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Questions and Answers
What is the fluid in the tissue called?
What is the fluid in the tissue called?
lymph
Where do lymphocytes perform surveillance activities?
Where do lymphocytes perform surveillance activities?
Lymph nodes are primary organs responsible for the education of lymphocytes.
Lymph nodes are primary organs responsible for the education of lymphocytes.
False
Neutrophils are highly adherent, motile, and __________ leukocytes.
Neutrophils are highly adherent, motile, and __________ leukocytes.
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What is the surface immunoglobulin on a B-cell antigen receptor called?
What is the surface immunoglobulin on a B-cell antigen receptor called?
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T-cell receptor (TCR) is similar in structure to immunoglobulins.
T-cell receptor (TCR) is similar in structure to immunoglobulins.
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What are the cells that actively secrete antibodies known as?
What are the cells that actively secrete antibodies known as?
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The cluster of differentiation (CD) designation refers to proteins found on the surface of _____.
The cluster of differentiation (CD) designation refers to proteins found on the surface of _____.
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Match the following terms to their correct description:
Match the following terms to their correct description:
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What is the term for coating the organism with antibodies?
What is the term for coating the organism with antibodies?
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What is the process referred to as targeted engulfment?
What is the process referred to as targeted engulfment?
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What are the three pathways that can initiate complement activation?
What are the three pathways that can initiate complement activation?
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Match the following terms to their definitions:
Match the following terms to their definitions:
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Which two types of chains comprise the Fab2 portion of an antibody?
Which two types of chains comprise the Fab2 portion of an antibody?
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Approximately 60% of human antibodies utilize the Lambda light chain.
Approximately 60% of human antibodies utilize the Lambda light chain.
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What specific properties do the constant regions of antibodies confer?
What specific properties do the constant regions of antibodies confer?
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The variable domain, responsible for antigen binding, is comprised of the light-chain and heavy-chain heterodimers, each containing three unique regions called ______, making up the complementarity-determining region (CDR).
The variable domain, responsible for antigen binding, is comprised of the light-chain and heavy-chain heterodimers, each containing three unique regions called ______, making up the complementarity-determining region (CDR).
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Match the antibody isotype with its heavy-chain designation:
Match the antibody isotype with its heavy-chain designation:
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Which cells are attracted to the site of infection by complement components and released chemokines?
Which cells are attracted to the site of infection by complement components and released chemokines?
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Monoclonal antibodies are derived from a clone of antibody producing cells with single specificity.
Monoclonal antibodies are derived from a clone of antibody producing cells with single specificity.
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What is one drawback of polyclonal antibodies?
What is one drawback of polyclonal antibodies?
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Antibodies are composed of two heavy chains and two light chains, each made up of ______ (V) and constant (C) region domains that have similar 3-dimensional structures. The V regions make up the antigen binding site, while the C regions are responsible for the biologic activity of the antibody.
Antibodies are composed of two heavy chains and two light chains, each made up of ______ (V) and constant (C) region domains that have similar 3-dimensional structures. The V regions make up the antigen binding site, while the C regions are responsible for the biologic activity of the antibody.
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What is the purpose of humanizing antibodies?
What is the purpose of humanizing antibodies?
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Give an example of a humanized antibody and mention one of its medical uses.
Give an example of a humanized antibody and mention one of its medical uses.
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To isolate antibodies from serum or tissue culture media, one can take advantage of __________ proteins which bind antibodies with high specificity.
To isolate antibodies from serum or tissue culture media, one can take advantage of __________ proteins which bind antibodies with high specificity.
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Match the following antibody modifications with their uses:
Match the following antibody modifications with their uses:
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What is the chief function of the immune system?
What is the chief function of the immune system?
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The innate immune system components exist from birth.
The innate immune system components exist from birth.
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What is the term used for any substance or physical structure that can be recognized by the immune system?
What is the term used for any substance or physical structure that can be recognized by the immune system?
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______ immunity involves B lymphocytes that synthesize and secrete antibodies.
______ immunity involves B lymphocytes that synthesize and secrete antibodies.
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Match the following immune system elements with their corresponding functions:
Match the following immune system elements with their corresponding functions:
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Study Notes
The Immune System: An Overview
- The immune system provides constant surveillance of the human body, maintaining a balanced state of health by effectively eliminating infectious agents and controlling malignancies.
- The immune system has evolved to interact with the environment to protect against harmful invaders, while also tolerating the naturally occurring microbiome.
- The chief function of the immune system is to discriminate between self and non-self.
Innate and Adaptive Immunity
- The immune system is divided into two major functional categories: innate and adaptive immunity.
- Innate immunity provides the first line of defense against infectious diseases, with mechanisms that exist from birth and include physical and biochemical barriers.
