Ch. 43 The Immune System
1 Essential Questions:
How does our immunity arise?
How does our immune system work?
2 Overview of immunity: Two kinds of defense: A. innate immunity present at time of birth before exposed to pathogens nonspecific responses, broad in range skin and mucous membranes internal cellular and chemical defenses that get through skin macrophages, phagocytic cells
B. acquired immunity (adaptive immunity)develops after exposure to specific microbes, abnormal body cells, foreign substances or toxins highly specific lymphocytes produce antibodies or directly destroy cells
3 Overview of Immune System
nonspecific
Specific
4 I. Innate immunity Nonspecific defenses
A. First line of defense: skin, mucous membranes
skin protects against chemical, mechanical, pathogenic, UV light damage mucous membranes line digestive, respiratory, and genitourinary tracts prevent pathogens by trapping in mucus *breaks in skin or mucous membranes = entryway for pathogen
5 secretions of skin also protect against microbes sebaceous and sweat glands keep pH at 35 stomach also secretes HCl (Hepatitis A virus can get past this) produce antimicrobial proteins (lysozyme) ex. in tears
http://vrc.belfastinstitute.ac.uk/resources/skin/skin.htm
6 B. Second line of defense internal cellular and chemical defenses (still nonspecific) phagocytes produce antimicrobial proteins and initiate inflammation (helps limit spread of microbes) bind to receptor sites on microbe, then engulfs microbe, which fused with lysosome nitric oxide and poisons in lysosome can poison microbe lysozyme and other enzymes degrade the microbe *some bacteria have capsule that prevents attachment *some bacteria are resistant to lysozyme
macrophages
7 Cellular Innate defenses
Tolllike receptor (TLR) recognize fragments of molecules characteristic of a set of pathogens [Ex. lipopolysaccharides on surface of bacteria (TLR4), double stranded RNA(TLR3)] helps trigger phagocytosis
8 Process of Phagocytosis
9 Phagocytic blood cells
1. neutrophils6070% of WBC enter infected tissue destroy microbes self destruct when undergoing phagocytosis life span few days
10 2. macrophages5% of WBC large cells, develop from monocytes some migrate, some stay in tissues, organs (lymphatic)
12 3. Eosinophils low phagocytic activity work against parasitic worms (ex. blood flukes) do not engulf attach to invader and discharge destructive enzymes
http://www.funsci.com/fun3_en/blood/blood.htm#20
13 4. dendritic cells low phagocytic activity can ingest microbes stimulate development of acquired immunity located mainly in lymphatic tissue and skin
dendritic cell from lymph node
http://www.rcsed.ac.uk/Journal/vol46_1/4610003.htm
14 Antimicrobial Peptides and Proteins
used to attack microbes or impede their reproduction A. Interferonsproteins against viral infections infected cells release this inducing nearby cells to produce substances that inhibit viral reproduction limit cell to cell spread of viruses can mass produce these by DNA recombinant technology
B. Complement system 30 plasma proteins that fight infection are normally inactive until come in contact with surface of certain microbes causes cell signaling to trigger lysis of invading cell also functions in inflammation
15 Inflammatory Response triggered by histamine stored in mast cells being released a. causes blood vessels to dilate and become more permeable b. Activated macrophages give off signaling molecules to promote blood flow to area c. redness d. heat e. swelling f. fever caused by pyrogens released by macrophages
16 If inflammation too intense can cause septic shock a. very high fever b. low blood flow c. low blood pressure fatal in 1/3 of cases (mostly very young or very old)
17 5. Natural killer (NK) cells do not attack microbes directly recognize surface receptors destroy virus containing cells and abnormal cancer cells not phagocytic attack membrane causing cell to lyse (apoptosis) not 100% effective
http://www.immunecentral.com/immunesystem/iss9.cfm
18 Pathogens that avoid our immune system. pneumonia bacteria have outer capsules that hides the polysaccharides on the cell walls = aren't recognized
Streptococcus pneumoniae
