Immune System Flashcards

What is the Immune System?

• A complex network of organs, tissues, cells, and molecules.

• Protects the body from harmful pathogens and foreign substances.

• Recognizes and eliminates damaged and malignant (cancer) cells.

Immune Response

• A reaction to microbes and molecules recognized as foreign or abnormal.

Immunology

• The study of immune responses.

Components of the Immune System

• Organs: Appendix, Bone Marrow, Thymus, Tonsils, and Adenoids, Peyer’s Patches, Lymph Nodes, MALT (Mucosal Associated Lymphoid Tissues), Spleen.

• Tissues

• Cells

• Molecules

Functions of the Immune System

• Identify threats.

• Mount an attack.

• Eliminate pathogens.

• Remember pathogens.

Divisions of the Immune System

• Innate Immune System

• Adaptive Immune System

Role of the Immune System

• Defense against infections.

• Defense against tumors.

• Control of tissue regeneration and scarring.

• Can injure cells and induce pathologic inflammation.

• Recognizes and responds to tissue grafts and newly introduced proteins.

Implications of Immune System Function

• Deficient immunity results in increased susceptibility to infections (e.g., AIDS).

• Vaccination boosts immune defenses and protects against infections.

• Potential for immunotherapy of cancer.

• Repair of damaged tissues.

• Immune responses are the cause of allergic, autoimmune, and other inflammatory diseases.

• Immune responses are barriers to transplantation and gene therapy.

Sizes of Various Cells and Pathogens (Micrometers)

• Red Blood Cell: 7.5 \mu m

• Neutrophil: 10 \mu m

• Macrophage: 21 \mu m

• E-coli: 2 \mu m

• Staphylococcus aureus: 1 \mu m

• Rabies Virus: 0.18 \mu m

• HIV: 0.13 \mu m

• Coronavirus: 0.1 \mu m

• Rhinovirus: 0.03 \mu m

• Ebola Virus: 0.97 \mu m

• IgG Antibody: 0.015 \mu m

Leukocytes (White Blood Cells)

• mast cells

• eosinophils

• basophils

• neutrophils

• monocytes/macrophages

• dendritic cells

• B lymphocytes

• T lymphocytes

• natural killer (NK) cells

Origin of Blood Cells: Hematopoiesis

• Hematopoiesis involves the production, development, differentiation, and maturation of blood cells (erythrocytes, megakaryocytes, and leukocytes) from multipotent stem cells.

• The site of hematopoiesis changes during development.

Types of Stem Cells

• Totipotent stem cells

  • Hematopoietic Stem Cell (HSC): All blood cells (RBCs, WBCs, platelets)

  • Mesenchymal Stem Cell (MSC): Bone, cartilage, fat, muscle cells

  • Neural Stem Cell: Neurons, astrocytes, oligodendrocytes

• Pluripotent stem cells

• Multipotent stem cells

Hematopoiesis During Development

• During embryogenesis and early fetal development, the yolk sac is the site of hematopoiesis.

• Once organogenesis begins, hematopoiesis shifts to the liver and spleen, and finally, to the bone marrow, where it will remain throughout adulthood.

Multipotent Stem Cells in Bone Marrow

• These cells undergo asymmetric division.

  • One daughter cell renews the stem cell population (self-renewal).

  • The other daughter cell gives rise to either a common lymphoid progenitor cell or a common myeloid progenitor cell (potency).

Differentiation of Stem Cells

• Multipotent stem cells differentiate into lymphoid and myeloid cells in response to cytokines and growth factors.

  • The common lymphoid progenitor cell gives rise to B lymphocytes, T lymphocytes, and natural killer (NK) cells.

  • The common myeloid progenitor cell gives rise to erythrocytes, megakaryocytes/thrombocytes, mast cells, eosinophils, basophils, neutrophils, monocytes/macrophages, and dendritic cells.

White Blood Cell Functions

• Myeloid lineage cells (except erythrocytes and megakaryocytes) perform non-specific, stereotypic responses and are part of the innate immune response.

• B lymphocytes and T lymphocytes (lymphoid lineage) perform focused, antigen-specific roles in immunity.

• Natural killer cells (lymphoid lineage) participate in innate immunity.

