FLG 327 Essential Immunology in Psychoneuroimmunology Study Unit 2 Lecture 2 Human Physiology: An Integrated Approach Author: Dee Silverthorn Chapter 24

UNIY!IIIT!IT YAM PIUOIIA UNIYEIIITY OF PRETORIA YUNIIESITHI YA PRETORIA.

Organisation of the Adaptive Immune System. Adaptive immune system also known as the lymphoid system Consists of organs such as: Thymus gland (T-lymphocytes mature) Bone marrow (B-lymphocytes mature) Spleen (lymphocytes remove blood pathogens) Lymph nodes (lymphocytes intercept pathogens that enter interstitial fluid, prevent pathogens spreading throughout lymphatic circulation) T onsils (posterior nasopharynx) G ut associated lymphoid tissue (GALT) (under epithelium of esophagus and intestines).

Fig. 24.10 FOCUS ON ... The Thymus Gland The thymus gland is a two- lobed organ located in the thorax just above the heart. The thymus gland reaches its greatest size during adolescence.Then it shrinks and is largely replaced by adipose tissue as a person ages. During development in the thymus, those cells that would be self-reactive are eliminated. Those that do not react with "self" tissues multiply to form clones. 0 2013 Pearscn Educatico. Thymus Thyroid gland Trachea The thymus gland produces: •T • Peptides thymosin thymopoietin thymulin FIGURE QUESTION New T lymphocyte production in the thymus is low in adults, but the number of T lymphocytes in the blood does not What conclusion(s) about T can you draw from this information?.

. Fig. 24.3 ANATOMY SUMMARY The Immune System The Lymphatic System Tonsil is diffuse lymphoid tissue. Thymus prcxjuces T lymphocytes. Lymph nodes Encapsulated lymphoid tissues Spleen Gut-associated lyrnphoid tissue (GALT) is a diffuse lymphoid tissue. Bone marrow rncEt blood cells. Lymph vessels Structure Of a Lymph Node Lymph node artery and vein Efferent lymph vessel Afferent lymph vessel Clusters of immune cells intercept pathogens that invade interstitial fluid. @ 2013 Pearson Education, Inc..

• Fig. 24.4 FOCUS ON ... The Spleen The spleen is the lymphoid organ in the body, located in the left quadrant of the atxlomen close to the stomach. Vein 2013 Pearson Education. Inc. Splen Venous sinuses Capillary The outer surface Of the splæn is a connective tissue capsule that extends into the interior to create an framework that supports the blood vessels and lymphoid tissue. Darker regions Of red pulp are closely associated with extensive blood vessels and open venous sinuses.The red pulp contains many macrophages that act as a filter by trapping and destroying foreign material circulating in the blood. In addition, the macrophages ingest old, damaged, and abnormal red blood cells, breaking down their hemoglobin molecules into amino acids, iron, and bilirubin that is transported to the liver for excretion. Regions of white pulp resemble the interior of lymph nodes and are composed mainly Of lymphocytes. Capsule.

Adaptive immune system. 2-20ER. (Figure 2.20, I. Roitt, Roitt's Essential Immunology, Ninth Edition (1997) Blackwell Science Ltd., London).

Adaptive immune system. Cellular/-mediated immunity : T-lymphocytes(cytotoxic T cells) defending the body against intracellular pathogens Humoral immunity : B-lymphocytes differentiate into plasma cells that secret antibodies (immunoglobulins) defending the body against extracellular pathogens.

Major Histocompatibility Complex Classes. MHC Class I : Bind endogenous antigens (cancer cells/ viral proteins) → target cell CTL (CD8+) → CD8 binds domain of MHC class I MHC Class II: Bind exogenous antigens ( bacteria) → APC TH (CD4+) → CD4 binds domain of MHC class II.

MHC Classes. Image result for MHC 2 binds exogenous antigens.

T LYMPHOCYTES (a) T lymphocyte development During embryonic development, T insert their T-cell receptors into the membrane. migrates to Thymus gland kill Multipotent stem cell in bone marrow T-cell precursor Cytotoxic T cells MHC Class I target cells Cytokines that secrete activate other immune cells T cells Bind to MHC-II antigen- præenting cells (b) T lymphocyte activation When T-cell receptors bind to antigen preænted on MHC receptors. MHC-antigen complex MCH receptor 02013 Pearson Education, Inc. Cell binds to T lymphocyte. T lymphocyte Signal transduction activates T lymphocyte. — T-cell receptor FIGURE QUESTIONS What kind of T cell is shown if the MHC receptor is MHC-I? MHC-II?.

Categories of T Cells. 1 . Cytotoxic (cell-killing) T lymphocytes (CTLs, also called T cytotoxic (Tc) cells: CD8 Destroy cells that display MHC I- antigen complexes Prevents reproduction of intracellular invaders (viruses, parasites, bacteria in the intracellular environment) 1.1 Release a cytotoxic pore-forming molecule called perforin and granzymes (trypsin, chymotrypsin) Granzymes in target cell, activate enzyme cascade induces apoptosis 1.2 Cytotoxic T cell instructs target cell to undergo apoptosis by activating FS-7-associated surface antigen ( Fas) death receptor protein on the target cell membrane that is linked to the enzyme cascade A activates intracellular FADD domain L eads to activation of initiator caspases (8+9) Eventually activates execution caspases(3+7) Results in cell apoptosis.

