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Transcript
Immune
System
Carlos Penilla
Vocabulary
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Passive Immunity- temporary immunity gained by taking in anti-bodies or immune
cells (lasts only a few weeks or months) temporary because the system has been
stimulated by antigens
Active immunity- immunity gained from recovering from an infectious disease
Acquired Immunity- when the body develops an immunity for a specific pathogen by
slowly building up a resistance to it
Primary Immune Response- selective proliferation and differentiation of lymphocytes
that occurs first time the body is exposed to an antigen
Secondary Immune Response- when the individual is exposed to the some antigen at
some later time, the response is faster, of greater magnitude, and more prolonged
Humoral Immunity- involves B cell activation and results from the production of
antibodies that circulate in the blood plasma and lymph, fluids that were long ago
called humors
Cell mediated response- depends on the action of T-cells, immunity gained through
the transfer of humoral immunity (antibodies)
Nonspecific Defenses against
Infection
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The skin and the mucous both play their part as a physical barrier as well as a way to
use chemical defenses to counter pathogens
In addition the secretions from the sebaceous and sweat glands give the skin a pH
between 3-5, this pH is acidic enough to prevent colonization of microbes
Saliva, tears, and mucous are all secreted and constantly cover exposed epithelia
The lysozyme (protective protein) also helps by digesting the cell walls of many
bacteria thus destroying many bacteria entering the upper respiratory tract and the
opening around the eyes
Stomach contains a highly acidic environment, which destroys most microbes before
they enter the intestinal tract (hepatitis A is a virus which can survive the gastric acids)
Phagocytosis- the ingestion of invading organisms by certain types of cells (associated
intimately with an effective inflammatory response)
Inflammation and phagocytosis help limit the spread of microbes in advance for
specific immune responses
Phagocytic and Natural Killer
Cells
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Neutrophils are a class of phagocytic cells that contribute to 60%-70% of all the white
blood cells in the body (while they do attack damaged cells and destroy them, they tend
to self destruct after killing off the damaged cell and only have a normal life span of a
few days
Monocytes make up only 5% of the white blood cells in your body but they are much
more effective, they circulate the blood for only a few hours then migrate to tissues
were they will become macrophages
Macrophages- largest phagocytic cells, are especially effective, live the longest (engulf
a microbe in a vacuole that then fuses with a lysosome
Lysosome then breaks it down in one of these two ways: first it can make toxic
versions of Oxygen; superoxide anion or nitric oxide. The second version would be the
use of lysosomal enzymes to digest microbial components
Although some microbes have evolved and can avoid phagocytic destruction for
example some bacteria have an outer capsule that prevents the macrophage from
attaching, others are engulfed but are resistant to lysosomal destruction and can even
reproduce inside a macrophage(those are especially a problem)
Continued…
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About 1.5%of leukocytes are eosinophils which specialize in defending against
parasitic invaders
Natural Killer cells or NK cells do not attack the virus directly, it attacks the virus
infected body cells instead (cause the cell to lyse)
Inflammatory Response
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When a microorganism enters a damaged or cut area it triggers an inflamatory response
During this response the precapillary arteries dilate and postcapillary venules constrict which
increases the ammount of blood In the area
Causes the redness and heat
Histamine- a type of chemical signal that is released by cells of the body in response to tissue injury
(increases dilation and permeability)
Basophils produce histamine and mast cells( found in connective tissue)
Leukocytes and damaged tissue cells also release prostagladins to promote blood flow to the damaged
area, this helps by delivering the elements that help clot the wound
This also helps the migration of phagocytic cells from the blood into the injured tissues (chemokines
also attract phagocytic cells to the area)
Another systematic response is a fever which starts when it picks up certain toxins released from the
Certain leukocytes release pyrogens which increase the temp. of the body (high fevers can be
dangerous moderate ones help the body fight by limiting growth of microorganism)
Wide spread of inflammation (septic shock) is the most common cause of death U.S. critical care
units
Antimicrobial Proteins
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Complement system- a type of system that carries out a cascade of steps leading to the
lysis of microbes
Some complement components help chemokines attract phagocytic cells to the sites of
infection
Interferons- are nonspecific defense proteins that are secreted by virus infected cells
(don’t help the cell that has been infected instead they warn the nearby cells which then
develop chemicals that inhibit viral reproduction)
That effect limits the cell to cell spread of viruses in the body
