BIO 5, ch 21 Immune system

17. What are the two types of humoral immunity? S36-37.

1.Active immunity: when B cells encounter antigens and produce specific antibodies against them. (can be naturally or artificially acquired [got sick vs vaccine] And... 2.Passive immunity: Where B cells are not challenged by antigens, therefore immunological memory does not occur and pool of antibodies made in another organism is received.

Comparison of Humoral and Cell-Mediated Response (S52)

1.Antibodies of the HUMORAL response: •The simplest ammunition of the immune response Targets •Bacteria and molecules in extracellular environments (body secretions, tissue fluid, blood, and lymph) 2. T cells of the CELL-MEDIATED response: •Recognize and respond only to processed fragments of antigen displayed on the surface of body cells •Targets •Body cells infected by viruses or bacteria •Abnormal or cancerous cells •Cells of infused or transplanted foreign tissue

8.What is a complement?

A major mechanism for destroying foreign substances, enhancing both specific and nonspecific defenses. It consists of about 20 proteins circulating in the blood in inactive form. When activated, they: • Enhance inflammation • Promote phagocytosis • Cause cell lysis via initiating formation of a membrane attack complex (MAC), which causes cell lysis by inducing a massive influx of water. Note complement: • Include C1-C9, factors B, D, and P, and regulatory proteins • Initiates formation of a membrane attack complex

18. Learn the types of active and passive immunity. S39

Active: a. Naturally acquired: Infection; contact with pathogen b. Artificially acquired: Vaccine; dead or attenuated pathogens. Passive: (temporary) a. Naturally acquired: Antibodies pass from mother to fetus via placenta; or to infant in her milk .b. Artificially acquired: Injection of immune serum (gamma globulin).

15. What is an antibody? Learn the structure of an antibody.

An antibody is a protein secreted by B-lymphocytes [specifically their plasma cells] that binds to a specific antigen detected by B cells. Also called immunoglobulins—gamma globulin portion of blood. Each antibody consists of four polypeptides- two heavy chains and two light chains joined to form a "Y" shaped molecule. The amino acid sequence in the tips of the "Y" varies greatly among different antibodies.

Antibody targets (S44)

Antibodies inactivate and tag antigens •Form antigen-antibody (immune) complexes Defensive mechanisms used by antibodies •Neutralization and agglutination (the two most important) •Precipitation and complement fixation note: image shows MAC (membrane attack complex) process.

14.Which one type of cells are responsible for producing and releasing antibodies?

B lymphocytes.

4.What is inflammation?

Can be triggered by an infection OR by tissue injuries. Its four characteristics/cardinal signs = heat, redness, pain, and swelling (And sometimes 5. Impairment of function). S:•Prevents the spread of damaging agents "The inflammatory reaction brings in phagocytic cells to the damaged area to clear cellular debris & set stage for wound repair."

#26. AIDS (S 61-62)

Caused by human immunodeficiency virus (HIV) transmitted via body fluids—blood, semen, and vaginal secretions. HIV enters the body via: •Blood transfusions •Blood-contaminated needles •Sexual intercourse and oral sex HIV: •Destroys TH cells •Depresses cell-mediated immunity Treatment with antiviral drugs Reverse transcriptase inhibitors (AZT): •Protease inhibitors (saquinavir and ritonavir) •New Fusion inhibitors that block HIV's entry to helper T cells

What is agglutination? (S46)

Cell-bound antigens. •Antibodies bind the same determinant on more than one cell-bound antigen •Cross-linked antigen-antibody complexes agglutinate •Example: clumping of mismatched blood cells

10. What are complete antigens?

Functional antigens that are immunogenic. Two properties an antigen must have to be complete is: a. Immunogenicity (able to stimulate proliferation of specific lymphocytes and antibodies) and b. Reactivity (able to react with products of activated lymphocytes and antibodies released). Examples include: foreign protein, polysaccharides, lipids, and nucleic acids.

