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Define First line of defense. Is it considered a true immune response?
Any barrier that blocks invasion at the portal of entry - innate/ non specific
No because it includes any barrier that blocks invasion
What are examples of physical, chemical, and genetic barriers of first line of defense?
Physical: Skin, tears, coughing, sneezing
Chemical: Low pH, lysosome, digestive enzymes
Genetic: Resistance inherent in genetic makeup of host
Define second line of defense
Internalized system of protective cells and fluids which includes inflammation and phagocytosis- innate/ non specific
What are examples of the second line of defense?
Inflammatory response, fever, phagocytosis, interferons, complement
Define the third line of defense.
Acquired on an individual basis with exposure to foreign substance; produces protective antibodies and creates memory cells that come into play if the microbe is encountered again - specific
What are examples of the third line of defense?
Specific to a particular microbe
Acquired immunity- natural or artificial and active or passive
T lymphocytes, B lymphocytes, antibodies
What are pathogen associated molecular patterns (PAMPs)?
Molecular markers in pathogens that serve as a “red flag” to signal WBCs. Detection of PAMPs by PRRs provide an early alert of invasion and triggers reactions that help control pathogens.
What are pattern recognition receptors (PRRs)?
Special molecules on WBCs membranes that are like “feelers” for sensing pathogens and recognizing foreign cells.
What are the four major subdivisions of the immune system?
Mononuclear phagocyte system (MPS), Extracellular fluid (ECF), Bloodstream, Lymphatic system
What is the mononuclear phagocyte system?
It is a network of connective tissue fibers that interconnects other cells and meshes with the connective tissue network surrounding organs. It is critical to the immune system because it allows phagocytic WBCs to move within and between tissues. It is inhabited by phagocytic cells.
What is serum?
The liquid portion of the blood (minus clotting factors) after a clot has formed
What is plasma?
Contains clotting factor; 92% water, metabolic proteins, globulins, clotting factors, hormones, and all other chemicals and gases to support normal physiological functions
Diagram of myeloid and lymphoid stem cells differentiate.
Which are the first immune cells to defend against infection?
Neutrophils; main job is phagocytosis.
What do cytoplasmic granules do?
They carry digestive enzymes that degrade phagocytosed material
What do eosinophils primarily target?
Eukaryotic pathogens especially larval forms of worm parasites and fungi. They are involved with inflammation and allergies
What chemical mediators do basophils release?
Potent chemical mediators (histamine and heparin).
What conditions do basophils respond to? How do they affect blood vessels?
Inflammation, allergic reactions and asthma.
They cause blood vessels to dilate in response to injury and helps prevent blood from clotting. They have a bilobar nucleus.
What are Mast cells?
Similar to basophils: Granules release histamine and heparin during inflammatory and allergic reactions
Different: larger and contain more granules, have widely distributed nonmotile elements bound to connective tissue (ie skin, mucosa, conjunctiva), round nucleus
Which WBC is the key to the third line or specific immune response?
Lymphocytes
What two types of cells do lymphocytes differentiate into and where do they mature?
B cells (bone marrow)
T cells (thymus)
Which type of lymphocyte provides humoral immunity aka antibody mediated immunity?
B lymphocytes
How do B lymphocytes fight bacterial infections?
They secrete antibodies into bloodstream and lymphatic fluid
What do monocytes differentiate into?
Macrophages and dendritic cells
What is the role of a macrophage?
Specific and nonspecific phagocytic and killing functions (mops up messes created by inflammation and infection). They process foreign molecules and present them to lymphocytes
What is the roles of dendritic cells?
Immature cells move to the mononuclear phagocyte system and lymphatic tissues where they trap pathogens. Once they ingest pathogens, they mature and migrate to the lymph nodes and spleen. Highly effective processors and presenters of foreign proteins
What type of immunity are natural killer cells?
Innate/ nonspecific immunity- active against cancer/ virally infected cells. not considered part of the third line defense because they do not display specificity or involve immunologic memory .
Do natural killer cells require activation?
They do not to kill cells that are missing “self” markers
What is lymph?
A plasma like liquid carried by lymphatic circulation that is formed when blood components move out of blood vessels into extracellular spaces
What is the function of the lymphatic system?
Provides an auxiliary route for return of extracellular fluid to the circulatory system.
Acts as a drain-off system for the inflammatory response.
Renders surveillance, recognition, and protection against foreign material through the use of lymphocytes, phagocytes, and antibodies
Which direction is the movement of lymphatic flow?
One direction; toward the heart; eventually returns to the bloodstream
What are the primary lymphoid organs?
Sites of lymphocytic origin and maturation- thymus and bone marrow
What are the secondary lymphoid organs?
Circulatory based; Spleen and lymph nodes; collections of cells dispersed throughout body tissues (skin and mucous membranes) .
MALT (mucosal associated lymphoid tissue) -GALT, SALT, BALT
When does the thymus start to shrink?
Gradually after puberty
What are the actions of the second line of defense: Recognition of foreign cells?