In addition to its role as an antiviral agent it also activates phagocytes, which enhances
their ability to ingest and kill microorganisms
Specific Immunity
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Lymphocytes(key cells in immune system) generate efficient selective immune
responses that eliminate particular invaders in the body(B cells and T cells are the two
main lymphocytes)
Bothe circulate in the blood, concentrated in: spleen, lymph nodes and other lymphatic
tissues
Antigen- foreign molecule that causes a specific lymphocyte to respond
B and T cells respond to different types of antigens, respond in different ways that
compliment one another
Antibodies- are secreted by B cells to counter specific antigens based on the shape of
the molecule
B cells and T cells recognize specific antigens by using their antigen receptors
T cell receptors- are similar to membrane antibodies, but they are never produced in a
secreted form
B and T cells are created long before coming in contact with foreign antigens, through
this the body already has an enormous variety of B and T cells with specific receptors
Antigens interact with specific
lymphocytes
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Clonal Selection-A lymphocyte is stimulated to divide and differentiate by the
microbes antigens
Makes two clones, one that carries short lived cells that combat the same antigen
(effector cells) or long living cells with receptors for the same antigen in case it needs
to fight it off later in life (memory cells)
Primary Immunity Response- selective proliferation and differentiation of lymphocytes
that occurs the first time the body is exposed to an antigen
During the 10-17 day phase of the P.I.R. selected b cells and t cells make antibody
producing effector B cells known as plasma cells
Secondary immune response- occurs when the individual is exposed to the same
antigen at some later time, this response is much faster 2-7 days and of greater
magnitude and is more prolonged
Secondary response has a much larger amount of antibodies produced and they are
more effective
Distiguishing of Self from
Nonself
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Lymphocytes that migrate from the bone marrow to the thymus develop into T cells
whereas lymphocytes that continue to mature in the bone marrow become B cells
All lymphocytes are tested to see if there receptors match other molecules in the body
which would then lead to harming the body, if such a lymphocyte is found they are
either rendered non functional or are destroyed by apoptosis (programed cell death)
MHC molecule carry a fragment of intercellular protein antigen in its hemock groove,
it then shows it to a antigen receptor so T cells become aware of an infectious agent
(two classes of MHC molecules)
Cytotoxic T cells-have antigen receptors that bind to protein fragments (respond to
presentation of fragments by killing the infected cells)
Helper T cells- have receptors that bind to peptides displayed by the body’s II MHC
molecules
Wide distribution of I MHC molecules is critical to our health
Class II MHC are mostly macrophages and B cells, these antigen presenting cells
collect remnants and present them to helper T cells which incite other cells types to
fight the pathogen
Immune Responses
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Humoral Immunity- involves B cell activation and results from the production of
antibodies that circulate in the blood plasma and lymph, fluids that were long ago
called humors
Cell mediated response- depends on the action of T-cells, immunity gained through the
transfer of humoral immunity (antibodies)
Circulating antibodies of the humoral response defend mainly against bacteria, toxins,
viruses that are present in body fluids
T cells of the cell mediated response are active against protozoa, fungi, and parasitic
worms
Cell mediated response is crucial for fighting off cancer cells classified as nonself
Closer look at Helper T-Cells
and Cytotoxic T cells
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Found mainly in cell types that engulf foreign antigens
Interaction between APC’s and helper T cells is greatly enhanced by the presence of
CD4 (surface protein present on most helper T cells)
Activated helper T cells secrete several cytokines, proteins or peptides that stimulate
other lymphocytes
Antigen activated cytotoxic T lymphocytes kill cancer cells and cells infected by
viruses or other intercellular pathogens
A cytotoxic T cell when activated by I MHC and stimulated by IL-2 from a helper T
cell becomes an active killer, kills its target cell(APC) by releasing perforin a protein
that forms pores in the target cells membrane
Ions and water then flow into the target cell which swells and eventually lyses this
forces the pathogen into the open were it is destroyed by the circulating antibodies
The body defends against tumors in a similar way, but when this fails the body uses
Natural Killer cells that can also lyse virus infected and or cancer cells
Humoral Response
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Once stimulated by both cytokines and antigens the B cells proliferate and differentiate
into a clone of antibody secreting plasma cells and a clone of memory B cells
Those antigens are called T dependent antigens because they can stimulate antibody
production only with help from Th cells
T independent cells- polysaccharides and proteins with many identical polypeptides
B cells have class II MHC molecules