Tuberculosis some are resistant to the breakdown within the lysosomes after phagocytosis
Mycobacterium tuberculosis
19 defensins secreted by activated macrophages can damage pathogens without harming body cells
20 II. Acquired Immunity third line of defense
Lymphocytes are in charge of this activated by cytokines of innate immunity two types both made in bone marrow: B lymphocytes (B cells mature in bone marrow) and T lymphocytes (T cells mature in thymus gland) both circulate through blood, concentrated in lymph nodes and spleen are specific to particular microbes respond to antigens =macromolecule in foreign invaders that triggers a response by lymphocytes cause B cells to secrete proteins called antibodies (immunoglobulins) B cells have antigen receptors on membrane T cells have T cell receptors (are not secreted)
21 Lymphocyte development
22 Primary immune response the selective proliferation and differentiation of lymphocytes during the first exposure to an antigen takes 1017 days B cells and T cells produce plasma cells (antibodyproducing effector B cells) host might be ill during this time until enough antibodies get made
Secondary immune response immune response when exposed a second time to an antigen 27 days antibodies have greater affinity for antigen process is called immunological memory
23 Immunilogical memory enhanced response to foreign molecule encountered before; lasts a long time gives us protection against things like chicken pox
24 Antigen recognition by lymphocytes
Clonal selection of lymphocytes each antigen activates a fraction of lymphocyte cells which give rise to clones of thousands of cells, all specific for that antigen, single cell has 100,000 antigen receptors
25 Antigen binding site is formed by variable regions (change from cell to cell) and constant regions (vary little or not at all)
26 epitope
Epitope antigenic determinant = a small, accessible portion of an antigen a single antigen has several different epitopes
27 When B cells and T cells mature initially if their antigen receptors recognize molecules already in body destroy the receptors leave only lymphocytes that recognize foreign molecules
B cells bind to an intact antigen, whether free or on surface of pathogen
T cells bind to antigen fragments that are displayed or presented on surface of host cell
Major histocompatability complex (MHC) produces a host cell protein that can present an antigen fragment to T cell receptors
28 Antigen presentation by an MHC molecule for recognition by antigen receptor lymphocyte
29 Major histocompatibility complex (MHC)a large set of cell surface antigens (glycoproteins)encoded by a family of genes. either activates immune responses against an antigen or targets an infected cell that displays the antigen for destruction
Two classes of MHC molecules
Class I Class II
trigger T cell responses that may lead to rejection of transplanted tissue
30 Class I found in all nucleated cells bind to peptide fragments of foreign antigens synthesized within the cell.
31 Class II MHC molecules made by dendritic cells, macrophages and B cells bind to peptides derived from foreign materials that have been internalized and fragmented through phagocytosis or endocytosis
32 Cytotoxic T cells respond to Class I molecules
Helper T cells respond to Class II molecules
33 Class I MHC present fragments of proteins made by infecting microbes like viruses to cytotoxic T cells Cytotoxic T cells kill infected cells
Class II MHC collect degradation peptide remnants and present them to Helper T cells helper T cells send out chemical signals to call other cells to fight pathogen
34 Three major properties of the acquired immune system
1. diversity of receptors ensures new pathogens will be recognized
2. able to recognize self so that immune system doesn't attack self
3. response to an antigen that has been encountered before creates a more powerful and faster response (immunological memory)
35 Generation of Lymphocyte Diversity by gene rearrangement each person had 1 million different B cells and 10 million different T cells, each with a specific antigen binding site, but only 20,500 coding genes.
How is this so?
