The Concept of Immunity Immunity: Latin immunis, exempt Susceptibility: Lack of resistance to a disease, also known as Vulnerability Innate immunity: Inborn Adaptive immunity: Acquired, resistance to a specific pathogen

An Overview of the Body’s Defenses ANIMATION Host Defenses: The Big Picture Figure 16.1

First Line of Defense: I. Skin & Mucous Membranes Keratin, a protective protein Mucous membranes Hairs Cilia Tears, Saliva, Urine, Vaginal secretions Lysozyme

Ciliary Escalator Figure 24.7

II. Normal Microbiota Normal microbiota compete with pathogens for nutrients Keep pH unfavorable for disease microbes

Second Line of Defense I. Blood components Red Blood Cells Transport O2 and CO2 White Blood Cells: Neutrophils Phagocytosis Basophiles Histamine Eosinophils Kill with toxin

Macrophage Phagocytosis Dendritic cells Natural killer cells Destroy target cells by apoptosis T cells Cell-mediated immunity B cells Produce antibodies Platelets Blood clotting

Differential White Cell Count Percentage of each type of white cell in a sample of 100 white blood cells Early and late in infection: Neutrophil then Macrophage Neutrophils 60–70% Basophils 0.5–1% Eosinophils 2–4% Monocytes 3–8% Lymphocytes 20–25%

II. Lymphatic System Tissue + Fluid Figure 16.5a

III. Phagocytosis Neutrophils Macrophage Presents Ag Secret cytokines (lymphokines + interleukins) Figure 16.6

IV. Inflammation Releasing histamine Vasodilation (histamine, kinins, prostaglandins, and leukotrienes) Redness Swelling Pain Heat Tissue repair and wall-off

Fever Abnormally high body temperature Body’s defensive mechanism Increase enzyme activity and cytokine activity Increase blood flow Some bacteria can not survive at higher temperature Disadvantage: Tachycardia Acidosis Dehydration 44–46°C fatal

V. Antimicrobial Substances Complements C3a + C5a cause inflammation C5b + C6 + C7 + C8 + C9 cause cell lysis

V. Antimicrobial Substances Interferons a- and b- interferon: Virus infected cells to produce AVPs g- interferon: Neutrophils and macrophages Limitations: Side effects Short lived Only prevents, not stop viral synthesis No effect on a number of cancers Ion-binding Proteins AMPs: Natural antibiotics

Types of Adaptive Immunity Naturally acquired active immunity Resulting from infection Naturally acquired passive immunity Transplacental or via colostrum Artificially acquired active immunity Injection of Ag (vaccination) Artificially acquired passive immunity Injection of Ab

Dual Nature of Adaptive Immunity Figure 17.8

Dual Nature of Adaptive Immunity Humoral immunity: B-cells Ag-Ab Cellular immunity T-cells Cytokines ANIMATION Humoral Immunity: Overview

I. Antigens It has to be large Ag determinants = epitopes Hapten and Carrier

Antigens Figure 17.1

Haptens Figure 17.2

II. Antibodies They are immunoglobulins (Ig) The antigen-binding sites recognize epitope and determine valence Constant Region / Variable Region Heavy Chain / Light Chain

Antibodies Figure 17.3a,b

IgG Antibodies Monomer Most common and abundant (80%) Fix complement Cross placenta Enhance phagocytosis; neutralize toxins and viruses; protects fetus and newborn Half-life = 23 days

IgM Antibodies Pentamer Agglutination Fix complement Agglutinates microbes; first Ab produced in response to infection Half-life = 5 days

IgA Antibodies Dimer 10–15% of serum Abs In secretions Mucosal protection Half-life = 6 days

IgD Antibodies Monomer In blood, in lymph, and on B cells On B cells, initiate immune response Half-life = 3 days

IgE Antibodies Monomer Allergic reactions; lysis of parasitic worms Half-life = 2 days

