PBS 803 Class 3 The Innate Immune System

PBS 803 Class 3: The Innate Immune System Part I Parham – cover page Chapter 2 Goblet cells –source of mucus that helps protect epithelial surfaces from invading microbes

Microbial routes of entry Fig. from Murray’s Medical Microbiology

Majority of microbes do not cause infection due to barriers, innate immunity and adaptive immunity Doan Fig. 1. 2

Innate immunity: characterized by mechanical, chemical and microbiological barriers Parham Fig. 2. 1

Strong barriers (blue) protect more vulnerable mucosal tissues (red) Parham Fig. 1. 5

Epithelial Cells and Innate Immunity Abbas Fig. 2. 6

Elements of the Immune System and their Roles in Defense Parham Fig. 1. 8

Importance of both innate and adaptive immunity Parham Fig. 1. 10

Specificity and receptors of innate and adaptive immunity Abbas Fig. 2. 1

Cellular locations of innate immunity receptors Abbas Fig. 2. 2

Toll Like Receptors Abbas Fig. 2. 3

Toll Like Receptor Signaling Abbas Fig. 2. 4

All non-immune cells lining mucosal layers can create IFN and IFN in response to viral infection Type I interferons / will help prevent viral infections of cell PLUS neighboring cells Maybe a way to remember / vs. IFNγ: Old supermarket Alpha Beta, Everyone needs to go to the supermarket Therefore non-immune cells can produce and respond to IFN / “Tell a friend” was their slogan, Virally infected epithelial cell will worn neighbors of viral infection

Inflammasome produce active pro-inflammatory cytokines (IL-1) Inflammasome is a therapeutic target due to its involvement in inflammatory disorders in addition to potentially other diseases (e. g. neurodegenerative diseases) Abbas Fig. 2. 5

Leukocytes of the Immune System Doan Fig. 4. 1

Stem cells generate a continuous supply of terminally differentiated cells stem cells can continue to divide for lifetime of organism Adult stem cells are specialized, will only produce certain types of differentiated cells Figure 20 -35 Essential Cell Biology (© Garland Science 2010)

Stem cells can remain stem cells after division or differentiate into progenitor/precursor cells Progenitor (precursor) cells can subsequently differentiate into different leukocytes Figure 20 -35 Essential Cell Biology (© Garland Science 2010)

Hematopoietic stem cells responsible for producing all types of blood cell types Radiation and/or chemotherapy lead to: anemia due to ↓ in # of erythrocytes ↑ risk of infections due to ↓ in # of leukocytes -Platelets and RBC’s are not leukocytes leukocyte = nucleated white blood cell Figure 20 -39, 20 -38 Essential Cell Biology (© Garland Science 2010)

HEMATOPOIESIS Majority of steps shown occur in bone marrow Monocyte Macrophage differentiation occurs in tissues where does conversion of naïve effector lymphocyte typically occur? Parham Fig. 1. 13

Cells of the hematopoietic system Parham Fig. 1. 11

Cells of the hematopoietic system Langerhans cells- specialized dendritic cells found in the skin Parham Fig. 1. 11

Clonal selection of T and B cell lymphocytes Parham Fig. 1. 9

Cells of the hematopoietic system (continued) Parham Fig. 1. 11

Neutrophils -also called PMN’s (polymorphonuclear leukocytes) PMN term describes distinctive nuclear morphology -neutrophil levels rise in response to inflammatory signals -neutrophilia –high levels of neutrophils in blood Abbas Fig. 2. 7 A

Neutrophils are most prominent leukocytes in blood Neutropenia (low neutrophil count) can occur as a result of chemotherapy, radiation and as a side effect of certain drugs Parham Fig. 1. 14

Neutrophils are stored in the bone marrow and move in large numbers to sites of infection, where they act and then die Parham Fig. 1. 15

Monocytes are the circulating precursors to macrophages -macrophages are largest leukocytes in tissues able to phagocytose bacteria, dead neutrophils, debris, diseased or dead human cells Abbas Fig. 2. 8

Some tissue-specific macrophages derived from hematopoietic stem cells of fetus (early-stage fetus doesn’t have bone marrow) i. e. ; Kuppfer cells are in liver, Microglial cells in brain Abbas Fig. 2. 8

Activation and functions of macrophages Abbas Fig. 2. 9

NK cells kill infected host cells Abbas Fig. 2. 10 A

NK cells and Macrophages stimulate each other in response to infection -example of a positive feedback loop Abbas Fig. 2. 10 B

Cells of the hematopoietic system (continued) Parham Fig. 1. 11

Eosinophils, Basophils and Mast Cells granular cells that are designed to fight larger parasites, are also implicated in allergies. Flaherty Figs. 1. 2 A, 1. 3 B and 1. 4