Study of the Immune System

1. Study of the Immune System

2. Now that we know all about microbes….. • What provokes us to fight against microbes? • How do we know that they are foreign? • What initiates the response?

3. Antigen (Ag) Any substance that stimulates an immune response Requirements for antigenicity foreignness (recognition of nonself) large size complexity Introduction to Antigens most antigenic

4. Epitope antigenic determinant small molecular group that is recognized by: Antibodies B cells T cells Characteristics of Antigens

5. Defense Mechanisms of the Host • Immune system • relies on a multilevel network of physical barriers, immunologically active cells, and a variety of chemicals • 3 main lines of defense: • first line of defense • any barrier that blocks invasion at the portal of entry • nonspecific • second line of defense • protective cells and fluids • inflammation and phagocytosis • nonspecific • third line of defense • acquired with exposure to foreign substance • Stronger immune response • produces protective antibodies and creates memory cells • specific

7. Skin and mucous membranes: outermost layer of skin few pathogens can penetrate if intact flushing effect of sweat glands mucous coat impedes attachment and entry of bacteria blinking and tear production stomach acid nasal hair traps larger particles Vaginal secretions Physical or Anatomical Barriers: First Line of Defense

8. Immunology study of the body’s second and third lines of defense Functions of a healthy functioning immune system: Constant surveillance of the body Recognition of foreign material Destruction of entities deemed to be foreign Structure and Function of the Organs of Defense and Immunity

9. Plasma Serum - fluid portion complement proteins and antibodies Three types of formed elements Erythrocytes Platelets Leukocytes Divided into granulocytes and agranulocytes Blood

10. White Blood Cells Leukocytes Housekeeping and defense Scavenge dead or worn-out cells Disease organisms Squeeze out of blood vessels and enter tissues Develop from stem cells in bone marrow Granulocytes Neutrophils Eosinophils Basophils Agranulocytes Monocytes Macrophages Lymphocytes B-cells T-cells

11. White Blood Cells • Neutrophils • 55-90% • lobed nuclei with lavender granules • phagocytes • Eosinophils • 1-3% • orange granules and bilobed nucleus • destroy eukaryotic pathogens • Basophils, mast cells • 0.5% • constricted nuclei, dark blue granules • release potent chemical mediators • Lymphocytes • 20-35% • large nucleus • involved in specific immune responses • B (humoral immunity) • T cells (cell-mediated immunity) • Monocytes, macrophages • 3-7% • large nucleus • Phagocytic • Dendritic cells • Activate lymphocytes • Produce cytokines

13. Innate Immunity “Second” line of defense

14. Second Line of Defense • cells and mechanisms that defend the host from infection by other organisms • genetically-encoded to recognize: • common pathogenic features • foreign substances • does not confer long-lasting or protective immunity to the host • provide immediate defense against infection

15. Actions of the Second Line of Defense • Recognition • Inflammation • Phagocytosis • Interferon • Complement

16. Toll-like receptors (TLRs) protein receptors within cell membrane of macrophages recognize structurally conserved molecules derived from microbes Detect foreign molecules and signal the macrophage to produce chemicals cytokines stimulate an inflammatory response (nonspecific) promote the activity of B and T cells (specific) 1. Recognition

17. 2. Functions of inflammation • Mobilize and attract immune cells to site • Set mechanisms to repair tissue damage • Destroy microbes and block further invasion

18. Classic signs and symptoms characterized by: Redness increased circulation and vasodilation in injured tissue Warmth heat given off by the increased blood flow Swelling increased fluid escaping into the tissue as blood vessels dilate edema WBC’s, microbes, debris and fluid collect to form pus helps prevent spread of infection Pain stimulation of nerve endings Possible loss of function 2. Inflammatory Response

19. Fever • Initiated by circulating pyrogens • cytokines produced by some leukocytes • reset the hypothalamus to increase body temperature • signals muscles to increase heat production and vasoconstrict • Benefits of fever: • inhibits multiplication of temperature-sensitive microorganisms • impedes nutrition of bacteria • increases metabolism and stimulates immune reactions

20. nonspecific defense mechanism clear microbes from infected tissues capture and digestion of foreign particles 3. Phagocytosis

21. Phagocytes 3 main types of phagocytes: • Neutrophils • general-purpose • react early to bacteria and other foreign materials, and to damaged tissue • Eosinophils • attracted to sites of parasitic infections and antigen-antibody reactions • Macrophages • derived from monocytes • scavenge and process foreign substances to prepare them for reactions with B and T lymphocytes

22. Type of cytokine Produced in response to viruses, RNA, immune products, and various antigens Bind to cell surfaces and induce expression of antiviral proteins Inhibit expression of cancer genes 4. Interferon

23. 5. Complement (C) • Consists of 26 blood proteins • proteins are activated • work in concert to destroy bacteria and viruses

24. Adaptive Immunity “Third” line of defense

25. Adaptive Line of Defense • acquired immunity • stronger immune response as well as immunological memory • Production of specific antibodies • dual system of B and T lymphocytes • in response to an encounter with a foreign molecule • allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells

26. Specific Immunity – Adaptive Line of Defense • Two features that characterize specific immunity: • specificity • antibodies produced • function only against the antigen that they were produced in response to • memory • lymphocytes are programmed to “recall” their first encounter with an antigen • respond rapidly to subsequent encounters

27. Classifying Immunities • Active immunity • person is challenged with antigen that stimulates production of antibodies • creates memory, takes time and is lasting • Passive immunity • preformed antibodies are donated to an individual • does not create memory, acts immediately, and is short term • Natural immunity • acquired as part of normal life experiences • Artificial immunity • acquired through a medical procedure such as a vaccine

