Anatomy chapter 20 immune system
Summarize the role of TC Cells (from the notes):
1) Activated TC cell binds to its target cell. 2) Protein called perforin is released and perforates the target cell's plasma membrane 3) TC cell then releases enzymes that enter the target cell's cytosol and catalyze reactions that degrade target cell nucleus, leading to fragmentation of the target cell's DNA and its death. TC cells can also induce the process of programmed cell death (apoptosis), or programmed cell death. 4) TC cell detaches from target cell and looks for another one
Type I hypersensitivity response (from book):
1) An allergen binds to a B cell 2) The B cell differentiates into plasma cells that secrete IgE antibodies, which bind to a mast cell sensitizing it 3) The allergen binds to the sensitized mast cell, and IgE molecules on the cell form cross-links that cause the cell to release inflammatory mediators from its granules, triggering an inflammatory response
The Big Picture of the Immune Response to a Bacterial Infection:
1) Bacteria damage cells and induce an inflammatory response, as local macrophages ingest the bacteria 2) Neutrophils enter the area in large number and phagocytize bacteria 3) In lymphatic tissue, dendritic cells activate TH cells, and B cells bind bacterial antigens and are activated by TH cells 4) B cells differentiate into plasma cells that secrete antibodies to agglutinate bacteria 5) TH cells secrete cytokines that enhance phagocyte and B cell activity
T Cell Activation, Clonal Selection, and Differentiation. Summarize the process by which T cells are activated:
1) Dendritic cells display the antigen fragments on their MHC molecules, and the MHC-antigen complex binds to the receptor of a specific naïve TH or TC cell clone triggering T cell activation known as clonal selection 2)TH or TC binds a co-stimulator (CD-4 for TH or CD-8 for Tc) and becomes activated 3)Activated TH or Tc cell clones proliferates and differentiates into effector cells (those that cause immediate effects) and memory T cells (responsible for cell-mediated immunological memory)
State the 3 Steps of Naïve B Cell Maturation:
1) Hematopoietic Stem cells from the Lymphoid line divide in the bone marrow 2) B cells mature in the bone marrow where self-reactive B cells are destroyed 3) Mature Naïve B cells leave the bone marrow and travel to lymphoid organs
List everything about neutrophils (from notes)
1) Most numerous granulocyte; phagocytes that ingest pathogens and kill with chemicals such as hydrogen peroxide, hypochlorous acid, and lysozyme -Bacterial pathogens -Damage plasma membranes of pathogens -Reside in blood and are recruited
State the 4 Steps of B cell activation, clonal selection and differentiation (from notes):
1) Naïve B cell binds its' antigen to its' B cell receptor and becomes activated. 2) Sensitized B cell processes the antigen and presents it on its class MHC class II molecules. 3) The B cell then binds to a helper T cell to become fully activated. 4) B cells differentiate into (1) Plasma cells , which secrete antibodies; and (2) memory B cells , which are long-lived cells that do not secrete antibodies but will respond to antigens upon a second exposure
The basic effects of secreted antibodies are:
1) agglutination and precipitation 2) opsonization 3) neutralization 4) complement activation 5) stimulation of inflammation
When tumor cells are discovered via immune surveillance, they are eliminated by the following process: (the big picture of the immune response to cancer cells)
1) cancer cells damage surrounding cells and induce an inflammatory response 2) NK cells migrate to the area and begin to destroy the cancer cells and secrete interferons 3) Dendritic cells ingest cellular debris and migrate to lymph nodes, where they activate naive TH and Tc cells 4) Activated TH cells secrete cytokines that stimulate effector Tc cells to kill cancer cells
there are three main series of enzymatic reactions, or pathways, by which complement proteins may be activated:
1) classical pathway 2) the lectin pathway 3) the alternative pathway
When a virus does gain entry, the response proceeds by the following steps: (immune response to the common cold)
1) infected cells trigger an inflammatory response and secrete interferons 2) Interferons prevent infection in neighboring cells and activate natural killer (NK) cells, which lyse infected cells 3) Dendritic cells activate TH and Tc cells in lymphatic tissue, and cytokines from TH cells activate B cells bound to viral particles 4) B cells differentiate into plasma cells, which secrete antibodies that bind and neutralize the virus 5) TH cells secrete cytokines that amplify the immune response, and Tc cells destroy virally infected cells
the basic immune response in three different scenarios:
1) infection with the common cold virus 2) infection with a strain of toxin-producing bacteria 3) a cancerous tumor
The stages proceed as follows:
1) local macrophages are activated 2) neutrophils migrate by chemotaxis to the damaged tissue and phagocytize bacteria and cellular debris 3) Monocytes migrate to the tissue by chemotaxis and become macrophages, which phagocytize pathogens and cellular debris 4) The bone marrow increases production of leukocytes, leading to leukocytosis
Many situations could lead to development of autoimmunity Some of these situations include the following:
1) release of self antigens not previously encountered by T cells 2) Foreign antigens mimic self antigens 3) Cells may inappropriately express class II MHC molecules 4) Certain pathogens nonspecifically activated B cells
State the 4 Steps of B cell activation, clonal selection and differentiation (from book):
1) the B cell clone binds its antigen and is activated 2) The sensitized B cell processes the antigen and presents it on its class II MHC molecules. It then binds to a TH cell, which secretes cytokines that activates the B cell 3) The B cell divides repeatedly; the resulting cells differentiate into plasma cells and memory cells 4) Plasma cells secrete antibodies
Function of TC cells (from book):
1) the activated Tc cell binds to its target cell 2) The Tc cell releases perforin, which forms pores in the target cell's plasma membrane 3) The Tc cell then releases enzymes that can now enter the target cell and fragment its DNA 4) When the target cell begins to degrade, the Tc cell detaches and searches for a new target cell
What are the three steps of the inflammatory response, part 1: effects of inflammatory mediators (from the picture)
1) tissue damage occurs 2) Damaged cells and mast cells release inflammatory mediators 3) Inflammatory mediators trigger: vasodilation of arterioles, increased capillary permeability, occurrence of pain, recruitment of other cells: chemotaxis
MHC molecules in essence serve as ------- for specific components of antigens that are then displayed to naïve T cells
"docking sites"
Chemotaxis=
"movement"
The thymus does what
"screens" these cells and mediates the destruction of those clones that cannot recognize antigens
This bacterium causes a variety of infections, the most common of which is streptococcal pharyngitis; commonly called
"strep throat"
Local macrophages are activated (in the notes)
("first responders") are activated within minutes of cellular injury; phagocytize pathogens and damaged cells; contain invading pathogens
There are two basic stages to the inflammatory response:
(1) Damaged cells release inflammatory mediators that cause local changes in the damaged tissue; and (2) phagocytes arrive at the area and clean up the damaged tissue
This reaction occurs in three situations:
(1) Foreign antigens bind to normal self antigens; (2) donor erythrocytes infused into an individual are mismatched in the ABO/Rh antigen groups; and (3) self-reactive B cells are not destroyed in the bone marrow, which leads to autoimmunity
An endogenous antigen, however, is one of two things:
(1) a foreign antigen present on a pathogen that lives inside your cell, such as an intracellular bacterium, or (2) a foreign or self antigen encoded by your DNA
Innate immunity consists of two main components:
