytes undergo apoptosis

45. The other cells.... Cytotoxic T cells- kills cells through lysis Helper T cells- bind to antigen cell and secretes cytokine Antigen-presenting cells (APCs)- engulfs bacteria (virus) and presents fragment of these pathogens to other lymphocytes

46. Humoral response and cell-mediated response Humoral immunity- involves B cell activation, production of antibodies in blood plasma and lymph called humor Cell-mediated immunity- action of T cells

47. Overview of humoral response Macrophage engulfs the pathogen Class II MHC binds to fragment of pathogen MHC-antigen complex is presented by the phagocytic cell A helper T cell with specific receptor for the antigen makes contact with the macrophage and releases cytokines

48. Overview of humoral response Activated T cell presents the antigen to a B cell Cytokines activates the B cell Activated B cells differentiate into plasma and memory cells Plasma cells will produce the specific antibodies

49. Cell-mediated immune response Occurs when antigen displayed by APC activates Cytotoxic T cell Cytotoxic cell can differentiate to Memory T cells or active cytotoxic T cells Active against cancer cells and pathogens Kills these cell through lysis

50. Antibodies Do not destroy antigens directly Rather, neutralizes it or present it as a target for opsonization, agglutination, precipitation, or complement fixation, neutralization

51. Antibodies Opsonization- coating of antigens by antibodies to facilitate phagocytos Neutralization- binds to the antigen and inactivates it Agglutination- clumping of bacteria or virus to effectively neutralize or opsonize it Complement fixation or precipitation- immune adherence occurs Microbes coated with antibodies and complement proteins adhere to BV walls