Differences between humoral and cell-mediated immunity

HUMORAL is: 1.antibody mediated. 2.controls extracellular pathogens. 3.B cells play a major role CELL MEDIATED is: 1.cell mediated. 2.controls INTRAcellular pathogens [or antigens] 3.T cells play a major role. DETAILS: HUMORAL: -B cell binds to antigen, recruits T helper cell. -TH secrete cytokines and the cytokines transform B cells into plasma cells that produce antibodies FOR THAT antigen/pathogen the B cell binded too. -The antibodies neutralize the extracellular pathogen & eliminate it. CELL-MEDIATED: Intracellular pathogens are flagged by APCs #"displayed corpses" on the surface of cells like macrophages [or dendrites]. -T cells bind to MHC complexes on the surface of the infected cell, activating the T cell with its cytokine receptors. -The activated T cell secretes cytokines which in turn activates TH cells & macrophages. After that -T cell transforms to cytotoxic T cell. The cytotoxic T cell induces apoptosis in infected cell.

1. What is immunity? What are the two types of immunity?

Immunity = resistance to disease. •Immune system has two intrinsic systems 1.Innate (nonspecific) defense system 2.Adaptive (specific) defense system

25. What is an immunodeficiency? Learn the examples of the immunodeficiency covered in this chapter

Immunodeficiency is when congenital and acquired conditions cause immune cells, phagocytes, or complement to behave abnormally. SCID: •Genetic defect •Marked deficit in B and T cells. fatal if untreated; treatment is with bone marrow transplants. Hodgkin's Disease: •An acquired immunodeficiency •Cancer of the B cells •Leads to immunodeficiency by depressing lymph node cells. AIDS: (see separate card "#26.) TEXTBOOK IMMUNODEFICIENCIES A: selective IgA deficiency -- inability to produce secretory IgA --- predisposition to lung and gastrointestinal infections. B: severe combined Immunodeficiency disease (SCID) - deficient humoral and cell-mediated immune responses --- early development of severe and life-threatening opportunistic infections. C: x-linked agammaglobulinemia - flawed differentiation of B cells and the absence of specific antibodies --- recurrent infections almost exclusively due to pathogens that cause pyogenic infections. Secondary immunodeficiencies: A: immunosuppressive therapies (chemotherapy/radiotherapy) - impaired humoral and/or cell-mediated immune responses - opportunistic infections, rare cancers. B: malnutrition -- impaired humoral and/or cell-mediated immune responses --- opportunistic infections and rare cancers C: viral infection -- impaired cell-mediated immune responses due to CD4 T-cell lymphopenia --- opportunistic infections, rare cancers.

9. What are haptens?

Incomplete antigens/small molecules (lower molecular weight) that are too small to elicit an immune response. Only when attached to a large carrier (like a peptide, nucleotide, hormone or other body protein) can they cause the immune system to attack invaders, as by themselves are not immunogenic. Examples include poison ivy, animal dander, detergents & cosmetics.

2. What are the differences between a specific and nonspecific immune responses?

Innate (nonspecific): • First line of defense is external body membranes (skin and mucosae AND SECRETIONS & Gut flora) • Second line of defense is antimicrobial proteins, phagocytes, other cells, inflammation and fever -Inhibit spread of invaders -Inflammation is its most important mechanism Adaptive (specific): Third line involves immune cells, complement & antimicrobial substances. specialized lymphocytes: B cells & T cells.

3. Learn the components of the first, second, and third lines of defense

Innate defense system has two lines of defense: 1. First line of defense is external body membranes (skin and mucosae) 2.Second line of defense is antimicrobial proteins, phagocytes, other cells, inflammation and fever •Inhibit spread of invaders •Inflammation is its most important mechanism Adaptive defense system: 3.Third line of defense attacks particular foreign substances •Takes longer to react than the innate system •Innate and adaptive defenses are deeply intertwined •Humoral = B cells, Cellular = T cells.

23. What is an autoimmune disease? Learn the examples of the autoimmune diseases that we covered in this chapter. (S63)

Is when the immune system loses its ability to distinguish self from foreign #they become misdirected. The production of autoantibodies and sensitized TC cells destroy body tissues. Examples include multiple sclerosis, myasthenia gravis, Graves' disease, type I diabetes mellitus, systemic lupus erythematosus (SLE), glomerulonephritis, and rheumatoid arthritis.