B and T Lymphocyte Development

• B lymphocytes and T lymphocytes are morphologically indistinguishable at the light microscopic level but represent two interdependent cell lineages.

  • B lymphocytes remain in the bone marrow to complete development.

  • T lymphocytes leave the bone marrow and develop in the thymus.

• Natural killer (NK) cells are large granular lymphocytes that recognize tumor and virally infected cells through non-specific binding.

Blood Composition

• 1 Drop of Blood

• 250,000,000 Red Blood Cells

• 400,000 Immune Cells

• 15,000,000 Platelets

• 13,000,000,000,000 Antibodies

• 53% Plasma

• 43% Red Blood Cells

• 2% Platelets

• 2% Immune Cells

• 92% Water

• 7% Proteins (Antibodies, Complement, Albumin, etc.)

• 1% Nutrients, gases, waste, etc.

Immune System: An Overview

• Pathogens: Bacteria, Viruses, etc.

Cell Types and Their Roles

• Neutrophil: Kills, communicates, causes inflammation (Innate Immunity).

• Macrophage: Communicates, activates other cells, kills enemies, causes inflammation (Innate Immunity).

• Dendritic Cell: Identifies enemies, activates other cells (Innate Immunity).

• Monocyte: Becomes macrophage, identifies and kills (Innate Immunity).

• Natural Killer Cell: Communicates, kills infected/cancer cells (Innate Immunity).

• Eosinophil: Causes inflammation, battles parasites, activates other cells (Innate Immunity).

• Basophil: Causes inflammation, battles parasites, activates other cells (Innate Immunity).

• Mast Cell: Causes inflammation, communicates, activates other cells (Innate Immunity).

• B Cell: Produces antibodies, activates other cells (Adaptive Immunity).

• Plasma Cell: Produces antibodies, activates other cells (Adaptive Immunity).

• Long-Lived Plasma Cell: Produces antibodies (Adaptive Immunity).

• Virgin B Cell: Standby mode, activates other cells (Adaptive Immunity).

• Memory B Cell: Remembers enemies, produces antibodies (Adaptive Immunity).

• Virgin Helper T Cell: Standby mode, activates other cells (Adaptive Immunity).

• Memory Helper T Cell: Remembers enemies, communicates, activates (Adaptive Immunity).

• Virgin Killer T Cell: Standby mode, kills infected/cancer cells (Adaptive Immunity).

• Memory Killer T Cells: Remember enemies, kill infected/cancer cells (Adaptive Immunity).

• Killer T Cell: Kills infected/cancer cells (Adaptive Immunity).

• Helper T Cell: Communicates, activates other cells (Adaptive Immunity).

Other Components and Their Roles

• Complement: Marks and cripples enemies, activates and guides immune cells (Innate Immunity).

• Antibodies: Mark and disable enemies, activate complement (Adaptive Immunity).

Most Important Players of the Immune System

• T Cell

• B Cell

• Antibodies

• Macrophage

• Dendritic Cell

• Neutrophil

• Complement

• Natural Killer Cell

• Basophil

• Eosinophil

• Mast Cell

Cell Types and Principal Functions

• Lymphocytes: Specific recognition of antigens and generation of adaptive immune responses.

  • B lymphocytes: Mediators of humoral immunity

  • T lymphocytes: Mediators of cell-mediated immunity

• Antigen-presenting cells: Capture of antigens for display to lymphocytes.

  • Dendritic cells: Initiation of T cell responses

  • Macrophages: Effector phase of cell-mediated immunity

  • Follicular dendritic cells: Display of antigens to B lymphocytes in humoral immune responses

• Effector cells: Elimination of antigens.

  • T lymphocytes: Activation of phagocytes, killing infected cells

  • Macrophages: Phagocytosis and killing of microbes

  • Granulocytes: Killing microbes

Cytokines

• Cell signaling proteins, often released by immune cells and travel locally to stimulate inflammatory response.

  • Chemokines: Cytokines that attract immune cells.

  • Interleukins: Travel between leukocytes (e.g., IL-1, IL-2).

  • TNF: Cause tumor death.

  • TGF: Transforming growth factor.

  • Interferons: Interfere with viral replication.

