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