(1) a group of antimicrobial proteins, including the antimicrobial complement proteins and a variety of cytokines; and (2) several types of cells, including neutrophils, macrophages, and NK cells
Each of these chains has two types of regions:
(1) constant (C) regions, which are relatively similar among antibodies and are responsible for many of the antibodies' effects; and (2) variable (V) regions, which are unique sequences of amino acids responsible for antigen recognition and binding
Three most common antigen presenting cells:
(macrophages, dendritic cells, and B lymphocytes)
Other classes of anti-allergy medications and treatments include the following:
-Antileukotriene: block the enzyme that produces leukotrienes, which inhibits many aspects of the allergic inflammatory response -Corticosteroids: block the synthesis of leukotrienes and prostaglandins and are potent inhibitors of allergic inflammation. They are commonly used for related allergic disorders such as asthma -Allergen immunotherapy: commonly known as "allergy shots," involves administration of the allergen in increasing doses, with the aim of inducing tolerance to the allergen and a diminished IgE response
What does a fever do (in the notes)
-Fevers denature bacteria's proteins that are enzymes so they can't carry their normal metabolism and either stop growing or die. Fever also shortens the time the immune system takes to respond because the leukocytes become more active -increase activity of leukocytes and denature enzymes in invading bacteria
There are several key differences between the two responses:
-First, the secondary immune response has a shorter lag phase (about 1-3 days), and its antibody levels peak more rapidly (3-5 days) and reach a peak 100-1000 times larger -Also, the main antibody involved in the secondary response is IgG, thanks to the fact that many of the memory B cells have already undergone class switching, whereas it's IgM in the primary response. -In addition, the secondary response lasts longer than the primary response. -Finally, the antibodies secreted in the secondary immune response are more effective
Increased capillary permeability (in the notes):
-Increased capillary permeability: increase "leakiness" of local capillary beds -Allows protein-rich fluid to leak from blood vessels into tissue spaces; leads to cardinal sign of swelling -Proteins in fluid include clotting proteins such as fibrinogen, complement proteins, and proteins needed for tissue repair
Name anti-inflammatory medications:
-Nonsteroidal anti-inflammatories (NSAIDs) ibuprofen -Corticosteroids mimic cortisol's anti-inflammatory effects; prednisone (give to auto-immune conditions because they have inflammatory problems; asthma) -Nasprin -Naproxen -Anti-leukotriene
Vasodilation (in the notes):
-Vasodilation: occurs due to histamine and bradykinin -Relax smooth in arterioles; allows blood to flow to injured tissues, and area becomes congested with blood (hyperemia) -Accounts for redness and heat accompanying inflammation as blood is warmer than surface body temperature
The four basic kinds of tissue and organ transplants, also known as grafts, are as follows:
-autografts -isografts -allografts -xenografts
Basophils are located primarily in the -----, although a related type of cell called the mast cell is located in --------
-blood -mucous membranes
Occurrence of pain (in the notes)
-bradykinin and prostaglandins, trigger action potentials in peripheral process of sensory neurons (at there end are going to be nociceptors at free nerve endings), which lead to pain; serves numerous protective functions -Lets us know when our tissues are being damaged to avoid further damage -Causes a temporary loss of function; both of which allows body to begin to repair damage
Class I MHC molecules present ------ antigens, whereas class II MHC molecules present -----antigens
-endogenous, or those synthesized inside cell -exogenous, or those cell takes in by phagocytosis
Macrophages: Neutrophils: Monocytes:
-first responders -second responders -third responders
It's easy to think of exogenous as meaning "------" and endogenous as meaning "---," but don't forget that endogenous antigens can be -------
-foreign -self -foreign or self
C3b also binds to-----—clusters of antigens bound to antibodies— and triggers their ------
-immune complexes -phagocytosis
Interferons are generally produced in response to ---------------, and are named for their capacity to
-infection with intracellular agents such as viruses or intracellular bacteria -"interfere" with the ability of the pathogens to infect other cells
Some of the main functions of activated effector TH cells include the following:
-innate immunity: stimulation of macrophages -Adaptive cell-mediated immunity:activation of Tc cells -Adaptive antibody-mediated immunity: stimulation of B cells
A vaccine may be any of several types, depending on its components, which can include the following:
-live, attenuated vaccines -Inactivated (killed) vaccines -subunit vaccines
However, their phagocytic functions appear to be less critical than those of -----, and they are primarily involved in responses to -------
-neutrophils -parasitic pathogens
List everything about interleukins (from notes)
-produced by leukocytes; -stimulate production of neutrophils by bone marrow, stimulate NK cells, trigger production of interferons, and activate T cells (stimulate leukopoiesis-white blood cells)
List everything for Interferons (from notes)
-produced by macrophages, dendritic cells, NK cells, and cells of adaptive immunity in response to infection with intracellular viruses or bacteria; -inhibits viral replication inside host cells
List everything about tumor necrosis factor (from notes):
-secreted by macrophages in response to bacteria and other pathogens; -attracts phagocytes to infection, -increases phagocytes activity and -stimulates phagocytes to release more cytokines
and they are due to the following actions of inflammatory mediators:
-vasodilation of arterioles -Increased capillary permeability -occurrence of pain -recruitment of other cells: chemotaxis
2. Activated complement proteins
trigger the release of inflammatory mediators from cells such as basophils and mast cells, and act as inflammatory mediators themselves
Several complement proteins, particularly C5a and C3a, enhance this response by
triggering basophils and mast cells to release chemicals that mediate inflammation
This is why you feel cold, or have "chills," when you have a fever—the hypothalamus is
triggering responses to elevate body temperature to the new, higher range
Stimulation of inflammation:
IgE binds mast cells and basophils, and triggers release of inflammatory mediators
his first exposure generates a primary immune response, which occurs slowly and produces few symptoms, but does result in the formation of large numbers of
IgE molecules that coat mast cells and basophils
---- antibodies are also opsonins able to coat pathogens and bind and activate phagocytes, which greatly enhances phagocytosis
IgG
Opsonization:
IgG coats antigens and binds phagocytes, enhancing phagocytosis
Most neutralizing antibodies are of either the
IgG or the IgA class
This gives us the types --------which you can remember with the mnemonic GAMED
IgG, IgA, IgM, IgE, and IgD
Several antibodies, particularly -------, bind and activate the complement proteins of innate immunity
IgM and IgG
Immune surveillance is absolutely critical to the prevention of
tumor development
The basic subunit of an antibody, is a Y-shaped protein formed from four peptide chains,
two heavy (H) and two light (L) chains
This appears to be the case with -------, in which the immune system destroys the insulin-producing cells of the pancreas
type 1 diabetes mellitus
The most common type of hypersensitivity disorder is
type I, or immediate, hypersensitivity
A decrease in the function of one or more components of the immune system results in an
Immunodeficiency disorder
Memory T cells are responsible for cell-mediated --------, in which these cells respond more quickly and efficiently to subsequent exposures to an antigen
Immunological memory
The phenomenon whereby cells of adaptive immunity respond more quickly and efficiently to subsequent exposures to an antigen.
