THE IMMUNE SYSTEM

1. THE IMMUNE SYSTEM Prof. Khaled H. Abu-Elteen

3. Terminology • Types of Symbiosis ( Living togathers) - Amensalism • A symbiotic relationship in which one species is harmed, but it isdifficult to see how the other species benefit. • Mutualism • A symbiotic relationship in which both species benefit • Commensalism • A symbiotic relationship in which one species benefits, and the other species is neither helped nor harmed

4. Types of Symbiosis (cont.) • Parasitism • A symbiotic relationship in which one species benefits, and the other species is harmed • Generally, the species that benefits (the parasite) is much smaller than the species that is harmed (the host)

5. Disease and Infectious Disease • Disease • Any deviation from a condition of good health and well-being • Infectious Disease • A disease condition caused by the presence or growth of infectious microorganisms or parasites

6. Immunology lingo • Antigen • Any molecule that binds to immunoglobulin or T cell receptor • Pathogen • Microorganism that can cause disease • Antibody (Ab) • Secreted immunoglobulin • Immunoglobulin (Ig) • A glycoprotein produced in response to the introduction of an antigen • Vaccination • Deliberate induction of protective immunity to a pathogen • Immunization • The ability to resist infection

7. TYPES OF IMMUNITY. • Nonspecific: Skin and mucous membranes, Phagocytosis, Inflammation, and The Complement System. • Specific: Humoral(Antibody-Mediated) and Cell-Mediated.

8. Nonspecific Immune Response • Physical and Mechanical Barrier’s • Chemical Factor’s • Biological Factor’s • Phagocytosis and Associated with Blood and lymph • Defenses that protect from ANY pathogen regardless of type and species( Bacteria, Fungi, Protozoa, etc).

9. Physical and Mechanical Barrier’s • THE SKIN: First Line Of Defense. • Repels many organisms: difficult to get through. • Epithelium lines all body systems exposed to external environments including the respiratory, digestive and urinary systems. • Secretes liquid which are mildly acidic which hinder bacterial growth. • Lack of nutrition for microbial growth.

11. DEFENSES • Dry • usual infection sites are wet areas, skin folds, armpit, groin • Acidic (pH 3.0- 5.0) • Temperature less than 37oC • Some pathogens grow best <37oC • Lysozyme and toxic lipids • pore, hair follicles, sweat gland • Resident microflora • mainly G+ • Skin-associated lymphoid tissue (SALT)

12. Tears and saliva contain lysozymes which dissolve the wall of bacteria. • Cilia of respiratory tract trap bacteria in mucus.

13. SKIN AND MUCOUS MEMBRANES:1st line of defense • Mechanical Factors: • Skin. • The Epidermis. • Keratin. • Mucous Membranes. • Lacrimal Apparatus ------> • Cilliary Escalator [ mucocilliary Escalator Action).

14. LACRIMAL APPARATUS.

15. CILIARY ESCALATOR.

16. Flushing Mechanisms • Epiglottis. • Urine and Vaginal secretions. • Sneezing, coughing, swallowing reflex • Movement of Fluids across their surfaces (Saliva) • Washing action of tears

17. CHEMICAL FACTORS. • Sebum and fatty acids in skin ( e.g. unsaturated fatty acids as Olic acid). • Gastric Juice (Low pH stomach ). • Lyzozyme: degrade the bacterial cell wall • Antimicrobial peptides (β Lysine) with high quantity of Lysine or Arginine. Act by disruption of plasma membrane of microorganisms.

18. Complement:complex of 17 proteins (Glycoproteins) present in normal serum) C1, C2, C3 …..etc. Function: Lysis of microbes, Neutralization of viruses, Enhancement of phagocytosis, Damage of plasma membrane, Recruitment of Phagocytes, • Interferons : Family of Glycoproteins that block Viral Replication by rendering host cells,

19. NORMAL MICRIBIOTA AND NONSPECIFIC RESISTANCE. • Microbial Antagonism. • Commensalism. • Competitive Exclusion: Opportunistic pathogens. • Natural Resistance: Microorganisms has a host range

20. Cells of the Immune system: FORMED ELEMENTS IN BLOOD. • Many cells of the immune system derived from the bone marrow • Hematopoetic stem cell differentiation

21. Components of blood Serum vs. Plasma • Serum: cell-free liquid, minus the clotting factors • Plasma: cell-free liquid with clotting factors in solution (must use an anticoagulant) • Contain protein: Albumin, Globulin and Fibrinogen.

22. Components of blood

23. LEUKOCYTES. • Divided into two main categories based on their appearance under the light microscope: • Granulocytes Versus Agranulocytes. • Granulocytes: Neutrophils(stain lilac), Basophils (stain blue-purple), and Eosinophils (stain red or orange).