B cells are much more specific to which antigen it binds too as opposed to
macrophages
APC’s are general B cells specify
Humoral response stimulates a variety of different B cells, each giving rise to a clone
of thousands of plasma cells
Each plasma cell estimated to secrete about 2000 antibody molecules per second over
the its life span (4-5 days)
Antibody Structure and
Function
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Neither membrane version of the antibody nor the secreted body binds the entire
molecule
This antibody interacts with a small accesible portion of the antigen called the epitope
(antigenic determinent)
Single antigen such as a bacterial surface has many epitopes, each able to produce a
specific antibody
Most antibody have two identical antigen sites for the epitope that caused the
production
Molecule consists of 4 polypeptide chains, Two identical heavy chains and two
identical light chains ( form a Y shaped molecule joined by disulfide bridges) highly
stable complex
Polyclonal- prepared from many different B cells: Monoclonal- composed from the
same B cell
Five major classes of antibodies: IgM, IgG, IgA, IgD, IgE
Antibody Mediated Disposal
of Antigen
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Neutralization- way in which antibody binds and blocks the activity of an antigen EX:
antibodies neutralize virus by attaching to the molecules that the virus needs to infect
the host cell
Opsonization- bound antibodies enhance macrophage attachment to, and thus
phagocytosis of, the microbes
Agglutination is also used to effectively neutralize viruses by clumping
Complement Fixation- one of the most important antibody mediated disposal
mechanism
Activate during an infection and are inactive in the absence of one, completion of the
complement cascade results in the lysis of many types of viruses and pathogenic cells
Can be activated in two ways the classical pathway ( triggered by antibodies and bound
by antigens and is important to humoral response) and alternate pathway (triggered by
substances that are naturally present on many bacteria) does not involve antibodies so it
nonspecific
Rudimentary Immune system
in Invertabrates
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Also have a very effective immune system, which allows it to distinguish self from
nonself
If two sponges are mixed the two cells will reaggerate separating each others cells
Mostly dispose of nonself through phagocytosis, lately immunobioligists have
discovered that some have cytokines which enhance their ability to fight off infection
Depend mostly on nonspecific defenses helomin binds to microbes and assists in the
disposal (only in bugs) are likely ancient precursors of antigens
immunological memory found in earthworms but not in sea stars
Immunity in Health and
Disease
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Active immunity- immunity gained from recovering from an infectious disease
Immunization- also known as vaccination which involves the individual receiving dead
or weakened cellls of the disease so they can develop immunity towards it ( stimulates
the immune response and immunological memory) because of the antigens
Passive Immunity- temporary immunity gained by taking in anti-bodies or immune
cells (lasts only a few weeks or months) temporary because the system has been
stimulated by antigens
Mothers can pass off passive immunity to their children while they are pregnant
provides protection for the baby until its own immune system has matured
This is used against fast acting viruses like rabies, the injected antibodies will fight off
the virus for a few weeks until the persons own immune system kicks in effectively
the immune system also fights off other peoples cells for example a skin transplant that
does not match will look healthy for 1or 2 days but then immune responses will attack
and disfigure it (the structure of the placenta prevents the mothers system from harming
the baby
Blood groups and Blood
Transfusion
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Type A has “A” antigens, Type B has “B” antigens, Type AB has both and type O has
none
Blood transfusions are tricky because the persons blood type must match or else the
immune system will react to the antigens of the foreign blood type
Antibodies to foreign blood are already in the body even if it has never been exposed to
it before (they rise against certain bacteria with similar epitopes) So if it Is type A it
does not have antibodies for A-Like bacterial epitopes since it considers it as “Self”
It can be harmful to the baby when a mother who is rH negative lacks the rH factor but
has a fetus which is rH positive
Tissue Grafts and Organ
Transplants
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Major Histocompatibility Complex- encodes the protein fingerprint that is unique in
every individual causes the stimulation that rejects tissue grafts or organ transplants
Foreign MHC is antigenic which causes immune system to respond against donated
tissues or organs
Use closest compatible MHC available ( usually siblings if there is no identical twin) in
addition various medicines are required to suppress the immune systems reactions
(however during this treatment a patient is much more susceptible to diseases
Blood transfusions follow the same route as for MHC as in the marrow is matched as
closely as possible (before this treatment the patient is treated with irradiation to
eliminate his or her own marrow cells or abnormal cells)