Upload
juxhin-xhahysa
View
224
Download
0
Embed Size (px)
Citation preview
7/31/2019 Chapters 29 and 30, Immunology
1/28
1
ImmunologyChapters 29 and 30
ImmunityA. Innate immunity
1. Physical and chemical barriers (previous chapter)2. Phagocytes-nonspecific but activate specific immunity
B. Specific immunity-specific recognition ofantigens1. Cell mediated immunity (CMI): Lymphocytes-
recognize specific antigens and divide very rapidly
forming clones. Some of these clones destroy the
antigen directly. 2. Humoral immunity (antibody mediated immunity):
Other clones make solubleproteins called antibodies
that specifically recognize the antigen that triggered the
response.
Table 29-1
7/31/2019 Chapters 29 and 30, Immunology
2/28
7/31/2019 Chapters 29 and 30, Immunology
3/28
3
Lymph system
Lymph vessels are closely associated with the circulatory system vessels and resemble the
veins of the circulatory system.
Contraction of skeletal muscles forces the lymph through valves in the lymph vessels.
Lymph organs include thebone marrow, lymph nodes, spleen, and thymus.
Bone marrow produces stem cells that eventually mature into several types of different cells.
Lymphocytes mature intoB-cells in thebone marrow and into T-cells in the thymus gland.
Lymph nodes and spleenLymph nodes are areas in the lymphatic veins where leukocytes (lymphocytesandmacrophages) are found in high concentration. The arrangement of these cells in
the nodes allows them to filter out any microorganisms or other antigens that passthrough the lymph system. This is why lymph glands get infected and swollen
during some types of infections.
The spleen performs a similar function and filters or purifies the blood that flows
through it.
If the spleen is damaged or removed, the individual is more susceptible toinfections.
Lymph node
Lymph nodes filter and purify lymphSpleen filters and purifies blood
(Antigen Presenting Cells)
Lymphoid organs
The bone marrow and thymus are called primary lymphoid organs because theprimary or initial differentiation of lymphocytes occurs in these organs.
After they are formed they migrate through the lymph and blood to the lymph nodes and
spleen that are called secondary lymphoid organs.
7/31/2019 Chapters 29 and 30, Immunology
4/28
4
ImmunityPathogens are destroyed bythree mechanisms: (1) Nonspecific innate
immunity-phagocytes(2) Specific humoral
antibody-mediatedimmunity
(3) Specific cell-mediatedimmunity.
Innate immunity: PhagocytesTwo types1. Polymorphonuclear leukocytes (PMNs or neutrophils) actively motile granulocytes
that contain lots of lysosomes. Derived from myeloid stem cells. Found normally
in the blood and bone marrow but migrate to sites of infection as part of the
inflammatory response.2. Monocytes and macrophages
a.Monocytes circulate throughout blood and lymph-precursors of macrophages.b.Macrophages are attached to tissue surfaces and are found primarily in the
secondary lymphoid tissues (What are these? spleen and lymph nodes). These are
antigen presenting cells-APC. When a macrophage eats a bacterium or other foreign particle it digests it andtakes the antigens from the particle and passes them through it's membrane to the
macrophage cell surface. These macrophages then contact the T-cells and B-cells and "show" them theirantigens. This lets the T and B cells know what they're up against and they then beginforming an immune response.
Neutrophil (PMN)
Note segmented nucleus and granular cytoplasm.
Monocyte
7/31/2019 Chapters 29 and 30, Immunology
5/28
5
MHC
TCR
Antigenprocessing
Antigen presentation
PRM
Antigendestruction
Pathogens with PAMPsand antigens
Adaptive immunity
Innate immunity
T cell
1
Antigenbinding
Complement,opsonization
2 Antigen-specific,antibody-mediatedimmunityActivate
B cells
Produceantibody
Innate immunityPathogen recognition by phagocytes involves an
interaction between the surface molecules of the
pathogen and the surface molecules of the
phagocytes called Pattern Recognition
Molecules (PRMs).
The PRMs on the phagocyte recognize unique
molecules or molecular arrangements found in
bacteria or viruses called Pathogen-Associated
Molecular Patterns (PAMPs).
For instance there is a PRM that recognizes LPS
which allows phagocytes to identify what type
of bacteria?
Others recognize peptidoglycan and even
unmethylated CpG-unique to bacterial DNA.When detected, the PAMP-PRM interaction
causes a transmembrane signal to occur and this
stimulates the transcription of several genes
involved in host defense. Some of these are involved in making toxic
oxygen species.
