Immune System Part III PDF

Immune System Part III  Cells of the Immune System Major cells of the immune system ◦ Lymphocytes ◦ Antigen-Presenting Cells ◦ Macrophages ◦ Dendritic cells Especially concentrated in strategic places such as lymphatic organs, ski...

Immune System Part III  Cells of the Immune System Major cells of the immune system ◦ Lymphocytes ◦ Antigen-Presenting Cells ◦ Macrophages ◦ Dendritic cells Especially concentrated in strategic places such as lymphatic organs, skin, and mucous membranes © McGraw Hill 2  Lymphocytes 2 There are three types of lymphocytes Natural killer (NK) cells: immune surveillance T lymphocytes (T cells) B lymphocytes (B cells) © McGraw Hill 3  The Life History and Migrations of B and T Cells Figure 21.20 © McGraw Hill 4  T Lymphocytes (T Cells) 1 Three stages in life of T Cell: Born in bone barrow Educated in thymus Deployed to carry out immune function Within the thymus Cortical epithelial cells release chemicals that stimulate maturing T cells to develop surface antigen receptors With receptors, the T cells are now immunocompetent: capable of recognizing antigens presented to them Positive selection © McGraw Hill 5  T Lymphocytes (T Cells) 2  Within the thymus (continued) Medullary epithelial cells test T cells by presenting self- antigens to them; T cells can fail by: Being reacting to the epithelial cell Reacting to the self-antigen  Would attack one’s own tissues T cells that fail are eliminated by negative selection Clonal deletion—self-reactive T cells die and macrophages phagocytize them Anergy—self-reactive T cells remain alive but unresponsive © McGraw Hill 6  T Lymphocytes (T Cells) 3 Negative selection leaves the body in a state of self- tolerance—the surviving T cells respond only to suspicious antigens (ignoring the body’s own proteins) Only 2% of T cells pass the test  Naive lymphocyte pool: immunocompetent T cells that have not yet encountered foreign antigens  Deployment Naive T cells leave thymus and colonize lymphatic tissues and organs everywhere in the body © McGraw Hill 7  B Lymphocytes (B Cells) B cells develop in bone Some fetal stem cells remain in bone marrow and differentiate into B cells B cells that react to self-antigens undergo either anergy or clonal deletion, same as T cell selection Self-tolerant B cells synthesize antigen surface receptors, divide rapidly, produce immunocompetent clones Leave bone marrow and colonize same lymphatic tissues and organs as T cells © McGraw Hill 8  Antigen-Presenting Cells 1 T cells cannot recognize antigens on their own. Antigen-presenting cells (APCs) are required Dendritic cells, macrophages, reticular cells, and B cells function as APCs Function of APCs depends on major histocompatibility (MHC) complex proteins Act as cell “identification tags” that label every cell of your body as belonging to you Structurally unique for each individual, except for identical twins © McGraw Hill 9  Antigen-Presenting Cells 2 Antigen processing APC encounters antigen Internalizes it by endocytosis Digests it into molecular fragments Displays relevant fragments (epitopes) in the grooves of the MHC protein © McGraw Hill 10  Antigen-Presenting Cells 3 Antigen presentation Wandering T cells inspect APCs for displayed antigens If APC only displays a self-antigen, the T cell disregards it If APC displays a non-self-antigen, the T cell initiates an immune attack APCs alert the immune system to presence of foreign antigen Key to successful defense is to quickly mobilize immune cells against the antigen With so many cell types involved in immunity, they require chemical messengers to coordinate their activities—interleukins © McGraw Hill 11  CELLULAR IMMUNITY 1  Cellular (cell-mediated) immunity A form of specific defence in which the T lymphocytes directly attack and destroy diseased or foreign cells The immune system remembers the antigens and prevents them from causing disease in the future Uses four classes of T-cells: cytotoxic, helper, regulatory, and memory © McGraw Hill 12  CELLULAR IMMUNITY 2  Cytotoxic T (TC) cells: killer T cells (T8, CD8, or CD8+) “Effectors” of cellular immunity; carry out attack on enemy cells  Helper T (TH) cells Help promote TC cell and B cell action and innate immunity  Regulatory T (TR) cells: T-regs Inhibit multiplication and cytokine secretion by other T cells; limit immune response Like TH cells, TR cells can be called T4, CD4, CD4+  Memory T (TM) cells Descend from the cytotoxic T cells Responsible for memory in cellular immunity © McGraw Hill 13  © McGraw Hill 14  Recognition  Aspects of recognition in cellular immunity: antigen presentation and T cell activation  Antigen presentation APC