Chapter 1- Elements of the Immune System Flashcards
Immune
When a person is resistant to infection after being exposed
Immune system
The tissues, cells, and molecules involved in defending the body against pathogens
Immunity
The ability to resist a specific infection. For this to happen, the immune system needs to fight off the pathogen. Children are at the highest risk when they are infected by a microorganism for the first time
Vaccination
Administering killed or nonpathogenic forms of a pathogens, or its proteins, to induce an immune response. The vaccinated person develops protective immunity against the pathogen
Commensal microorganisms
Organisms that live on or in the human body. Normally they don’t cause harm and can be beneficial. They constitute around 4.5 kg of the body’s weight
Microbiota
The commensal microorganisms, which live in the skin, mouth, gut, and vagina. Different ecological niches in the body have different microbiota. Animals co-evolve with their commensal species and become tolerant of and dependent on them. In humans, these organisms process digested food and make vitamins. They also protect against disease by preventing the colonization of pathogens
Colicins
Antibacterial proteins secreted by E. coli. E. coli is a major component of the gut microbiota. It secretes colicins to incapacitate other species of bacteria and prevent them from colonizing the infections
C. difficile
A bacteria present in small numbers in healthy people. Patients treated with antibiotics may experience a depletion of the gut microbiota and an overgrowth of C. difficile. It secretes a toxin that inflames the colon, causing diarrhea and bleeding. Antibiotics can disrupt the natural ecology of the colon
Pathogen
Any microorganism that causes disease. Includes both the microbes that always cause disease and the microbes that may cause disease if the immune system or other defenses are weakened
Opportunistic pathogens
Pathogens that only cause disease in people with compromised immune systems
4 kinds of pathogens
Viruses, bacteria, fungi, and parasites
Parasites
A heterogenous group of unicellular protozoa and multicellular invertebrates (worms).
Evolutionary relationships between pathogens and hosts
Pathogens evolve adaptations that allow them to invade hosts, replicate, and propagate throughout the population. Causing rapid death of the host is not in the best interest of the pathogen. Humans can also evolve genetic resistance to pathogens over time
Epithelium
Either a single layer or layers of cells bound tightly to each other. The epithelium lines the outer surface and inner cavities of the body. The skin is an epithelium that is protected by a tough layer of keratinized cells. Epithelia that line the respiratory, gastrointestinal, and urogenital tracts
Mucosal surfaces
The epithelium that lines the internal surfaces- respiratory, intestinal, and urogenital tracts. These surfaces secrete and are covered by mucus
Mucus
Secreted by mucosal epithelium. Contains glycoproteins, proteoglycans, and enzymes that protect the epithelial cells from damage and contribute to limiting infection. Cilia removes mucus from the respiratory tract
Antimicrobial peptides
Produced by all epithelia- kill bacteria, fungi, and enveloped viruses by damaging their membranes. Lysozymes are one example, found in tears and saliva
Innate immune response
Genetically programmed, initiated immediately upon infection. Depends on host defenses like complement, neutrophils, macrophages and NK cells. These defenses are non-specific and do not generate immunological memory
Phases of the innate immune response
First phase- recognition that a pathogen is present. Involves soluble proteins and cell-surface receptors can bind to the pathogen or human cells, and plasma proteins. The second phase recruits effector mechanisms that kill the pathogen.
Effector mechanisms
The physiological and cellular processes used by the immune system to destroy pathogens. Mediated by effector cells
Effector cells
The terminally differentiated immune cells that are responsible for killing pathogens. In the innate immune system, these are neutrophils, NK cells, and innate lymphocytes. In the adaptive immune system, these are antibody producing plasma cells and terminally differentiated T cells
Complement
A system of plasma proteins that guides the effector cells by tagging pathogens with molecular flags. Complement proteins can also kill pathogens without assistance from effector cells by disrupting pathogen membranes
Cytokines
Local cells secrete small proteins that act to change the behavior of neighboring cells. Cytokines bind to specific receptors on their target cells. In innate immunity, cytokines bind receptors on effector cells to trigger the innate immune response and induce inflammation in the infected tissue
Interleukins
Cytokines made by lymphocytes and other immune system cells
Inflammation symptoms
Heat, pain, redness, and swelling
How do cytokines induce inflammation symptoms?