Antigendestruction
Killing
Inflammation
Cytokine andchemokine production
Antigen-presenting cell
PRM
Activatephagocytes
T cell
ActivateT cells
3
Cytokine andchemokine production
Cell-mediatedimmunity
Pathogens with PAMPsand antigens
MHC
TCR
InflammationThis is a nonspecific response to toxins
and pathogens that is mediated by the
release of cytokines and chemokines by
immune cells, especially phagocytes
and lymphocytes. Cytokines and chemokines are types of
proteins involved in inflammation and
the difference between them is
primarily based on their molecular
structures. Chemokines are
chemotactic cytokines-they cause
chemotaxis of immune cells toward the
site of injury. They also cause a
number of other physiological changes
such as vasodilatation and increased
vascular permeability (producing
swelling and redness).
Antigendestruction
Killing
Inflammation
Cytokine andchemokine production
Antigen-presenting cell
PRM
Activatephagocytes
T cell
ActivateT cells
3
Cytokine andchemokine production
Cell-mediatedimmunity
Pathogens with PAMPsand antigens
MHC
TCR
Septic Shock
Inflammation usually localizes the
infection and destroys the pathogen and
damaged tissue and generally helps
overcome the infection.Occasionally, a severe inflammatory
response becomes overwhelming and
spreads the inflammatory cells and
molecules throughout the lymph or
circulatory systems causing septic
shock.
7/31/2019 Chapters 29 and 30, Immunology
6/28
6
Antigendestruction
Killing
Inflammation
Cytokine andchemokine production
Antigen-presenting cell
PRM
Activatephagocytes
T cell
ActivateT cells
3
Cytokine andchemokine production
Cell-mediatedimmunity
Pathogens with PAMPsand antigens
MHC
TCR
Septic ShockOften caused by Gram negatives. This
can happen when an infection by
Salmonella orE. coli becomes systemic or
as a result of bowel injury resulting in the
release of enterics into the blood stream. The LPS on the surface of the G- bacteria
causes the release of cytokines and
chemokines which facilitate the destruction
of the bacteria but also act as endogenous
pyrogens, causing high fever. Widespread vasodilatation and increased
vascular permeability also occurs causing
movement of fluid from the bloodstream
into the tissues. This causes severe edema in the tissues and
a dramatic loss of blood pressure and is
fatal in about 30% of the patients affected.
Phagocytic killingPhagocytes kill bacteria in a number of ways:
1. Acid-When they ingest bacteria they enter into fermentative metabolism andas a result they produce lactic acid.
Hydrolytic enzymes in phagolysosomes are most active in acid pH so
when the pH drops, these enzymes become very active and digest the
bacteria more efficiently. These include proteases, lipases, nucleases,and lysozyme.
2. Phagocyte stimulation. The phagocyte becomes10 times more active aftereating its first bacterium.
3. Toxic oxygen. Phagocytes contain several enzymes that produce toxic formsof oxygen that in turn destroy the phagocytized bacterium.
Toxic oxygen species
Peroxide, singlet oxygen, nitric oxide, hypochlorous acid and superoxide are
all toxic forms of oxygen that are formed in phagocytes to kill bacteria.
7/31/2019 Chapters 29 and 30, Immunology
7/28
7
Countermeasures against phagocytesSome bacteria carry antioxidants with them that make them resistant to
phagocytic death.
Staphylococcus aureus (aureus means golden) gets its characteristic
yellowish color from the presence ofcarotenoid pigments that act as
antioxidants and make this organism very resistant to oxidative death and
therefore phagocytic killing. Carotenoid pigment is therefore a virulence
factor.
Mycobacterium leprae (leprosy) and M. tuberculosis can actually grow in
phagocytic cells because they make a group of membrane associated
glycolipids that inactivate toxic oxygen compounds.
Another Staphylococcus aureus
virulence factor
Countermeasures against phagocytesMany of the disease causing streptococci and staphylococci produce
compounds that kill the phagocytes.
These are called leucocidins. The dead phagocytes form what iscommonly called pus and these compounds are referred to as pyogenic-
pus forming. Streptococcus pyogenesstrep throat, also
Staphylococcus aureus produce leucocidins.
Capsules: Size and blocks adherence of the phagocyte to the bacterialcell. Streptococcus pneumoniae best example. Strains with no capsule
cannot cause disease.