Image result for activating Fas death receptor protein on the target cell membrane.

Categories of T Cells. 2. T helper or inducer (TH): CD4 Secrete cytokines that activate other immune cells Th1 cells produce inflammatory cytokines, especially tumour necrosis factor (TNF), interferon-gamma (IFN- γ ), interleukin 2 (IL-2), activates macrophages, mast cell degranulation, cytotoxic T cell production Th2 cells produce high levels of IL-4/5, IL-10 and IL-13, → promote antibody secretion 3. T suppressor (Ts): Suppress B cell transformation and antibody (Ab)production.

Helper T Cells. Class II MHC protein CD4 protein Cytotoxi cell acrophage Helper cel Interleukin 1 and other cytokines Interleukin 2 and other cytokines B cell Cell-mediated immunity (attack on infected cells) Humoral immunity (secretion of antibodies by plasma cells).

Categories of T Cells.

primary exposure to antigen phagocytosis by macrophage antigen prresentation stimulates Helper T cells B cells Helper T cell ....................> cytotoxic T cells stimulates gives rise to Memory Helper T cells second exposure to antigen gives rise to plasmacytes memory B cells antibodies seconday antibody response Memory active T cells cytotoxic T cells.

Humoral immunity: Antibodies. Humoral immunity Recognition of pathogens outside of cells B-lymphocytes (B cells) developed in the bone marrow Clones of B cells differentiate into plasma cell Plasma cells secrete antibodies (immunoglobulins).

Image result for chapter 24 silverthorn diagrams lymphocytes clones.

B cells. Mature B lymphocytes insert antibody molecules into their cell membrane Antibodies become surface receptors marking members of each clone B cell clone responds to an antigen exposure Group of lymphocytes specific to one antigen form a clone At birth, each clone of lymphocyte is represented by a ( naïve cells ) At antigen exposure appropriate clone is activated and start to divide= clonal expansion.

B cells. Some of the effector cells differentiate into plasma cells Plasma cells do not have antibody proteins bound to their membranes Instead they synthesise and secrete additional antibody molecules at increased rates After pathogens are killed short lived plasma cells die off Memory cells of the clone remain behind to respond to 2 nd exposure to the antigen.

B cells. Primary immune response : after initial exposure, antibody production by plasma cells is slow. Secondary immune response : after 2 nd and subsequent exposure, quicker and larger because memory cells remain. Clonal expansion : enhanced by lymphocytes that carry a molecular memory of the first exposure to the antigen. Allows antibody production to begin sooner and reach higher concentrations.

(a) Antibody structure An antibody molecule is composed of two identical light chains and two identical heavy chains, linked by disulfide bonds. Antigen-binding sites Light chain Hinge region allows movement of the arms. Heavy chain 2013 Pearson Educatm. be. Fab region Fc region.

The 5 Immunoglobulin Classes. IgG lgD lgE IgM.

Antibody: Mechanism of Action. Neutralization (masks dangerous parts of bacterial exotoxins; viruses) Inactivates by Agglutination (cell-bound antigens) Enhances Antigen—antibody complex Precipitation (soluble antigens) Enhances Phagocytosis Inflammation Antibody Fixes and activates Cornplement Leads to Cell lysis Chemo- taxis Histamine release •g.

Functions of Antibodies. (c) functions 1 Activate B lymphcwy'tß Plasma cells Memory 2 Act as opsonins to tag for phagcxytosis @Cause clumping and inactivation of bacterial toxins Bacterial toxins Enhanced antibodies 4 Activate cellular activity @Activate complement Complement 6 Trigger mast æll 02013 Pearson Educatbn, Inc. NK cell Or.

Immunological Response.

Fig. 24.12 ESSENTIALS Immune Responses to Extracellular Bacteria Bacterial infections cause inflammation and trigger specific immune responses. External Skin or mucous membrane o | 0] o IOIOPIO o 0000 Opsonins and disable Phagocytes antigens to TH cells Plasma cells o Bacteria enter extracellular fluid from outside o Bacteria activate Complement proteins Acute phase proteins Plasma proteins Membrane attack Mast cells Chen.otaxins Histamine Circulating 4_ attract @ 2013 Pearson Education, Inc..

• Fig. 24.13 ESSENTIALS Immune Responses to Viruses This figure assumes prior to the virus and prelisting antibodies. ir•wtød twst coil by cytotoxic T cens cell @2013 Pearson Education, Inc. Preexisting s ingests virus. Viral presents Cytokines Plasma cells the and in this.

EXPOSURE Allergen MCH-II activates becomes Plasma cell secretes Antibodies 2013 Edueatb•t. Inc. Allergen ingested and processed by antigen-presenting cell. Antigen-presenting cell activates helper T cell. Helper T cell B lymphocyte Memory B and T cells retain memory of exposure to allergen..

Antibodies REEXPOSURE Degranulation Cytokines, histamine, etc Vasodilation lgE IgG Mast cell Activation of complement proteins Memory B and T cells retain memory of exposure to allergen. Activated T cells Cytokines Bronchoconstriction 4 Vascular permeability @ 2013 Pearson Education, Inc. Inflammation.