- Induce dilation of capillaries, increasing blood flow, which makes the skin warm and red.
- Vasodilation creates gaps between the cells of the endothelium, making the endothelium more permeable, and blood plasma leaks into connective tissue, causing edema
- Edema causes swelling, which puts pressure on nerve endings and causes pain
Edema
Expansion of the local fluid volume
How do cytokines allow white blood cells to leave the blood?
Cytokines alter the adhesive properties of the vascular endothelium, which allows white blood cells to leave the blood and enter the inflamed tissue. These white blood cells contribute to inflammation. Infiltration of the inflammatory cells increases swelling and causes cells to release chemicals that cause pain
Benefit of inflammation
Allows many immune system cells and soluble effector molecules to quickly get to the infected tissue
Lymphocytes
A general white blood cell lineage, consists of B cells, T cells, and NK cells. Lymphocytes are used in the adaptive immune response to increase the strength and focus of the immune response
Adaptive immune response
When antigen-specific B and T cells respond to antigens, which allows an individual to develop immunological memory. Adaptive immunity is powerful, long lasting, and pathogen-specific. It has only evolved in vertebrates and can take days to weeks to mount an effective response
How do receptors differ between adaptive and innate immunity?
The receptors of innate immunity are structurally different from each other, and there are many different types. Each receptor recognizes molecular features shared by groups of pathogens. None is specific for a particular pathogen. Conversely, in adaptive immunity, lymphocytes recognize pathogens using only one type of cell surface receptor that is made in billions of different versions. The response is pathogen-specific by only including the lymphocytes expressing a receptor that recognizes the pathogen
Clonal selection
The mechanism by which adaptive immune responses derive only from individual antigen-specific lymphocytes, which are stimulated by an antigen and proliferate and differentiate into antigen-specific effector cells. This process takes time, so the adaptive immune response takes 7-10 days to develop
Clonal expression
The multiplication of lymphocytes after their activation by an antigen. Large clones of rare antigen-specific lymphocytes are generated to fight the pathogen
Immunological memory
The capacity of the immune system to make quicker and stronger adaptive immune responses to successive encounters with an antigen. Immunological memory is specific for a particular antigen and is long-lived
Memory cells
General term for a lymphocyte (B cell) that’s responsible for the phenomenon of immunological memory. They allow for subsequent encounters with a pathogen to elicit a stronger and faster adaptive immune response. This response can eliminate an infection before a person has symptoms
Primary immune response
The first time that a person makes an adaptive immune response to a pathogen
Secondary immune response
The adaptive immune response provoked by the second exposure to an antigen. It differs from the primary response by starting sooner and building more quickly. This is due to the presence of memory B cells and T cells that are specific to the antigen
Hematopoiesis
The generation of blood cells- red and white blood cells and platelets. All of these cells originate from pluripotent hematopoietic stem cells. Their differentiated daughter cells divide under the influence of different growth factors
Pluripotent hematopoietic stem cells
The stem cell in the bone marrow that gives rise to all blood cells. Stem cells are self-renewing
Megakaryocytes
These cells come from erythroid lineage. They are produced in the bone marrow and stay there. Blood platelets are produced by fragmentation of megakaryocytes. Megakaryocytes are giant cells arising from the fusion of multiple precursor cells. They have nuclei containing multiple sets of chromosomes
Hematopoietic cells
All blood cells (WBCs, RBCs, and platelets) and their developmental precursors
Anatomical site for hematopoiesis in fetuses
In an early embryo, blood cells are produced in the yolk sac and later produced in the fetal liver. The site changes to the spleen from the third-seventh month of pregnancy. As the bones develop during month 4-5, hematopoiesis begins to shift to the bone marrow. By birth, nearly all hematopoiesis takes place there
Anatomical site for hematopoiesis in adults
Concentrated in the bone marrow of the skull, ribs, sternum, vertebral column, pelvis, and femurs. Blood cells are short lived and must be constantly renewed throughout life
Platelets
Essential for blood clotting. They are non-nucleated, membrane-bound packets of cytoplasm that are fragmented from megakaryocytes. They circulate in the blood and close off badly damaged blood cells to reduce blood loss
