The Immune System

1. The Immune System ch. 43

2. 2 Major defense systems at work in vertebrates: Innate & Acquired Immunity

3. Innate Immunity—present at birth, before exposure to any pathogens; these defenses are non-specific to pathogens. (This type is also found in invertebrates.) • 1st line of Defense: • External barriers such as skin (pH of 3-5), • Mucous membranes (trap microbes) • Tears, saliva and sweat (all with pH of 3-5) • Lysozymes(enzymes in digestive tract that destroy bacterial cell walls) • 2ndline of Defense: Internal cellular and chemical defenses: • Phagocytic WBCs (AKA leukocytes): neutrophils (most common), monocytes macrophages, eosinophils, dendritic cells.

4. Innate Immunity • 2nd line of Defense (continued) • 30 antimicrobial proteins (activated by chemicals on microbe surface) make up the complement system, which leads to lysis of invading cells. • Interferons are proteins that provide defense against viruses. • Natural killer (NK) cells attack virus-infected body cells and cancer cells that lack the self-identification molecule (MHC) by releasing chemicals that lead to apoptosis of the diseased cell.

5. Tissue damage from injury or entry of pathogens triggers the inflammatory response. • Mast cells secrete histamine, which triggers blood vessels to dilate and become more permeable more macrophages secrete chemical signals which increase blood flow to area causes heat, redness, and swelling at site of injury. • Enhanced blood flow to area brings antimicrobial proteins (complement system), which promote further release of histamines, which helps attract phagocytes. • The result is an accumulation of pus—fluid filled with white blood cells, dead microbes, and cell debris • Systemic responses: fever or septic shock

6. Acquired, Specific Immunity (or adaptive immunity; the 3rd line of Defense)—develops after exposure to an antigen, which is any foreign molecule that is specifically recognized by lymphocytes and elicits a response from them. WBCs called lymphocytes (B cells or T cells) recognize specific antigens and produce 2 types of immune responses: • Humoral Response: activation and clonal selection of B cells, which cause antibodies to circulate in the blood and lymph (makes memory B cells and antibody-producing plasma cells with the help of helper T cells). • Cell-Mediated Response: activation and clonal selection of cytotoxic T cells, which directly destroy certain target cells (makes memory cytotoxic T cells and active cytotoxic T cells with the help of helper T cells).

7. 2 types of lymphocytes, both of which originate in the bone marrow from pluripotent stem cells. They mature in either the bone marrow(B) or the thymus gland (T), then circulate in the blood, lymph, and lymphatic tissue (spleen, lymph nodes, tonsils, and adenoids). Both B cells and T cells recognize antigens by antigen-specific receptors in their cell membrane (about 100,000 identical receptors per cell!)

8. B lymphocytes (B cells) mature in the bone marrow and are part of the humoral response. The B cell receptors (on the plasma membrane) for antigens are Y-shaped molecules made of 4 polypeptide chains. The tips of the Y are the antigen-binding sites, which vary extensively among B cells (since they are specific for certain antigens!).

9. B cells secrete antibodies, or immunoglobulins (Ig), which look the same as B cell receptors (Y-shaped).

10. T lymphocytes (T cells) mature in the thymus gland and are part of the cell-mediated response.

11. There are helper T (Th) cells and cytotoxic T (Tc) cells. • The T cell receptors are l-shaped and bind to fragments of antigens that are attached to the outside of an infected cell on surface proteins called MHC molecules (part of the major histocompatibility complex)—these MHC molecules are different for each individual, and help the immune system to recognize “self” or foreign materials. • The process of antigens being bound to MHC molecules and then moving to the infected cell’s surface is called antigen presentation. T cells then detect this fragment and bind to the antigens.

12. 2 classes of MHC molecules depending on how foreign antigens end up in the cell: • Class I MHC molecules: found on nearly all body cells, infected or cancerous cells then display antigens on these Class 1 MHC molecules at the cell membrane surface. Cytotoxic T cells will bind to these MHC molecules. Tc cells will release perforin molecules and enzymes that attack the infected cell (lead to apoptosis). • Class II MHC molecules: found on macrophages, dendritic cells, and B cells. After foreign materials have been phagocytized by these cells, antigen fragments are bound to Class II MHC molecules on the cell surface. Macrophages, dendritic cells, and B cells are known as antigen-presenting cells (APCs), because they “present” or display antigen fragments to the helper T cells, which will bind to them. Th cells then release cytokines, chemicals that activate Tc cells, B cells, and more Th cells.

