Overview on Immunology and Introduction to Innate Immunity

Over view What are the main types of white blood cells? Name the two main types of immunity? What are the main distinctions between these two categories? What cells are involved in which aspects of the immune system?

Lymphocytes Many types; important in both humoral and cell-mediated immunity B-cells produce antibodies (APC cell) T- cells Cytotoxic T cells Helper T cells Memory cells

Lymphocytes Natural Killer cells Large granular lymphocytes (not B or T) Kills tumor cells Kills cells infected with certain viruses (intracellular pathogens)

Monocytes/Macrophage Phagocytosis and killing of microorganisms Activation of T cells and initiation of immune response Monocyte is a young macrophage in blood There are tissue-specific macrophages APC cells

Dendritic Cells Phagocytosis and killing of microorganisms Function as antigen presenting cells (APC) In the blood and tissues – mature and migrate to the lymph nodes

Neutrophil Granulocyte Polymorphonuclear Phagocytosis Cytoplasmic granules Polymorphonuclear Phagocytosis Short life span (hours) Very important at “clearing” bacterial infections Innate Immunity

Eosinophils Kills Ab-coated parasites through degranulation Involved in allergic inflammation A granulocyte Double Lobed nucleus Orange granules contain toxic compounds

Basophils Might be “blood Mast cells’ A cell-killing cells Blue granules contain toxic and inflammatory compounds Important in allergic reactions

Antigen-presenting cells (APC) Highly specialized Process antigen and display peptide fragments on cell surface Involved in T-cell activation Macrophages, dendritic cells and B-cells

Over view What are the main types of white blood cells? Name the two main types of immunity? What are the main distinctions between these two categories? What cells are involved in which aspects of the immune system?

Immune system divisions Innate immunity First line of defense Adaptive (acquired) immunity Takes time to develop Humoral immunity (antibody–mediated specific immunity) Cell-mediated immunity (The aspect of the adaptive immune response where antigen-specific T cell have a main role) Active immunity Passive or maternal immunity Injection of Immunoglobulin Absorption of maternal antibodies

Innate vs. adaptive immunity Innate immunity First line of defense (present in all individuals at all times) Immediate (0 – 4 hours) Non-specific Does not generate lasting protective immunity Adaptive immune response (late: > 96 hours) Is initiated if innate immune response is not adequate (> 4 days) Antigen-specific immunity Generates lasting protective immunity (e.g. Antibodies, memory T-cells)

Over view What are the main types of white blood cells? Name the two main types of immunity? What are the main distinctions between these two categories? What white blood cells are involved in which aspects of the immune system?

Immune system cells Adaptive immunity Lymphocyte Memory cells Innate immunity Granulocytes (i.e. neutrophils) Macrophages Dendritic cells Natural killer (NK) cells Adaptive immunity Lymphocyte B cells T cells Cytotoxic T cells (CTLs) Helper T cells (Th) Memory cells

Innate immune system The first line of defense: Penetration of the epithelial surface of the body by microorganism (e.g. bacteria) Engulfment of microorganism by macrophages, neutrophils, and dendritic cells Release of cytokines and chemokines Inflammation (Immunology animation: Janeway) http://www.blink.biz/immunoanimations/#

Killing by granulocytes Macrophages and neutrophils recognize pathogen by means of cell-surface receptors Example: mannose receptor, CD14 receptor, scavenger receptors, glucan receptor etc. Binding of MØ/neutrophils with pathogen leads to phagocytosis Bound pathogen is surrounded by phagocyte membrane Internalized (phagosome) Killing of pathogen (Phagolysosome*) Oxidative burst (synthesis of hydrogen peroxide (H2O2)or free oxygen radicals) Acidification Antimicrobial peptides (e.g. defensins) * Phagolysosome = lysosome +phagosome

Phagocytosis Mannose receptor Scavenger receptor LPS receptor (CD14) Lipid mediators Cytokines Mannose receptor Lysosome Phagosome Scavenger receptor LPS receptor (CD14) Bacteria binding to macrophage receptors initiate the release of cytokines and small lipid mediators of inflammation Phagolysosome The macrophage expresses receptors for many bacterial constituents Macrophages engulf and digest bacteria to which they bind

Phagocytosis (Immunology animation: Janeway) Immune response (IV) http://www.blink.biz/immunoanimations/# Immune response (IV) 9.1 - Phagocytosis

Humoral immune response V region; At binding Cell-surface immunoglobulin receptors (BCR) detect extracellular pathogens Once activated, secrete immunoglobulins as soluble antibodies Antibodies Variable region (2 identical antigen-binding sites) Constant region (determines how antibody disposes of the pathogen once it is bound) Fc region

Cell killing – NK cells NK cells do not require prior immunization or activation They attach to ‘target’ cells (ADCC) Cytotoxic granules are released onto surface of cell Effector proteins penetrate cell membrane and induce programmed cell death

Bacteria trigger macrophages to release cytokines and chemokines Inflammation Cytokines Chemokines Inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain Fluids Proteins Bacteria trigger macrophages to release cytokines and chemokines Vasodilation and increased vascular premeability cause redness, heat, and swelling

Cytokines Adaptive immune system Low molecular weight, soluble proteins that are produced in response to an antigen and function as chemical messengers for regulating the innate and adaptive immune system Innate immune system Macrophages and Dendritic cells Tumor necrosis factor-alpha (TNF-) Interleukin-1 (IL-1) Interleukin-12 (IL-12) Adaptive immune system T-lymphocytes Interleukin-2 (IL-2) Interleukin-4 (IL-4)