Immunological memory
Antigenic determinant:
unique portion of antigen to which receptor binds
A -------, also known as an immunization, involves exposing an individual to an antigen to elicit a primary immune response and generate memory cells
vaccination
The cytokines known as interferons, abbreviated IFN, are produced by a
variety of cells, including macrophages, dendritic cells, NK cells, and cells of adaptive immunity
These substances trigger the
vasodilation and increased capillary permeability of an inflammatory response
The nonphagocytic cells include
NK cells and basophils
Passive immunity may be
Naturally acquired through passage from mother to fetus, and in breast milk or Artificially acquired through injection of antibodies to toxins or venoms
Neutrophils migrate by chemotaxis to the damaged tissue and phagocytize bacteria and cellular debris (in the notes)
Neutrophils migrate by chemotaxis, margination and diapedesis; neutrophil migrate (chemotaxis) to damaged tissue and phagocytize bacteria and cellular debris attracted by inflammatory mediators and activated complement proteins allow them to adhere to capillary wall (process called margiantion); increased capillary permaeability provides space between endothelial cells for neutrophils to squeeze through into damaged tissue (known as diapedesis)
What do anti-inflammatory medications do
Reduce inflammation and pain by blocking enzymes needed for production of prostaglandins and leukotrienes
Subsequent exposures to the allergen in a sensitized person result in rapid responses that occur within a few minutes. This happens because
when the allergen binds the sensitized mast cell or basophil, the IgE molecules on the cell form cross-links
Alternative pathway—
which begins at the cleavage of an inactive complement protein called C3 into its active form C3b; begins when inactive complement proteins encounter foreign cells such as bacteria or may happen spontaneously
membrane attack complex, or MAC does what
which inserts itself into the plasma membrane of the target cell, creating a pore that causes it to lyse
We can divide the arrival and activation of phagocytes into stages, based on
which phagocytes enter the area and the processes occurring there
In this second scenario, we examine the immune response to the bacterium
Streptococcus pyogenes
It then presents the antigen to a particular ------, which is specific for its individual MHC-antigen complex
T cell clone
Every distinct T cell has a receptor on its surface, called (appropriately enough) the -------- that binds a specific antigen
T cell receptor
The immune system is quite effective at eliminating cancers before they ever get the chance to damage other tissues. This effectiveness is largely due to certain cells of the immune system, especially
T cells and NK cells, that "scan" the cells in the body for tumor antigens, a function known as immune surveillance
For poorly understood reasons, other cell types may also inappropriately express class II MHC molecules. This activates
T cells and triggers an immune response to these normal self antigens
Type IV: Delayed-Type Hypersensitivity mediated by (from notes)
T cells rather than antibodies. TH cells recognize antigens bound to MHC molecules and activate macrophages and TC cells. Poison ivy and oak; tuberculin skin test
Other viruses are able to block display of viral antigens on class I MHC molecules, which prohibits
TC cell activation
Note that the immune response to this bacterium did not involve
TC cells
Adaptive antibody-mediated immunity: stimulation of B cells:
TH cells directly bind to B cells and stimulate them to proliferate and differentiate. They also secrete various interleukins that stimulate B cell proliferation and increase antibody production
Adaptive cell-mediated immunity: activation of TC cells
TH cells secrete the cytokine interleukin-2 (IL-2), which is required to activate TC cells
Innate immunity: stimulation of macrophages
TH cells secrete the cytokine interleukin-3 (IL-3), which stimulates macrophages to become more efficient phagocytes. It also causes macrophages to produce interleukin-12, which stimulates TH cells to generate more IL-3 in a positive Feedback Loop
pus:
The accumulation of dead leukocytes, dead tissue cells, and fluid leads to a whitish mixture
What good, then, does a fever do us?
The best current hypothesis is that our phagocytes function more efficiently at a slightly higher body temperature, which helps to increase the rate of recovery from whatever caused the inflammation
Inflammatory mediators trigger several effects, which you have almost certainly seen first-hand on occasion (shown in step ❸❸):
The injured area becomes red and swollen, feels warm to the touch, and hurts
there is one key difference between this response and a normal response:
The plasma cells secrete IgE instead of IgG or IgM
Inflammatory mediators attract and activate
a number of leukocytes, particularly macrophages and neutrophils
immunocompetent:
able to mount a normal response to foreign antigens
This protective mechanism prevents
abnormal TC cell activation
Secondary immunodeficiencies—
acquired through infection, trauma, cancer, or certain medications
Many of the inflammatory mediators, particularly bradykinin and prostaglandins, trigger ----------------
action potentials in the peripheral processes of sensory neurons
Antibodies, also known as immunoglobulins or gamma globulins, are the "action" component of antibody-mediated immunity, in that they are directly responsible for its
actions or effects in mediating the destruction of antigens to which they bind
This allows complement to ---- and ----- the foreign cell with its membrane attack complex
activate lyse
Indeed, in the absence of TH cells and IL-2, most TC cells fail to
activate and become unresponsive to the antigen
Many of these effects represent an integration of adaptive and innate immunity—the antibodies of adaptive immunity often -------
activate phagocytes and complement proteins of innate immunity
However, if an individual comes into contact with these pathogens, co-stimulatory signals
activate these T cells, which then attack self cells
Naïve T cells must bind their specific antigens before they become
activated
T cells respond to these antigens by becoming
activated
TNF is secreted primarily by
activated macrophages in response to certain bacteria and other pathogens
3) Cells may inappropriately express class II MHC molecules (from notes)
activates T cells that destroy self antigens in Type I diabetes mellitus
In addition, they secrete an antimicrobial cytokine that ----------
activates macrophages and enhances phagocytosis
There are two types of antibody-mediated immunity:
active and passive
Bacteria also have ways of evading the immune response, including
adaptations that allow them to attach more strongly to host cells, secretion of substances that destroy antibodies, and inhibition of phagocytosis
note that complement and cytokines have roles in -------, as well
adaptive immunity
The clumping of cells is known as
agglutination
This type of hypersensitivity is more commonly known as
allergies, and the disorders that accompany it are called allergic disorders
These drugs are able to bind to erythrocytes in certain patients, which
alters their antigens and causes them to be recognized as foreign
Immediate hypersensitivity reactions occur when an individual reacts to a foreign antigen,
an allergen
involves a systemic release of histamine and other inflammatory mediators
anaphylactic shock
Conditions such as heat stroke, certain brain diseases, and reactions to medications can cause fevers, and these fevers will not reduce with administration of
anti-inflammatory medications
What reduce fever
anti-pyretics (not inflammation)
Active immunity-make
antibodies
Passive immunity-receive
antibodies
antibody-mediated immunity involves B cells and proteins secreted by B cells, called
antibodies
Neutralization:
antibodies bind pathogenic components of toxins and block toxic effects
Agglutination and precipitation:
antibodies clump antigens together to enhance phagocytosis
This form of immunity lasts only the amount of time that the ------- which is about 3 months on average
antibodies stay in the bloodstream,
In fact, we'll see that the structure of a B cell receptor is almost identical to that of an
antibody
The second phase begins when the
antibody level in the blood rises dramatically
We now look to the second arm of adaptive immunity:
antibody-mediated immunity, also called humoral immunity
The memory B cells are responsible for
antibody-mediated immunological memory
Like memory T cells, the memory B cells respond more efficiently when the
antigen is encountered a second time
An antibody has V regions at the tips of the two arms of the protein, so the basic subunit of an antibody has two -------, one on each arm
antigen-binding sites
Like macrophages, these cells function as
antigen-presenting cells
In addition, they can function as --------, cells that display portions of the pathogens (antigens) they ingest on their plasma membranes
antigen-presenting cells (APCs)
The unique portion of the antigen to which the receptor binds is known as its
antigenic determinant
The two classes of molecules also differ in the types of ----- they display
antigens
Self Antigens:
antigens present on your own cells (glycoprotein)
However, both allografts and xenografts do contain
antigens that the organ recipient's immune system recognizes as foreign
Given the enormous number of people who suffer from allergic disorders, the market for medications that treat allergies is huge. Most medications available over the counter are -------, or medications that block cells' receptors for histamine
antihistamines
In addition to cells, the innate immune response is mediated by a variety of plasma --------, including complement proteins and several types of cytokines
antimicrobial proteins