- Innate immune components are particularly powerful at limiting infections, but once an infection is established, adaptive immunity is required to combat the specific organism.
- Adaptive immunity is responsible for specific recognition of foreign antigenic substances, with lymphocytes recognizing unique shapes associated with foreign antigens.
Key Elements of Innate and Acquired Immune Responses
- Innate immunity:
- Rapid response (minutes to hours)
- Polymorphonuclear leukocytes and phagocytes
- Preformed effectors with limited variability
- Pattern recognition molecules
- Soluble activators
- Proinflammatory mediators
- Nonspecific
- No memory, no increase in response to secondary exposure
- Adaptive immunity:
- Slow response (days to weeks)
- B cells and T cells
- Highly selective specificities to foreign agents
- Memory, maturation of secondary response to re-exposure
Anatomy of the Immune System
- The immune system is a network of protective barriers, organs, cells, and molecules.
- Primary lymphoid organs (e.g., bone marrow, thymus) are sites where lymphoid cells are generated and differentiate.
- Secondary lymphoid organs (e.g., spleen, lymph nodes) are sites where antigen-driven proliferation and maturation of lymphocytes occur.
- Lymphoid organs are connected via the lymphatic system, which allows for the circulation of lymphocytes and antigens.
Cells of the Immune System
- Leukocytes are white blood cells that play a functional role in either innate or adaptive responses.
- Myeloid cells:
- Include neutrophils, monocytes, macrophages, and dendritic cells
- Involved in innate immunity and provide immediate protection against pathogens
- Lymphoid cells:
- Include B lymphocytes, T lymphocytes, NKT cells, and NK cells
- Involved in adaptive immunity and provide specific recognition of foreign antigens
Myeloid Cells
- Neutrophils:
- Highly adherent, motile, and phagocytic
- First cells recruited to acute inflammatory sites
- Engulf and devour pathogens using granular enzymes and toxic molecules
- Eosinophils:
- Specialized molecules stored as granules
- Defend against large multicellular parasites
- Basophils and mast cells:
- Produce cytokines that help defend against parasites
- Involved in allergic inflammation### Immune System Components
- Basophils and mast cells have surface receptors for specific antibodies, releasing histamine and vascular mediators when cell-bound antibodies recognize allergens
- Macrophages are involved in phagocytosis and intracellular killing of microorganisms, and can reside in tissues for long periods
- Macrophages are highly adherent, motile, and phagocytic, and regulate other immune cells, such as T lymphocytes
- There are different subsets of macrophages, including M1 and M2, which secrete different mediators and are involved in different functions, such as bacterial control and wound healing
Dendritic Cells (DCs)
- DCs provide a critical link between innate and adaptive immunity by interacting with T cells
- DCs originate from cell precursors and have a unique function in delivering strong signals for the development of memory responses
- DCs recognize foreign agents through specific receptors and have the ability to guide the specificity and magnitude of subsequent immune responses
Antigen Presentation
- Macrophages and DCs are known as antigen-presenting cells (APCs)
- APCs destroy pathogens and then present pieces of the pathogen to T lymphocytes, mediating a connection with the adaptive immune response
- The pathogen is digested inside the presenting cell, and small fragments are shown on the cell surface for recognition by adaptive lymphocytes
Lymphocytes
- Lymphoid cells provide efficient, specific, and long-lasting immunity against microbes and pathogens
- Lymphocytes respond to infectious invasion only after myeloid cells have begun their work
- B lymphocytes secrete antibodies, while T lymphocytes operate in a supervising role to mediate cellular and humoral immunity
- Natural Killer (NK) cells are critical in defense against viral agents
Antigen Receptors
- The B-cell antigen receptor is the surface immunoglobulin, which has unique regions to bind specific antigenic shapes
- B-cell activation occurs when the receptor encounters the antigen, leading to a morphological change and the production of antibodies
- T lymphocytes have a surface receptor, the T-cell receptor (TCR), which is structurally similar to the antibody and recognizes specific pieces of the antigen
Cluster of Differentiation (CD)
- The CD designation refers to proteins found on the surface of cells
- Each unique surface molecule is assigned a different number, allowing cell phenotypes to be identified
- CD molecules may be specific for just one cell or cell lineage, or they may not
Inflammatory Response
- The inflammatory response is the coordinated effort of cells and blood components to elicit a response to infection
- Innate immune mechanisms provide the first line of defense against infectious disease
- The inflammatory response is triggered by the detection of microorganisms, leading to a signaling cascade and the activation of cell types that are adept at controlling infection
Cardinal Signs of Inflammation
- Redness occurs due to changes in localized blood flow (vasodilation)
- Swelling comes from the influx of fluid and cells from blood vessels to tissue
- Heat is caused by increased blood arriving to areas of damage