7/31/2019 Chapters 29 and 30, Immunology
8/28
8
Characteristics of theAdaptive
immune responseThree fundamental characteristics of the specific immune
response.
Specificity
Memory
Tolerance
Specificity1. Specificity-highly specific-organism, protein, even epitope.
Memory2. Memory-The first time an antigen is introduced the immune response takes
a while to develop. However, if the antigen ever enters the body again, it
is recognized and the immune response happens immediately.
7/31/2019 Chapters 29 and 30, Immunology
9/28
9
Tolerance3. Tolerance; We generally don't make an immune response against
ourselves. In some cases this happens and it causes disease-Multiplesclerosis. These are calledautoimmune diseases.
Cells of the immune response
LymphocytesPhagocytes
Lymphocyte
Note: Very little cytoplasm and smaller than phagocytes
7/31/2019 Chapters 29 and 30, Immunology
10/28
10
Specific immunity-lymphocytesLymphocytes very common in blood and lymph. Tissues that contain lymphocytes are
called lymphoid tissues. All come from stem cells in the bone marrow. However,
they mature into different types of cells in other tissues. 1. B-cells: Stem cells that mature in the bone marrow.
a. Responsible for antibody interaction and antibody production.b. Have a single type of antibody molecule on their surface that recognizes a
single antigenic determinant (epitope) and this causes the B-cell to begin
producing a particular type of antibody. 2. T-cells: Stem cells that mature in the thymus.
T-Cells have antigen-specific T-cell receptors (TCRs)on their surface that allows
them to recognize a specific antigen. These receptors have two chains and
resemble antibody molecules. The part that binds antigen is called the variable
region and is specific for each different antigen. The other part that is stuck in the
membrane is called the constant region. Therefore these cells are as specific as
antibodies at recognizing foreign substances (antigens).
AntigensAntigens are substances that react with either antibodies or with
antibody-like molecules on the surface of T-cells called T-cell
receptors (TCRs).Immunogens are substances that induce an immune response.
Most (but not all) antigens are immunogens (see Haptens-below). Haptens are antigens that bind to antibodies but cannot induce an
immune response by themselves. Must be bound to a carrier
molecule. Penicillin is a hapten. It binds to glycoproteins that act
as carriers present in some individuals and stimulates an immune
reaction against the carrier-hapten conjugate in these individuals.
Antigens and haptens are both immunogens.
AntigensThree intrinsic factors affect the ability of a molecule to induce an
immune response:1. Molecular size: Small molecules are generally not
immunogenic. Sugars are bad immunogens, proteins are goodimmunogens.
2. Complexity: Greater diversity = greater immunogenicity.Proteins are very good immunogens-Nucleic acids are not.
3. Form: The more particulate and insoluble an antigen, the betterit is taken up by phagocytes and the better immunogen it is.Precipitated proteins make better antigens than soluble proteins.
7/31/2019 Chapters 29 and 30, Immunology
11/28
11
AntigensThree extrinsic factorsalso affect the ability of a molecule to
induce an immune response:1. Dose: Because of tolerance, more is not always better.
Generally dose is between 10 g and 1 gm. 2. Route: Injections are usually (but not always) more effective
than oral or topical.3. Foreign nature: More different from host molecules, better
antigen (because of tolerance).
Antigenic determinants-epitopesThe entire antigen does not interact with the antibody or TCR.
The region on an antigen that specifically reacts with the antibody
or TCR is known as the antigenic determinantor epitope.
AntigensSometimes an antibody will recognize and bind to a
molecule other than the one it was made to recognize
(similar epitope).
In this case the antigen that was used to stimulate theresponse is called the homologous antigen and the one
that it binds to it " accidentally" is the heterologous antigen.
The interaction of an antibody with a heterologous antigen is
called a cross reaction.
7/31/2019 Chapters 29 and 30, Immunology
12/28
12
The immune response1. Antigens are processed (partially digested) by antigen
presenting cells (APCs) and the pieces are moved to the
surface of the APCs.2. APCs have proteins on their surface called Major
Histocompatibility Complex (MHC) proteins that hold the
antigen pieces on the surface of the cell so other cells can bump
into them. The cells that bump into the APCs are T-
lymphocytes (T-cells) and they have special antigen
recognition proteins on their cell surfaces call TCRs (T-cell
receptors)3. The APCs present the antigen pieces to the T-cells so that they
can begin forming an immune response. This is called antigen
presentation.