III. B Cells Diversity Self – non-self discrimination Memory

1st exposure to Ag First Clones 2nd exposure to Ag

T-independent Activation of B Cells Figure 17.6

T-dependent Activation of B Cells Figure 17.4

Ag Response Ig Memory T-dependent Proteins Strong IgG Yes T-independent Polymers (Lipid or Polysaccharides) Weak IgM No

Clonal Selection ANIMATION Humoral Immunity: Clonal Selection and Expansion Figure 17.5

Clonal deletion: eliminates harmful B cells

Immune Responses to an Antigen Figure 17.16

Immune Responses to an Antigen

Monoclonal Ab Production

The Results of Ag-Ab Binding Destroy Made unavailable Figure 17.7

IV. Cellular Immunity T cells mature in the thymus Thymic selection eliminates many immature T cells T cells respond to Ag by T-cell receptors (TCRs) T cells require antigen-presenting cells (APCs)

T Helper Cells CD4+ or TH cells (When activated) Produce cytokines Help in B cell and Tc cell activation

T Cytotoxic Cells CD8+ or TC cells Target cells are self carrying endogenous antigens Activated into cytotoxic T lymphocytes (CTLs) CTL causes apoptosis

T Cytotoxic Cells Figure 17.11

T Regulatory Cells Treg cells Suppress T cells against self CD4 and CD25 on surface Suppress T cells against self

Antigen-Presenting Cells Digest antigen Ag fragments on APC surface with MHC B cells Dendritic cells Activated macrophages ANIMATION Antigen Processing and Presentation: MHC

A Dendritic Cell Figure 17.13

Activated Macrophages Figure 17.14

Natural Killer (NK) Cells Granular leukocytes destroy cells that don’t express MHC I Kill virus-infected and tumor cells Attack parasites

Cells Communicate via Cytokines Representative Activity Interleukin-1 (IL-1) Stimulates TH cells in presence of antigens; attracts phagocytes Interleukin-2 (IL-2) Proliferation of antigen-stimulated CD4+ T helper cells, proliferation and differentiation of B cells; activation of CD8+ T cells and NK cells Interleukin-12 (IL-12) Inhibits humoral immunity; activates TH1 cellular immunity Cytokine Representative Activity Lymphokines Induce the migration of leukocytes TNF-α Promotes inflammation Hematopoietic cytokines Influence differentiation of blood stem cells IFN- and IFN- Response to viral infection; interfere with protein synthesis IFN- Stimulates macrophage activity

Immunological Disorders Hypersensitivity Type I: Immediate or anaphylactic Type II: Cytotoxic Type III: Complex Type IV: Delayed or Cell-mediated Autoimmune Immunodeficiency Primary: Genetic, developmental defects Secondary: Due to infection, cancer, malnutrition / stress

Type I Hypersensitivity (Anaphylactic) IgE Histamine

Type II Cytotoxic ABO blood types Hemolytic disease of the newborn:

Hemolytic Disease of the Newborn

Type III: Immune Complex Serum Sickness: Arthus Reaction:

Type IV: Delayed (Cell-mediated) Contact dermatitis: Poison ivy Tuberculin skin test Feature: Always localized

Type I Type II Type III Type IV IgE IgG, IgM T cells Therapy Steroids Main Mediator IgE IgG, IgM T cells Therapy Desensitization, antihistamines , steroids, epinephrine Steroids

Autoimmune Disease Rhumatoids Examples

Transplantation Issues Rejection Tolerance Immunosuppression

Immunodeficiency Disorders Primary Agammaglobulinemia: No Ig DiGeorge syndrome: Thymus undeveloped, no T cell Severe combined immunodeficiency (SCID): Defect in IL12 gene Secondary AIDS Leukemia

Precipitation Tests Precipitation Immunodiffusion

Agglutination Tests Agglutination Hemagglutination

Complement Fixation Ab/Ag complex competition

Immunological Tests (cont.) Neutralization Immuno- fluorescence

ELISA Tests

Western Blots Protein profiling