Innate Immunity and Inflammation:

Diapedesis (extravasation): movement of leukocytes out of the circulatory system and towards the site of tissue damage or infection
Innate immunity: immunity that is present at birth and lasts a person’s entire life
Adaptive Immunity: specialized immune cells and antibodies that attack and destroy foreign invaders and are able to prevent disease in the future
Acute-phase proteins: plasma proteins synthesized in the liver whose concentration increase (or decrease) by 25 % or more during inflammation
Acute-phase response: systemic reaction against inflammation, infection, or tissue injury
Adaptive immune response: carried out by white blood cells called lymphocytes
Complement: a system of plasma proteins that interacts with pathogens to mark them for destruction by phagocytes
Innate immune response: the first line of defense against invading pathogens
Opsonin: an antibody or other substance which binds to foreign microorganism or cells making them more susceptible to phagocytosis
Pyrogen: bacterial cell wall fragments
Toll-like receptor: important family of receptors that constitute the first line of defense system against microbes
Fever: important adaptive function in activating the immune system; increase body temperature leads to faster neutrophil migration, activation and proliferation of lymphocytes, production of cytokines including interferon and increased movement of lymphocytes
Concepts:
 Describe the cells associated with the innate response

 Describe diapedesis of white blood cells

 Understand the roles of cell adhesion molecules, selectins, integrins, and
chemokines in diapedesis

II. Mechanism of Diapedesis

• A. Rolling Adhesion

  • Interaction between leukocytes and endothelial cells.

  • Mediated by selectins (e.g., P-selectin, E-selectin).

• B. Activation

  • Chemokines released by damaged tissues activate leukocytes.

  • Changes in integrin affinity on leukocytes.

• C. Firm Adhesion

  • Integrins (e.g., LFA-1, Mac-1) bind tightly to ICAMs on endothelial cells.

• D. Transmigration

  • Leukocytes squeeze between endothelial cells (paracellular) or through the cells (transcellular).

  • Involves cytoskeletal rearrangement and membrane dynamics.

 Describe the barriers that prevent microbial infection of the skin

-skin, mucous membranes, endothelia and tight junctions
 Describe the respiratory tract barriers that prevent microbial infection

-first is the mucous covering the respiratory surface and the second is the various components present in the lining fluid (surfactants: reduces surface tension)
 Define Pathogen-Associated Molecular Patterns (PAMPs):

-molecular motiffs associated with pathogens such as bacteria and viruses; Toll-like receptors have the important job of recognizing PAMPs
 Define Toll-like receptors on leukocytes and describe their function

- recognize both invading pathogens and endogenous danger molecules released from dying cells and damaged tissues
 List 11 different Toll-like receptor ligands (NOT NECESSARY TO MEMORIZE)

TLR1 THROUGH TLR13
 Compare and contrast the roles of Toll-like receptors in innate and adaptive
immunologic responses

 List five acute-phase proteins synthesized by the liver and their function

Innate immune mechanisms or responses
 Inflammatory responses and innate immune mechanism:

-Inflammatory response: inflammation is caused in response to injury by bacteria, trauma, toxins, heat

-Innate immune mechanism: during inflammation, macrophages present antigens, undergo phagocytosis and modulate the immune response by producing cytokines and growth factors
 Complement functions: facilitate the uptake and destruction of pathogens by phagocytic cells
 Defense proteins: antibodies, lectins and antiviral proteins; they identify and bind to very specific foreign molecules
 Processes:
Phagocytosis:

Complement cascade (general) “OIL”:

 Diseases:
MBL deficiency: people with this condition have low levels of an immune system protein called mannose-bonding lectins; mannose-binding lectin facilitates opsonization by phagocytosis and initiates complement activation through the classic pathway

Leukocyte Adhesion deficiency: immunodeficiency disorder involving both B and T cells, characterized by the inability of leukocytes to migrate to site of infection to kill offending microbes

Video link for the picture above: https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.osmosis.org%2Fvideo%2FLeukocyte_adhesion_deficiency&psig=AOvVaw3uS5rSFt46J-3xfPM5YwNE&ust=1726582153438000&source=images&cd=vfe&opi=89978449&ved=0CBQQjhxqFwoTCIiNj4_Sx4gDFQAAAAAdAAAAABAE