The immune response4. Some T-cells interact directly with invading cells that have the
antigen and destroy the invader. These T-cells are called
cytotoxic T-cells or TC cells.
5. Other T-cells called T-helper cells (TH cells) interact withantigen and secrete proteins called cytokines that activate
several types of host defense cells to destroy the invading
antigen containing invaders. Destruction of invading antigen
by host cells is called the cell mediated immunity.
The immune response6. The TH cells also interact with another group of antigen specific
cells called B-lymphocytes or B-cells. When this interaction
occurs, the B-cells that come in contact with the TH cells are
stimulated to produce proteins called antibodies that very
specifically recognize and bind to the antigen that stimulated
the initial response. Immunity that occurs because of antibodies
is called humoral immunity.
7/31/2019 Chapters 29 and 30, Immunology
13/28
13
The immune response1. Antigens are processed and passed along to T-lymphocytes (T-cells). Th is is
called antigen presentation.
The immune response2. Some T-cells interact directly with invading cells that have the antigen and
destroy the invader. These T-cells are called cytotoxic T-cells or TC cells.
The immune response3. Other T-cells called T-helper cells (TH cells) interact with antigen and
secrete proteins called cytokines that activate several types of host defense
cells to destroy the invading antigen containing invaders. Destruction of
invading antigen by host cells is called cell mediated immunity.
7/31/2019 Chapters 29 and 30, Immunology
14/28
14
The immune response4. The TH cells also interact with another group of antigen specific cells called B-
lymphocytes or B-cells. When this interaction occurs, the B-cells that come in
contact with the TH cells are stimulated to produce proteins called antibodies that
very specifically recognize and bind to the antigen that stimulated the initialresponse. Immunity that occurs because of antibodies is called humoral
immunity.
T-cell Receptors (TCRs)TCRs are surface proteins that pass through the T-cell membrane. Each T-cell has thousands ofidentical TCR molecules on its
surface.TCR1. Alpha chain ()variable domain (V)constant domain(C)2. Beta chain ()variable domain (V)constant domain(C)The V and V combine to
form the antigen binding
site.
Major Histocompatibility Complex (MHC)MHC proteins are present in all vertebrates. Also known as Human
leukocyte antigens (HLAs) First discovered because of their role in tissue rejection in transplant
patients.
7/31/2019 Chapters 29 and 30, Immunology
15/28
15
Major Histocompatibility Complex (MHC)MHC proteins are essential
components of the immune
system.They function as antigen-
presenting molecules and
they interact with antigens
and with T-cell receptors.
(MHC)
(Antigen)
T-cell receptor
Major histocompatibility complexThere are two classes of MHC proteins, Class I and Class IIVariations in the MHC proteins from one individual to another are responsible for
tissue rejection.
Class I: Found on surface of all cells with nuclei. Primarily involved in defenseagainst viral infection or tumors.
Class II: Only on surface of phagocytes, B lymphocytes, and other Antigen PresentingCells.
Class 1 Class II
Class I MHC proteinsSince viruses use host cells to
replicate, viral antigens are bound
by MHC Class I enzymes that are
made and assembled in the
endoplasmic reticulum along with
the foreign viral or tumor specific
proteins. Viral proteins degradedTransported through ER by TAP pore.Bind to MHC-ITransported to surfaceInteract with CD8 Tc cellsTc cells release cytokines and cytotoxins
killing the infected cell
7/31/2019 Chapters 29 and 30, Immunology
16/28
16
Class I MHC proteinsSome tumors make proteins that areunique to that type of tumor called tumor-
specific antigens.
When the Tc cells recognize a virus
infected cell or a tumor cell theysecrete lymphokines and cytotoxins
that kill the cell.
Kill me, I'm infected
with a virus!
Class II MHC proteinsClass II proteins are also
assembled in the cell
endoplasmic reticulum but
they are bound to a specific
blocking peptide called the
invariant chain (Ii) and
transported to a lysosome
(phagolysosome). This is
where degradation of foreign
material occurs. The Invariant chain is a
chaperone that prevents the
Class II proteins from
interacting with any otherproteins along the way.
