Bodys Defense SystemPart II: Specific (Immune) Responses Overview: Specific Body Defenses (Immune System) Antibody-mediated (humoral)

) Defends against free bacteria and viruses in body fluids Cell-mediated Defends against abnormal cells (i.e., cells transformed by cancer, viral infections; foreign cells [transplant cells]) Both categories have three stages: (1) Antigen encounter and recognition (binding to receptor) by lymphocyte (2) Lymphocyte activation and clonal expansion
to get from encounter to activation, must have activation of specific helper T cells (3) Attack

Both categories require activation of specific helper T cells Forms of Immunity Innate Genetic immunocompetent (able to recognize specific antigen); born with them
Also used to refer to nonspecific defenses (also born with that)

Acquired Active (vaccinations) Passive (get antibodies from someone else)

Properties of Immunity Specificity each lymphocyte programmed for one specific antigen

Versatility due to genetic reshuffling before born, preprogrammed to recognize specific antigens Memory set memory by either getting vaccinations or diseases Tolerance -

Types of Lymphocytes (Table 18.12 V) NK cells also derive from lymphocytes (lymphoid stem cell) T lymphocytes Mature (acquire receptors) in thymus
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Three types Cytotoxic T cells effectors of cell mediated defense (capable of recognizing cells that have been transformed and killing them) Helper T cells Suppressor T cells B lymphocytes Mature (acquire receptors) in bone marrow Give rise to antibody-secreting plasma cells Types of Lymphocytes Cytotoxic T (TC) cells Effectors for cell-mediated immunity Attack infected/transformed cells (i.e. cancer) CD8 receptors

Helper T (TH) cells Regulatory function in both cell-mediated and antibodymediated (humoral) immunity CD4 (T4) receptors look for amount of receptors is way to tell if have Helper T cells

Suppressor T cells Inhibit B and T cells CD8 receptors B cells Carry out antibody-mediated (humoral) immunity

Lymphocyte Receptors: How Lymphocytes Recognize Antigens (Ags) T cell Receptors Two-chained proteins, which cannot bind (see) antigen unless Ag is complexed to MHC self proteins (processing of Ag) Cytotoxic T cells CD8 receptors Helper T cells CD4 receptors

B cell Receptors
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Immunoglobulin (Ig) attached to B cell

Immunoglobulins includes B cell receptors and antibodies

Ig is a copy of antibody that cell can produce.

Definitions Immunocompetence (Maturation) Lymphocytes acquire ability to recognize Ag when they acquire receptors specific to Ag. This process is genetically and randomly determined! Confers specificity + versatility to specific immune system

Antigen Any foreign molecule that can trigger specific immune response Also known as antigenic determinants (epitopes- real antigenic

site)

Antibody Specific defense protein secreted by specific B lymphocytes

Immunoglobulin (Ig)

Y shape Variable (specific receptor regions, bind specific epitope) regions binds Ag Constant region involved in effector mechanism, including complement

Classes of Antibodies IgG Typical Ab (80%) Can cross placenta (passive immunity) IgE Allergic responses IgD Functions unclear IgM First to appear after Ag IgA Colostrum; breast milk (passive immunity)

Histocompatibility Major Histocompatibility Complex (MHC) Proteins identify self MHC Class I: On all nucleated cells (not RBC) Recognized by Cytotoxic T cells (CD8 receptors)

MHC Class II: On (1) macrophages, (2) B cells and (3) dendritic cells able to do Antigen Processing Antigen Presenting Cells (APCs) for helper T cells Recognized by helper T cells (CD4 receptors)

Antigen Processing Necessary for T cells to recognize Ag (activate T cell) Ag must be taken into cell and complexed with MHC protein then cell presents processed Ag (with MHC protein) on surface, along with copy of self. Which MHC protein is recognized depends on type of CD marker is in T cell membrane CD8: Cytotoxic (and Suppressor T cells) CD4: Helper T cells

Antigen Presentation Infected cells present antigen to cytotoxic T cells APCs present antigen to helper T cells (3 cells)

Cytokines: Cell chemicals that mediate immune response see Table 18.2V Already mentioned: Interferons, Leukotrienes, CSFs Interleukins IL-1; IL-2 and more TNF Lymphotoxins Perforins Antigen Processing and Presentation to Helper T Cells (Fig. 18.11V)

Where are Class II MHC proteins located? APCs What are APCs? Macrophages, B cells, and dendritic cells
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Which lymphocyte has CD4 markers? (T4 Helper T cell)

