HNSC 3162 Biological Concepts in Public Health (Cai)

Learning Objectives:

By the end of this section, you will be able to:

• List and describe various defense components of the innate nonspecific host defenses.

Content

Despite relatively constant exposure to pathogenic microbes in the environment, humans do not generally suffer from constant infection or disease. Under most circumstances, the body is able to defend itself from the threat of infection thanks to a complex immune system designed to repel, kill, and expel disease-causing invaders. Immunity as a whole can be described as two interrelated parts: nonspecific innate immunity and specific adaptive host defenses.

The nonspecific innate immune response provides a first line of defense that can often prevent infections from gaining a solid foothold in the body. These defenses are described as nonspecific because they do not target any specific pathogen; rather, they defend against a wide range of potential pathogens. They are called innate because they are built-in mechanisms of the human organism. Unlike the specific adaptive defenses, they are not acquired over time and they have no “memory” (they do not improve after repeated exposures to specific pathogens).

Physical Defenses

• The physical defenses of innate immunity include physical barriers, mechanical actions that remove microbes and debris, and the microbiome, which competes with and inhibits the growth of pathogens.
• The skin, mucous membranes, and endothelia throughout the body serve as physical barriers that prevent microbes from reaching potential sites of infection. Tight cell junctions in these tissues prevent microbes from passing through.
• Microbes trapped in dead skin cells or mucus are removed from the body by mechanical actions such as shedding of skin cells, mucociliary sweeping, coughing, peristalsis, and flushing of bodily fluids (e.g., urination, tears)
• The resident microbiota provide a physical defense by occupying available cellular binding sites and competing with pathogens for available nutrients.

Chemical Defenses

• Numerous chemical mediators produced endogenously and exogenously exhibit nonspecific antimicrobial functions.
• Many chemical mediators are found in body fluids such as sebum, saliva, mucus, gastric and intestinal fluids, urine, tears, cerumen, and vaginal secretions.
• Examples of chemical mediators include the complement system, which involves numerous precursor proteins that circulate in plasma, and the cytokines, which play a key role in the inflammatory response.

Cellular Defenses

• The formed elements of the blood include red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Of these, leukocytes are primarily involved in the immune response. Neutrophils that combat bacterial infection, natural killer (NK) cells that recognize and kill abnormal or infected cells, macrophages and dendritic cells are all examples of white blood cells.
• All formed elements originate in the bone marrow as stem cells (HSCs) that differentiate through hematopoiesis.

Pathogen recognition and Phagocytosis:

• Phagocytes are cells that recognize pathogens and destroy them through phagocytosis, which involves engulfing the pathogen. Macrophages and neutrophils are both capable of phagocytosis.
• Recognition often takes place by the use of phagocyte receptors that bind molecules commonly found on pathogens.

Inflammation and fever

• Inflammation results from the collective response of chemical mediators and cellular defenses to an injury or infection.
• Acute inflammation is short lived and localized to the site of injury or infection. Chronic inflammation occurs when the inflammatory response is unsuccessful, and may result in the formation of granulomas (e.g., with tuberculosis) and scarring (e.g., with hepatitis C viral infections and liver cirrhosis).
• Fever is a system-wide sign of inflammation that raises the body temperature and stimulates the immune response.
• Both inflammation and fever can be harmful if the inflammatory response is too severe.

Knowledge Check

Learning Objectives:

By the end of this section, you will be able to:

• explain two important characteristics of adaptive immunity.
• describe primary and secondary response to a pathogen.
• summarize the functions of two types of cells in adaptive immunity.
• define antigen, antibodies and major histocompatibility complex (MHC).
• describe 4 ways to achieve adaptive immunity.
• explain herd immunity.

Content

Adaptive immunity is defined by two important characteristics: specificity and memory. Specificity refers to the adaptive immune system’s ability to target specific pathogens, and memory refers to its ability to quickly respond to pathogens to which it has previously been exposed. For example, when an individual recovers from chickenpox, the body develops a memory of the infection that will specifically protect it from the causative agent, the varicella-zoster virus, if it is exposed to the virus again later.

Specificity and memory are achieved by essentially programming certain cells involved in the immune response to respond rapidly to subsequent exposures of the pathogen. This programming occurs as a result of the first exposure to a pathogen or vaccine, which triggers a primary response. Subsequent exposures result in a secondary response that is faster and stronger as a result of the body’s memory of the first exposure (Figure 18.2). This secondary response, however, is specific to the pathogen in question. For example, exposure to one virus (e.g., varicella-zoster virus) will not provide protection against other viral diseases (e.g., measles, mumps, or polio).

Adaptive immunity is a dual system involving humoral immunity (antibodies produced by B cells) and cellular immunity (T cells directed against intracellular pathogens). Although B cells and T cells arise from a common hematopoietic stem cell differentiation pathway, their sites of maturation and their roles in adaptive immunity are very different. B cells are produced in the bone marrow, where the initial stages of maturation occur. Immature T lymphocytes are produced in the red bone marrow and travel to the thymus for maturation.

Terminologies in Adaptive Immunity:

• Antigens, also called immunogens, are molecules that activate adaptive immunity. A single antigen possesses smaller epitopes, each capable of inducing a specific adaptive immune response.
• Antibodies (immunoglobulins) are Y-shaped glycoproteins. The five classes of antibody are IgM, IgG, IgA, IgE, and IgD, each differing in size, arrangement, location within the body, and function. The five primary functions of antibodies are neutralization, opsonization, agglutination, complement activation, and antibody-dependent cell-mediated cytotoxicity (ADCC).
• Major histocompatibility complex (MHC) is a collection of genes coding for glycoprotein molecules expressed on the surface of all nucleated cells. MHC molecules are expressed on all nucleated cells and are essential for the presentation of normal “self” antigens. They play an important role in marking the infected cell for destruction and for the activation of T cells.

Antibody:

A protein produced by the immune system in response to a foreign substance such as a virus or bacterium. Antibodies protect the body from disease by binding to these pathogens and neutralizing or destroying them.

Vaccination:

• Adaptive immunity can be divided into four distinct classifications: natural active immunity, natural passive immunity, artificial passive immunity, and artificial active immunity (Figure 18.24).
• Artificial active immunity is the foundation for vaccination and vaccine development. Vaccination programs not only confer artificial immunity on individuals, but also foster herd immunity in populations.
• For any given disease, an individual may be considered immune or susceptible depending on his or her ability to mount an effective immune response upon exposure. Thus, any given population is likely to have some individuals who are immune and other individuals who are susceptible. If a population has very few susceptible individuals, even those susceptible individuals will be protected by a phenomenon called herd immunity. Herd immunity has nothing to do with an individual’s ability to mount an effective immune response; rather, it occurs because there are too few susceptible individuals in a population for the disease to spread effectively.

Knowledge Check