Fevers may be alleviated, or made to "break," either spontaneously or through the action of certain medications. Medications that reduce an inflammation-mediated fever are known as
antipyretics
T cell receptor:
are found on surface of every T cell; receptor must bind a specific antigen before cell can become activated
Indeed, many anti-inflammatory medications such as ----- and ----- are also antipyretics
aspirin ibuprofen
Effects of TNF include inducing the flu-like symptoms we just described:
attracting phagocytes to the area of infection, increasing the activity of phagocytes, and stimulating phagocytes to release additional cytokines
This produces an
autoimmune disorder
This prevents the development of -------, in which B cells recognize self antigens as foreign and produce ------ that bind self antigens
autoimmunity autoantibodies
relatively rare cell that is generally nonphagocytic is the
basophil
Classical pathway—
begins when inactive complement proteins bind to antibodies bound to antigen
Note that as this is occurring, complement proteins are also ------
being activated
lack the ability to metastasize and do not divide indefinitely and are not considered cancerous
benign tumors
The actions of antibodies are based on their ability to ------, which leads to multiple effects on pathogens
bind antigens
This action, known as opsonization, makes phagocytes do what
bind more strongly to the pathogen and enhances phagocytosis
IgG antibodies, produced in higher amounts in the secondary immune response,
bind more tightly to and have a higher affinity for their antigens
In type II hypersensitivity, also known as antibody-mediated hypersensitivity, the antibodies produced by the immune response that
bind to foreign antigens also bind to self antigens
Another function of C3b and the components of the membrane attack complex is
binding to certain viruses and neutralizing them, or blocking them from infecting host cells
IgE:
binds parasitic worm antigens and allergens to basophils and mast cells, and stimulates them to release granules (degranulation) with histamine and heparin (allergic reactions)
This is mediated by C5b, which
binds to the surface of a pathogen and provides a docking site for several other activated complement proteins
Prostaglandins and leukotrienes are important targets for medications that
block the inflammatory response
Neutrophils generally reside in the ----- and must be recruited to ------ by chemical signals
blood damaged tissues
Fever is defined simply as a
body temperature above the normal range, which is generally between 36 and 38° C (or 97 and 99° F)
B cells develop in the ------from the lymphoid cell line, where billions of B cells are produced each day
bone marrow
T cells are formed in the-----, but they leave the bone marrow and migrate to the ---- to mature
bone marrow thymus
The complement system play a critical role in
both innate and adaptive immunity
In addition, they activate various components of
both innate and adaptive immunity, such as stimulating nearby cells to produce antimicrobial proteins
Our final scenario involves a disease that is responsible for over 8 million deaths per year worldwide:
cancer
These complexes deposit in various places in the body, including the
capillary beds in the kidneys, blood vessel walls, the synovial membrane of joints, and the choroid plexus in the brain
When antigens enter the body, they are ----- in these lymphoid organs
captured
2.) Foreign antigens mimic self antigens (from notes)
cardiac cell antigens resemble Strep in rheumatic fever
These four signs—redness, heat, swelling (or edema), and pain—are known as the
cardinal signs of inflammation
Given the importance of the immune system, it is probably no surprise that disorders of this system can result in
catastrophic homeostatic imbalances
The first arm of the adaptive immune system is
cell-mediated immunity
These cells respond primarily to
cells infected with intracellular pathogens (viruses and intracellular bacteria), cancer cells, and foreign cells such as those from a transplanted organ
Naïve T:
cells remain that have not yet encountered their specific antigens
Macrophages are activated by a variety of stimuli, including
certain substances present on pathogens, chemicals secreted by damaged cells, and signals from the cells of adaptive immunity
Basophils are granulocytes whose granules contain
chemicals that mediate inflammation (inflammatory mediators)
Like regular basophils, mast cells contain granules with
chemicals that trigger inflammation, particularly that involved in allergic responses
Naïve cytotoxic T (TC) cells generally interact only with
class I MHC molecules
naïve helper T (TH) cells generally interact with
class II MHC molecules
The elevated numbers of leukocytes allow the damaged area to be
cleared and any pathogens removed so that cells such as fibroblasts can begin the process of healing
Each population of T cells that can respond to a specific antigen is known as a
clone
The proteins in the fluid include
clotting proteins such as fibrinogen, complement proteins, and proteins needed for tissue repair
Antibodies can bind to antigens on more than one cell. This creates a ----- of cells that are cross-linked by their attachment to antibodies
clump
One reason for this efficiency is that memory T cells have no need of a ------, which makes the response considerably more rapid
co-stimulator
Normally, T cells specific for these antigens do not attack self cells because of the lack of
co-stimulatory signals
Antibodies also trigger inflammation indirectly through their activation of ----
complement
Activated B cells secrete antibodies that lead to
complement activation and complement-mediated lysis of erythrocytes
Opsonization involves proteins such as
complement coating the pathogen and activating phagocytes
Complement system—
consists of 30 plasma proteins produced primarily by liver; play a critical role in both innate and adaptive immunity
Though few in number, these "first responders," the only phagocytes present within the first hour or so of the inflammatory response, perform the critical function of
containing invading pathogens
When a person is infected with a parasite, eosinophils do what
cover it and release the contents of their granules
Many pathogens can induce the production of
cytokines that nonspecifically activate B cells, resulting in the production of autoantibodies
NK cells are also -----, releasing substances that destroy their target cells
cytotoxic
Macrophages also have -------, meaning that they can secrete these substances onto pathogens that are too large to ingest
cytotoxic effects
The chemicals from the granules do what
damage the parasite and either destroy it or make it easier for other immune cells to destroy
Inflammation begins when a cell is ------ by anything, including trauma, bacterial or viral invasion, toxins, heat, or chemicals
damaged
This triggers a series of events that together act to wall off the
damaged area from the rest of the body, clean up damaged cells and cell components, and bring cells and proteins to the area to repair the damaged tissue
after tissue damage occurs (such as that caused by the splinter in step ❶❶), the inflammatory response begins when the
damaged cells and nearby mast cells release inflammatory mediators
After several minutes, neutrophils from the blood migrate to the
damaged tissue
Cancer cells are formerly normal body cells that have undergone mutations causing them to
de-differentiate (become less specialized), lose control of their cell cycles, and lose their attachments to the surrounding cells and extracellular matrix
Both conditions make you feel hot, although your body temperature is actually ------
decreasing
The process of T cell activation begins with a
dendritic cell processing and displaying antigen fragments on its MHC molecules
The final group of phagocytic cells is the
dendritic cells
Once the neutrophils are in the tissue, they then begin to
destroy bacteria and other cellular debris
T cells are generally exposed to self antigens during development, and those self-reactive T cells are
destroyed
This is largely because B cell clones that recognize self antigens (self-reactive B cells) are
destroyed
Neutrophils can ingest many types of cells, but are particularly effective at
destroying bacterial pathogens
Some complement proteins are able to lyse, or "pop," the plasma membranes of pathogens, leading to their ------
destruction
TC cell __________ from target cell and looks for another one
detaches
Their ability to interact with class I MHC molecules means they can
detect abnormalities in any cell type with a nucleus, which is critical for the detection of cancer cells, foreign cells, and cells infected with intracellular pathogens such as viruses and bacteria
This is a process known as
diapedesis
However, if the B cells are not exposed to their specific antigens within a few days to a few weeks, the cells -----
die
Eventually, all of the neutrophils and many of the macrophages
die themselves
TH and TC cells have very --------, although they do interact and depend on each other to function properly
different roles
The neutrophils and macrophages in the damaged tissue go to work
digesting pathogens and damaged cells
TH or TC cells increase in number when activated and differentiate into -----, or those that cause the immediate effects, and -----
effector cells memory T cells
In the damaged tissue, monocytes
enlarge and mature into macrophages, which ingest pathogens and damaged cells with the neutrophils
The inflammatory mediators also increase capillary permeability, which provides
enough spaces between endothelial cells for neutrophils to squeeze through into the damaged tissue
TC cell then releases _________ that enter the target cell's cytosol and catalyze reactions that degrade target cell nucleus, leading to fragmentation of the target cell's DNA and its death. TC cells can also induce the process of --------, or programmed cell death.