24. NEUTROPHILS ( 60% of WBC) • Commonly called polymorphonuclear leukocytes (PMNs). • Multinucleated. • Highly phagocytic and motile. • Active in the initial stages of infection. • Short life span (hours) • Very important at “clearing” bacterial infections • Innate Immunity

25. BASOPHILS (1% of WBC) • Role is not clear. • Release substances, such as histamine, that are important in inflammation. • Might be “blood Mast cells’ • Important in allergic reactions

26. Eosinophils ( 3% of WBC) • Somewhat phagocytic. • Have the ability to leave the blood. • Major function is to produce toxic proteins against certain parasites such as worms. • Involved in allergic inflammation • Double Lobed nucleus • Orange granules contain toxic compounds

27. AGRANULOCYTES. • Monocytes ( 5% of all WBC). • Macrophages. • Lymphocytes ( 30% of all WBC) .

28. MONOCYTES. • Phagocytosis and killing of microorganisms • Activation of T cells and initation of immune response • Monocyte is a young macrophage in blood • There are tissue-specific macrophages • Antigen Presentation

29. MACROPHAGES. • Maturation and proliferation of is one factor that is responsible for the swelling of lymph nodes during an infection.

30. Lymphocytes • Many types: • B-cells produce antibodies( Humoral immunity) • T- cells (Cellular immunity) • Cytotoxic T cells • Helper T cells • Memory cells

31. Lymphocytes • Plasma Cell (in tissue) • Fully differentiaited B cells, secretes Ab • Natural Killer cells • Kills cells infected with certain viruses • Both innate and adaptive • Antigen presentation

33. TH cells play a central role in the immune system Antigen Presenting Cell

34. Dendritic Cells • Activation of T cells and initiate adaptive immunity • Found mainly in lymphoid tissue • Function as Antigen Presenting Cells (APC) • Most potent stimulator of T-cell response

35. Mast Cells • Expulsion of parasites through release of granules • Histamine, leukotrienes, chemokines, cytokines • Also involved in allergic responses

36. Other Blood Cells • Megakaryocyte • Platelet formation • Wound repair • Erythrocyte • Oxygen transport

37. Cells, tissues and organs of the immune system • Immune cells are bone marrow-derived, & distributed through out the body • Primary lymphoid organs: • Thymus: T cell maturation • Bone marrow (bursa of Fabricius in birds): B cell maturation • Secondary lymphoid organs: • Lymph nodes • Spleen • Mucosal lymphoid tissues (lung, gut)

38. 2º 2º Major Tissues 1º 2º 2º • Primary Lymph tissues • Cells originate or mature • Secondary Lymph Tissues 2º 2º 2º 1º

39. COMPONENTS OF THE LYMPHATIC SYSTEM.

40. Dendritic cell (sentinel)

42. The bursa of Fabricius in birds

43. ACTION OF PHAGOCYTIC CELLS. • Wandering macrophages. • Fixed macrophages. • Mononuclear phagocytic (reticuloendothelial) system. • During the initial infection, granulocytes, especially neutrophils are many and they dominate.

44. Opsonization. • Opsonization - coating micro-organisms with plasma proteins – aids phagocytosis. • Complement binds to antibody-antigen targets. • Promotes adhesion between opsonized cell & macrophages. • Opsonin binds to receptors on phagocyte membrane.

46. PHAGOCYTOSIS: 2ND LINE OF DEFENSE. • Cell Eating. • Phagocytes: Cells that perform phagocytosis. • Are mostly types of white blood cells or derivatives of white blood cells.

47. THE MECHANISM OF PHAGOCYTOSIS. • Chemotaxis. • Adherence. • Ingestion. • Digestion.

48. 3. Phagocytosis & oxidative burst. • Certain WBCs - phagocytosis. • Chemotactically attracted to disease / tissue damage foci. Stages: • Engulfment of particulate matter into phagosome. (e.g. bacteria, virions, cell debris, etc.). • Phagosomefuses with lysosomes = phagolysosome.

49. Human macrophage engulfing the fungus Candida albicans. 3. Phagocytosis & oxadative burst. • Lysosomes contain enzymes = degrade biomolecules. • E.g. acid hydrolases, lysozyme, neutral proteases, myeloperoxidase, lactoferrin, & phospholipase A.

50. Yeast Neutrophil Human neutrophil kills yeast cell using oxidative burst. Dye shows extent of reactions. 3. Phagocytosis & oxidative burst. • Engulfed organisms killed in WBC by “respiratory (oxidative) burst". • Many pathogens / parasites succeed because avoid phagocytosis.