Antigen Receptor Diversity & Antigen-Presenting Cells (APCs)(S26-28)

Lymphocytes make up to a billion different types of antigen receptors. Coded for by ~25,000 genes APC's: •Engulf antigens •Present fragments of antigens to be recognized by T cells Major types of APC's/"Professional APCs" = •Dendritic cells(in connective tissues and epidermis) •Macrophages(in connective tissues and lymphoid organs) •B cells (Atypical/nonproffessional APCs = Mast cells, basophils & eosinophils)

What is neutralization? (S45)

Masks dangerous parts of bacterial exotoxins; viruses. •Simplest mechanism •Antibodies block specific sites on viruses or bacterial exotoxins •Prevent these antigens from binding to receptors on tissue cells Antigen-antibody complexes undergo phagocytosis

Fate of Clones (lymphocytes & antibodies?) (S30-31)

Most clone cells become plasma cells •secrete specific antibodies at the rate of 2000 molecules per second for four to five days Secreted antibodies •Circulate in blood or lymph •Bind to free antigens •Mark the antigens for destruction Clone cells that do not become plasma cells become memory cells •Provide immunological memory •Mount an immediate response to future exposures of the same antigen

19. What defensive mechanisms are used by antibodies? (see slide 48)

Neutralization - antibodies bind to and block specific sites on viruses or exotoxins, thus preventing these antigens from binding to receptors on tissue cells Agglutination - antibodies bind the same determinant on more than one antigen a.Makes antigen-antibody complexes that are cross-linked into large lattices b. Cell-bound antigens are cross-linked, causing agglutination Precipitation - soluble molecules are cross-linked into large insoluble complexes. Takes two solubles to make an insolubles so it can't be absorbed. Complement fixation and cell lysis and activation of phagocytosis a.The main mechanism used against cellular antigens b.Enhances the inflammatory response *Immunoglobulins too probably.

Roles of Helper T(TH) Cells (S54, 55 image)

Play a central role in the adaptive immune response. Once primed by APC presentation of antigen, they: •Help activate T and B cells •Induce T and B cell proliferation •Activate macrophages and recruit other immune cells Without TH, there is no immune response.

20. Learn the differences between the primary and secondary immune responses (see also Immunological memory)

Primary response is the initial encounter with new antigen. Here, activated B cells proliferate to form clones. Antigen binding to a receptor on a specific B lymphocyte (B lymphocytes with non-complementary receptors remain inactive). Plasma cells = effector B cells; secrete antibody molecule. Memory B cell- primed respond to same antigen next time. Secondary response can be years later. Clone of cells identical to ancestral cells. Subsequent challenge by same antigen results in more rapid response. More plasma cells to secrete antibody molecules. + memory B cells.

13. 'B' lymphocytes develop immunocompetence in the...

Red 'B'one marrow. (whereas 'T' cells mature in the 'T'hymus under negative and positive selection pressures). BOTH originate in red bone marrow though. S23. Naive (unexposed) B and T cells are exported to lymph nodes, spleen, and other lymphoid organs.

7.What is fever? How does the fever generated?

S14-15 •Systemic response to invading microorganisms •Leukocytes and macrophages exposed to foreign substances secrete pyrogens •Pyrogens reset the body's thermostat upward •heat denatures enzymes (so high temp dangerous) Benefits of moderate fever: •Causes the liver and spleen to sequester iron and zinc (needed by microorganisms) •Increases metabolic rate, which speeds up repair Note: not a failure of homeostasis.

What are antigens?

S17 •Substances that can mobilize the adaptive defenses and provoke an immune response •Most are large, complex molecules not normally found in the body (nonself).

What is positive and negative selection in T cells?

S25. T CELLS mature in the thymus under negative and positive selection pressures: Positive selection: • Selects T cells incapable of binding to self-MHC proteins (MHC restriction) Negative selection: • Prompts apoptosis of T cells that bind to self-antigens displayed by self-MHC

Humoral Immunity Response:

S29. Antigen challenge •First encounter between an antigen and a naive immunocompetent lymphocyte •Usually occurs in the spleen or a lymph node If the lymphocyte is a B cell •The antigen provokes a humoral immune response •Antigen-specific antibodies are produced

Immunological memory: Primary immune response (see also Q 20)

S33. • Occurs on the first exposure to a specific antigen •Lag period: three to six days •Peak levels of plasma antibody are reached in 10 days •Antibody levels then decline

Immunological memory: Secondary immune response (see also Q 20)

S34. •Occurs on re-exposure to the same antigen •Sensitized memory cells respond within hours •Antibody levels peak in 2 to 3 days at much higher levels •Antibodies bind with greater affinity •Antibody level can remain high for weeks to months

15 pt 2. Learn the structure of an antibody. (see S43 image)

S41 •T-or Y-shaped monomer of four looping linked polypeptide chains •Two identical heavy (H) chains and two identical light (L) chains •Variable (V) regions of each arm combine to form two identical antigen-binding sites Constant (C) region of stem determines •The antibody class (IgM, IgA, IgD, IgG, or IgE) •The cells and chemicals that the antibody can bind to •How the antibody class functions in antigen elimination Note: Antibodies are found on B cells surfaces or in soluble form (humoral) in serum and other body fluids. Y shaped. molecule is made up of two heavy chains and two light chains. disulfide bonds link the chains.