enzymes apoptosis
Such microorganisms are especially pathogenic and difficult for the immune system to
eradicate
Note, however, that they are not present on the surface of -------, which is why blood is considerably easier to donate than other organs and tissues
erythrocytes
Although the immune response works most of the time in preventing serious homeostatic disruptions, certain pathogens have evolved ways to ----- elements of the innate and/or adaptive immune responses
evade
Instead, TH cells primarily
exert their effects through the secretion of cytokines that then activate and enhance various components of the immune response
For example, the agranulocytes known as monocytes do what
exit bloodstream and take up residence in various tissues where they develop into macrophages
The next group of cells to be attracted to the area by chemotaxis is the circulating monocytes, which
exit the blood in the same way as neutrophils
Antigens may be classified as
exogenous or endogenous
When several antibodies bind a single cell, their complement-binding sites are
exposed
innate immunity is present in the body without needing
exposure to a specific antigen
The length of time during which active immunity lasts depends on several factors, particularly the
extent of exposure
For this reason, failure of TH cells to function, which we see with conditions such as acquired immunodeficiency syndrome (AIDS), can lead to
failure of the entire immune response
an individual with a fever is referred to as
febrile
One of the most recognizable, and unpleasant, signs of illness is
fever
Interestingly, many cytokines induce "flu-like" symptoms, including
fever, chills, and aches (the aches are due to stimulation of inflammation)
IgM:
first type secreted when B-cell is activated; RBC Ab's anti-A and anti-B are this type, so agglutination can occur; can activate complement proteins. (largest of all the antibodies and has the most antigen binding sites) (agglutination and precipitation)
Many cytokines induce "--------" symptoms; including fever, chills, and body aches
flu-like
Type II: Antibody-Mediated Hypersensitivity occurs when (from notes)
foreign antigens bind to self-antigens; transfusion reactions; penicillin allergy; self-reactive B cells not destroyed leads to autoimmunity
There are ---- types of hypersensitivity disorder (numbered I-IV) that are classified according to the exact immune components causing the hypersensitivity
four
Dendritic cells—(from notes)
function as antigen-presenting cell; present to T cells and some B cells and activate them
Secondary Immune Response:
future exposure to same antigen activates memory B cells formed during the primary immune response; antibodies secreted now are more effective as they bind more tightly and have a higher affinity for their antigens
Inactivated (killed) vaccines
generally require several repeat vaccinations, known as "boosters." (weak primary immune response)
The name "antigen" comes from the phrase "antibody generating," a reference to their ability to
generate the production of antibodies from B cells
Primary immunodeficiencies—
genetic or developmental in nature
As T cells mature, they undergo gene rearrangements that lead to a huge variety of
genetically distinct T cells
Basophils—(from notes)
granules contain chemicals that are inflammatory mediators such as histamine and heparin; involved in allergic responses
Some very small antigens, called -----, are immunogenic only if they are attached to a protein carrier
haptens
The cancer cells invade and destroy ------ as they crowd out normal cells and compete for nutrients
healthy tissues
In this way, they "-----" immune response, hence their common name
help
cell-mediated immunity involves the different classes of T cells, including the
helper T (TH) cells, also known as CD4 cells, and the cytotoxic T (TC) cells, also known as CD8 cells
The common cold is due to a variety of viruses that typically have a -------, which is why researchers have yet to develop a vaccine for the pathogens
high mutation rate
commonly referred to as a "-----------."
high white cell count
Pyrogens cause the hypothalamic thermostat to reset to a
higher range
Inflammatory mediators such as ------ and ------ are potent vasodilators
histamine bradykinin
These links cause the cell to release the inflammatory mediators in its granules, including
histamine, leukotrienes, and prostaglandins
These mediators can include
histamine, serotonin, cytokines, a peptide called bradykinin, and a group of related lipids known as prostaglandins and leukotrienes
This allows them to create chemicals such as
hydrogen peroxide, hypochlorous acid, and hydroxide anions, which kill ingested pathogens
Pyrogens act on the -----, the small component of the diencephalon (the central core of the brain) that regulates the homeostasis of many regulated physiological variables
hypothalamus
Regardless of what makes the fever break, it results from the
hypothalamus being reset back to the normal temperature range
Type III: Immune Complex-Mediated Hypersensitivity mediated by (from notes)
immune complexes or clusters of soluble antigens bound to antibodies; deposit in organs
Normally, several processes ensure immune self tolerance—that the
immune system does not react to self antigens and damage the body's own tissues and cells
This ensures that an individual is -----, or able to mount a normal response to foreign antigens
immunocompetent
Only certain antigens generate a response from the immune system. Those with this capability are called
immunogens "immune generating"
Each antibody is named with the two-letter abbreviation "Ig," which stands for "-------," followed by a letter that designates its ------
immunoglobulin class
Involves B cells and proteins secreted by B cells, called antibodies also called _________________ or _________________. B cells have B cell receptors that bind to specific ___________, and a group of B cells that bind to a specific antigen is known as a ----- . The antibodies secreted by a B cell _____ bind to the same antigen as the B cell receptor
immunoglobulins gamma globulins antigens clone clone
immunosuppression
impaired ability to provide an immune response
IgA:
in glandular secretions like mucous, tears, saliva; functions in agglutination and neutralization (found in secretions like saliva and milk in oral cavity protecting you from invading organisms)
Complement proteins circulate primarily in their
inactive forms and must be activated by a complex cascade of events mediated by enzymes
In severe infections, the amount of TNF secreted can ------ dramatically
increase
Activated T cells in turn secrete substances that
increase the activity of the macrophages, in an example of a positive feedback loop
Cytokines produced by the activated phagocytes act on cells in the bone marrow to
increase the production of neutrophils and monocytes over the next 3-4 days
This results in
increased blood flow to the damaged tissue, and the area becomes congested with blood, a condition known as hyperemia (hyper- = "above" or "elevated," -emia = "blood")
Act on hypothalamus and raises set point so body responds by
increasing body temperature by increasing muscle activity such as shivering
The cytokine known as tumor necrosis factor, or TNF, is named for the fact that it was originally discovered through its ability to
induce necrosis (death) of tumor cells
This is evidenced by the fact that fevers may be seen in the absence of any
infectious pathogens following severe trauma, burns, or even childbirth
Although we tend to associate fevers with infection, remember that fever is a nonspecific response and can tell you only that widespread ------ is present
inflammation
It is also important to remember that occasionally fevers are not related to
inflammation
From a clinical perspective, fever is a critical warning sign of ------ processes occurring somewhere in the body
inflammatory
tissue damage initiates inflammatory response as damaged cells and local mast cells release ---------
inflammatory mediators
In addition, certain activated complement proteins trigger the release of
inflammatory mediators from cells such as basophils and mast cells, and act to a limited degree as inflammatory mediators themselves
Recruitment of other cells (in the notes)
inflammatory mediators recruit leukocytes to damages tissue (chemotaxis) particularly macrophages (first responders) and neutrophils (second responders) while complement proteins are simultaneously being activated
When they deposit in these organs and tissues, they initiate an
inflammatory reaction that attracts neutrophils and causes damage to the affected areas
