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2.D.4 Immune System & Our Chemical Defenses

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1 2.D.4 Immune System & Our Chemical Defenses
Animals (& plants) have a variety of chemical defenses against infections that affect dynamic homeostasis.

2 (Acquired or Adaptive Response)
Immune System Nonspecific Response (Innate Response) Plants Invertebrates Vertebrates Specific Response (Acquired or Adaptive Response) Vertebrates Only

3 A pathogen is  a biological agent such as a virus, bacterium, prion, or fungus, that causes a disease or infection in its host.

4 Plants, invertebrates and vertebrates have multiple, nonspecific immune responses to pathogens.

5 Example: Invertebrate immune systems lack pathogen-specific defense responses. Innate immunity in invertebrates consists of the exoskeleton and the digestive system and its associated microorganisms.

6 Immune cells called hemocytes are found inside the hemolypmh of insects. They engulf pathogens via phagocytosis .

7 (Acquired or Adaptive Response)
Vertebrate immune systems have specific and nonspecific defense mechanisms against pathogens. Immune System Nonspecific Response (Innate Response) Specific Response (Acquired or Adaptive Response)

8 Nonspecific immunity, or innate immunity, is present before any exposure to pathogens and is effective from the time of birth.

9 Innate immunity provides broad defenses against infection
Innate immunity provides broad defenses against infection. A pathogen that successfully breaks through an animal’s external defenses soon encounters several innate cellular and chemical mechanisms that impede its attack on the body. 3m

10 Intact skin and mucous membranes form physical barriers that bar the entry of microorganisms and viruses. Certain cells of the mucous membranes produce mucus, a viscous fluid that traps microbes and other particles.

11 In the trachea, ciliated epithelial cells sweep mucus and any entrapped microbes upward, preventing the microbes from entering the lungs.

12 Secretions of the skin and mucous membranes provide an environment that is often hostile to microbes. The skin has a pH between 3 and 5, which is acidic enough to prevent colonization of many microbes. Also, lysozymes are enzymes abundant in a number of secretions, such as tears, saliva, human milk, and mucus that break down the cell walls of many bacteria.

13 Internal cellular and chemical defenses depend mainly on phagocytosis
Internal cellular and chemical defenses depend mainly on phagocytosis. Phagocytes are types of white blood cells that ingest invading microorganisms and initiate the inflammatory response.

14 Macrophages, a specific type of phagocyte, can be found migrating through the body and in various organs of the lymphatic system.

15 Phagocytes such as macrophages attach to their prey via surface receptors and engulf them, forming a vacuole that fuses with a lysosome.

16 Numerous antimicrobial proteins function in innate defense by attacking microbes directly of by impeding their reproduction. They have been demonstrated to kill Gram negative and Gram positive bacteria, mycobacteria, enveloped viruses, fungi, and even transformed or cancerous cells.

17 About 30 antimicrobial proteins make up the complement system
About 30 antimicrobial proteins make up the complement system. The complement system can cause lysis of invading cells and help trigger inflammation. Interferons (IFNs) provide innate defense against viruses and help activate macrophages.

18 Inflammatory Response
In local inflammation, histamine and other chemicals released from injured cells promote changes in blood vessels that allow more fluid, more phagocytes, and antimicrobial proteins to enter the tissues.

19 Inflammatory Response
Neutrophils and monocytes migrate to the site of injury Neutrophils and mast cells phagocytize pathogens Monocytes differentiate into macrophages

20 Natural killer (NK) cells patrol the body and attack virus-infected body cells and cancer cells. They trigger apoptosis in the cells they attack.

21 (Acquired or Adaptive Response)
Immune System Nonspecific Response (Innate Response) Physical barriers such as skin, mucus membranes, cilia, sweat, saliva, stomach acid Complement System Proteins Macrophages Natural Killer (NK) Cells Inflammatory Response Specific Response (Acquired or Adaptive Response)

22 (Acquired or Adaptive Response)
Specific immunity, also called acquired immunity or adaptive immunity, develops only after exposure to inducing agents such as microbes, toxins, or other foreign substances. Immune System Nonspecific Response (Innate Response) Specific Response (Acquired or Adaptive Response)