Three Events are Required for the Activation of Helper T Cells (Figure 18.12 V) Presentation of Ag bound to class II MHC protein on an APC
Costimulation (second binding site): The binding of matching

nonantigenic proteins in membrane of APC and helper T cell

APC secretes cytokines (cell chemicals) that act on helper T cell IL-1 (Interleukin I) stimulate Helper T cell to start to divide TNF (Tumor Necrosis factor)

Humoral (Antibody-Mediated) Immunity Defends against free bacteria and viruses in body fluids Specific B lymphocytes are activated to produce specific antibodies, which tag antigen
antigentic determinant sites = epitopes

Antibody-Mediated Immune Response figure 18.14V***** Ag recognized by specific B cell (selection/recognition stage); and processed + presented by APC to specific Helper T cell (need to select B cell) Helper T cytokines required for clonal expansion (division state) Selected B cell proliferates and differentiates plasma (dont have receptors, dont need themrelease antibodies in blood) and memory cells
Primary Immune Response

Effector Mechanisms in Antibody-Mediated Responses Antibodies tag antigen do not directly destroy it
Coupled with another killing mechanism instead

Antibodies link tagged microbe to one or more effector (killing) mechanisms Fig. 18.15 V illustrates direct enhancement of phagocytosis by antibody Fig. 18.16 illustrates activation of the classical complement pathway Note that both effector mechanisms are non-specific. See also Table 18.6 V
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MAC lyses cell, C3B activates phagocytosis - Both nonspecific

Secondary Immune Response When challenged by same antigen, memory cells produce a rapid and amplified immune response

Cell-Mediated Immunity Defends against abnormal cells/transformed Cells transformed by viral infection or cancer Foreign cells (cause of transplant rejection) Fungi, protozoa (e.g., Giardia lamblia) Defense is carried out by Cytotoxic T cells Specific TC cell must first recognize Ag complexed with MHCI protein CD8 receptors T cells respond only to antigenic determinants displayed on surfaces of bodys own cells Infected cell processes and presents antigen to T C cell

Processing and Presentation of Viral Ag to Cytotoxic T cell Fig. 18.13V*** TC cells recognize Ag bound to MHC I proteins Presented by any nucleated cell Ag Recognition / Activation of Helper T Cells Fig. 18.11a V Helper T (TH) cells recognize Ag bound to MHC II proteins APCs (what are they?) Cell-Mediated Response to Virus-Infected Cells Fig. 18.18V Similar sequence for cancer cells Oncogenes code for proteins that act as antigens

Cytokines from Helper T cell required for clonal expansion

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Cytotoxic T cells can directly kill infected / transformed cells (Perforin- made by cytotoxic T cells; series of proteins inserted into target cell to blow it up, then goes finds another target cell- can blow up several) similar to MAC Cell-Mediated Response Activated TC cells roam tissues, and destroy other cells displaying processed antigen Perforin** Lymphotoxin (cytokine) Activate genes causing apoptosis (cell-suicide; programmed cell death) Memory TC cells are not activated Remain available to respond to next challenge by same Ag Can produce immediate, amplified Secondary Immune Response Central Role of Helper T cells The cytokines released by activated specific Helper T cells are required for forming a clone of activated B or Cytotoxic T cells

Without clonal expansion immune response stops at first (recognition) stage

TH cells required for most humoral as well as cell-mediated immunity

Cytokines include IL-2 and Gamma Interferon Roles: Stimulate T cell divisions and formation of memory cells Enhance nonspecific defenses e.g. macrophages Stimulate NK cells Activate B cells

Summary of Host Responses to Viruses Fighting a virus in the blood Systemic Responses to Infection or Injury (Fig. 18.20 V)
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Autoimmune Disease Myesthenia Gravis Antobodies to ACh receptors weak skeletal muscles

Rheumatoid Arthritis (-itis = inflammation) Antibodies to connective tissue of joints

Allergy Hypersensitivity Allergens can sensitize; mast cells, basophils Anaphylaxis (Later) Histocompatibility Problems Transfusion reactions (IN LAB) Rejection of tissue transplants Erythroblastosis fetalis What is Rhogam? HIV / AIDS- why Helper T cells are important Human Immunodeficiency Virus Acquired Immune Deficiency Syndrome Retrovirus destroys Helper T cells (CD4 cells) Anti-AIDS drugs include Reverse Transcriptase Inhibitors Protease Inhibitors