Chapter 43: The Immune System Flashcards
Innate vs. adaptive immunity
Innate immunity is common to all animals and is present from birth
Adaptive immunity is found only among vertebrates and develops after exposure to pathogens
Components of the innate immune system
Barrier defenses
Cellular innate defenses
Local inflammatory response
Antimicrobial peptides and proteins
Cellular innate defenses
Phagocytic cells dedicated to detecting, devouring, and destroying pathogens that include:
- Neutrophils
- Macrophages
- Dendritic cells
- Eosinophils
- Natural killer cells
- Mast cells
Many cellular involve the lymphatic system
Toll-like receptor
Found expressed on the surface of phagoctic cells or on the inner surface of vesicles formed by endocytosis
Binds to fragments of molecules characteristic of a set of pathogens to signal phagocytosis such as:
- Double-stranded RNA characteristic of certain viruses
- Lipoplysaccharides commonly found on the surface of baterium
Neutrophils
Phagocytic cells of the innate immune system that circulate in the blood and are attracted by signals from infected tissues
Macrophages
LARGER phagocytic cells of the innate immune system that stimulate adaptive immunity by presenting antigens that they engulf
Some migrate throughout the body while others are found in specific organs or tissues such as the spleen
Dendritic cells
Phagocytic cells of the innate immune system that stimulate adaptive immunity by presenting antigens that they engulf
Mainly populate tussues such as the skin that are in contact with the environment
Eosinophils
Phagocytic cells of the innate immune system that are defend against multicellular pathogens such as parasitic worms by discharging destructive enzymes
Often found beneath the epithelium
Natural killer cells
Phagocytic cells of the innate immune system that circulate through the body and detect abnormal surface proteins on some virus-infected and cancerous cells
Do NOT enfulf stricken cells but instead release chemicals that lead to cell death which inhibit the spread of virally infected or cancerous cells
Lymphatic system structures
Consists of lymphatic vessels and structures that trap foreign substances such as the lymph nodes and lymphoid organs:
- Adenoids
- Tonsils
- Thymus
- Spleen
- Peyer’s patches- in small intestines
- Appendix
Antimicrobial peptides and proteins
Function in innate defense by attacking pathogens or impeding their reproduction
- Interferons
- Complement system
Interferons
Proteins secreted by virus-infected cells that induce nearby uninfected cells to produce substances that inhibit viral replication
Limit cell-to-cell spread of viruses in the body
Control viral infections such as colds and influenza
Complement system
Consists of roughly 30 proteins in blood plasma that circulate in the inactive state and are activated by substances on the surface of many pathogens
Activation by antibodies results in a cascade of biochemical reactions that form pores in the membranes of target cells which lead to lysis of the invading cells
Local inflammatory response
- Begins when activated macrophages discharge cytokines that recruit neutrophils to the site of injury
- Mast cells release signaling molecule histamine that triggers nearby blood cessels to dilate and become more permeable
- Activated complement proteins promote further histamine release attracting more phagocytic cells
- Enhanced blood flow to the site helps deliver antimicrobial peptides that result in an accumulation of pus
- Pus and excess fluid are eventually taken up in lymph and transported to lymph nodes where pathogens are phagocytized by macrophages
- Dendridic cells are usually located outside of the lymphatic system but migrate to the lymph nodes after interacting with pathogens
Systemic inflammatory response
Cells in injured or infected tissue often secrete molecules that stimulate the release of additional neutrophils from the bone marrow
Fever can be induced in response to substances released by activated macrophages that cause the body’s thermostat to reset to a higher temperature
Primary components of the adaptive immune system
The adaptive response relies on two types of lymphocytes:
- Those that mature in the thymus above the heart are called T cells
- Those that mature in bone marrow are called B cells
Epitope
A small accessible portion of an antigen that binds to an antigen receptor
B cell antigen receptor
Y-shaped protein with two identical heavy chains and light chains linked together by three disulfide bridges
Each chain has a constant (C) region and a variable (V) region that recognizes a specific antigenic epitope
- The constant region of the heavy chain contains a transmembrane region that anchors the receptor in the cell’s membrane
Each chain thus has two identical antigen binding sites
Antigen recognition by B cells
Binding of the B cell antigen receptor to an antigen leads to the eventual secretion of a soluable, free-floating copy of the B cell antigen receptor called an antibody, also known as an immunoglobulin
Antibodies have the same Y-shapped structure as B cell antigen receptors but lack a membrane anchor
IgD is membrane bound while the other four, IgA, IgE, IgG, and IgM are soluble
T cell antigen receptor
Rod-shaped protein with two different α and β chains linked together by one disulfide bridges
Each chain has a constant (C) region and a variable (V) region that recognizes a specific antigenic epitope