Characteristics of Innate Immune Defenses

• Present intrinsically with or without previous stimulation.

• Have limited specificity for shared microbe and cellular structures.

• Have limited diversity as reflected by a limited number of pattern recognition receptors.

• Are not enhanced in activity upon subsequent exposure—no memory.

Diversity and Specificity

• Diversity: How many different things the immune system can recognize.

• Specificity: How precisely it recognizes and responds to a specific target.

How the Innate Immune System Handles Pathogens

• Inflammation.

• Interferons, NK cells (Elimination of viruses).

• Elimination of microbes.

Innate Immunity

• Provides the body’s first line of defense against infectious agents.

• Involves several defensive barriers:

  • Anatomic and physical (skin, mucous membranes, and normal flora).

  • Physiologic (temperature, pH, anti-microbials, and cytokines).

  • Complement.

  • Cellular: phagocytes and granulocytes.

  • Inflammation.

Physical Barriers

• The first line of defense against invaders consists of physical barriers.

• Viruses, bacteria, parasites, and fungi must penetrate these shields to cause real trouble.

• Anatomic and physical (skin, mucous membranes, and normal flora).

Respiratory System Defenses

• Defenses are a balanced system that fends off intruders and clears pollution while allowing for gas exchange.

  • Mucus Layer

  • Alveolar Macrophage

  • Nasal Hair

  • Epithelial Cells

Adaptive Immunity

• The components of the adaptive immune response are B and T lymphocytes and their effector cells.

Characteristics of Adaptive Immune Defenses

• Each B and T lymphocyte is specific for a particular antigen.

• As a population, lymphocytes have extensive diversity.

• Are enhanced with each repeat exposure—immunologic memory.

• Are capable of distinguishing self from non-self.

• Are self-limiting.

Features of Adaptive Immunity

• Designed to give the individual the best possible defense against disease.

  • Specificity and immunologic memory: Required to protect against persistent or recurrent challenge.

  • Diversity: Required to protect against the maximum number of potential pathogens.

  • Specialization of effector function: Necessary so that the most effective defense can be mounted against diverse challenges.

  • Ability to distinguish between self (host cells) and non-self (pathogens): Vital in inhibiting an autoimmune response.

  • Self-limitation: Allows the system to return to a basal resting state after a challenge to conserve energy and resources and to avoid uncontrolled cell proliferation resulting in leukemia or lymphoma.

Specificity and Diversity in Immune Responses

• Immune responses are specific for distinct antigens and often for different portions of a single complex protein, polysaccharide, or other macromolecule.

Epitope

• Also known as antigenic determinant.

• The part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells.

• Determine the specificity of the antigen.

Cross-Reactive (Heterophile) Antigens

• Antigens that share one or more similar epitopes.

  • Heterophile antigens: A group of similar antigens found in unrelated animals.

  • Heterophile antibodies: Produced against heterophile antigens of one species will cross-react with others.

Heterophile Antibodies Example (EBV-Infection Mononucleosis)

• Someone infected with EBV-infection mononucleosis, their immune system may produce heterophile antibodies, that cross-react with red blood cells from other species, like horse or sheep.

• If patient’s serum is mixed with horse or sheep RBC, agglutination (clumping occurs).

Functional Significance of Immune Response Features

• Specificity: Ensures that immune responses are precisely targeted to microbial pathogens.

• Diversity: Enables the immune system to respond to a large variety of antigens.

• Memory: Leads to enhanced responses to repeated exposures to the same antigens.

• Clonal expansion: Increases the number of antigen-specific lymphocytes from a small number of naive lymphocytes.

• Specialization: Generates responses that are optimal for defense against different types of microbes.

• Contraction and homeostasis: Allows the immune system to respond to newly encountered antigens.

• Nonreactivity to self: Prevents injury to the host during responses to foreign antigens.

Lymphocyte Maturation and Activation

• Lymphocyte clones mature in generative lymphoid organs in the absence of antigens.

• Clones of mature lymphocytes specific for diverse antigens enter lymphoid tissues.

• Antigen-specific clones are activated ("selected") by antigens.

Characteristics of Innate and Adaptive Immunity

Collaboration Between Innate and Adaptive Immunity

• The innate and adaptive arms of the immune response work in collaboration to stop an infection.