14. Once B or T cells have been activated by binding to an antigen (this is called selection), they begin proliferation (production of thousands of clone cells) and differentiation, in which clone cells become memory cells or plasma cells this process is called clonal selection. • Memory cells: long-lived, these can respond rapidly upon subsequent exposure to the same antigen. • Effector (or plasma) cells: short-lived, these secrete antibodies specific for the antigen that will fight the current infection/disease.

15. T cells do a similar thing… T cells are activated, receptor is specific generates memory T cells and plasma (effector) T cells

16. Primary Immune Response: the clonal selection of lymphocytes that occurs the first time the body is exposed to a particular antigen (takes about 10-17 days from initial exposure). • Secondary Immune Response: proliferation and differentiation of memory cells the second time an individual is exposed to the same antigen; this response is faster (2-7 days), of greater magnitude, and more prolonged. (Immunological Memory – uses BOTH memory B and T cells)

18. Helper T Cells: help with both humoral and cell-mediated immune responses. Th cells bind to antigen-presenting cells, then proliferate and release cytokines which will activate both B cells and cytotoxic T cells. • Animation

19. Cytotoxic T cells: once activated by Th cells, these release perforin molecules to poke holes in the infected cell’s membrane, leading to apoptosis (programmed cell death). -Animation • Memory T cells: activated along with Memory B cells to initiate the secondary immune response

20. B cells: once activated by Th cells, B cells begin the humoral immune response. B cells go through clonal selection and plasma cells secrete antibodies. • Animation

21. Antibodies destroy free-floating antigens by: • Neutralization of the virus or opsonization of the bacteria • Agglutination, causing them to clump, forming an antigen-antibody complex, which is then phagocytized by macrophages. • Precipitation, causing the antigens to clump • Antibodies bind to antigens and activate the complement system, which leads to cell lysis of the infected cells using perforin. • Animation

23. There are 5 different classes of antibodies (Immunoglobulins): • IgM, IgG, IgA, IgE, and IgD (see figure 43.20 on p. 945 for the specific structure and function of each)

24. OVERVIEW OF ACQUIRED IMMUNE RESPONSE (3rd line of defense):

25. Active v. Passive Immunity • Active immunity occurs by natural exposure to an infectious agent • Antigens naturally enter body • Immunization (vaccination), where weakened or dead antigens are introduced to the body and the body produces antibodies for the antigen • 1st vaccine = cowpox in 1796 • Passive Immunity is transferring antibodies from an individual who is immune to a certain antigen to someone who is not • Antibodies passed from mother to fetus during pregnancy (IgG) and breastmilk (IgA) • Antivenom injections to treat snake bites have antibodies

26. Blood Groups/Transfusions • A, B, AB, or O blood types • Rh+ or Rh- proteins • Mother-fetus incompatibility too • Can only receive blood from certain types of blood, or your WBCs will reject the blood (WBCs recognize “non-self” cells)

27. Tissue/Organ Transplants • Must match MHC molecules between donor and recipient (as close as possible) or recipient will reject the organ • WBCs will recognize it as “non-self” and will rapidly AND with great magnitude REJECT THE ORGAN! • Bone marrow transplants • Irradiate bone marrow of recipient to completely wipe out their immune system • Danger is that lymphocytes (B and T cells) in donated marrow will start to react against the recipient and attack their normal body cells

28. Autoimmune Disease Immunodeficiency Disease • Immune system starts to attack its own body molecules/cells • Ex – lupus  inflammatory disorder of joints, skin, kidneys, other organs • Ex – rheumatoid arthritis  inflammatory disorder when immune system attacks cells in joints • Ex – Type I diabetes  body attacks beta cells in pancreas, eliminating ability to produce insulin to control blood sugar • Ex - multiple sclerosis  body attacks myelin sheath around axons of nervous system • Immune system is lacking in B or T cells • Person usually dies from common infections/sickness because immune system is so weak and cannot fight the pathogens • Ex – SCID (severe combined immunodeficiency)  caused by a severe defect in B and T cells • “BUBBLE BOY DISEASE” • Ex - AIDS (acquired immuno- deficiency syndrome) caused by HIV which affects T cells and destroys them • ANIMATION – how does it work?