Class II MHC proteinsIn the phagolysosome, the Ii is
removed and replaced with
antigens from the degraded
material and this complex
migrates to the surface of the cell
and presents the antigen to CD4-
THcells by interaction with the
TCRs and the CD4 receptor. When the foreign antigens are
recognized by TH cells they
secrete cytokines that stimulate
B-cells to produce antibody.
7/31/2019 Chapters 29 and 30, Immunology
17/28
17
Types of T-cellsTwo main groups of T-cells exist based upon the type of surface protein
they have.1. CD4: Have the CD4 protein on surface-Two groups
a. T-Helper 1 cells (TH1): Attract and activate cells involvedin non-specific cellular defenses such as macrophages.
b. T-Helper 2 cells (TH2): Stimulate B-cells to produce largeamounts of antibody.
2. CD8: Have CD8 protein on surface-One type: T-cytotoxic cell
(Tc) also known as cytotoxic T lymphocytes (CTLs). Destroy
invading cells after recognizing specific antigens on their
surfaces through direct contact with an antigen specific T-cell
receptor. Thus, these cells are responsible for tissue rejection.
Cell-cell contact is required and results from secretion of
perforin by Tc cells (perforates the cells)
Cell-mediated immunityNatural killer cells: Lymphocytes that are neither T or B cells but recognizeforeign cells in the absence of specific antigen and kill the cell. Effective defense
against tumor cells and virus infected cells.
CMI effector moleculesThe cell mediated response is initiated by a variety of
substances that are released by these cells in response
to foreign matter. These are called Lymphokines if produced by
lymphocytes and cytokines if produced by other cells
Interleukins and interferon-modulate immune
response.
7/31/2019 Chapters 29 and 30, Immunology
18/28
18
The humoral responseAntibody mediated response. TH2 cells stimulate B cells to produce
soluble proteins called antibodies. Humoral immunity can be
transferred in serum.
The Humoral Response: AntibodiesAntibodies: Also called immunoglobulins-or gamma globulins. A
type of protein that recognizes an antigen in a very specific
chemical way. They are found in the serum (hence term antiserum) and in most
secretions including milk.This is why breast feeding is generally better than bottle feeding. Mother has antibodies made to most pathogens that might threaten
the infant and infant has very poorly developed immune system
when born. In this way the motherpassively immunizes her baby when she is
feeding it.
AntibodiesBasic unit is four protein chains-2 long and 2 short shaped like Y and
held together by disulfide bonds (S-S) between cysteine residues.
Long chains are called the Heavy chainsShort chains are called the Light chains:
2 cysteines 1 cystine
7/31/2019 Chapters 29 and 30, Immunology
19/28
19
AntibodiesPapain is a protease that digests the antibody protein into three fragments. Toptwo parts are called the Fab (Fragment of Antigen Binding)-Binds antigen
Bottom part is called the Fc (Crystallizable)-Does not bind antigen.
Only a small part of the Fab is actually involved in antigen binding and this iscalled the variable region because it varies from antibody to antibody. The rest
of the antibody is called the constant region
AntibodiesThe Light chain has 2 regions: Variable (antigen binding) and Constant
The variable region binds antigen and is different from one antibody molecule to thenext.
AntibodiesThere are two types of constant regions found on the light chain: lambda andkappa. Each antibody molecule has either two lambda or 2 kappa portions. Never
two different types on the same molecule.
The heavy chains have one variable region and three constant regions CH1, CH2,and CH3.
7/31/2019 Chapters 29 and 30, Immunology
20/28
20
Types of antibodiesThere are five different classes of antibodies based on theirstructure, molecular weight and where they are found.
IgA
IgD
IgE
IgG
IgM
IgGImmunoglobulin GMost common antibody in blood. 80% of circulating antibody.
Two light and two heavy chainsCan bind two antigens at same time (bivalent)
Four subclasses IgG 1=>4
IgG
7/31/2019 Chapters 29 and 30, Immunology
21/28
21
IgMActually 5 immunoglobulin molecules (pentameric) hooked together by shortproteins called J-chains.
Heavy chains have an extra Constant region-CH4First antibody to be made in response to bacterial infection
Multivalent: 10 antigen binding sites.
IgASecretory antibodyPresent in body secretions: Breast milk. Mothers give babies their antibodies
for protection.
Before being secreted it is a monomer but the secreted form consists of twoantibody molecules held together by a J-chain peptide and a peptide known as
the secretory piece that is responsible for the secretion of the IgA.