Erythrocyte function
Oxygen transport
Dendritic cells
They have similar properties and functions to macrophages. Dendritic cells determine whether and when the innate immune response needs reinforcement with the adaptive immune responses. When adaptive immunity is necessary, dendritic cells in the infected tissue take intact and degraded pathogens to the lymphoid tissues, where they activate T cells in the adaptive immune response. These cells have a star-shaped morphology
Plasma cell
Terminally differentiated form of B cells (effector B cells) that synthesizes and secretes antibodies
Mast cells
Resident in all connective tissues. Expels parasites from the body by release of granules containing histamine and other active agents, which cause spasms of smooth muscle that eject parasites from the respiratory tract and gut. Their blood-borne progenitor is unknown
Natural killer (NK) cells
Large granular lymphocytes. They are cytotoxic and part of the innate immune response. NK cells are recruited to infected tissue by macrophages. They kill virus-infected cells and secrete cytokines that impair viral replication. Killing requires cell-to-cell contact, through the balancing of + and - signals. They secrete perforin, which forms pores in the membrane of the target cell, creating an aqueous channel. Granzymes then enter to induce apoptosis. NK cells are replenished in the bone marrow
Monocyte
A circulating precursor of the macrophage. Macrophages recruit monocytes to infected tissue, where the monocytes differentiate into macrophages and reinforce the resident macrophages. Once the pathogen has been eliminated, monocytes repopulate the tissue, which will differentiate to become tissue-resident macrophages. Sometimes macrophages are overwhelmed and die during infection. Monocytes are larger cells with an indented nucleus and uniform appearance
Neutrophil
Responsible for phagocytosis and the killing of microorganisms. Enters infected tissues in large numbers and engulfs and kills extracellular pathogens. It is a type of granulocyte that contains granules which stain with neutral dyes, hence the name. It’s the most abundant WBC. Neutrophils are stored in the bone marrow and released to infected tissue
Macrophage
Responsible for phagocytosis and the killing of microorganisms, dispose of neutrophils that die during the immune response. They are large, irregularly shaped phagocytic cells that have an extensive cytoplasm and numerous vacuoles that contain engulfed material, which is in the process of being digested. In contrast to neutrophils, macrophages are long lived and orchestrate the local response to infection. When they respond to an infection, macrophages secrete inflammatory cytokines that recruit neutrophils and other leukocytes into the infected area
Eosinophil
Kills antibody-coated parasites through the release of toxic granule contents. Contains granules that stain with eosin, hence the name. The contents of the granules are secreted when the cell is stimulated.
Basophil
Controls immune responses to parasites- specializes in defending the body against intestinal parasites, particularly helminth worms. Present in small numbers in the blood, acts more like a regulatory cell than an effector cell. Granulocyte- contains granules that stain with basic dyes, hence the name
Self renewal
The ability of a population of cells to maintain itself permanently by mitosis. With stem cells, self renewal involves mitosis and limited differentiation.
Hematopoietic stem cell differentiation
These stem cells can divide to give daughter cells that are also hematopoietic stem cells- this is the process of self renewal. Alternatively, daughter cells can differentiate to become more mature stem cells. These mature stem cells commit to one of 3 cell lineages- erythroid, myeloid, and lymphoid lineages
3 lineages for mature stem cells
erythroid, myeloid, and lymphoid lineages
Megakaryocyte-erythroid precursor cells give rise to
Erythroblasts (which become erythrocytes) and megakaryocytes (which become platelets)
Percentage of total leukocytes in the blood
Neutrophils: 40-75%
Eosinophils: 1-6%
Basophils: less than 1%
Monocytes: 2-10%
Lymphocytes: 20-50%
Myeloid precursor cell
The stem cell in the bone marrow that gives rise to the myeloid lineage- granulocytes, monocytes, mast cells, and dendritic cells
Granulocytes
Also called polymorphonuclear leukocytes due to their irregularly shaped nuclei with 2-5 lobes. White blood cell with irregularly shaped, multilobed nuclei, and cytoplasmic granules. There are 3 types- neutrophils, eosinophils, and basophils
Phagocytosis
The engulfment and destruction of extracellular material, such as microorganisms, dead cells, and macromolecules by specialized cells called phagocytes. The main phagocytes are macrophages, neutrophils, and dendritic cells
