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Increased ESR
Cell-mediated
Primary Cells
B cells &
circulating
antibodies
T cells
Functions
Causes direct inactivation of
a microorganism or the
activation of inflammatory
mediators
T-cell differentiation
Protection
Protects against
bacteria and viruses
Protects against
viruses and cancer
Antigen
A molecule that can react with antibodies or receptors on B & T cells
Mostly protein but can be other molecules as well
Immunogenic antigen: an antigen that can trigger an immune response
Sites for binding to antibodies & lymphocytes
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T-Cell Activation
Initiates cellular immune response
Binds antigens to TCRs
Allows
o Direct killing of foreign or abnormal cells (Tc cells or cytotoxic T
lymphocytes [CTLs])
o Assistance or activation of other cells
T-regulatory cells (Treg)
o Regulate the immune response to avoid attacking self
T-memory cells
Activation = a series of Cellular interactions
o Recognize antigen that has been processed and presented by MHC
class I molecules or CD8 T cells are class I restricted
o Appropriate signaling pathways are needed for the maturation of T
cells
B7 on the cell-presenting antigen
CD28 on the T cell
Cd48 on the APC
CD2 on the T cell
Variety of other adhesion molecules
Requires cytokines, especially IL-2, produced by the Th-1 cell
Cellular differentiation
o Produces active Tc cells with the capacity to identify antigens on the
surface of infected or malignant cells and then to destroy these cells
o Produces memory T cells
Have the capacity to respond rapidly if further exposure to the
same antigen occurs
Helper T cells assist with antigen presentation
B-Cell Maturation
Occurs in bone marrow
Stem cell matures & develops surface markers [skipped rest]
o CD45R and the interleukin (IL)-7 receptor
IL-7: produced by stromal cells
Critical in driving the further differentiation & proliferation
of the B cell
Production of BCRs [skipped]
o Heavy & light chains
o V, D, and J genes
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Central Tolerance
Large number of auto-reactive B cells are eliminated if exposed to self
antigenover 90%
Concept of not attacking cells
B-Cell Activation
Results from the recognition of soluble antigen by BCReceptors, processing
of antigen, and presentation by MHC class II antigens to Thelper2 cells
When an immunocompetent B cell encounters an antigen for the first time,
B cells with specific BCRs are stimulated to differentiate and proliferate
A differentiated B cell becomes a plasma cell***
Plasma cell is a factory for antibody production
o May be a single class or subclass of a specific antibody
Secondary Lymphoid Organs
Spleen
Lymph nodes
Adenoids
Tonsils
Peyer patches (intestines)
Appendix
T Lymphocytes
Generated from immature precursors in thymus
o Originate from PPSC in bone marrow
o Differentiate into the lymphoid stem cell
o Processed through thymus gland
o Thymocytes- T cell precursors
Mature, T cells are found****
o In the blood, constituting 60-70% of lymphocytes
In T-cell zones of peripheral lymphoid organs, such as the
paracortical areas of lymph nodes, and periarteriolar sheaths of
the spleen
Each T cell is genetically programmed to recognize a specific cell-bound
antigen by means of an antigen-specific T-cell receptor (TCR)
The TCR recognizes antigens that are displayed by molecules on surfaces of
antigen-presenting cells
T cells (in contrast to B cells) cant be activated by soluble antigens
Presentation of processed antigens by antigen-presenting cells
(macrophages, dendritic cells) is required for induction of cell-mediated
immunity***
T Lymphocytes Continued
T Lymphocytes Continued
CD4+ T cells
o Essential for both cell-mediated and antibody-mediated of
immune system
Cell-mediated immunity
o These CD4+ cells bind to antigen presented by antigen-presenting
cells (APCs) like phagocytic macrophages & dendritic cells
o T cells then release lymphokines that attract other cells to the area
Result is inflammation: the accumulation of cells & molecules
that attempt to wall off & destroy the antigenic material
Ex. abscess, rash after poison ivy
Antibody-mediated immunity
o These CD4+ cells, called helper T cells, bind to antigen presented by
B cells
o Result is the development of clones of plasma cells secreting
antibodies against the antigenic material
o CD4 cells main role = helper cell**
o CD-4 cells facilitate both inflammation & antibody responses
CD8+ cells or killer T cells
o Cytotoxic T Cell (Tc)
Kill cancer cells
Kill cells infected with a virus
CD8+ cells secrete molecules that destroy the cell to which
they have bound
Regulatory T cells (Tregs)
o Shut down immune system after invading organisms have been
eliminated - so doesnt continue regulated
CD4-CD8 Cells
There is some disagreement about the normal range for CD4 and CD8 cell
counts
o Normal CD4 counts between 500-1600
o Normal CD8 counts between 375-1100
CD4 counts drop dramatically in people with HIV- in some cases down to
zero
The ratio of CD4 cells to CD8 cells is often reported
o Calculated by dividing CD4 value by the CD8 value
o Normal: ratio between 0.9-1.9
Meaning there are about 1 to 2 CD4 cells for every CD8 cell [in
a normal physiologic situation]
But common for more CD8 than 4 in certain diseases
Dendritic Cells
Originate from hematopoietic stem cells in the bone marrow
o Myeloid stem cell
Precursors - monocytes/macrophages, granulocytesneutrophils/eosinophils, thrombocytes, basophils/mast cells,