Protein receptors w/in cell membrane of macrophages (toll-like receptors)
Detect foreign molecules and signal the macrophage to produce chemicals to stimulate an immune response
What are the actions of the second line of defense: Inflammatory response?
Blood vessels briefly vasoconstrict, blood clots and mast cells release chemokines and cytokines into injured area
Nearby blood vessels dilate, inc blood flow, inc vascular permeability, inc leakage of fluid forms exudates
Collection of fluid; edema/ swelling; infiltration by neutrophils and formation of pus
Macrophages, lymphocytes and fibroblasts migrate in; initiate immune response and repair of injury; scar and loss of normal tissue
What are the actions of the second line of defense: Phagocytosis?
Survey tissue compartments and discover microbes, particulate matter, dead or injured cells
Ingest and eliminate materials
Extract immunogenic information (antigens) from foreign matter
What are the actions of the second line of defense: Interferon?
When a cell is infected with a virus, its nucleus is triggered to transcribe and translate the IFN gene.
IFN diffuses out of the cell and binds to IFN receptors on infected cells, where it induces production of proteins that eliminate viral genes and block viral replication.
What are the action of the second line of defense: Complement?
3 pathways that have different triggers but the end product is the same - Membrane Attack Complement (MAC).
Initiation: Initiator reacts with the first complement chemical which starts the cascade
Amplification and cascade: Several inflammatory cytokines are produced by enzymatic cleavage
Polymerization: Reactive site for final assembly of the MAC
Membrane Attack: Membrane attack complex destroys bacteria, cells, and enveloped viruses
What are the signs and symptoms of the inflammatory response?
Redness: Inc circulation and vasodilation in injured tissues in response to chemical mediators
Warmth: Heat given off by inc blood flow
Swelling: Inc fluid escaping into the tissue as blood vessels dilate (edema, WBCs, microbes, debris, fluid collect to form pus)
Pain: Stimulation of nerve endings
Diapedesis
Migration of cells out of blood vessels into the tissues
Chemotaxis
Migration in response to specific chemicals at the site of injury or infection
What circulating substances cause fever?
Pyrogens which reset the hypothalamus to increase body temperature; signals muscles to increase heat production and peripheral arterioles to decrease heat loss through vasoconstriction
How is an elevated temperature beneficial for fighting infections?
Inhibits multiplication of temperature- sensitive microorganisms
Impedes nutrition of bacteria by reducing the available iron (inc hepcidin during inflammation leading to dec in serum iron levels)
Inc metabolism and stimulates immune reactions and protecitve physiological processes
What are the phases of phagocytosis?
Chemotaxis: Attraction to the inflammatory reaction site by cytokines
Ingestion: Engulfment of the cell or particle
Phagolysosome formation: Cytoplasmic body formed by the fusion of a phagosome with a lysosome (adds digestive chemicals and fuses with phagosome)
Destruction: Lysosomal enzymes destroy microbe
Elimination: Debris is released by exocytosis
What is the end product of the complement system and how does it affect the cell membrane?
Membrane Attack Complement (MAC)- insertion produces hundreds of tiny holes in the cell membrane causing lyses and death of eukaryotic cells and many gram negative bacteria
What are the molecules that stimulate response of acquired specific immunity?
B and T cell lymphocytes
What are the two features that characterize acquired immunity?
Specificity: Abs produced, function only against the antigen that they were produced in response to (Abs produced for mumps will not protect against chickenpox)
Memory: Lymphocytes are programmed to “recall” their first encounter with an antigen and respond rapidly to subsequent encounters
Does cell-mediated immunity involve antibodies?
NO
Which T cells have CD4 receptors? CD8 receptors?
CD4-Helper T cells
CD8- Cytotoxic T cells
Where are Class I MHC genes located and what cells do they present antigens to?
Virtually on all cell surfaces of the body that contain nuclei
They present antigens to cytotoxic T cells w/ CD8 receptors
Where are Class II MHC genes located and what cells do they present antigens to?
Macrophages, dendritic cells, and B cells
They present antigens to helper T cells with CD4 receptors
Know the variable and constant chains, antigen binding sites, complement binding sites, fabs.
Antigen
Molecule that binds to components of the immune response and has the potential of invoking an immune response
Epitope (Antigenic determinant)
Molecular fragment of an antigen that serves as the primary signal to lymphocytes that the molecule is foreign
Immunogens
Molecules that ALWAYS provoke a specific immune response when introduced into the body
Haptens
Small foreign molecules that are too small by themselves to elicit an immune response
Alloantigens
Cell surface markers and molecules that occur in some members of the same species but not in others
Superantigens
Potent T cell stimulators that provoke an overwhelming response and massive release of cytokines
Allergen
Antigen that evokes allergic reactions
Autoantigens
Molecules on self tissues for which tolerance is inadequate and accounts for some autoimmune diseases. They can be mistaken as foreign
Opsonization
Process of coating microorganisms or other particles with specific antibodies so they are more readily recognized by phagocytes
Neutralization
Abs fill the surface receptors on a virus or the active site on a microbial enzyme to prevent it from attaching to their target cells
Agglutination
Ab aggregation; cross linking cells or particles into large clumps renders microbes immobile and increases the speed with which they are phagocytized
Complement fixation
Activation of the classical complement pathway can result in the specific rupturing of cells and some viruses
Precipitation
Aggregation of free antigen molecules increases the speed they are phagocytized
Which class of immunoglobulins is the most prevalent antibody; produced by plasma cells (primary response) and memory cells (secondary response)?