36 Immunoglobulin gene arrangement
due to variety of variable elements
37 Amplifying Lymphocytes by clonal selection binding of an antigen receptor to its specific antigen starts events that activate lymphocytes
Acitvated B or T cells amplify the response by dividing multiple times, forming two clones:
Effector cells short lived, attack antigen and any pathogens producing that antigen
Memory cells longlived with specific antigen receptors
38 Clonal Selection of B cells
39 Immunological Memory
40 Humoral Response to antigens B cell activation results from production of antibodies carried in blood plasma and lymph defend against free bacteria, toxins and viruses in body fluid
Cellmediated immunity to antigens depends on action of T cells active against viruses and bacteria in infected cells, fungi, protozoa and parasitic worms important in response against transplanted tissue and cancer cells
41 42 Helper T cells
1. infected cell displays antigen fragments with help of MHCII. Specific helper T cell binds to displayed complex with help of CD4
43 Cytotoxic T cells
44 B cell activation in the humoral immune response
45 When antibodies attach to antigens forming a complex the following can happen:
1. neutralization when antibody binds to antigen, it blocks the activity of it ex. antibody may bind to viral antigen that would cause the infection of a cell could bind to surface of bacteria and are then phagocytized (opsonization) enhances macrophage attachment to microbe
46 2. agglutination clumping and then phagocytized
3. precipitation form precipitates, then phagocytized
47 Classes of antibodies
48 fig 43.16
49 4. complement fixation activation of complement system (serum proteins) activates them in a series or cascade results in lysis of cell
50 immune adherence when microbes coated with antibodies and complement proteins adhere to walls of blood vessels and make it easier for phagocytosis
positive feedback mechanism macrophages act as antigen presenting cells that stimulate helper T cells that stimulate B cells to produce antibodies which contribute to phagocytosis
51 Invertebrate immune response can distinguish self from nonself ex. sponges can do phagocytosis have nonspecific defense mechanisms, not acquired (memory) some use hemolin binds to microbes for disposal earthworms do exhibit rejection of nonself tissue
52 Active vs. passive immunity
Active Immunity immunity received when infected by a disease ex. chicken pox
is naturally acquired or artificially acquired by immunization (vaccination) use inactivated toxins or killed microbes or viable weakened strains can't cause disease, but can act as antigens
53 54 Passive Immunity antibodies transferred from one individual to another when antibodies of woman crosses the placenta to her child or transferred in breast milk (colostrum) does not last long, but helps baby until can develop own immune system can also inject antibodies from one person into another ex. rabies
55 How does immune system affect blood groups?
ABO blood groups
Type A has A antigens on RBC surface Type B has B antigens on RBC surface Type AB has both A and B antigens on its surface Type O has neither A nor B antigens on its surface
Type A has antibodies against B Type B has antibodies against A Type AB has no antibodies Type O has antibodies against both A and B
So if A and B blood mixed causes agglutination (clumping)
56 Rh factor
Rh is antigen found originally on rhesus monkey problem if Rh negative mother has Rh positive fetus if fetus blood crosses placenta or during birth and mixes with mother's blood, mother starts building antibodies no problem for first child second child problem her antibodies can cross placenta and destroy the fetal red blood cells causes child to be anemic or hypoxic if left untreated causes brain damage can treat baby by transfusion now can inject mother with anti Rh antibodies after birth of first baby
57 Tissue grafts and organ transplants
MHC responsible for tissue rejection try to match MHC between donor to recipient as much as possible identical twin or siblings are best also need meds to suppress immune response to transplant (more prone to infection) bone marrow transplant try for match recipient treated with irradiation to kill their own bone marrow cells (also kills immune system) bone marrow (containing lymphocytes)harvested from hip of donor injected into recipient could have graft vs. host reaction happens if match is not good
58 Allergies
hypersensitive responses to environmental antigens most common involve IgE class IgE antibodies attach to mast cells in connective tissue, but don't bind to allergen later, when allergen enters body, attaches to mast cell binding sites causing cross links to form. causes mast cell to degranulate release histamine causes dilation and increased permeability of small blood vessels get allergy symptoms
59 60 anaphylactic shock due to widespread mast cell degranulation to cause abrupt vasodilation causes blood pressure to drop can cause death ex. bee stings, peanuts, penicillin, fish use epipens (epinephrine) counteracts allergic response
61 Autoimmune disorders body can't distinguish self from nonself Ex. Lupus affects connective tissue rheumatoid arthritis affects joints diabetes mellitus body targets beta cells of pancreas that produce insulin multiple sclerosis destroys myelin sheath of neurons believe to involve immune regulation failures
62 Immunodeficiency Diseases inborn affect both humoral and cell mediated immune defenses requires bone marrow transplant Inborn a = genetic defect or developmental defect acquired immunodeficiency = develop later in life acquired not inborn get during lifetime AIDS= acquired immunodeficiency syndrome cause HIV = human immunodeficiency virus (RNA virus) transmitted by body fluids (semen, blood) enters cells by using CD4 (on helper T cells) and a coreceptor called fusin no cure, but drugs can slow progression virus mutates with each round of reproduction can get drug resistant strains (so use "cocktail" of drugs) weakens immune system (compromised) so susceptible to other infections like pneumonia
63 T cell with HIV HIV infecting lymphocytes
64 65 66 67