Like all innate responses, the series of events known collectively as the -------- occurs in reaction to any cellular injury
inflammatory response
It is common to associate pus with infection; however, pus indicates only that an
inflammatory response took place
One of their primary actions is to
inhibit viral replication inside host cells
Most antipyretics work in the same manner as anti-inflammatories, by
inhibiting the formation of prostaglandins
The antibody IgE directly triggers inflammation by
initiating the release of inflammatory mediators from mast cells and basophils
This is one of many instances of ----- and ------ immunity working together
innate adaptive
Primary Immunodeficiency Disorders may impair either
innate or adaptive immunity
Like inflammation, fever is an ------ to cellular injury
innate response
TH cells are required for normal function of all components of the immune system, including
innate, antibody-mediated, and cell-mediated immunity
Full T cell activation requires the
interaction of the naïve T cell with other molecules on the cells, called co-stimulators
For example, many viruses block or inhibit cytokines such as
interferons
Isografts—
involve organs and tissues transplanted between two genetically identical individuals; like autografts these result in no response from Tc cells because antigens bound to class I MHC molecules are not recognized as foreign (uncommon)
Autografts—
involve tissue transplanted form one site to another in same individual; skin grafts; no response from Tc cells because antigens bound to class I MHC molecules are not recognized as foreign
vaccination:
involves exposing an individual to an antigen to elicit a primary immune response and generate memory cells
Lectin pathway—
is initiated when proteins called lectins bind to carbohydrates on the surface of microbes
However, an intracellular bacterium, or one that lives inside its host cell, causes a response that involves TC cells because
its antigens are displayed on class I MHC molecules
The primary function of cytotoxic T cells is evident from their name—they
kill other cells, specifically those with foreign antigens bound to class I MHC molecules
Inflammatory mediators increase the permeability, or "------," of local capillary beds
leakiness
The structure of most capillaries prevents them from
leaking all of their contents to the interstitial fluid
The final response occurs in the bone marrow, where
leukocytes are produced
This leads to an elevated number of circulating leukocytes, a condition called
leukocytosis
However, monocytes live ------ and are more ----- than neutrophils
longer aggressive
This causes the hypothalamus to sense the febrile temperature as being too high, and it triggers negative feedback mechanisms to
lower the body's temperature
Naïve B cell clones that complete maturation enter the circulation and eventually take up residence in
lymphoid organs such as the spleen and lymph nodes
The phagocytic cells include
macrophages, neutrophils, eosinophils, and dendritic cells
The name comes from the fact that MHC molecules are
major determinants of compatibility among tissue and organ donors and recipients
T cells cannot directly interact with an antigen. Instead, they can interact only with pieces of antigen bound to glycoproteins, called
major histocompatibility complex (MHC) molecules
These mutations result in a mass of unspecialized cells called a ------, whose cells are capable of indefinite growth and can -----, or spread, through the lymphatic system or blood to other parts of the body
malignant tumor metastasize
how this works: The inflammatory mediators make the capillary endothelium in the damaged area "sticky," and the neutrophils adhere to the capillary wall, a process called
margination
Live, attenuated vaccines:
meaning that their ability to cause disease has been greatly reduced (weakened) -varicella (strong primary immune response)
Together these complement proteins form a structure collectively known as the
membrane attack complex, or MAC
It results in the production of
memory cells and large numbers of antibodies and is, therefore, relatively long-lasting, ranging from years to a lifetime
The granulocytes known as eosinophils are phagocytes that can
migrate from the blood to the tissues where they are needed
There are ----- of different clones in the immune system, but only a few cells of each clone exist in the ----- at any given time
millions body
Then if the individual is exposed to the antigen a second time, a secondary immune response will occur and symptoms will be
minimal
Within ----- of a cellular injury, macrophages already present in the tissue enlarge and begin to ---------
minutes phagocytize pathogens and damaged cells
Type I: Immediate Hypersensitivity: (from the notes)
most common type known allergies; First exposure to an allergen: the allergen binds a B cell which triggers B cell differentiation into plasma cells that secrete IgE antibodies. Subsequent exposures to identical allergens in a sensitized individual result in a rapid response that occurs within a few minutes. Local reactions, such as those in the nasal cavity, produce the common symptoms of runny nose and itchy eyes; urticaria (hives); asthma; anaphylactic shock;
Allografts—
most common type of grafts; involve organs and tissues transplanted between two nonidentical individuals of same species (most common is the kidney)
Each of these situations also relies on
multiple genetic factors that increase an individual's tendency to develop autoimmunity
One of the biggest challenges to effective vaccination is posed by pathogens that have a high rate of ------:random changes in their genetic makeup
mutation
1) Release of self antigens not previously encountered by T cells (from notes)
myelin sheath: blood brain barrier and multiple sclerosis
The first group of nonphagocytic cells we'll cover is the
natural killer (NK)
MHC molecules are found on
nearly nucleated cells
A rejected organ or tissue first fails to function properly, and then its cells die as TC cells destroy them, a condition known as
necrosis
Bacterial toxins, viral proteins, and animal venoms are molecules with specific components that are harmful. Antibodies bind to these components, as well as certain viruses and bacteria, and prevent them from interacting with our cells. This renders the toxin inactive, which is known as
neutralization
The most predominant granulocyte is the
neutrophil
Inflammatory mediators and activated complement proteins attract
neutrophils and enable them to leave the blood and enter the tissue
Passive immunity results in
no memory cells formed and no lasting protection
The inflammatory response is a
nonspecific response to cellular injury
NK cells (natural killer cells) cytotoxic: (from notes)
nonspecifically kill cancerous cells and cells infected with viruses; secrete antimicrobial cytokine that activates macrophages and enhances phagocytosis
Certain viral and bacterial antigens closely resemble
normal self antigens
These cells, which are known as naïve T cells because they have
not yet encountered their specific antigens, eventually reside in the blood, lymphoid organs, or other lymphatic tissue
Autoimmune disorders may be localized and affect only ---- organ or tissue, or they may be systemic and affect ----parts of the body
one multiple
The complement protein C3b acts as an -----, binding both pathogens and phagocytes
opsonin
An exogenous antigen is one that
originates outside the cell and must be taken into the cell by phagocytosis
Although one tends to blame the pathogen for these symptoms, usually it is your ---------- that actually causes them
own immune response
When neutrophils are activated, their
oxygen consumption increases, a phenomenon called the respiratory burst
This leads to the extremely important and underappreciated effect of ------, which serves numerous protective functions
pain
IgD :
participates in antigen recognition and the activation process (B cell receptors)
is found when preformed antibodies are passed from one organism to another
passive immunity
Macrophages kill
pathogens they have ingested with chemicals, including hydrogen peroxide and hypochlorous acid (the active component in bleach)
An example of the first situation is the reaction to antibiotic medications such as
penicillin
These other substances must usually be coupled with a ----- to function fully as an antigen
peptide
Antigens are usually-----, but they may also be substances such as carbohydrates, lipids, and metals (nickel is a notoriously antigenic metal)
peptides
Protein called ________ is released and _________ the target cell's ------
perforin perforates plasma membrane
