Introduction. Skin. The Immune System. Chapter 51

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1 The Immune System Chapter 51 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 2 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 3 1

2 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 4 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) 5 Leukocytes Macrophages -Large, irregularly shaped cells -Kill microbes by phagocytosis -Mature from monocytes that enter tissues from the blood 6 2

3 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 7 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 8 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 9 3

4 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 10 Interferon Interferons (IFN) are proteins that play a key role in body defense -Three major types: IFN-α, IFN-β, IFN-γ -IFN-α and IFN-β are produced by almost all body cells in response to viral infection -Induce degradation of viral RNA -IFN-γ is produced only by T-lymphocytes and natural killer cells -Protects from infection and cancer 11 The Specific Immune System The scientific study of immunity began with Edward Jenner in Observed that milkmaids who had cowpox rarely experienced smallpox -Inoculated individuals with fluid from cowpox vesicles to protect them from smallpox -Vaccination 12 4

5 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 13 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 14 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 15 5

6 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 16 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 17 T Cells T lymphocytes are of two types: -Cytotoxic T cells (T c ) -CD8 + cells -Helper T cells (T H ) -CD4 + cells -Distinguished by type of MHC markers recognized and roles after activation 18 6

7 T Cells In humans, the MHC complex is also termed human leukocyte antigens (HLAs) -Markers that distinguish self from nonself 19 T Cells Cytotoxic T 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 20 T Cells Helper T cells -Activated T H cell gives rise to a clone of T H cells including both effector cells and memory cells -Most effector T H cells leave the lymphoid organs and circulate around the body -Secrete proteins called cytokines -Promote humoral and cell-mediated immune responses 21 7

8 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 -T H 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 22 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 23 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 24 8

9 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 25 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

10 Immune Responses The first encounter with a foreign antigen is called the primary immune response -Only few B or T cells can recognize antigen The second encounter is called the secondary immune response -This time there is a large clone of memory cells that can recognize the antigen -Immune response is more effective

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