dendritic cells, & erythrocytes
o Lymphoid stem cell
Seem to be also derived from lymphoid precursors
Found in the lymph nodes & spleen
Engulf pathogens & degrade them into protein fragments*****
Antibody
General
Information
Functions
IgG
Most prevalent,
abundant
-Most of
protective
activity against
infection
-Crosses the
placenta
IgA
Mostly in
secretions
-Most of
protective
activity in
body
secretions
IgE
Most rare
-Mediator of
many common
allergic
responses
-Defends against
parasitic
infections
IgD
Not well
known
Functions as
one type of
B-cell
antigen
receptor
IgM
Largest #
First antibody
produced
during the
initial, or
primary,
response to an
antigen
-Large & early
arriver
Antibody Function
Directly through:
o Neutralization
o Agglutination
o Precipitation
Indirectly through:
o Opsonization
Degree of antibody protection is assessed by an antibody titer
o Prove when given immunization in past or when had infection
previously
Primary and Secondary Responses
Primary response
o Initial exposure
o Latent period or lag phase
B cell differentiation is occurring
o After 5-7 days, an IgM antibody for a specific antigen is detected
o An IgG response equal or slightly less follows the IgM response
Secondary response
o More rapid
o Larger amounts of antibody are produced
o Rapidity due to presence of memory cells that do not have to
differentiate
o IgM is produced in similar quantities to the primary response, but IgG
is produced in considerably greater numbers
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Pollens
Molds, fungus
Foods
Animals
Cigarette smoke
Household dust
o Drug allergens (penicillins)
o Haptens- antigens reacting with skin self-proteins
Metals (nickel)
Chemicals (rubber)
Resins (poison ivy, poison oak)
o Allergen is contained within a particle too large to be phagocytosed or
is protected by a nonallergenic coat
Immunologic Tolerance
Immune tolerance is the phenomenon of unresponsiveness to an antigen
induced by exposure of lymphocytes to that antigen
Self tolerance refers to the lack of responsiveness to an individuals own
antigens
Lymphocytes with receptors capable of recognizing self antigens are
generated constantly, and these cells must be eliminated or inactivated to
prevent them from causing harm
Mechanisms of self-tolerance
o Central tolerance
Immature, self reactive T & B lymphocytes clones that
recognize self antigens during their maturation in the central
lymphoid tissues (thymus & bone marrow) are killed or
rendered harmless
Negative selection or deletionT cells
Self-reactive lymphocytes are eliminated from the T-cell
pool
Receptor EditingB cells
25-50% of B cells undergo receptor editing during their
maturation process
o Peripheral tolerance
Central tolerance is imperfect; back up system is peripheral
tolerance
Some mechanisms:
Anergy
o Lymphocytes that recognize self antigens may be
rendered functionally unresponsive
Suppression by tregs
Deletion by apoptosis
o Cells that recognize self antigens may receive
signals to promote apoptosis
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Autoimmunity
Misdirected immune response against self antigens
Etiology:
o Genetic susceptibility
Twin studies
Association of HLA alleles
Lessons from genome wide studies
o Environmental triggers
o Role of infections
As triggers?
As protective?
Alloimmunity
Also called isoimmunity
Normal immune response against beneficial foreign tissue
Immune system reacts with antigens on the tissue of other genetically
dissimilar members of the same species
Transient neonatal alloimmunity
o Fetal antigens cross placenta
o Mother makes antibodies
o Antibodies cross placenta and cause disease
Transplant rejection and transfusion reactions
Hypersensitivity
Responses after re-exposure to an antigen
o Immediate
Occurs within minutes
If severe, called anaphylaxis described below
o Delayed
Takes several hours to appear
Maximum severity days after exposure
o Anaphylaxis
Most rapid and severe immediate response that occurs within
minutes
Typically systemic (generalized)
Itching & erythema
Vomiting
Abd cramps
Diarrhea
Breathing difficulties & laryngeal edema
Vascular collapse & hypotension
Anaphylactic shock & death
Hypersensitivity
Characterized by the immune mechanism
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o Type
o Type
o Type
o Type
I
IgE mediated
II
Tissue-specific reactions
III
Immune complex mediated
IV
Cell mediated
Type I Hypersensitivity
Most common allergic reactions
o Antibody mediated
o Initial sensitization to an allergen
o B cell stimulated to produce IgE
o IgE coats mast cell surface
o Further exposure to same allergen cross-links the surface bound IgE
and causes mast cell degranulation
o Histamine release
Genetic predisposition = atopic
Tests
o Food challenges
o Skin tests- wheal & flare reaction
Desensitization
o IgG-blocking antibodies
Type I Examples
o Common allergic reactions
o Extrinsic asthma
o Others
Type II Hypersensitivity
Tissue specific
o Specific cell or tissue (tissue-specific antigens) is the target of an
immune response
o Antibody mediated
Five mechanisms
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Type II Examples
o ITP
Platelets
o Hemolytic anemia
RBCs
o Graves disease
Autoimmune thyroiditis
o Myasthenia Gravis
Post synaptic acetylcholine receptors
o Others
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Virus
o Cytomegalobirus (CMV)
o Herpes virus
Bacteria
o Mycobacterium avium intracellulare (MAI)
o others
Fungi and yeasts
others
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