- Pain results from edema (fluid accumulation), which increases pressure on local nerves surrounding the damaged site
Initiation of the Inflammatory Response
- The skin provides an effective mechanical barrier against microorganisms
- Breach of the inflammatory barrier triggers an immediate cascade
- Release of lipids from cellular membranes leads to the production of signaling molecules, which exert effects on blood vessels
- Breakdown of cell membranes produces arachidonic acid, which has effects on cyclooxygenase and lipoxygenase activity, producing prostaglandins and leukotrienes### Pathogen Recognition and Cytokine Signaling
- Phagocytes have unique receptors that recognize microbial components, bind bacterial carbohydrates, and induce phagocytosis
- Recognition occurs through:
- Mannose receptors
- Scavenger receptors
- Toll-like receptors (TLRs)
- Pathogen-associated molecular patterns (PAMPs)
- Recognition triggers a proinflammatory response, activating gene regulation and releasing cytokines
Cytokines
- Small chemical mediators that allow cells to communicate with each other
- Regulate development and behavior of immune effector cells
- Facilitate cross-talk at low concentrations (10^-10 to 10^-15 M)
- Short-lived and bind to cell surface receptors
- May act alone or in concert with one another synergistically
- Exert multiple actions on multiple different cell types, with overlapping and redundant functions
- Also known as lymphokines, produced by cells of the lymphoid lineage
- Some cytokines function as growth factors for specific cell subsets
Danger-Associated Molecular Patterns (DAMPs)
- Subset of molecules that can trigger an immune response
- Released from injured tissue, includes components from the nucleus, cytosol, and mitochondria
- Jump-start an immune response in the absence of PAMPs
Feedback and Adaptation
- Cell-to-cell contact allows for direct delivery of cytokines and mediators
- Enables functional lymphocyte development in the immediate area
- Systemic communication via cytokines and chemokines directs cells and organs to respond to tissue damage
Chemokines
- Special subclass of chemical mediators that attract cells to the area of inflammation
- Assist in leukocyte migration into tissue (diapedesis)
- Synthesized by a wide variety of cell types
Inflammatory Response
- Initiation of the proinflammatory response is extremely potent to limit the spread of microorganisms
- Full clearance of the infectious agent typically requires adaptive immune components
- The inflammatory response culminates in the draining of fluid, cells, and antigens to local lymph nodes
B Lymphocytes and Antibodies
- B lymphocytes produce antibodies, which are responsible for humoral immunity
- Antibodies are glycoproteins consisting of two heavy chains and two light chains
- The structure of antibodies confers multiple cellular processes, mediated by variable and constant region domains
- Antibodies are capable of binding to a nearly limitless number of specific antigens
Antibody Structure
- Consists of two heavy chains and two light chains
- Held together by interchain disulfide bonds
- Enzymatic cleavage of the disulfide bonds results in two fragments: Fc and Fab2
- The Fab2 portion is responsible for antigen binding, while the Fc region confers specific biological properties
Immunoglobulin Isotypes
- Five unique heavy chains are defined by differences in amino acid sequences
- Labeled according to Greek letter designations: alpha, gamma, mu, epsilon, and delta
- Each heavy chain pairs with one of two light chains (kappa or lambda) to form a specific antibody isotype
- Properties of each isotype are summarized in Table 3.1
Development and Selection of Mature B Cells
- B-cell development involves V(D)J recombination of heavy-chain genes
- Successful rearrangement results in a pre-B receptor, which inhibits further rearrangement of heavy-chain genes
- Immature B cells are tested for autoreactivity, and cells that react with self-antigens are removed from the cell repertoire
- Mature B cells that show no reactivity with self-antigens migrate to peripheral lymph tissues
Activation and Differentiation of B Cells
- Mature B cells in the periphery respond to antigen, which depends on the type of epitope recognized
- Signaling through nearby membrane receptors (CD19 and CD21) is required
- B cells specific for protein antigens require help from CD4+ T cells
- Interaction with T cells drives isotype switching, resulting in the generation of plasma cells
- Isotype switching is the process by which the antigen specificity of the antibody remains the same, but the heavy-chain gene locus is excised and replaced with another heavy-chain gene constant domain
How We Defend Against Infectious Agents
- The human host has a delicate balance between normal commensal flora and the ability to distinguish specific agents that are harmful to daily living
- The immune system balances responses to its normal microbiome with the need to control and eliminate infectious agents that cause disease
- Major immune defense mechanisms against pathogens include:
- Physical barriers
- Cellular recognition of pathogenic motifs
- Adaptive responses directed towards specific foreign antigens
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Description
Explore the basics of the immune system, including its components and functions, to understand how they work together to protect against disease. This chapter covers innate and adaptive immunity and more.