Function of neutrophils
Phagocytes rapidly mobilize to enter infected tissue and can function under anaerobic conditions that are found in damaged tissue. Neutrophils are short lived- they die in the infected tissue, forming pus
Tissue-resident macrophages
Self-renewing macrophages that derive from embryonic stem cells and begin to reside in the tissues during embryonic development. They are the first cells that detect infection in a specific tissue. Infection activates resident macrophages to kill pathogens and recruit neutrophils to the innate immune response
Lymphoid precursor cell
Stem cell in the bone marrow that gives rise to the lymphocytes. There are two morphologies of blood lymphocytes: large lymphocytes with granular cytoplasm and small lymphocytes with little cytoplasm
Innate lymphoid cells
Examples are ILC1, 2, and 3 and LTi. They are large lymphocytes that are resident in tissues. They do not circulate between blood and lymph. ILCs secrete cytokines that help to activate the responses of myeloid cells to infection
Small lymphocytes
Mediate all adaptive immune responses. Circulate in an immature and functionally inactive form. Pathogen-specific receptors on small lymphocytes recognize pathogens and drive a process of cellular selection, growth, and differentiation that produces a powerful and organism-specific immune response within 1-2 weeks. B cells and T cells are their main sub lineages
B cells
Makes immunoglobulins in the form of cell-surface antigen receptors and secreted antibodies. They can bind directly to pathogens and toxins
T cells
Originate in the bone marrow, develop in the thymus, and are responsible for cell-mediated immunity. There are various types- cytotoxic T cells, regulatory T cells, and helper T cells
B-cell receptors
The cell-surface pathogen receptors of B cells. They are Y-shaped immunoglobulin molecules, with a transmembrane tail anchoring it to the plasma membrane
Immunoglobulins
The general name for antibodies and B-cell antigen receptors. Composed of two identical heavy chains and two identical smaller light chains. They also have two identical antigen binding sites
T-cell receptors
The cell surface pathogen receptors of T cells. The receptor recognizes peptide antigens derived from the breakdown of proteins. They are only expressed as cell-surface receptors and not as soluble forms. T-cell receptors are membrane proteins with one antigen-binding site
Antibodies
A soluble form of B cell receptors. They lack a hydrophobic membrane anchoring sequence, but are otherwise identical to B cell receptors
Antigen
Any molecule or molecular fragment that either is recognized by an antibody or B cell receptor, or can be bound by an MHC molecule and presented to a T cell receptor
Antigen receptors
The highly variable cell-surface receptor on lymphocytes that recognizes an antigen. For a B cell, the receptor is a cell-surface immunoglobulin, and for a T cell, the receptor is a T cell receptor. All of the antigen receptors on an individual B or T lymphocyte are identical and recognize the same antigen epitope
On binding a specific antigen, how do B cells differentiate?
When a B cell encounters the antigen recognized by its B cell receptor, it divides and differentiates into antibody-producing plasma cells
On binding a specific antigen, how do T cells differentiate?
Antigen-activated effector T cells are of different functional types that are distinguished by their surface glycoproteins, the cytokines they respond to, the cytokines they secrete, and the type of target cell they interact with. The main subdivision of effector T cells is defined by the cell-surface expression of either the CD4 or CD8 co-receptor protein
Co-receptor T cell proteins
CD4 and CD8- CD stands for cluster of differentiation. The proteins associate with the T cell receptor at the T-cell surface. The co-receptors signal components to form a complex that recognizes and responds to a specific antigen
Cytotoxic T cells
Contain the CD8 co-receptor, kills cells infected with a virus or bacterium. Have similar functions to the NK cells of innate immunity
Helper T cells
Contain the CD4 co-receptor. They secrete cytokines that enable other cells to become fully activated effector cells
TH1 cells
A subset of helper T cell cells. Activate macrophages to increase phagocytosis and to kill those phagocytosed pathogens that resist the usual processes of intracellular degradation
TH17 cells
A subset of helper T cells that activate neutrophils to phagocytose and eliminate extracellular bacteria
TH2
A subset of helper T cells that responds to parasitic infections by secreting cytokines that activate mast cells, basophils, and eosinophils. The mediators released by these cells cause smooth muscle contractions to expel parasites.