IgEFound in very low amounts in the serum but is responsible for allergic reactions.Extra constant region can bind to mast cells and this is responsible for
stimulating the allergic response.
CH1CH2CH3CH4 Extra constant region
7/31/2019 Chapters 29 and 30, Immunology
22/28
22
IgDFound in lowest abundance. Function is to binding antigen and stimulating new B-cellsin the spleen to start making antibody.
CH1CH2CH3CH4
The antibody response
(Booster)
(anamnestic [memory] response)
The antibody response1. Antigen binds to specific receptors on B-cell surface. 2. Antigen engulfed by endocytosis.3. Antigen digested.4. Antigen peptides moved to B-cell surface as part of Class II
MHC.5. B-cell presents antigen to T Helper cells T Cell Receptor and
CD4 molecule.6. T-Helper releases interleukins.
7. The dividing B-cells then form two types of B-cells
a. Plasma cells: Large, produce tons of antibody and have a
short life(
7/31/2019 Chapters 29 and 30, Immunology
23/28
23
The B cell functions as an antigen-
presenting cell (APC) and concentrates
antigen using antigen-specific
immunoglobulin receptors. After processing, antigen is presented to
the TH2 cell which then signals the sameB cell to proliferate and form plasma
cells (antibody producers) or memory
cells. After subsequent antigen exposure,
memory cells quickly convert to plasma
cells.
Interleukins
released
The Complement SystemA group of 11 proteins in the serum that act to destroy foreign cells by formingholes in their membranes. The complement system is not specific itself and is
always present. The specificity comes from antibodies that trigger thecomplement system when they are activated by binding to antigen.
Actions of the complement system:
1. Bacterial lysis-especially G-
2. Non-lytic killing.3. Phagocytosis. Cells such as Streptococcus pneumoniae that are not
normally phagocytized can be made susceptible to phagocytosis if they are
recognized by antibody in the presence of complement. This is an importantprocess called opsonization.
The complement system proteins function as anaphylatoxins that trigger the
release of histamine and other cytokines from mast cells or basophils. If thishappens too rapidly it can cause a life threatening allergic response known as
anaphylactic shock.
Complement cascadeEach of the proteins that are part of the complement system are assembled on the
invading cell surface and when they are all attached, they form a hole in the membrane
that causes lysis in many bacteria-especially G-.
7/31/2019 Chapters 29 and 30, Immunology
24/28
24
Immunity and diseaseOne of the greatest steps in the progress of science was the development
of methods to produce immunity to infection in individuals . This
can be done in 2 ways: 1. Active immunity: The immune response is stimulated in an
individual by the presence of antigen. This causes a permanent
change in the individual so he/she will always be able to produce an
immune response to subsequent encounters with the antigen. A. Natural-immunity following recovery from a disease.B. Artificial-Induced by injection of antigen-immunization.
Vaccination is commonly used but immunization is the proper
term. Note, this isNOT inoculation! You don't get inoculated
against a disease. If you inoculate someone you are giving them
the disease! Vaccination or immunization.
Immune diseasesHypersensitivity. An immune response that causes tissue damage that resultsfrom a preexisting immunity. Can be cellular or humoral.
Four types: I, II, III, IV
Type I: Immediate hypersensitivity:
This is mediated by antibodies. Allergies. 10-20% of the population
Type II-cytotoxic autoimmune diseases. Destruction of specific types of cells.
Type III-Immune complex disease. Antigen antibody complexes cause damageto several tissues.
Type IV-Delayed hypersensitivity.
Results from a special class of T-cells called TH1-helper cells.
Type I hypersensitivityFirst exposure to antigen: Specific antibodies of the IgE type aremade.IgE antibodies bind to Mast cells ( non-motile connective tissuecells-next to capillaries) and Basophils (motile white blood cells).The second time the IgE sees the antigen and the antigen binds totwo different antibodies at the same time then the mast cell orbasophil to which they are attached releases a variety ofphysiologically active chemicals such as histamine and seratonin. These cause dilation of blood vessels and smooth muscle
contraction. Thus a person experiencing an allergic reaction has difficultybreathing, flushed skin, lots of mucus production, itchy watery eyesetc. The severity of the reaction depends upon the individual and thedegree of exposure to the antigen.In some people the reactions are very severe and result in a severedrop in blood pressure (vasodilatation) the inability to breath. Theseindividuals can die immediately if they are not given adrenaline tocounteract the smooth muscle contraction.
