Concepts of Inflammation and the Immune Response

Local inflammation

Cells that contribute to the inflammatory response

Tissue damage Mast cells signal to other cells Mast cells signal to other cells Macrophages White blood cells

Cytokines are signaling molecules Released by cells of the immune system Released by cells of the immune system Coordinate the immune response Coordinate the immune response

Cytokines Signaling Autocrine Autocrine

Cytokines Signaling 2. Paracrine 2. Paracrine

Cytokines Signaling 3. Endocrine 3. Endocrine

Immunity Purpose of inflammation and immunity is to neutralize, eliminate, or destroy organisms that invade the internal environment. Purpose of inflammation and immunity is to neutralize, eliminate, or destroy organisms that invade the internal environment.(Continued)

Immunity (Continued) Immune system cells distinguish self from non-self proteins and cells, which include infected body cells, cancer cells, and organisms. This ability to recognize self versus non-self is necessary to prevent healthy body cells from being destroyed along with invaders and is known as self- tolerance. Immune system cells distinguish self from non-self proteins and cells, which include infected body cells, cancer cells, and organisms. This ability to recognize self versus non-self is necessary to prevent healthy body cells from being destroyed along with invaders and is known as self- tolerance.

Human Leukocyte Antigens Antigens are a normal part of the person and act as antigens if they enter another person’s immune system. Antigens are a normal part of the person and act as antigens if they enter another person’s immune system. These antigens specify the tissue type of a person. These antigens specify the tissue type of a person.

Inflammation Provides immediate protection against the effects of tissue injury and foreign proteins. The capability for inflammatory response is critical to health and well-being. Provides immediate protection against the effects of tissue injury and foreign proteins. The capability for inflammatory response is critical to health and well-being. Causes visible symptoms and can rid the body of harmful organisms. Tissue damage may result from excessive inflammatory response. Causes visible symptoms and can rid the body of harmful organisms. Tissue damage may result from excessive inflammatory response.

CAUSES OF INFLAMMATION (ACUTE OR CHRONIC) 1. Microbial infections. 1. Microbial infections. 2. Hypersensitivity immune reactions. 2. Hypersensitivity immune reactions. 3. Chemical substances. 3. Chemical substances. 4. Physical agents. 4. Physical agents. 5. Necrosis. 5. Necrosis.

Infection Infection is usually accompanied by inflammation; however, inflammation can occur without invasion by organisms. Infection is usually accompanied by inflammation; however, inflammation can occur without invasion by organisms. Inflammation does not always mean that an infection is present. Inflammation does not always mean that an infection is present.

Sequence of Inflammatory Responses Warmth Warmth Redness Redness Swelling Swelling Pain Pain Decreased function Decreased function

Sequence of Inflammatory Responses Stage I (vascular): change in blood vessels Stage I (vascular): change in blood vessels –Phase I: constriction –Phase II: hyperemia and edema Stage II (cellular exudate): neutrophilia, pus Stage II (cellular exudate): neutrophilia, pus Stage III (tissue repair and replacement) Stage III (tissue repair and replacement)

Processes closely linked to the inflammatatory response: Immune reactions Immune reactions Wound healing Wound healing

1) Immune reactions: Cell mediated immunity - T-lymphocytes Humoral immunity - B-lymphocytes Concept of antigen presentation (p.173) - Langerhans cells (not to be confused with Langhans giant cells) Cytokines (basic principles – p. 169) - Act as messengers between inflammatory cells, coordinating the inflammatory response.

2) Wound healing Formation of granulation tissue and the process of organisation). (Organisation  formation of scar tissue) Role of growth factors - only basic principles

Vascular endothelial growth factor (VEGF)  stimulates proliferation of endothelial cells  granulation tissue. Fibroblast growth factor  stimulates fibroblasts to produce collagen  fibrosis (scarring).

Antibody Classification All antibodies are immunoglobulins, also called gamma globulins. All antibodies are immunoglobulins, also called gamma globulins. –Globulin is a protein in a globular shape. –Globular proteins provide immunity. –Resulting term is immunoglobulin. Five antibody types are classified by size, timing, and association. Five antibody types are classified by size, timing, and association.

Acquiring Antibody-Mediated Immunity Innate-native immunity—natural immunity Innate-native immunity—natural immunity Adaptive immunity Adaptive immunity Active immunity Active immunity Natural active immunity Natural active immunity Artificial active immunity Artificial active immunity Passive immunity Passive immunity

Cell-Mediated Immunity Helps protect the body by differentiating self from non- self cells; non-self cells most easily recognized by cell- mediated immunity are cancer cells and those self cells infected by organisms that live within host cells. Helps protect the body by differentiating self from non- self cells; non-self cells most easily recognized by cell- mediated immunity are cancer cells and those self cells infected by organisms that live within host cells. Important in preventing the development of cancer and metastasis after exposure to carcinogens. Important in preventing the development of cancer and metastasis after exposure to carcinogens.

Helper/Inducer T-cells Most correct name is CD4+ (cluster of differentiation 4) Most correct name is CD4+ (cluster of differentiation 4) Also called OKT4 positive or Leu-3 positive because of specific antigens on the membrane surface Also called OKT4 positive or Leu-3 positive because of specific antigens on the membrane surface Helper/inducer T-cells easily recognize self cells versus non-self cells. Helper/inducer T-cells easily recognize self cells versus non-self cells. (Continued) (Continued)

Helper/Inducer T-cells (Continued) Helper/inducer T-cells act as organizers in “calling in arms“ of various squads of WBCs involved in inflammatory, antibody, and cellular defensive actions to destroy or neutralize antigens. Helper/inducer T-cells act as organizers in “calling in arms“ of various squads of WBCs involved in inflammatory, antibody, and cellular defensive actions to destroy or neutralize antigens.

Transplant Rejection Hyperacute graft rejection Hyperacute graft rejection Acute graft rejection Acute graft rejection Chronic rejection Chronic rejection Treatment of transplant rejection Treatment of transplant rejection Maintenance Maintenance Rescue therapy Rescue therapy

TWO BASIC TYPES OF IMMUNE RESPONSE: - Humoral - Humoral - Cell-mediated - Cell-mediated Humoral = production of antibodies by plasma cells. Humoral = production of antibodies by plasma cells. Cell-mediated immunity = Interaction between T-lymphocytes and macrophages. Cell-mediated immunity = Interaction between T-lymphocytes and macrophages.

Two subpopulations of T-lymphocytes: T-helper cells: “Help” B-cells to differentiate into plasma cells. T-suppressor cells: Regulate (suppress) antibody production. (T-cytotoxic cells = subtype of T- suppressor cells  can directly kill “foreign” cells e.g. tumour cells, virally- infected cells etc.)

T-cells have receptors on their cell surfaces that may bind to specific antigens (e.g. microbial antigens) T-cells can only bind to antigens which have already been processed by macrophages ( = antigen-presenting function of macrophages

Interaction between T-cells and macrophages is regulated by cytokines.

Under certain circumstances, or in certain specific diseases, this interaction of T-cells and macrophages leads to the formation of granulomas (“granulomatous chronic inflammation”). Granulomas are small collections of epithelioid cells (transformed histiocytes). (Histiocytes are tissue macrophages).