Chapter 22 Lymphatic System and Immunity Lecture Outline Lymphatic system Functions: 1. reclaim fluid 2. protection a. nonspecific defense b. specific defense (immunity) Components: 1. lymph 2. vessels 3. tissues & organs 4. cells Lymph and Lymphatic vessels lymphatic capillaries lymphatic collecting vessels lymphatic trunks → subclavian veins lymphnodes Lymphangitis vasa vasorum Lymphoid cells 1. Macrophages 2. Dendritic cells 3. Lymphocytes a. TC, TH, TS cells b. B cells → plasma cells → antibodies c. NK cells Lymphopoiesis Hemocytoblast → Lymphoid stem cell Lymphoid tissue reticular CT Functions: 1. proliferation 2. surveillance Types: 1. Lymphoid follicles/nodules a. MALT Peyer’s patches b. Appendix c. Tonsils -Palatine -Pharyngeal -Lingual 2. Lymphoid organs a. Lymph nodes trabeculae cortex: follicles, T, dendritic cells medulla: T, B, plasma cells sinuses: macrophages afferent vessels efferent vessels Buboes Lymphadenopathy b. Thymus Thymosin Thymopoietin Amy Warenda Czura, Ph.D.

c. Spleen Functions: 1. cell removal 2. store iron 3. initiate immune response 4. store platelets 5. fetal hematopoiesis red pulp sinusoids white pulp follicles splenectomy Defense 1st line: prevent entry 2nd line: general antimicrobial 3rd line: immune Nonspecific/Innate Defense 1. barriers 2. phagocytes 3. immunological surveillance 4. interferons 5. complement 6. inflammatory response 7. fever Barriers Cutaneous membrane (skin): keratin Mucosa: acid, lysozyme, mucus Phagocytes Microphages Neutrophils & Eosinophils Defensins Macrophages Fixed Free Phagocytes: 1. emigrate 2. chemotax 3. binding receptors Phagocytosis 1. adhere 2. pseudopods 3. phagosome 4. lysosome 5. residual body → exocytosis Immunological Surveillance NK cells: perforins Interferons α IFN: leukocytes NK cells β IFN: virus-infected cells AVPs γ IFN: T, NK cells macrophages Complement 1

SCCC BIO132 Chapter 22 Handout

Classical pathway Antibody → C1 → C2C4 → C3 → C3b Alternate pathway Factors P, B, D → C3 → C3b Antimicrobial effects 1. phagocytosis: opsonization 2. inflammation 3. MAC (C5-C9) → lysis Inflammation Functions: 1. prevent spread 2. remove debris 3. repair Events: 1. histamine, vasodilation 2. clotting, complement 3. ↑ temp 4. neutrophils, respiratory burst, cytokines 5. macrophages 6. fibroblasts 7. pain 8. immune defense Abscess Necrosis Apoptosis Fever Pyrogens Specific/adaptive Defense = Immunity Cellular immunity = T cells Humoral immunity = B cells Antigen Forms of immunity: 1. Innate 2. Acquired A. Active 1. Naturally acquired 2. Induced B. Passive 1. Naturally acquired 2. Induced Properties of immunity: 1. specificity 2. versatility 3. memory 4. tolerance Cell-Mediated Immunity Targets: infected cells, cancer, transplants Cells: 1. TC (cytotoxic) 2. TH (helper) 3. TS (suppressor) Class I MHC: endogenous antigens Class II MHC: exogenous antigens APCs: Dendritic cells Langerhans cells Amy Warenda Czura, Ph.D.

Macrophages B cells CD markers CD8 = TC & TS CD4 = TH CD8 cell activation 1. antigen in Class I MHC 2. clonal selection 3. memory T & effector T 4. target destruction a. perforin b. lymphotoxin c. apoptosis graft rejection & tissue typing CD4 cell activation 1. antigen in Class II MHC 2. clonal selection 3. memory T & effector T 4. cytokines a. memory b. TC production c. macrophage & NK attraction d. B cell activation Antibody-Mediated Immunity Targets: bacteria, toxins, virus T-dependent Antigens 1. antigen + IgD receptor = sensitized 2. antigen + Class II MHC 3. TH → cytokines 4. clonal selection → memory B & plasma cells 5. antibodies T-independent Antigens Antibody production 1. initial exposure: IgM 2. second exposure: IgG peak titre Antibody structure 2 H chains 2 L chains Hinge region C segment V segment Classes: IgG: monomer free antigens IgE: monomer Basophils & Mast cells IgD: monomer B cells IgM: pentamer agglutination IgA: dimmer secretions Antigen-Antibody complexes Antigen binding site Antigenic determinant/Epitope 2