TFH cells
A subset of helper T cells- secrete cytokines that induce the differentiation of antigen-activated B cells to become antibody-secreting plasma cells.
Treg cells
A subset of helper T cells- closes down the effector CD4 and CD8 cells after the infection has been terminated to prevent further inflammation and tissue damage
Epitope
The portion of an antigenic molecule (carbohydrates, glycoproteins, proteoglycans, and glycolipids) that is bound by an antibody or gives rise to the MHC-binding peptide that is recognized by a T cell receptor
Major histocompatibility complex (MHC) molecule
T cell receptors require a peptide antigen to be bound by an MHC molecule, so the receptors can recognize the antigen. The MHC molecule presents the peptide antigen to the T cell receptor. The genes encoding MHC molecules are the most polymorphic of human genes
Tissue type
The particular set of MHC molecules a person expresses. Due to the extensive genetic polymorphism of the MHC genes, the tissue type differs in several respects between individuals. Immune responses against differences in tissue type are the main cause of organ rejection
MHC class 1
Defends against intracellular infections- all viral and some bacterial infections. All human cells are susceptible to viral infection, so MHC class 1 molecules are expressed by all cells. CD8 binds to MHC class 1 only
MHC class 2
Defends against some extracellular infections. The expression of MHC class 2 is restricted to professional antigen presenting cells- macrophages, dendritic cells, and B cells. CD4 binds to MHC class 2 only
Neutralization
The mechanism by which antibodies binding to sites on pathogens (like viruses) prevent growth of the pathogen and/or its entry into cells. The toxicity of bacterial toxins can be neutralized by a bound antibody
Humoral immunity
The immunity conferred by antibodies. Humoral immunity can be transferred to a nonimmune recipient by serum. Humors= an old fashioned term for body fluids
Opsonization
The coating of the surface of a pathogen or other particle with any molecule that makes it more readily ingested by phagocytes. Antibody and complement opsonize extracellular bacteria for phagocytosis by neutrophils and macrophages because the phagocytic cells carry receptors for these molecules
Lymphoid tissues
The majority of lymphocytes are present in lymphoid tissues, only a small amount circulates in the blood. The main lymphoid tissues are the bone marrow, thymus, spleen, adenoids, tonsils, appendix, lymph nodes, and Peyer’s patches. There is also less organized lymphoid tissue that lines the mucosal surfaces of the respiratory, GI, and urogenital tracts. Functionally divided into primary and secondary lymphoid tissue
Primary lymphoid tissues
Where lymphocytes develop and mature to the stage at which they are able to recognize and respond to a pathogen. The bone marrow and thymus are the only primary lymphoid tissues
Thymus
A primary lymphoid organ located behind the sternum. It is the site of T-cell development
Secondary lymphoid tissues
Includes all lymphoid tissues other than the bone marrow and thymus. These are the sites where mature lymphocytes encounter pathogen-derived antigens, and are activated to become effector cells that attack and eliminate pathogens
Lymphatic vessels
Thin-walled vessels that carry lymph. They are part of the lymphatic system, which transports lymph from tissues to secondary lymphoid tissues, and from there to the thoracic duct, which returns lymph to the blood
Lymph
The plasma that leaks out of blood vessels to become extracellular fluid. Lymph is not pumped, it flows slowly using one-way valves in the lymphatic vessels, which move lymph away from the peripheral tissues and toward ducts in the upper body. The flow of lymph is driven by the constant movement of one part of the body against another. Small lymphocytes uniquely travel through the body in both blood and lymph
Lymphocyte recirculation
The continual migration of naive lymphocytes from blood to secondary lymphoid tissues to lymph and back to the blood. An exemption occurs in the spleen, lymphocytes both enter and leave the spleen in the blood
Lymph node
Bean shaped, a secondary lymphoid tissue present at many sites where lymphatic vessels converge. Antigens are delivered by the lymph and presented to lymphocytes within the lymph node to initiate adaptive immune responses
Draining lymph node
The lymph node nearest to a site of infection, to which extracellular fluid containing antigen and cells from the site is transported. The draining lymph node collects all potentially dangerous materials, preventing them from entering the circulation
Lymphoid follicles
An aggregation of mainly B cells in secondary lymphoid tissues. Naive B cells must pass through follicles for their survival. After B cells are activated by antigen, they enter the follicles, where they proliferate and undergo somatic hypermutation and isotype switching
Afferent lymphatic vessel
Vessel that brings lymph into a lymph node. Lymph is arriving at the lymph node
Efferent lymphatic vessel
Vessel by which lymph and lymphocytes leave a lymph node en route to the blood. Lymph is exiting the lymph node
Germinal center
Area in secondary lymphoid tissue that is a site of intense B cell proliferation, selection, maturation, and cell death. Germinal centers form around follicular dendritic cell networks when activated B cells migrate into lymphoid follicles
Spleen
The organ that filters the blood to remove damaged and senescent erythrocytes. It also acts like secondary lymphoid tissue- it defends the body against bloodborne pathogens. Microorganisms and microbial products in the blood are taken up by splenic macrophages and dendritic cells, which then stimulate B and T cells to arrive in the spleen from the blood.
