The Concept of Immunity Susceptibility: Lack of resistance to a disease Immunity: Ability to ward off disease Innate immunity: Defenses against any pathogen Adaptive immunity: Immunity, resistance to a specific pathogen

An Overview of the Body’s Defenses

The Concept of Immunity Host Toll-like receptors (TLRs) attach to Pathogen-associated molecular patterns (PAMPs) TLRs induce cytokines that regulate the intensity and duration of immune responses

Physical Factors Skin Epidermis consists of tightly packed cells with Keratin, a protective protein Figure 16.2

Physical Factors Mucous membranes Mucus: Traps microbes Ciliary escalator: Microbes trapped in mucus are transported away from the lungs

Normal Microbiota and Innate Immunity Microbial antagonism/competitive exclusion: Normal microbiota compete with pathogens or alter the environment Commensal microbiota: One organism (microbe) benefits and the other (host) is unharmed May be opportunistic pathogens

Formed Elements in Blood Red Blood Cells Transport O2 and CO2 White Blood Cells: Neutrophils Phagocytosis Basophiles Histamine Eosinophils Kill parasites

Formed Elements in Blood Monocytes Phagocytosis Dendritic cells Natural killer cells Destroy target cells

Formed Elements in Blood 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 Neutrophils 60–70% Basophils 0.5–1% Eosinophils 2–4% Monocytes 3–8% Lymphocytes 20–25%

Components of Lymphatic System Figure 16.5a

Phagocytosis Phago: From Greek, meaning eat Cyte: From Greek, meaning cell Ingestion of microbes or particles by a cell, performed by phagocytes Figure 16.6

Phagocytosis Neutrophils Fixed macrophages Wandering macrophages

Phagocytosis Figure 16.7

Microbial Evasion of Phagocytosis Inhibit adherence: M protein, capsules Streptococcus pyogenes, S. pneumoniae Kill phagocytes: Leukocidins Staphylococcus aureus Lyse phagocytes: Membrane attack complex Listeria monocytogenes Escape phagosome Shigella, Rickettsia Prevent phagosome-lysosome fusion HIV, Mycobacterium tuberculosis Survive in phagolysosome Coxiella burnettii

Inflammation Acute-phase proteins activated (complement, cytokine, and kinins) Vasodilation (histamine, kinins, prostaglandins, and leukotrienes) Redness Swelling (edema) Pain Heat

Chemicals Released by Damaged Cells Histamine Vasodilation, increased permeability of blood vessels Kinins Prostaglandins Intensity histamine and kinin effect Leukotrienes Increased permeability of blood vessels, phagocytic attachment

The Process of Inflammation Figure 16.8a, b

Phagocyte Migration and Phagocytosis [Insert Animation Inflammation: Overview, Steps.]

Tissue Repair Figure 16.8d

Fever Abnormally high body temperature Hypothalamus normally set at 37°C Gram-negative endotoxin cause phagocytes to release interleukin–1 (IL–1) Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature Body increases rate of metabolism and shivering which raise temperature Vasodilation and sweating: Body temperature falls (crisis)

Fever Advantages Disadvantages Increases transferrins Tachycardia Increases IL–1 activity Produces Interferon Disadvantages Tachycardia Acidosis Dehydration 44–46°C fatal

The Complement System Serum proteins activated in a cascade Activated by Antigen-antibody reaction Proteins C3, B, D, P and a pathogen

The Complement System C3b causes opsonization C3a + C5a cause inflammation C5b + C6 + C7 + C8 + C9 cause cell lysis

The Complement System Figure 16.9

Effects of Complement Activation Opsonization or immune adherence: Enhanced phagocytosis Membrane attack complex: Cytolysis Attract phagocytes Figure 16.10

Some Bacteria Evade Complement Capsules prevent C activation Surface lipid-carbohydrates prevent membrane attack complex (MAC) formation Enzymatic digestion of C5a

Interferons (IFNs) IFN- and IFN-: Cause cells to produce antiviral proteins that inhibit viral replication Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria

Antiviral Actions of Interferons (IFNs) Figure 16.15

Innate Immunity Transferrins Antimicrobial peptides Bind serum iron Lyse bacterial cells

Immunity Innate immunity: Defenses against any pathogen Adaptive immunity: Induced resistance to a specific pathogen

Dual Nature of Adaptive Immunity Figure 17.8

Dual Nature of Adaptive Immunity T and B cells develop from stem cells in red bone marrow Humoral immunity B cells mature in the bone marrow Chickens: Bursa of Fabricius Due to antibodies

Dual Nature of Adaptive Immunity T and B cells develop from stem cells in red bone marrow Cellular immunity Due to T cells T cells mature in the thymus

The Nature of Antigens Antigen (Ag): A substance that causes the body to produce specific antibodies or sensitized T cells Antibodies (Ab) interact with epitopes or antigenic determinants Hapten: Antigen is combined with carrier molecules

Antigens Figure 17.1

The Nature of Antibodies Globular proteins called immunoglobulins The number of antigen-binding sites determines valence

IgG Antibodies Monomer 80% of serum Abs Fix complement In blood, lymph, and intestine Cross placenta Enhance phagocytosis; neutralize toxins and viruses; protects fetus and newborn Half-life = 23 days

IgM Antibodies Pentamer 5–10% of serum Abs Fix complement In blood, in lymph, and on B cells 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 0.2% of serum Abs In blood, in lymph, and on B cells On B cells, initiate immune response Half-life = 3 days

IgE Antibodies Monomer 0.002% of serum Abs On mast cells, on basophils, and in blood Allergic reactions; lysis of parasitic worms Half-life = 2 days

Activation of B Cells Major histocompatibility complex (MHC) expressed on mammalian cells T-dependent antigens Ag presented with (self) MHC to TH cell TH cell produces cytokines that activate the B cell T-independent antigens Stimulate the B cell to make Abs

Activation of B Cells Figure 17.4

Clonal Selection Figure 17.5

Activation of B Cells B cells differentiate into Antibody-producing plasma cells Memory cells Clonal deletion eliminates harmful B cells

The Results of Ag-Ab Binding Figure 17.7

T Cells and 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) Pathogens entering the gastrointestinal or respiratory tracts pass through M (microfold) cells over Peyer’s patches, which contain APCs

T Helper Cells CD4+ or TH cells TCRs recognize Ags and MHC II on APC TLRs are a costimulatory signal on APC and TH TH cells produce cytokines and differentiate into TH1 TH2 Memory cells

T Helper Cells TH1 produces IFN-gwhich activates cells related to cell-mediated immunity, macrophages, and Abs TH2 activate eosinophils and B cells to produce IgE

Activation of CD4+ T Helper Cells Figure 17.10

T Cytotoxic Cells CD8+ or TC cells Target cells are self carrying endogenous antigens Activated into cytotoxic T lymphocytes (CTLs) CTLs recognize Ag + MHC I Induce apoptosis in target cell CTL releases perforin and granzymes

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

Immunological Memory Antibody titer is the amount of Ab in serum Primary response occurs after initial contact with Ag Secondary (memory or anamnestic) response occurs after second exposure

Immune Responses to an Antigen Figure 17.16

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