The Immune System

1. The Immune System Chapter 51

2. Introduction Vertebrates have three levels of defenses -1. The Integumentary System -Skin and mucous membranes provide first line of defense -2. Nonspecific (innate) Immune System -Acts very rapidly after onset of infection -3. Specific Immune System -Eliminates microbes that escaped the second line of defense

3. Skin The skin is the largest organ of the body -Provides a nearly impenetrable barrier, reinforced with chemical weapons -Oil & sweat glands give skin a pH of 3-5 -Lysozyme breaks bacterial cell walls -Also contains many normal flora -Non-pathogenic microorganisms that out-compete pathogenic ones

4. Skin The skin is composed of three layers -Epidermis = 10-30 cells thick -Stratum corneum – Outermost layer; cells shed continuously -Stratum spinosum – Middle layer -Stratum basale – Innermost layer; cells actively dividing -Contains keratin, which makes skin tough and water-resistant

5. Skin -Dermis = Contains connective tissue and is 15-40 times thicker than epidermis -Provides structural support for epidermis, and matrix for blood vessels, muscles and nerve endings -Subcutaneous layer = Contains mainly adipose (fat) cells -Acts as shock absorbers and insulators

6. Mucosal Epithelial Surfaces The digestive, respiratory and urogenital tracts are lined by mucous membranes -Cells secrete mucus which traps microbes Digestive tract -Salivary lysozyme; acidic stomach Respiratory tract -Ciliary action Urogenital tract -Acidic urine

7. Nonspecific Immunity The nonspecific or innate immune system consists of cellular and chemical devices that respond to any microbial infection -The response is quite rapid Among the most important defenses are three types of leukocytes (white blood cells)

8. Leukocytes Macrophages -Large, irregularly shaped cells -Kill microbes by phagocytosis -Mature from monocytes that enter tissues from the blood

9. Leukocytes Neutrophils -The most abundant circulating leukocytes -First to appear at site of damage/infection -Kill microbes by phagocytosis Natural killer (NK) cells -Destroy pathogen-infected and cancer cells by programmed cell death or apoptosis -Produce perforins and granzymes

10. Leukocytes

11. Leukocytes (Cont.)

12. The Inflammatory Response Inflammation involves several body systems -Injured cells release chemical alarms, including histamine and prostaglandins -Cause nearby blood vessels to dilate and increase in permeability -Promote phagocyte accumulation -Hallmark signs = Redness, warmth, swelling, pain, and potential loss of function

13. The Inflammatory Response

14. The Inflammatory Response Inflammation is accompanied by an acute phase response,manifested by fever -Macrophages release interleukin-1 -Causes hypothalamus to raise body temperature -Promotes activity of phagocytes, while impeding microbial growth -However, very high fevers are hazardous as they may denature critical enzymes

15. Complement The complement system consists of about 30 different proteins that circulate in the blood in an inactive form -Upon pathogen encounter, a cascade of activation occurs -Some proteins aggregate to form a membrane attack complex (MAC) on surface of pathogen

16. Complement

17. Complement Other functions of complement proteins -C3b coats surface of invading pathogens, thereby enhancing their phagocytosis -Some stimulate the release of histamine from mast cells and basophils -Some attract more phagocytes to the area of infection

18. Interferon Interferons(IFN) are proteins that play a key role in body defense -Three major types: IFN-a, IFN-b, IFN-g -IFN-a and IFN-b are produced by almost all body cells in response to viral infection -Induce degradation of viral RNA -IFN-g is produced only by T-lymphocytes and natural killer cells -Protects from infection and cancer

19. The Specific Immune System The scientific study of immunity began with Edward Jenner in 1796 -Observed that milkmaids who had cowpox rarely experienced smallpox -Inoculated individuals with fluid from cowpox vesicles to protect them from smallpox -Vaccination

20. The Specific Immune System

21. The Specific Immune System The four characteristics of the specific, or adaptive, immune response are: -1. Specificity -2. Diversity -3. Memory -4. Ability to distinguish self from non-self

22. Antigens An antigen is a molecule that provokes a specific immune response -May be components of microorganisms or proteins/glycoproteins found on surface of red blood cells or transplanted tissue cells A single protein may have many different antigenic determinants or epitopes -Each can stimulate a distinct immune response

23. Antigens

24. Lymphocytes Lymphocytes are leukocytes with surface receptors for antigenic determinants -Direct an immune response against either the antigen or the cell that carries it When a naïve lymphocyte binds a specific antigen for the first time, it gets activated by a process called clonal selection -Produces a clone of cells: some respond immediately, others are memory cells