Splenic tissue
Red pulp- where red blood cells are monitored and elderly or damaged ones are removed. White pulp- a secondary lymphoid tissue
Immunodeficiency disease
Any inherited or acquired disorder in which some part or parts of the immune system are either absent or defective, resulting in failure to mount an effective immune response to pathogens
Mucosa-associated lymphoid tissue (MALT)
Aggregations of lymphoid tissues in the mucosal epithelia and in the lamina propria beneath. The two main ones are GALT and BALT
Gut-associated lymphoid tissue (GALT)
All lymphoid tissue closely associated with the GI tract, including the tonsils, Peyer’s patches in the intestine, isolated B cell follicles, and intraepithelial lymphocytes
Bronchial-associated lymphoid tissue (BALT)
The lymphoid cells and organized lymphoid tissues of the respiratory tract
Anatomic barriers of innate immunity (2)
- Skin
- Mucosal surfaces (airways,
intestine)
Myeloid
From the bone marrow
Chemical barriers of innate immunity (2)
- Complement system
- Antimicrobial proteins
Inherited immunodeficiency
The “boy in a bubble” is an example. Patients have a mutation in a gene that is critical for immune cell development or survival. Lack of B cells, T cells, or both
Allergy
Eosinophils and mast cells are supposed to protect against parasites but are also implicated in allergies
Acquired immunodeficiency
AIDS is one example
Autoimmunity
The immune system attacks things with “self” antigens- lupus, rheumatoid arthritis, and multiple sclerosis
Host vs graft disease
When the immune system attacks transplanted tissue (organ rejection)
Graft vs host disease
BMT patients- new cells attack the patient’s tissues
Cancer and the immune system phases (3)
- Elimination- when tumors arise, immune cells recognize and eliminate them
- Equilibrium- variant tumor cells arise that are more resistant to being killed. Over time, different variants develop
- Escape- eventually, one variant may escape the killing mechanism or recruit regulatory cells to protect it, so it can spread
Immunotherapy modalities (5)
- Checkpoint inhibitors
- Immune cell-based treatments
- Therapeutic antibodies
- Immune modulators
- Vaccine therapies
CAR T cell development (4)
- T cells are collected from the patient
- T cells are genetically engineered to find and kill cancer cells
- The re-engineered cells are multiplied until there are millions of these attacker cells
- CAR T cells are infused into the patient and multiply in number. The attacker cells recognize and kill cancer cells, and help to prevent recurrence
How does the skin act as a barrier to microbes?
Desquamation of skin removes bacteria (transient) that have adhered to epithelial surfaces. Skin also secretes a number of peptides and proteins with potent anti-microbial activity (i.e., psoriasin)
How do the mucous membranes act as barriers to microbes?
Saliva, tears, and mucous secretions produced by these tissues wash away microbes. The epithelial surfaces secrete antibacterial and antiviral substances (lysozyme, defensins, cathelicidins, surfactants). In addition, the cilia in respiratory tract propel mucus-entrapped microbes from body. Stomach contains acid and digestive enzymes. Normal flora colonize mucosal surfaces to out-compete pathogenic microbes for space and nutrients.
Acute inflammation
The initial response of the body to harmful stimuli involving the increased movement of leukocytes from the blood to the injured tissue(s).
Chronic inflammation
The prolonged inflammation characterized by simultaneous destruction and healing of the tissue; arthritis and cancer.