SCCC BIO132 Chapter 22 Handout

Complete antigen Hapten Effects of binding: 1. agglutination & precipitation 2. opsonization 3. neutralization a. adhesion b. inactivation 4. complement fixation and activation 5. inflammation 6. Ab-dependent cell-mediated cytotoxicity Immune disorders Autoimmune examples: -Type I diabetes mellitus -MS -RA -Graves disease Immunodeficiency examples: -SCID -Hodgkins -AIDS Allergies 1. Immediate hypersenitivity A. Anaphylaxis Anaphylactic shock B. Atopy 2. Delayed hypersensitivity Age related changes: ↓ thymus ↓ T cells ↓ antibodies ↑ infection & cancer

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Nonspecific Defenses

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Phagocytosis via receptors on the phagocyte

small solutes diffuse into the cytoplasm for use enzymes are neutralized

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Complement activation and fixation

Alternate Pathway: no antibodies required -Factors P,B,D interact in response to foreign material

Classical pathway: requires bound antibodies

-C3 converted to C3b -C3b binds foreign material

-C1 binds antibody on bacteria -turns on C2 +C4 -C3 converted to C3b -C3b binds bacteria

Complement fixation = attachment of C3b, results in activation of antimicrobial effects: 1. Trigger phagocytosis: attract phagocytes and makes bacteria easier to grab and digest (opsonization) 2. Promotes inflammation: causes release of histamine from basophils and mast cells 3. Catalyzes formation of the MAC: (membrane attack complex) C5-C9 assemble to form pores on the membrane of the target cells resulting in cell lysis/death Amy Warenda Czura, Ph.D.

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Inflammation

Inflammation Events: 1.) Histamine is released by mast cells in response to change in the local environment and triggers an acceleration of blood flow to the area (vasodilation). 2.) Clotting factors and complement enter the site. A clot forms around the injury and complement lyses bacteria and attracts phagocytes. 3.) The local temperature rises due to the increase blood flow, which accelerates enzymatic reactions to enhance killing of pathogens. 4.) Neutrophils arrive, emigrate and chemotax, and are activated to produce the respiratory burst releasing toxic compounds to kill pathogens. They also release cytokines to attract other phagocytes. 5.) Macrophages arrive to engulf pathogens and cell debris. 6.) Fibroblast are stimulated to create collagen patch (scar tissue) to reinforce the clot and begin repair. 7.) Mast cell chemicals trigger pain receptors. 8.) The specific/immune defenses are activated.

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transfer

acquired

Naturally acquired active immunity

transfer

acquired

acquired

acquired

acquired

(vaccination) antiserum = purified antibody solution against a particular antigen

Properties of Immunity 1. Specificity: immune response targets particular antigens; each B and T cell responds to and destroys only one specific antigen. 2. Versatility: a large diversity of lymphocytes prescribed by genes exist to respond to almost any antigen; when a particular antigen is encountered the one lymphocyte specific to it divides by clonal selection to produce many cells specific to that particular antigen 3. Memory: response after second exposure to the same antigen is faster, stronger and lasts longer; during the initial exposure memory cells were created to respond quickly upon second exposure 4. Tolerance: immune system responds only to non-self antigens; B and T cells that recognize self antigens are destroyed by clonal deletion to insure self tolerance

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Class I MHC Found on all nucleated cells Bind endogenous antigens: (peptides present in cytoplasm) Abnormal peptides trigger cell destruction by Tc cells

Class II MHC Found on lymphocytes and antigen presenting cells (APC) Bind exogenous antigens: (peptides that have been endocytosed) Activate TH cells which activate B cells and Tc cells

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Generalization of Lymphocyte activation:

Activation of TC/CD8 cells

1. Binds specific antigen 2. Clonal selection: proliferation of the one cell (original cell makes many clones of itself) (Proliferation often requires stimulation by T helper cells) 3. Formation of memory cells and activated cells 4. Activated cells perform defense function Memory cells wait to activate upon next exposure to same antigen

Activation of TH/CD4 cells

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Activation of B cells (T dependent)

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Antibody Monomer Structure

Antigens and Epitopes a.k.a epitope

Classes of Antibodies (Immunoglobulins) IgG antibodies • • • • •

IgG

Monomer most common produced upon second exposure produced at high levels provides resistance against viruses, bacteria, toxins can cross placenta

•

IgM IgA

IgM antibodies • • •

Pentamer first class produced upon initial exposure forms immune complexes (agglutination)

IgD

IgA antibodies • •

Dimer in secretions

IgD antibodies • • •

B cell

Monomer on surface of B cells as receptor sensitizes or activates B cell upon antigen binding

IgE

IgE antibodies • • •

Monomer on mast cells and basophils as receptor triggers histamine release upon antigen binding Amy Warenda Czura, Ph.D.

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Effects of antibody binding: 1.

4.

and enhance phagocytosis

2.

5.

Binding of antigen by IgE on Mast cell triggers release of histamine

3.

6. phagocytes and NK cells

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Overview Summary of Body Defense (Nonspecific defense and immunity are linked)

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