encounters and processes an antigen Migrates to nearest lymph node Displays it to the T cells When T cells encounter a displayed antigen on the MHC protein, they initiate the immune response © McGraw Hill 15  T Cell Activation 1 T cell activation Begins when TC or TH cell binds to a MHC protein displaying an epitope that the T cell is programmed to recognize T cell must then bind to another APC protein related to the interleukins T cell must check twice to see if it is really bound to a foreign antigen—co-stimulation Helps ensure the immune system does not launch an attack in the absence of an enemy Would turn against one’s own body and injure our tissues © McGraw Hill 16  T Cell Activation 2 Successful co-stimulation will trigger clonal selection Activated T cell undergoes repeated mitosis Gives rise to a clone of identical T cells programmed against the same epitope Some cells of the clone become effector cells and carry out the attack Other cells become memory T cells © McGraw Hill 17  Helper and cytotoxic T cells play different roles in the attack Attack 1 phase of cellular immunity Helper T cells play central role in coordinating both cellular and humoral immunity When helper T cell recognizes the Ag-MHC Protein complex: Secretes interleukins that exert three effects Attract neutrophils and NK cells Attract macrophages, stimulate their phagocytic activity, and inhibit them from leaving the area Stimulate T and B cell mitosis and maturation © McGraw Hill 18  Role of the Helper T Cell Figure 21.23 © McGraw Hill 19  Attack 2 Cytotoxic T (TC) cells are the only T cells that directly attack other cells When TC cell recognizes a complex of antigen and MHC-I protein on a diseased or foreign cell, it “docks” on that cell © McGraw Hill 20  Attack 3 After docking, 𝑇C cells deliver a lethal hit of chemicals: Perforin and granzymes—kill cells in the same manner as NK cells Interferons—inhibit viral replication Recruit and activate macrophages Tumor necrosis factor (TNF)—aids in macrophage activation and kills cancer cells After releasing chemicals, the TC cell goes off in search of another enemy cell while the chemicals do their work © McGraw Hill 21  Memory 1 Immune memory follows the primary response in cellular immunity Following clonal selection, some TC and TH cells become memory cells Long-lived (years…sometimes) More numerous than naive T cells Fewer steps to be activated, so they respond more rapidly © McGraw Hill 22  Memory 2 T cell recall response Upon re-exposure to same pathogen later in life, memory cells launch a quick attack so that no noticeable illness occurs The person is immune to the disease © McGraw Hill 23  Humoral Immunity Humoral immunity is a more indirect method of defense than cellular immunity B lymphocytes of humoral immunity produce antibodies that bind to antigens and tag them for destruction by other means Cellular immunity attacks the enemy cells directly Works in three stages like cellular immunity Recognition Attack Memory © McGraw Hill 24  Recognition 1 Recognition in humoral immunity Immunocompetent B cell has thousands of surface receptors for one antigen Activation begins when an antigen binds to several of these receptors, links them together, and is taken into the cell by receptor-mediated endocytosis Small molecules are not antigenic because they cannot link multiple receptors together B cell processes (digests) the antigen Links some of the epitopes to its MHC-II proteins Displays these on the cell surface © McGraw Hill 25  Recognition 2 Usually B cell response goes no further unless a helper T cell binds to this Ag–MHC protein complex Bound TH cell secretes interleukins that activate B cell Triggers clonal selection B cell mitosis gives rise to a battalion of identical B cells programmed against the same antigen Most differentiate into plasma cells Larger than B cells and contain an abundance of rough ER Plasma cells secrete antibodies at a rate of 2,000 molecules per second during their life span of 4 to 5 days First exposure to antigen triggers production of IgM antibodies, later exposures to the same antigen, IgG Antibodies travel through body in blood, other body fluids © McGraw Hill 26  Attack and Memory Attack in humoral immunity Antibodies bind to antigen, render it harmless, “tag it” for destruction Memory in humoral immunity Some B cells differentiate into memory cells © McGraw Hill 27  Clonal Selection and Ensuing Events of the Humoral Immune Response Figure 21.25 © McGraw Hill 28  B Cell and Plasma Cell Figure 21.26 © McGraw Hill a, b: Don W. Fawcett/Science Source 29  Humoral Attack 1 Antibodies have four mechanisms of attack against antigens: Neutralization