The third and final phase of antibody-mediated immunity is the
persistence of a population of B cells called memory B cells that react much more rapidly and efficiently if the antigen is encountered again
Certain granulocytes and agranulocytes can function as
phagocytes
Immune complexes are generally cleared by ------, but certain complexes are difficult for macrophages to ingest
phagocytes
Like macrophages, neutrophils are highly effective
phagocytes
The second component of the inflammatory response deals with the
phagocytes that ingest pathogens and cellular debris
We can divide the cells of innate immunity into two types
phagocytic cells and nonphagocytic cells
Unlike most other immune cells, helper T cells have no
phagocytic or cytotoxic abilities
the process by which cells ingest particles and other cells, called
phagocytosis
activated B cells divide into two populations:
plasma cells and memory B cells
Common allergens include
pollen, dust mites, pet dander, peanuts, shellfish, and bee venom
Clone:
population of T cells that respond to a specific antigen; millions of different clones in immune system, but only a few cells of each clone exist in body at any given time
However, sometimes these processes fail, and the result is
populations of self-reactive T cells or of B cells that secrete antibodies that bind to self antigens, called autoantibodies
Note that both processes end up with the same result:
portions of antigens displayed on the plasma membrane attached to MHC molecules. These MHC-antigen complexes then interact with and activate T cells
Similar to agglutination is the process called ------, which involves soluble antigens (proteins and other biological molecules) instead of whole cells
precipitation
This function is evident from the name, as opsonin means "--------"
prepare for eating
The substances they ingest are
presented to T cells (and, to a lesser extent, B cells), which are then activated
This clears these complexes from the circulation, which is critical to
preventing them from lodging in different tissues around the body
There are two basic types of immunodeficiency disorders:
primary immunodeficiencies, which are genetic or developmental in nature, and secondary immunodeficiencies, which are acquired through infection, trauma, cancer, or certain medications
AIDS Helper T cells are ------- Helper T cells are central to -------- Most patients die from "-------"
primary target both antibody and cell-mediated responses opportunistic infections
4) Certain pathogens nonspecifically activate B cells (from notes)
produce cytokines SLE (systemic lupus erythematosus)
The name "interleukin" means "between leukocytes," which reflects the fact that they are
produced by leukocytes and many of their actions affect other leukocytes
Interferons are actually partly responsible for
producing some of the symptoms associated with flu-like illnesses, including muscle aches and fever
IL-2 also stimulates the
proliferation of TC cells
T cell receptors normally have low affinity for their MHC-antigen complexes, which is a
protective mechanism that prevents unnecessary naïve T cell activation
This allows
protein-rich fluid to leak from the blood vessels into the tissue spaces, and leads to the cardinal sign of swelling
cytokines are:
proteins produced by several types of immune cells that enhance the immune response in some way
A wound filled with pus is said to be
purulent
Indeed, certain bacterial species, known as ------, are known for producing quite purulent wounds
pyogenic bacteria
Fever is initiated when chemicals called ------ ; pyro- = "fire," -gen = "causing") are released from damaged cells or certain bacteria
pyrogens
For this reason, innate immunity is typically
quick to respond to a pathogen, generally within seconds to a few hours
During this time, neutrophils stored in the bone marrow are released into the blood, which leads to a
rapid, acute rise in the level of circulating neutrophils
This leads to a
reaction from the immune system that, if left untreated, results in rejection of the organ or tissue
Active immunity may be
received naturally through exposure to an antigen via infection or artificially via a vaccination
NK cells are lymphocytes with the remarkable ability to
recognize cancerous cells and cells infected with certain viruses in spite of the fact they cannot recognize antigens
Other T cell clones, known as self-reactive T cells do what
recognize self antigens as foreign and would attack your cells if released into the circulation
When the T cell receptor ------and ------ this complex, multiple changes are triggered inside the T cell and the process of activation begins
recognizes and binds
Some T cell clones are capable of ------ and ------ to pathogens, whereas others are not
recognizing responding
The final effect of inflammatory mediators is the
recruitment of leukocytes to the damaged area through a process known as chemotaxis
injured area becomes
red and swollen, feels warm to touch, and hurts
Hyperemia accounts for the
redness and heat that accompany inflammation (because blood is warmer than the body's surface)
4 cardinal signs of inflammation
redness, heat, swelling (edema), pain
Xenografts—
relatively rare procedures that involves organs and tissues transplanted between two individuals of different species, such as a pig and a human (most common is heart valve)
T cells that do survive this screening are
released into the circulation when they mature
In some cases, it also causes a temporary loss of function—you're unlikely to run on your broken ankle when it's throbbing—which allows the body to -------
repair the damage
Activated local macrophages are generally the first cells to
respond to a cellular injury, where they ingest other cells and cellular debris
Currently, there are a number of drug therapies for HIV-1 including
reverse transcriptase and protease inhibitors and entry blockers
This occurs with the disease -------, which occurs after infection with a specific species of streptococcal bacterium whose antigens resemble those on the heart muscle
rheumatic fever
Some macrophages remain fixed in certain tissues, whereas others
roam freely in the body
They appear to do this by
scanning the cells for irregularities and by reacting to cells that have bound to antibodies (another example of innate and adaptive immunity working together)
it is not the first exposure, it is the ------
second
Antigens present on your own cells, called -----, are not immunogens in your body
self antigens
These self-reactive T cells are also destroyed, ensuring
self tolerance and preventing our T cells from attacking our own cells
Self Tolerance:
self-reactive T cells are destroyed; prevent T cells from attacking self cells
Autoimmune Disorders occur
self-reactive T cells or B cells that secrete antibodies bind to self antigens, called autoantibodies
As with type I hypersensitivity, TH cells must be ----- by an initial exposure, and the reaction occurs with subsequent exposures
sensitized
Such mast cells and basophils are said to be
sensitized
This results in the possibly fatal condition of ------, in which a marked drop in blood pressure, failure of organs such as the kidneys and liver, inappropriate blood clotting, and a severe drop in blood glucose concentration seriously disrupt homeostasis
septic shock
What are the three steps of the inflammatory response, part 1: effects of inflammatory mediators (from notes)
1. Release of inflammatory mediators 2. Activated complement proteins 3. List and describe the 4 Cardinal signs of inflammation
List everything about macrophages (from notes)
1.) First cells to respond to a cellular injury, where they ingest other cells and cellular debris 2.) Macrophages kill pathogens with chemicals, including hydrogen peroxide and hypochlorous acid (active component in bleach) Functions as 3.) Antigen-presenting cells (APCs) cells that display portion of pathogens (antigens) they ingest on their plasma membranes 4.) Activate T cells with these antigens that secrete substances that increase activity of macrophages; example of a positive feedback loop
There are several cytokines that are involved in innate immunity, including the following:
1.) Tumor necrosis factor 2.) Interferons 3.) Interleukins
1. Release of inflammatory mediators:
1.) by damaged cells and local mast cells including histamine, serotonin, cytokines, bradykinin, prostaglandins and leukotrienes
Describe the 5 effects of Activated complement proteins
1.) cell lysis by formation of a membrane attack complex (MAC) 2.) enhanced inflammation 3.) neutralization of viruses 4.) enhancing phagocytosis due to opsonization 5.) clearance of immune complexes.
