Chapter 22 Lymphatic System and Immunity Lecture … 22 Lymphatic System and Immunity Lecture Outline Lymphatic system Functions: 1. reclaim fluid ... Cellular immunity = T cells

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

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

Amy Warenda Czura, Ph.D. 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

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


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



Nonspecific Defenses


Phagocytosis

via receptors on the phagocyte

small solutes diffuse into the cytoplasm for use

enzymes are neutralized


Complement activation and fixation

1. Trigger phagocytosis: attract phagocytesand makes bacteria easier to grab and digest(opsonization)

2. Promotes inflammation: causes release ofhistamine from basophils and mast cells

3. Catalyzes formation of the MAC:(membrane attack complex) C5-C9 assembleto form pores on the membrane of the targetcells resulting in cell lysis/death

Classicalpathway:requires boundantibodies

Alternate Pathway: no antibodies required

-C1 binds antibodyon bacteria

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

-Factors P,B,D interact in response toforeign material

-C3 converted to C3b-C3b binds foreign material

Complement fixation = attachment of C3b,results in activation of antimicrobial effects:


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.

Inflammation


Properties of Immunity

1. Specificity: immune response targets particular antigens; each B and T cell responds to and destroys onlyone 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 toproduce many cells specific to that particular antigen

3. Memory: response after second exposure to the same antigen is faster, stronger and lasts longer; during theinitial 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 antigensare destroyed by clonal deletion to insure self tolerance

acquired acquired acquiredNaturally acquiredactive immunity

antiserum = purifiedantibody solutionagainst a particularantigen

acquired acquired

transfer transfer

(vaccination)


Class I MHC

Class II MHC

Found on all nucleated cells

Bind endogenous antigens:(peptides present in cytoplasm)

Abnormal peptides trigger celldestruction by Tc cells

Found onlymphocytes andantigen presentingcells (APC)

Bind exogenousantigens: (peptidesthat have beenendocytosed)

Activate TH cellswhich activate Bcells and Tc cells


Activation of TC/CD8 cells

Activation of TH/CD4 cells Activation of B cells (T dependent)

Generalization of Lymphocyteactivation:

1. Binds specific antigen

2. Clonal selection:proliferation of the one cell(original cell makes manyclones of itself)

(Proliferation often requiresstimulation by T helper cells)

3. Formation of memory cellsand activated cells

4. Activated cells performdefense function

Memory cells wait to activateupon next exposure to sameantigen


IgA

Classes of Antibodies (Immunoglobulins)

Antibody Monomer Structure Antigens and Epitopesa.k.a epitope

• Monomer• most common• produced upon second exposure• produced at high levels• provides resistance against viruses,

bacteria, toxins• can cross placenta

IgG antibodiesIgG

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

IgM antibodies

IgM

• Dimer• in secretions

IgA antibodies

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

antigen binding

IgD antibodiesB cell

IgD

• Monomer• on mast cells and basophils as receptor• triggers histamine release upon antigen binding

IgE antibodies

Mast Cell

IgE


and enhance phagocytosis

Effects of antibody binding:

2. 5.

phagocytesand NK cells

Binding of antigen by IgE on Mastcell triggers release of histamine

3. 6.

1. 4.


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


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Chapter 22 Lymphatic System and Immunity Lecture … 22 Lymphatic System and Immunity Lecture Outline Lymphatic system Functions: 1. reclaim fluid ... Cellular immunity = T cells