Antibodies mask pathogenic region of antigen Complement fixation IgM or IgG bind to antigen, change shape and initiate complement binding which leads to inflammation, phagocytosis, immune clearance, or cytolysis Primary defense against foreign cells, bacteria, and mismatched RBCs © McGraw Hill 30  Humoral Attack 2 Antibodies have four mechanisms of attack against antigens (continued): Agglutination Antibody has 2 to 10 binding sites; binds to multiple enemy cells, immobilizing them from spreading Enhances phagocytosis by creating “bigger bites” Precipitation Antibody binds antigen molecules (not cells); creates antigen– antibody complex that precipitates, allowing them to be removed by immune clearance or phagocytized by eosinophils © McGraw Hill 31  Humoral Memory 1 Primary immune response—immune reaction brought about by the first exposure to an antigen Appearance of protective antibodies delayed for 3 to 6 days while naive B cells multiply and differentiate into plasma cells As plasma cells produce antibodies, the antibody titer (level in the blood plasma) rises IgM appears first, peaks in about 10 days, soon declines IgG levels rise as IgM declines, but IgG titer drops to a low level within a month © McGraw Hill 32  Humoral Memory 2 Primary response leaves one with an immune memory of the antigen During clonal selection, some of the cells becomes memory B cells Found mainly in germinal centers of the lymph nodes Mount a very quick secondary response © McGraw Hill 33  Humoral Memory 3 Secondary (anamnestic) response—if re-exposed to the same antigen Plasma cells form within hours IgG titer rises sharply and peaks in a few days Response is so rapid that the antigen has little chance to exert a noticeable effect on the body No illness results Low levels of IgM also secreted (then quickly decline) IgG remain elevated for weeks to years Conferring long-lasting protection Memory does not last as long in humoral immunity as in cellular immunity © McGraw Hill 34 © McGraw Hill 35  Immune System Disorders Immune response may be: Too vigorous Too weak Misdirected against wrong targets © McGraw Hill 36  Hypersensitivity 1 Hypersensitivity—an excessive immune reaction against antigens that most people tolerate Includes: Alloimmunity: reaction to transplanted tissue from another person Autoimmunity: abnormal reactions to one’s own tissues Allergies: reactions to environmental antigens (allergens)—dust, mold, pollen, vaccines, bee and wasp venom, poison ivy and other plants; foods such as nuts, milk, eggs, and shellfish; drugs such as penicillin, tetracycline, and insulin © McGraw Hill 37  Hypersensitivity 2 Four kinds of hypersensitivity based on the type of immune agents involved (antibodies or T cells) and their method of attack on the antigen Type I acute (immediate) hypersensitivity: very rapid response Type II and Type III subacute hypersensitivity: slower onset (1 to 3 hours after exposure) Last longer (10 to 15 hours) Types I, II, and III are quicker antibody-mediated responses Type IV: delayed cell-mediated response © McGraw Hill 38  Type I Hypersensitivity 1 Type I (acute) Includes most common allergies IgE-mediated reaction that begins within seconds of exposure Usually subsides within 30 minutes, although it can be severe to fatal Allergens bind to IgE on the membranes of basophils and mast cells Stimulate them to secrete histamine and other inflammatory and vasoactive chemicals Chemicals trigger glandular secretion, vasodilation, increased capillary permeability, smooth muscle spasms, and other effects © McGraw Hill 39  Type I Hypersensitivity 2 Type I (continued) Clinical signs include: Local edema, mucus hypersecretion and congestion, watery eyes, runny nose, hives, and sometimes cramps, diarrhea, and vomiting Examples: food allergies and asthma—local inflammatory reaction to inhaled allergens © McGraw Hill 40  Type I Hypersensitivity 3 Anaphylaxis Immediate, severe type I reaction Local anaphylaxis can be relieved with antihistamines Anaphylactic shock Severe, widespread acute hypersensitivity that occurs when an allergen is introduced into the bloodstream or when certain foods are ingested by an allergic individual Characterized by bronchoconstriction, dyspnea (labored breathing), widespread vasodilation, circulatory shock, and sometimes death Antihistamines are inadequate by themselves Epinephrine relieves the symptoms by dilating bronchioles, increasing cardiac output, and restoring blood pressure Fluid therapy and respiratory support are sometimes required © McGraw Hill 41  Type I Hypersensitivity 4 Asthma Most common chronic illness in children Allergic (extrinsic) asthma is most common form Respiratory crisis