23 Consists of lymphatic vessels and the lymphoid organs
Lymph nodes - Red bone marrow (B-Cells) - Thymus gland (T-Cells) - Lymphatic vessels – Tonsils – Spleen

24 In acquired immunity, lymphocytes (white blood cells) provide specific defenses against infection.

25 Lymphocytes arise from stem cells in the bone marrow.

26 B cells mature in the Bone marrow. T cells mature in the Thymus.
Lymphoid stem cell B cell Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others) T cell Thymus

27 An antigen is any foreign molecule that is specifically recognized by lymphocytes and elicits a response from them. A lymphocyte recognizes and binds to just a small, accessible portion of the antigen called an epitope. Antigen- binding sites Antibody A Antigen Antibody B Antibody C Epitopes (antigenic determinants)

28 Vertebrates have two types of specific immune responses: cell mediated immunity and humoral immunity. Specific (Acquired or Adaptive) Immune Response Cell Mediated Immunity Humoral Immunity

29 The vertebrate body is populated by two main types of lymphocytes which circulate through the blood:
B lymphocytes (B cells) T lymphocytes (T cells) Specific (Acquired or Adaptive) Immune Response Cell Mediated Immunity T Cells Humoral Immunity B Cells

30 The plasma membranes of both B cells and T cells have about 100,000 antigen receptors that all recognize the same epitope.

31 B cell receptors bind to specific, intact antigens
B cell receptors bind to specific, intact antigens. They are often called membrane antibodies or membrane immunoglobulins. Antigen- binding site binding site Disulfide bridge Light chain Heavy chains Cytoplasm of B cell V A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges. (a) Variable regions Constant Transmembrane region Plasma membrane B cell C

32 Each T cell receptor consists of two different polypeptide chains.
Antigen- Binding site b chain Disulfide bridge a chain T cell A T cell receptor consists of one chain and one b chain linked by a disulfide bridge. (b) Variable regions Constant Transmembrane region Plasma membrane Cytoplasm of T cell V V C C

33 T cells bind to small fragments of antigens that are bound to normal cell-surface proteins called MHC molecules. MHC molecules are encoded by a family of genes called the major histocompatibility complex.

34 Infected cells produce MHC molecules which bind to antigen fragments and then are transported to the cell surface in a process called antigen presentation. A nearby T cell can then detect the antigen fragment displayed on the cell’s surface.

35 Depending on their source peptide, antigens are handled by different classes of MHC molecules.

36 Class I MHC molecules, found on almost all nucleated cells of the body, display peptide antigens to cytotoxic T cells. Infected cell Antigen fragment Class I MHC molecule T cell receptor (a) Cytotoxic T cell A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. 1 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. 2 1 2

37 Class II MHC molecules, located mainly on dendritic cells, macrophages, and B cells, display antigens to helper T cells. Microbe Antigen- presenting cell Antigen fragment Class II MHC molecule T cell receptor Helper T cell A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. 1 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. 2 (b) 1 2

38 As B and T cells are maturing in the bone and thymus, their antigen receptors are tested for possible self-reactivity. Lymphocytes bearing receptors for antigens already present in the body are destroyed by apoptosis or rendered nonfunctional.

39 Humoral and cell-mediated immunity defend against different types of threats. Acquired immunity includes two branches: Specific (Acquired or Adaptive) Immune Response Cell Mediated Immunity T Cells Humoral Immunity B Cells • The humoral immune response (B Cells) • The cell-mediated immune response (T Cells)

40 • The humoral immune response involves the activation and clonal selection of B cells, resulting in the production of secreted antibodies. • The cell-mediated immune response involves the activation and clonal selection of cytotoxic T cells . Specific (Acquired or Adaptive) Immune Response Cell Mediated Immunity T Cells Cytotoxic T Cells Humoral Immunity B Cells Antibodies

41

42 Cell Mediated Response

43 Helper T cells produce CD4, a surface protein that enhances their binding to class II MHC molecule–antigen complexes on antigen-presenting cells. Activation of the helper T cell then occurs.