5. What are the functions of the inflammatory response?

S9 •Inflammatory mediators •Histamine (from mast cells) •Blood proteins •Kinins, prostaglandins (PGs), leukotrienes, and complement •Released by injured tissue, phagocytes, lymphocytes, basophils, and mast cells

What is precipitation (S47)

Soluble antigens. •Soluble molecules are cross-linked •Complexes precipitate and are subject to phagocytosis

11. What is an adaptive defense? What are the two parts of the adaptive defense?

The third line of defense in the immune response, where specific antibodies are produced for invading cells, and a systemic response is mounted to destroy the pathogens, as well as remember them for the future. Its two parts are a.Humoral (antibody-mediated) and b.Cellular (cell-mediated). see S 16. Image here is CELLULAR immunity. It's specific, systemic & has a memory.

22. What are major types of cells important in cell mediated immunity? (S50, 51 image)

The two major cell types are: a.CD4 cells, which become helper T cells (TH) when activated AND b. CD8 cells, which become cytotoxic T cells (TC) that destroy cells harboring foreign antigens. Cell mediated immunity Types The main types of lymphocytes involved in cell-mediated immunity include helper T cells, killer T cells, and macrophages. When a "helper" T cell finds an antigen-presenting cell in the body, it releases a set of signaling proteins called cytokines S51: Other types of T cells: •Regulatory T cells (TREG) •Memory T cells

6.The redness and heat of an inflamed area are due to a local hyperemia caused by...

Vasodilation/dilation of arterioles. S10. Inflammatory chemicals cause •Dilation of arterioles, resulting in hyperemia •Increased permeability of local capillaries and edema (leakage of exudate) Exudate contains proteins, clotting factors, and antibodies. Functions of the surge of exudate: •Moves foreign material into lymphatic vessels •Delivers clotting proteins to form a scaffold for repair and to isolate the area

21. What is cell mediated immunity? (S49 image)

When T cells provide defense against intracellular antigens. Does not involve antibodies, but phagocytes, antigen-specific T cells, and the release of various cytokines in response to an antigen. S49: Two types of surface receptors of T cells: 1. T cell antigen receptors 2.Cell differentiation glycoproteins •CD4 or CD8 (form specific defense in which T lymphocytes directly attacks invading cells)

12. What is immunocompetence?

When mature lymphocytes (B & T cells) are able to recognize and bind to a specific antigen.

16. Learn the characteristics of T and B lymphocytes.

When mature they have • immunocompetence, and • self-tolerance/unresponsive to self antigens. T cells' role include directly killing infected host cells, activating other immune cells, producing cytokines and regulating the immune response. B cells' defining feature is that they are the only cells that rearrange genes to code for antibodies (immunoglobulins). They also secrete antibodies, present antigens (APCs) and secrete cytokines (signaling molecules).

24. What are the four varieties of organ transplants? (S56-57)

•Autografts: from one body site to another in the same person •Isografts: between identical twins •Allografts: between individuals who are not identical twins •Xenografts: from another animal species PREVENTION OF REJECTION: Depends on the similarity of the tissues Patient is treated with immunosuppressive therapy •Corticosteroid drugs to suppress inflammation •Immunosuppressant drugs Many of these have severe side effects.

Hypersensetivities (S64)

•Immune responses to a perceived (otherwise harmless) threat •Causes tissue damage •Antibodies cause: -immediate and -subacute hypersensitivities •T cells cause delayed hypersensitivity Immediate: •Acute (type I) hypersensitivities (allergies) begin in seconds after contact with allergen Subacute: •Caused by IgM and IgG transferred via blood plasma or serum •Slow onset (1-3 hours) and long duration (10-15 hours)

Anaphylactic shock (S66)

•Systemic response to allergen that directly enters the blood •Basophils and mast cells are enlisted throughout the body •Systemic histamine releases may cause: -Constriction of bronchioles -Sudden vasodilation and fluid loss from the bloodstream -Hypotensive shock and death •Treatment: epinephrine.