26. Lymphocytes B lymphocytes or B cells -Respond to antigens by secreting antibodies or immunoglobulins (Ig) -Participate in humoral immunity T lymphocytes or T cells -Regulate other immune cells or directly attack cells that carry specific antigens -Participate in cell-mediated immunity

27. Acquisition of Specific Immunity Immunity can be acquired in two ways -Active immunity results from activation of an individual’s own lymphocytes -Pathogen infection or vaccination -Passive immunity results from obtaining another individual’s antibodies -Transfer of maternal antibodies across placenta

28. Hematopoiesis All blood cells are derived from hematopoietic stem cells through hematopoiesis -A lymphoid progenitor gives rise to lymphocytes and natural killer cells -A myeloid progenitor gives rise to all other white blood cells, plus RBCs and platelets

30. Organs of the Immune System Organs of the immune system consist of the: -Primary lymphoid organs -Bone marrow and thymus -Secondary lymphoid organs -Lymph nodes, spleen, and mucosal- associated lymphoid tissue (MALT)

32. Primary Lymphoid Organs The bone marrow is site of B cell maturation -Each B cell has about 105 Ig molecules on its surface, all with the same specificity -However, different B cells will have different specificities -B cells recognize epitopes directly -Any lymphocytes that are likely to bind to self-antigens undergo apoptosis

33. Primary Lymphoid Organs The thymus is the site of T cell maturation -Each T cell has about 105 identical T-cell receptors, or TCRs on its surface -Recognize epitopes only if they are combined with major histocompatibility complex(MHC) peptides -Lymphocytes that cannot bind MHCs, or that bind self-MHC/self-peptide too tightly undergo apoptosis

35. Secondary Lymphoid Organs The locations of these organs promote the filtering of antigens that enter any part of an individual’s body -Mature but naïve B and T cells become activated in the lymph nodes -The spleen is site of immune responses to antigens found mainly in the blood -Mucosal-associated lymphoid tissue (MALT) include the tonsils and appendix

36. T Cells T lymphocytes are of two types: -Cytotoxic T cells (Tc) -CD8+ cells -Helper T cells (TH) -CD4+ cells -Distinguished by type of MHC markers recognized and roles after activation

37. T Cells In humans, the MHC complex is also termed human leukocyte antigens (HLAs) -Markers that distinguish self from nonself -MHC class I = Found on all nucleated cells -Recognized by Tc cells -MHC class II = Found only on antigen-presenting cells -Recognized by TH cells

38. T Cells

39. T Cells Cytotoxic T cells -Naïve TC cells are activated upon TCR recognition of foreign peptide displayed on self-MHC class I protein on dendritic cells -Clonal expansion and differentiation into activated cells and memory cells -Activated cells induce apoptosis in cells with same specificity as first cell -Likely a viral-infected or cancer cell

41. T Cells Helper T cells -TH cells respond to exogenous antigen that is taken up by an antigen presenting cell -Antigen is partially digested, then complexed with MHC class II proteins -Complex is transported to and displayed on the cell surface

42. T Cells Helper T cells -Activated TH cell gives rise to a clone of TH cells including both effector cells and memory cells -Most effector TH cells leave the lymphoid organs and circulate around the body -Secrete proteins called cytokines -Promote humoral and cell-mediated immune responses

43. B Cells Humoral immunity begins when naïve B cells in secondary lymph organs meet antigens -B cells are activated when their surface Igs bind to a specific epitope on an antigen -TH cytokines may also be required -Activation results in clonal expansion and differentiation into plasma and memory cells -Plasma cells produce soluble antibodies against the same epitope

45. Immunoglobulins An immunoglobulin consists of two identical short polypeptides, light chains, and two identical longer polypeptides, heavy chains -Four chains are held by disulfide bonds, forming a Y-shaped molecule -Fab regions = Two “arms” -Fc region = “Stem”

47. Immunoglobulins Each chain has a variable region (amino acid sequence differs between Igs) and a constant region -The variable regions fold together to form a cleft, the antigen-binding site Each Ig can bind two identical epitopes -Allows formation of antigen-antibody complexes -Indeed, Igs can agglutinate, precipitate or neutralize antigens

49. Immunoglobulins There are five classes of immunoglobulins -IgM =First type of antibody produced during an immune response -Monomer on B cells, but secreted as pentamer -IgD =Present on mature naïve B cells -Not secreted in normal situations

50. Immunoglobulins -IgG =Major form of antibody in blood -Main component of secondary response -Can cross placenta -IgA =Major form of antibody in secretions -Usually produced as a dimer -Can pass to nursing infant in mom’s milk -IgE =Present at very low levels in blood -Plays a role in allergic reactions