• Once a pathogen has broken through the anatomic and physiologic barriers, the innate immune response is immediately activated.

• Often, the innate immune response is able to contain and eliminate the infection.

• When the innate immune response is unable to control the replication of a pathogen, the adaptive immune response is engaged and activated by the innate immune response in an antigen-specific manner.

Adaptive Immune Response Timeline

• Typically, it takes 1-2 weeks after the primary infection for the adaptive immune response to begin clearance of the infection through the action of effector cells and antibodies.

• Once an infection has been cleared, both the innate and adaptive immune responses cease.

• Antibodies and residual effector cells continue to provide protective immunity, while memory cells provide long-term immunologic protection from subsequent infection.

Innate and Adaptive Feedback Mechanism

• The innate and adaptive immune responses do not act independently of one another; rather, they work by a positive feedback mechanism.

  • Phagocytic cells recognize pathogens by binding PAMPs through various pattern-recognition receptors leading to phagocytosis.

  • Phagocytic cells process and present antigen to facilitate stimulation of specific T lymphocytes with subsequent release of cytokines that trigger initiation of specific immune responses.

  • T lymphocytes produce cytokines that enhance microbicidal activities of phagocytes.

  • Cytokines released by phagocytes and T lymphocytes will drive differentiation of B lymphocytes into plasma cells and isotype switching.

  • Antibodies will aid in the destruction of pathogen through opsonization, complement activation, and antibody-dependent cellular cytotoxicity.

Antigens

• An antigen is a substance that can provoke the production of an antibody.

Immunogen

• An immunogen is a substance that can stimulate the immune system to produce an immune response.

• The terms immunogen and antigens are used interchangeably.

Criteria for a Molecule to be an Immunogen

• It must be recognized as foreign.

• It must have a certain degree of chemical complexity.

• It must have a large molecular weight.

Factors Determining Immunogenicity

1. Foreignness: Molecules recognized as “self” are not immunogenic; for immunogenicity to occur, molecules must be recognized as “nonself.”

2. Size: The most potent immunogens are usually large proteins. Molecules with a molecular weight less than 10,000 are weakly immunogenic, and very small ones (e.g., amino acids) are nonimmunogenic. Certain small molecules (e.g., haptens) become immunogenic only when linked to a carrier protein.

3. Chemical and structural complexity: A certain amount of chemical complexity is required. For example, amino acid homopolymers are less immunogenic than heteropolymers containing two or three different amino acids. Antigens are mainly proteins and some are polysaccharides. It is presumed that presence of an aromatic radical is essential for rigidity and antigenicity of a substance.

4. Physical Form: In general, particulate antigens are more immunogenic than soluble ones. Denatured antigens are more immunogenic than the native form. B lymphocytes are capable of recognizing molecules of almost any chemical composition. T lymphocytes recognize peptides only when presented to them in the groove of an MHC molecule on the surface of an antigen-presenting cell.

5. Genetic constitution of the host: Two strains of the same species of animal may respond differently to the same antigen because of a different composition of genes involved in the immune response (e.g., different MHC alleles).

6. Dosage, route, and timing of antigen administration: Since the degree of the immune response depends on the amount of antigen given, the immune response can be optimized by carefully defining the dosage (including number of doses), route of administration, and timing of administration (including intervals between doses).

Hapten

• A low molecular weight substance that is incapable of inducing an immune response alone but when coupled with a carrier molecule (protein), it can act as an antigen.

Examples of Haptens

• Drugs (e.g., penicillin).

Adjuvants

• Substances that can enhance the immune response to an immunogen are called adjuvants.

• The use of adjuvants is often hampered by undesirable side effects such as fever and inflammation.

Examples of Adjuvants

• Aluminum hydroxide

• Aluminum phosphate

• Monophosphoryl lipid A (MPL)

Antibodies

• Humoral immunity is mediated by antibodies, which are produced by the B-cell component of the immune response.

• Antibodies are immunoglobulins, which react specifically with the antigen that stimulated their production.

• They make up about 20% of plasma proteins.

• The antibody recognizes a unique molecule of the pathogen, called an antigen, via the Fab's variable region.