28. Natural active immunity acquired upon infection and recovery Natural passive immunity acquired by a child through placenta and breast milk Artificial active immunity acquired through inoculation with a selected Ag Artificial passive immunity administration of immune serum or globulin Combinations of acquired immunity

29. Development of the Immune Response System • Cell receptors or markers confer specificity and identity of a cell • Major functions of receptors are: • perceive and attach to nonself or foreign molecules • promote the recognition of self molecules • receive and transmit chemical messages among other cells of the system • aid in cellular development

30. B lymphocytes (B cells) involved in producing antibodies against epitopes Humoral immune response T lymphocytes (T cells) provide resistance through lysis of infected or abnormal cells Cell-mediated immune response Acquired Immunity Generates Two Responses to Most Pathogens

31. Lymphocyte Receptors • Lymphocyte’s role in surveillance and recognition is a function of their receptors • B-cell receptors • bind free antigens • T-cell receptors • bind processed antigens

32. Antibody Structure and Functions • Immunoglobulins • Large Y-shaped protein • Contains 2 identical fragments (Fab) with ends that bind to specific antigen • Fc binds to various cells and molecules of the immune system

33. Classes of Antibodies • IgD • important in B cell activation • IgM • released by plasma cells during the primary immune response • IgG • crosses the placenta and confers passive immunity • IgA • helps prevent attachment of pathogens to epithelial cell surfaces • IgE • causing histamine release when activated

34. B-cell Activation and Antibody Production • Antibodies in Serum (Antiserum) • The 1st introduction of an Ag to the immune system • produces a primary response • gradual increase in Ab titer • The 2nd contact with the same Ag • produces a secondary, or anamnestic, response • due to memory cells produced during the initial response

35. T Cells & Cell Mediated Immunity • Cell mediated immunity requires the direct involvement of T lymphocytes • T cells act directly against Ag and foreign cells when presented in association with an MHC carrier • T cells secrete cytokines that act on other cells • Sensitized T cells proliferate into long-lasting memory T cells

36. Antibody-Antigen Interactions • Opsonization • process of coating microorganisms or other particles with specific antibodies • more readily recognized by phagocytes • Agglutination • Ab aggregation • cross-linking cells or particles into large clumps • Neutralization • Abs fill the surface receptors on a virus or the active site on a microbial enzyme • prevent it from attaching • Antitoxins • special type of Ab that neutralize a bacterial exotoxin

37. Immunization • Passive immunization • patient is given preformed antibodies • form of immunotherapy • Active immunization • patient is vaccinated with a microbe or its antigens • providing a form of advance protection

38. Type of active immunity Provide an antigenic stimulus that does not cause disease Most vaccine preparations are based on one of the following antigen preparations: Killed whole cells or inactivated viruses Live, attenuated cells or viruses Antigenic molecules derived from bacterial cells or viruses Genetically engineered microbes or microbial antigens Vaccines

39. Disorders in Immunity

40. Allergy, hypersensitivity misdirected expression of immune responses to an allergen(antigen) Autoimmunity abnormal responses to self Ag Immunodeficiency deficiency or loss of immunity Four types….. Immunopathology

42. 1. Type I Hypersensitivity • Two levels of severity: • Atopy • any chronic local allergy • Ex: hay fever or asthma • Anaphylaxis • a systemic, often explosive reaction that involves airway obstruction and circulatory collapse

43. Contact With Allergens • Generalized predisposition to allergies is familial • not to a specific allergy • Allergy can be affected by age, infection, and geographic area • Atopic allergies may be lifelong or may be “outgrown” • may also develop later in life

44. Develop in stages: Sensitizing dose on first contact with allergen specific B cells form IgE which attach to mast cells and basophils generally no signs or symptoms Provocativedose subsequent exposure with the same allergen binds to the IgE-mast cell complex Mechanism of Type I Allergy

45. General targets include: skin, upper respiratory tract, GI tract, and conjunctiva Responses rashes, itching, redness, rhinitis, sneezing, diarrhea, shedding tears Systemic targets smooth muscles, mucous glands, and nervous tissue Responses vascular dilation and constriction resulting in change in blood pressure and respiration Chemical Mediators and Allergic Symptoms

46. Specific Diseases • Atopic disease • hay fever, rhinitis; seasonal, inhaled plant pollen or mold • asthma • Food allergy • intestinal portal can affect skin and respiratory tract • vomiting, diarrhea, abdominal pain • possibly severe • eczema, hives, rhinitis, asthma, occasionally anaphylaxis • Drug allergy • common side effect of treatment • reaction from mild atopy to fatal anaphylaxis • Sudden respiratory and circulatory disruption that can be fatal in a few minutes • Bee stings, antibiotics or serum injection

47. General methods include: Avoiding allergen Use drugs block the action of the lymphocytes, mast cells antihistamines Desensitization therapy injected allergens Treatment and Prevention

48. 2. Type II Hypersensitivity • Involve antibodies and complement • leading to lysis of foreign cells • Transfusion reactions • ABO blood groups • Rh factor • hemolytic disease of the newborn

49. Genetically determined RBC glycoproteins inherited as 2 alleles of A, B, or O 4 blood types: A, B, AB, or O type O persons lack both A and B antigens Tissues other than RBCs also carry A and B antigens Human ABO Antigens and Blood Types

50. Antibodies Against A and B Antigens • Serum contains pre-formed antibodies that react with blood of another antigenic type-agglutination • Type A • contains Abs that react against B antigens • Type B • contains Abs that react against A antigens • Type O • contains Abs that react against A and B antigens • Type AB • contains no Abs that react against A or B antigens