Ch. 43 The

1 Essential Questions:

How does our 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 ­, phagocytic cells

B. acquired immunity­ (adaptive immunity)­develops after exposure to specific microbes, abnormal body cells, foreign substances or toxins ­highly specific ­ ­ produce 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) ­ ­produce antimicrobial proteins and initiate (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

8 Process of Phagocytosis

9 Phagocytic blood cells

1. ­60­70% 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 ­some migrate, some stay in tissues, organs (lymphatic)

11

12 3. ­ 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

from

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 ­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. ­ 30 plasma proteins that fight ­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 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 ­ are specific to particular microbes ­respond to =macromolecule in foreign invaders that triggers a response by lymphocytes ­cause B cells to secrete proteins called antibodies (immunoglobulins) ­B cells have receptors on membrane ­T cells have receptors (are not secreted)

21 development

22 Primary ­ 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 (­producing 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

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 ­ antigenic determinant = a small, accessible portion of an antigen ­a single antigen has several different

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 by an MHC molecule for recognition by antigen receptor lymphocyte

29 Major 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 ­ 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 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.

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

­hypersensitive responses to environmental antigens ­most common involve IgE class ­IgE antibodies attach to mast cells in connective tissue, but don't bind to ­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 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 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