triggered by inhaled allergens Stimulate plasma cells to secrete IgE Binds to most cells in respiratory mucosa Mast cells release a mixture of inflammatory chemicals Triggers intense airway inflammation Nonallergic (intrinsic) asthma Triggered by infections, drugs, air pollutants, cold dry air, exercise, or emotions More common in adults, but effects are the same © McGraw Hill 42  Type I Hypersensitivity 5 Asthma (continued) Effects Bronchospasms within minutes Severe coughing, wheezing, and sometimes fatal suffocation Second respiratory crisis often occurs 6 to 8 hours later Interleukins attract eosinophils to bronchial tissue Secrete proteins that paralyze respiratory cilia Severely damage epithelium leading to scarring and long- term damage to lungs Bronchioles become edematous and plugged with thick, sticky mucus Treatment Epinephrine and other β-adrenergic stimulants to dilate airway and restore breathing, and with inhaled corticosteroids to minimize inflammation and long-term damage © McGraw Hill 43  Type II (antibody-dependent Type II Hypersensitivity cytotoxic) Occurs when IgG or IgM attacks antigens bound to cell surfaces Reaction leads to complement activation Lysis or opsonization of the target cell Macrophages phagocytize and destroy opsonized platelets, erythrocytes, or other cells Examples: blood transfusion reaction and some drug © McGraw Hill reactions 44  Type III Hypersensitivity Type III (immune complex) Occurs when IgG or IgM forms antigen–antibody complexes Precipitate beneath endothelium of blood vessels and other tissues At site, activate complement and trigger intense inflammation Examples: two autoimmune diseases—acute glomerulonephritis and systemic lupus erythematosus © McGraw Hill 45  Type IV Hypersensitivity Type IV (delayed) Cell-mediated reaction in which the signs appear 12 to 72 hours after exposure Begins when APCs in lymph nodes display antigens to helper T cells T cells secrete interferon and cytokines that activate cytotoxic T cells and macrophages Result is a mixture of innate and immune responses Examples: haptens in cosmetics and poison ivy, graft rejection, TB skin test, beta cell destruction that causes type 1 diabetes mellitus © McGraw Hill 46  Autoimmune Diseases 1 Autoimmune diseases—failures of self-tolerance Immune system does not correctly distinguish self- antigens from foreign ones Produces autoantibodies that attack body’s own tissues Three reasons for failure of self-tolerance: Cross-reactivity Some antibodies against foreign antigens react to similar self- antigens Rheumatic fever—streptococcus antibodies also react with heart valves © McGraw Hill 47  Autoimmune Diseases 2 Three reasons for failure of self-tolerance (continued): Abnormal exposure of self-antigens in the blood Some of our native antigens are not normally exposed to blood Changes in structure of self-antigens Viruses and drugs may change the structure of self-antigens or cause the immune system to perceive them as foreign Self-reactive T cells Not all are eliminated in thymus and are normally kept in check by regulatory T (TR) cells © McGraw Hill 48  Immunodeficiency Diseases 1 Immune system fails to react vigorously enough Severe combined immunodeficiency disease (SCID) Hereditary lack of T and B cells Vulnerability to opportunistic infection and must live in protective enclosures © McGraw Hill 49  Immunodeficiency Diseases 2 Acquired immunodeficiency syndrome (AIDS) Nonhereditary diseases contracted after birth Group of conditions that severely depress the immune response AIDS is caused by infection with the human immunodeficiency virus (HIV) © McGraw Hill 50  Acquired Immunodeficiency Syndrome 4 HIV is transmitted through blood, semen, vaginal secretions, breast milk, or across the placenta Most common means of transmission Sexual intercourse (vaginal, anal, oral) Contaminated blood products Contaminated needles Not transmitted by casual contact Undamaged latex condom is an effective barrier to HIV © McGraw Hill 51  Acquired Immunodeficiency Syndrome 3 Signs and symptoms Early symptoms: flu-like symptoms of chills and fever Progresses to night sweats, fatigue, headache, extreme weight loss, lymphadenitis Normal TH count is 600 to 1,200 cells/µL of blood, but in AIDS it is less than 200 cells/µL Person susceptible to opportunistic infections (Toxoplasma, Pneumocystis, herpes simplex virus, cytomegalovirus, or tuberculosis) Candida (thrush): white patches on mucous membranes Kaposi sarcoma: cancer originates in endothelial cells of blood vessels; causes purple lesions in skin © McGraw Hill 52  Kaposi Sarcoma Figure 21.31 © McGraw Hill Source: National Cancer Institute (NCI) 53 © McGraw Hill 54