7/31/2019 Chapters 29 and 30, Immunology
25/28
25
IgEFound in very low amounts in the serum but is responsible for allergic reactions.Extra constant region can bind to mast cells and this is responsible for
stimulating the allergic response.
CH1CH2CH3CH4 Extra constant region
Type I hypersensitivity
Hay
Fever
http://en.wikipedia.org/wiki/File:Mast_cells.jpg
7/31/2019 Chapters 29 and 30, Immunology
26/28
26
Type II and III hypersensitivitiesType II-cytotoxic autoimmune diseases. Destruction of specific typesof cells.
Type III-Immune complex disease. Antigen antibody complexes
cause damage to several tissues.
Juvenile diabetes-antibodies against insulin producing cells ( Type II).
Systemic lupus erythematosis-antibodies against everything (Type III).
Hashimotos disease-thyroglobulin destruction of thyroid gland. (Type II)The propensity to develop these and other autoimmune diseases is
probably determined genetically.
Type IV hypersensitivityDelayed hypersensitivity. Results from a special class of T-cells called T H1-helper cells. Can be caused by microbes or by chemicals.If it is caused by chemicals it is called contact dermatitis: Poison Ivy.The reaction to microbes is used to determine the preexisting exposure to
Mycobacterium tuberculosis: The Mantoux (man-too) tuberculin skin test (After Charles Mantoux (1877-1947),
French physician) involves injecting a very small amount of purified protein
derivative (PPD) fromM. tuberculosis just under the top layer of the skin
(intracutaneously). If the delayed hypersensitivity TH1-cells recognize the antigen
and are sensitized, then they will release lymphokines and this will cause the
formation of an inflammatory response in this area.Tissue destruction is caused by the lytic enzymes and phagocytic cells destroyingthe tissue that is bound to antigen.
SuperantigensThese are exotoxins that are not metabolically toxic but instead stimulate an
enormous immune response: This is the case with the pathogenic
Staphylococcus aureus during toxic shock syndrome. Also with Streptococcus
pyogenes and the flesh eating disease(necrotizing fasciitis). The exotoxins from these organisms bind to the beta chain of the T-Cell
Receptors (TCRs) in a different place than normally binds antigen. This can
cause an enormous cell mediated response and the release of lymphokines and
the cell mediated destruction is why these diseases are so dramatic and deadly.
7/31/2019 Chapters 29 and 30, Immunology
27/28
27
Immunity and diseaseOne of the greatest steps in the progress of science was the development
of methods to produce immunity to infection in individuals . This
can be done in 2 ways: 1. Active immunity: The immune response is stimulated in an
individual by the presence of antigen. This causes a permanent
change in the individual so he/she will always be able to produce an
immune response to subsequent encounters with the antigen. A. Natural-immunity following recovery from a disease.B. Artificial-Induced by injection of antigen-immunization.
Vaccination is commonly used but immunization is the proper
term. Note, this isNOT inoculation! You don't get inoculated
against a disease. If you inoculate someone you are giving them
the disease! Vaccination or immunization.
Immunity and disease2. Passive immunity: Temporary immunity due to the presence
of antibodies made by another individual or organism. No
permanent change in the individual. A. Natural-Infants have antibodies from their mothers whenthey are born and they get IgA in mothers milk. B. Artificial-The individual may receive injections of pre-formed antibodies (antiserum) such as those from another
individual or animal that has been immunized (gamma-
globulin injections). Frequently used to treat individuals
believed to have been exposed to Hepatitis A-clear the virus
before it can cause a full blown infection.
VaccinationVaccine: An antigen or mixture of antigens used to induce active
immunity.Toxoid: A vaccine composed of an inactivated toxin so that it can still
produce an immune response is no longer toxic. Example is tetanus
vaccine. Commonly inactivated with formaldehyde. For endotoxins the entire organism must be injected (why) so the entirecell must be killed. Cells are commonly killed with phenol or
formaldehyde.Antiserum: Serum containing antibodies against a particular antigen.Antitoxin: serum containing antibodies against a particular toxin such
as botulism or Diptheria.
7/31/2019 Chapters 29 and 30, Immunology
28/28
Vaccination Since children are susceptible to a number of infectious diseases, it is
desirable to immunize them as soon as possible. This is usuallybegun at a few months of age. The duration of immunization depends primarily upon the antigen.
Some antigens provide immunity for life while others require
boosters to initiate a secondary response.