44 Activated helper T cells secrete several different cytokines that stimulate other lymphocytes.

45 The activated cytotoxic T cell secretes proteins that destroy the infected target cell
Perforin Granzymes CD8 TCR Class I MHC molecule Target cell Peptide antigen Pore Released cytotoxic T cell Apoptotic target cell Cancer Cytotoxic A cytotoxic T cell binds to a class I MHC–antigen complex on a target cell with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell. 1 The activated T cell releases perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes, which enter the target cell by endocytosis. 2 The enzymes initiate apoptosis within the target cells, leading to fragmentation of the nucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells. 3

46 Humoral Response

47 Activation of B cells is aided by cytokines and antigen binding to helper T cells.

48

49 An antibody, also known as an immunoglobulin (Ig), is a large Y-shaped protein produced by B-cells that is used by the immune system to identify and neutralize pathogens.

50 Each antibody is specific to a particular antigen
Each antibody is specific to a particular antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. 

51 The binding of antibodies to antigens is also the basis of several antigen disposal mechanisms. It further leads to elimination of microbes by phagocytosis and complement-mediated lysis.

52 Antibody-mediated mechanisms of antigen disposal:
Binding of antibodies to antigens inactivates antigens by Viral neutralization (blocks binding to host) and opsonization (increases phagocytosis) Agglutination of antigen-bearing particles, such as microbes Precipitation of soluble antigens Activation of complement system and pore formation Bacterium Virus Bacteria Soluble antigens Foreign cell Complement proteins MAC Pore Enhances Phagocytosis Leads to Cell lysis Macrophage

53 A primary immune response is the response that occurs after a harmful antigen has been encountered for the first time.

54 In a primary immune response, the binding of an antigen to a mature lymphocyte induces the lymphocyte’s proliferation and differentiation, a process called clonal selection.

55 Clonal selection of B cells generates a clone of short-lived activated effector cells and a clone of long-lived memory cells. Antigen molecules Antigen receptor B cells that differ in antigen specificity Antibody molecules Clone of memory cells Clone of plasma cells bind to the antigen receptors of only one of the three B cells shown. The selected B cell proliferates, forming a clone of identical cells bearing receptors for the selecting antigen. Some proliferating cells develop into short-lived plasma cells that secrete antibodies specific for the antigen. Some proliferating cells develop into long-lived memory cells that can respond rapidly upon subsequent exposure to the same antigen.

56 The secondary immune response is a much quicker and more effective response that occurs after a previously encountered antigen reappears.

57 Antibody concentration
In the secondary immune response, memory cells facilitate a faster, more efficient response. Antibody concentration (arbitrary units) 104 103 102 101 100 7 14 21 28 35 42 49 56 Time (days) Antibodies to A to B Primary response to antigen A produces anti- bodies to A 2 Day 1: First exposure to 1 Day 28: Second exposure to antigen A; first antigen B 3 Secondary response to anti- gen A produces antibodies to A; primary response to anti- gen B produces antibodies to B 4

58 Immunization 1. Vaccines provide antigen to which immune system responds 2. Pathogens or pathogen products treated to remove virulence

59 Passive Immunity Occurs when an individual is given prepared antibodies (immunoglobins) to combat a disease -Short-lived -Newborns are often passively immune due to mother’s blood & milk

60 Immunity Side Effects Tissue Rejection Autoimmune Diseases
Antibodies and cytotoxic T cells bring about destruction of foreign tissues in the body Immune system is correctly distinguishing between self and nonself Autoimmune Diseases Cytotoxic T cells or antibodies mistakenly attack the body’s own cells

61 Autoimmune Diseases result as an attack on tissues by body’s own antibodies and T cells. It is the bodies INABILITY to distinguish self from non-self.  

62 Type 1 Diabetes: an autoimmune disease that results in the destruction of insulin-producing cells of the pancreas.

63 Type 2 Diabetes: diet-related insulin resistance brought on by too much sugar in the diet and lack of exercise.

64 Autoimmune Diseases Lupus - a chronic inflammatory disease that occurs when your body's immune system attacks your own tissues and organs There are no cures for autoimmune diseases but they are controlled by drugs

65 broad range of microbes
A summary of innate and acquired immunity: INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Mucous membranes Secretions Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Invading microbes (pathogens)

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67 Learning Objectives: LO 2.29 The student can create representations and models to describe immune responses. [See SP 1.1, 1.2] LO 2.30 The student can create representations or models to describe nonspecific immune defenses in plants and animals.[See SP 1.1, 1.2]


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