IgG; only antibody that crosses the placenta and provides protection to the fetus
Which class of immunoglobulins has two forms (Monomer- circulates in blood) and (Dimer- circulates in mucous and serous secretions)?
IgA; defends mucosal surfaces against attack by infectious microorganisms
Which class of immunoglobulins has tremendous capacity for binding antigen with 10 binding sites and is the first class synthesized following Ag encounter?
IgM
Which class of immunoglobulins serves as a receptor for antigen on B cells (usually along with IgM) and is a triggering molecule for B cell activation?
IgD
Which class of immunoglobulin is involved in allergic responses and parasitic worm infections?
IgE
What is an anamnestic response, is it primary or seconday?
After second contact with the same antigen the immune response produces a more rapid, stronger response due to memory cells; Secondary response
What is the body’s immune response when T cells are exposed to superantigens?
Drastic consequences, Provoke overwhelming immune response by large numbers of T cells:
-release of cytokines
-blood vessel damage
-Toxic shock
-Multiorgan damage
Which immunity is acquired as part of normal life experiences?
Natural Immunity
Which immunity is acquired through a medical procedure such as a vaccine and immune systems?
Artificial Immunity
Which immunity results when a person is challenged with antigen that stimulates production of antibodies; creates memory, takes time (several days), and is lasting (stimulated by natural or artificial means)?
Active Immunity
Which immunity has antibodies produced by the immune system of another human are donated to an individual; does not create memory, acts immediately, and is short term because the antibodies have a limited period of function?
Passive Immunity
What is an example of natural active immunity?
Person develops his own immune response to a microbe-childhood virus infections (ie measles or mumps)
What is an example of natural passive immunity?
Provides an infant with antibodies for the first few months
What is an example of artificial active immunity?
Individual develops an immune response after a vaccination
What is an example of artificial passive immunity?
Immunotherapy with gamma globulin injections (rabies, tetanus)
What is a live attenuated vaccine and should it be used in immunocompromised individuals?
It contains live virus particles or bacterial cells (eliminates virulence factors)
It is not suitable for people with compromised immune systems because the vaccine strain could replicate too much and cause an extensive, serious infection.
What are examples of a live attenuated vaccine?
MMR, Chickenpox, Yellow fever, Bacteria-TB, Typhoid
What is an inactivated vaccine? Why does it require boosters?
It contains whole bacterial cells or virus particles that have been killed or inactivated; does not destroy antigenicity.
It requires boosters because the microbe does not multiply.
What are examples of an inactivated vaccine?
Hepatitis A, Influenza (shot only), Polio (shot only), Rabies, Typhoid (shot)
What is a viral vector vaccine?
It uses a modified version of a different virus to deliver protection. It uses low-pathogenic viruses that produce some of the same proteins as disease-causing virus.
What is an example of a viral vector vaccine?
Ebola and COVID-19 (AstraZeneca and J&J)
What is a subunit/ acellular vaccine?
Acellular: Vaccines made from bacterial cell parts
Subunit: Vaccines made from viruses
-Made from a piece of the pathogen, not the whole organism, does not contain a live pathogen
What are examples of subunit/acellular vaccines?
Subunit- Hep B, HPV, Shingles
Acellular- Pneumococcal pneumonia, meningitis (meningococcal and Haemophilus influenzae type B)
What is a toxoid vaccine?
Consists of a purified fragment of bacterial endotoxin that has been inactivated; they elicit production of antitoxins that can neutralize the natural toxin
What are examples of of toxoid vaccines?
Typically used for boosters in teens and adults
Diphtheria, tetanus
What is resistance to the spread of an infectious disease within a population that is based on pre-existing immunity?
Herd Immunity
What is an abnormal response to self Ag due to inability to distinguish between self and nonself?
Autoimmune disease
What is an exaggerated, misdirected expression of immune responses?
Hypersensitivity/Allergies
What is deficiency or loss of immunity (incompletely developed, suppressed. or destroyed)?
Immunodeficiency disease
What are examples of type I hypersensitivities?
Anaphylaxis, Allergic rhinitis, Asthma, Eczema, Angioedema
What are examples of type 2 hypersensitivities?
Hemolytic disease of the newborn, transfusion reactions
What are examples of type 3 hypersensitivities?
Serum sickness, Arthus reaction
What are examples of type 4 hypersensitivities?
Graft rejection, GVHD, Contact dermatitis
What are examples of autoimmune diseases?
SLE, rheumatoid arthritis, graves disease (hyperthyroidism), Hashimoto’s (Hypothyroidism), Type 1 diabetes, Myasthenia gravis, MS