- The variable region of both the α and β chain come together to form a single antigen binding site
- The constant region of the heavy chain contains a transmembrane region that anchors the receptor in the cell’s membrane
Antigen recognition by T cells
T cells bind only to fragments of antigens that are displayed or presented on the surface of host cells
Host protein that displays antigen fragment is called a major histocompatability complex (MHC) molecule
- Class I MHC is found on all nucleated human cells; activate cytotoxic T cells
- Class II MHC are found on macrophages, dendritic cells, and B cells; activate helper T cells
The display of protein antigen fragments occurs when a pathogen infects a host cell or when an immune cell engulfs a pathogen and degrades it
The T cell can then bind both the antigen fragment and the MHC molecule
Lymphocyte development
B and T cells
Capacity to generate diversity is built into structure of Ig genes
Receptor chain is encoded by three gene segments: a variable (V), joining (J), and constant (C) segment
Alternative copies of the V and J segments are arrayed along the gene in a series can be rearranged to prodice a wide array of different chains
Self-tolerance
As lymphocytes mature in bone marrow or the thymus they are tested for self-reactivity
Some B and T cells with receptors specific for the body’s own molecules are destroyed by apoptosis
The remaining self-reactive lymphocytes are typically rendered nonfunctional
Clonal selection
Binding of of an antigen repeptor to a matching epitope activates the lymphocyte bearing the receptor
Once activated a B or T cell undergoes multiple cell divisions to produce a clone of identical cells
Some cells from the clone become effector cells that act immediately against the antigen
- B cell effectors form plasma cells that secrete antibodies
- T cell effectors form helper T cells and cytotoxic T celss
Some cells from the clone become long-lived memory cells that can give rise to effector cells if the same antigen is encountered again
Immunological memory
Prior exposure to an antigen alters the speed, strength, and duration of the immune response
Primary response- slower onset; peaks about 10−17 days after initial exposure
Secondary response- faster onset; peaks about 2−7 days after exposure and is of greater magnitude and more prolonged
Adaptive immune response
In the humoral immune response antibodies help neutralize or eliminate toxins and pathogens in the blood and lymph fluid
In the cell-mediated immune response specialized T cells destroy affected host cells
Both can include primary and secondary immune responses wiht memory cells enabling the secondary response
Helper T cells
Trigger both the humoral and cell-mediated immune responses
The antigen must be displayed on the surface of an antigen presenting cell such as a dendridic cell, a macrophage, or a B cell
Antigen receptors on the helper T cell bind to the antigen fragment on the Class II MHC molecule
Simultaneously, an accessory CD4 protein binds to the Class II MHC molecule itself to help keep the cells joined
The helper T cell is activated, proliferates, and forms a clone of helper T cells, which then activate the appropriate B cells or cytotoxic T cells
Cytotoxic T cells
Use toxic proteins to kill cells infected by viruses or other intracellular pathogens
Are activated by cytokines secreted by helper T cells and interaction with an infected antigen presenting cell
Antigen receptors on the cytotoxic T cell bind to the antigen fragment on the Class I MHC molecule
Simultaneously, an accessory CD8 protein binds to the Class I MHC molecule and triggers cytotoxic T cell activity
Humoral activation of B cells
Activation of B cells involves stimulation by both helper T cells and pathogenic epitopes
B cells present antigens to which they have bound on Class II MHC proteins that are recognized by previously activated helper T cells
Activate helper T cells then secrete cytokines that lead to proliferation of the B cell and differentiation into memory B cells and antiody-secreting plasma cells
Antibody function
Antibodies do not directly kill pathogens but mark them for destruction in a variety of ways:
- In neutralization antibodies bind to viral surface proteins, preventing infection and entry into a host cell
- In opsonization antibodies bind to epitopes on bacteria, triggering phagocytosis by macrophages or neutrophils
- Antigen-antibody complexes may bind to a complement protein which triggers a cascade of complement protein activation
Active vs. passive immunity
Active immunity develops naturally when a pathogen invades the body and elicits a primary or secondary immune response
- Artificial active immunity develops following immunization
Passive immunity provides immediate, short-term protection conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk
- Artificial passive immunization occurs when antibodies from an immune animal are injected into a non-immune animal
Immune rejection
Differences in MHC molecules stimulate rejection of tissue grafts and organ transplants
Allergic reactions
IgE antibodies are produced after first exposure to an allergen attach to receptors on mast cells
The next time the allergen enters the body it binds to mast cell-associated IgE molecules and trigger the release of histamine and other mediators that cause typical allergy symptoms