List everything about Eosinophils (from notes)
1.) phagocytes that can migrate from blood to tissues where they are needed -parasitic pathogens -cover parasites and release contents of their granules -chemicals from granules damage parasite and either destroy it or make it easier for other immune cells to destroy
There are two types of MHC molecules:
1.Class I MHC molecules 2.Class II MHC molecules
They remain in the bone marrow to mature, but only about ----- of these cells finish their maturation process
10%
This includes the familiar sign of
shivering, increased muscle activity that generates heat to bring body temperature to the new set point
Antibody Structure (from notes):
2 heavy (H) and 2 light (L) chains, constant regions where complement-binding sites are found and variable regions where antigen-binding sites are located
complement system consists of around
30 plasma proteins that are produced primarily by the liver
Antibody levels peak about 7-14 days after the antigen is encountered. It is during the lag phase that you generally feel "------"
sick
For this reason, you may not feel "-----" when exposed to the same antigen or may experience only mild symptoms
sick
IgG:
80% of all Antibodies; targets viruses, bacteria; can cross placenta (anti-Rh); function in opsonization, neutralization and activates complement (most common making up 80 percent, the rest are 25 percent) (long lasting antibody u are going to produce to protect you)
Over ----- of all T cells die in the thymus in this manner
95%
Mast cells—(from notes)
similar function as basophils. Mast cells are in the tissues while basophils are in the blood. They will also secrete histamine
Primary Immune Responses:
A B cell specific for that antigen recognizes it, the activated B cell proliferates and differentiates into plasma and memory B cells, and plasma cells begin to secrete antibodies
Note that neutrophils are able to ingest only a
single microbe before they themselves also die
The primary immune response is effective, but it's -----—there is an initial 4- to 5-day lag phase as the B cells proliferate, differentiate into plasma cells and memory cells, and begin to secrete antibodies
slow
This response is much ------than that of neutrophils, because it takes several hours for monocytes to mature and there are far fewer monocytes than neutrophils stored in the bone marrow and the circulation
slower
dendritic cells are the most important ----- in the immune response
APCs
Complement activation:
Antibodies activate complement proteins, leading to cell lysis
Examples of these effects include
stimulating production of neutrophils by the bone marrow, stimulating NK cells, triggering the production of certain types of interferons from different leukocytes, and activating T cells
Although it might seem that you frequently get sick with a cold, in truth most pathogens, viruses included, are deterred by the body's ----- and so never even gain entry into the body
surface barriers
class II MHC molecules are found only on the
surfaces of antigen-presenting cells, including dendritic cells, macrophages, and B lymphocytes
The pus is generally absorbed into the ----------- when healing has completed
surrounding tissues and lymphatic vessels
These include ----- and ------------ serving the skin, which makes the skin appear red or flushed
sweating dilation of the blood vessels
When too high what happens
sweating and vasodilation occur
This is the proposed mechanism behind the disease --------, in which infection with a certain virus is followed by production of antibodies to proteins in DNA, erythrocytes, platelets, and leukocytes
systemic lupus erythematosus
Activated TC cell binds to its ------
target cell
The antibodies secreted by a B cell clone bind to the same antigen as
the B cell receptor
Autografts and isografts result in no response from TC cells because
the antigens bound to class I MHC molecules are not recognized as foreign
Subunit vaccines
the bacteria responsible for tetanus and diphtheria secrete disease-causing toxins. Vaccinations called toxoids contain inactivated toxins from these bacteria, which induce the immune system to produce antibodies to the toxins (weak primary immune response)
active immunity, so named because
the body's cells actively respond to an antigen
The hypothalamus normally functions as
the body's thermostat, and maintains body temperature within the normal range through a series of negative feedback loops
The first phase involves a
B cell clone recognizing its specific antigen, which triggers it to undergo changes and start secreting antibodies
Just as T cells have T cell receptors, B cells have ------ that bind to specific antigens, and a group of B cells that bind to a specific antigen is known as a ------
B cell receptors clone
only ---- and ------ normally display class II MHC molecules
B cells antigen-presenting cells
an antigen is a substance that
B or T cells recognize
The bone marrow increases production of leukocytes, leading to leukocytosis (from notes)
Bone marrow increases production of Leukocytes, leading to leukocytosis; bone marrow increases production of leukocytes due to cytokines produces by activated phagocytes, leading to elevated number of leukocytes in blood called leukocytosis
Pathogens that have moved past our surface barriers next meet our bodies' second line of defense:
the cells and proteins of innate immunity
Let's start with one of the most frequent infectious conditions in the world:
the common cold
There are five basic classes of antibody, which are grouped according to the structure of their
C regions
The three pathways converge when
C3b is activated, which in turn cleaves the inactive protein C5 into its active component C5b
HIV-1 preferentially binds and interacts with cells displaying
CD4 molecules so therefore _____________ T cells are affected
Disorders take three forms:
the immune system may overreact and damage tissues, which results in a hypersensitivity disorder; (2) one or more components of the immune system may fail, which is an immunodeficiency disorder; and (3) the immune system may treat self antigens as foreign and attack the body's own tissues, which is an autoimmune disorder
You have probably experienced at least one type of the group of immune system dysfunctions known as the hypersensitivity disorders, in which
the immune system's response causes tissue damage
This process is known as ----- because the antigen "selects" a particular T cell clone
Clonal selection
Autoimmunity results in a type II, III, or IV hypersensitivity reaction, which is what produces
the organ and tissue damage characteristic of the disease
Class I MHC molecules are found on
the surface of the plasma membrane on nearly all nucleated cells
This is particularly true of TC cells, because
their effects are so destructive when they are activated
Cytokines have been studied for their ------ uses in conditions such as persistent viral infections and certain cancers
therapeutic
However, some antigens are sequestered, meaning that
they are not exposed to the developing T cells
TH cells are so important to B cell activation that they derive their name from this role—
they are required to "help" initiate B cell response
What do they do?
they relax the smooth muscle in arterioles supplying the damaged tissue, causing the vessels to "open up" and blood to flow through them more freely
The antibody-mediated immune response has ---- basic phases
three
Immunocompetent:
thymus "screens" T cells and mediates destruction of those clones that cannot recognize antigens
Pain lets us know when our -----------
tissues are being damaged so that we can try to avoid further damage
major histocompatibility complex (MHC) molecules:
Glycoproteins found on the surface of cells that bind and display antigen fragments.
AIDS caused by
Human Immunodeficiency Virus 1 (HIV-1), which is spread through contact with infected blood, semen, vaginal fluid, or breast milk
At this higher range, the hypothalamus interprets normal body temperature as being -------, which triggers the negative feedback loop
too low
TC cells are activated in the same way as TH cells, with the addition that they require
IL-2 from TH cells to activate fully
Outline the 4 basic steps of how exogenous antigens are processed and displayed by Class II MHC molecules:
❶❶ The cell ingests a pathogen by phagocytosis. ❷❷ The phagocytic vesicle fuses with a lysosome; the pathogen is degraded and its antigens are fragmented. ❸❸ The lysosome fuses with a vesicle from the RER that contains class II MHC molecules, and an antigen fragment binds to the MHC molecule. ❹❹ The MHC-antigen complex is inserted into the cell's plasma membrane.
Outline the 4 basic steps of how endogenous antigens are processed and displayed on Class I MHC molecules:
❶❶ The cell synthesizes either a self antigen or a foreign antigen. ❷❷ The antigen is broken down by enzymes in the cytosol. ❸❸ An antigen fragment containing the antigenic determinant is transported into the rough endoplasmic reticulum (RER) and is coupled with a class I MHC molecule in the RER membrane. ❹❹ The MHC-antigen complex leaves the RER by a vesicle and is inserted into the cell's plasma membrane.
