H&E: 2:00-3:00
Scribe: Dylan Vaught
Tuesday, October 20, 2009
Proof: Sally Hamissou
Dr. Zsuzsa Bebők
Immune System #1
Page 1 of 5
I.
[S1] Title Slide
a. The key terms on the following three slides are for our benefit. She did not go over them.
II. [S2] Key Terms
a. Antibody: Serum protein formed in response to immunization; antibodies are generally defined in terms of their
specific binding to the immunizing antigen.
b. Antigen (immunogen): Any material that initiates immune response
c. Antigenic determinant (epitope): immunologically active regions of an antigen that bind to antigen-specific
membrane receptors on lymphocytes or to secreted antibodies.
d. Antigen-presenting cell (APC): A specialized type of cell, bearing cell surface class II MHC (major
histocompatibility complex) molecules, involved in processing and presentation of antigen to inducer, or helper,
T cells. Examples: macrophage, dendritic cells.
e. B lymphocyte (B cell): The precursors of antibody-forming plasma cells; these cells carry immunoglobulin and
class II MHC (major histocompatibility complex) antigens on their surfaces. C
f. Complement: A series of serum proteins involved in the mediation of immune reactions. The complement
cascade is triggered classically by the interaction of antibody with specific antigen.
g. Complement components: An enzymatic system of serum proteins triggered by the classical and alternative
pathways, and resulting in target cell lysis, phagocytosis, opsonization and chemotaxis.
h. Complement receptor: A structure found on erythrocytes, lymphocytes, neutrophils, monocytes and
macrophages that binds C3 fragments.
III. [S3] Key Terms
a. Cluster determinant (CD): Cluster of antigens with which antibodies react that characterize a cell surface
marker.
b. CD4: The antigen cluster associated with the T cell receptor on the surface of T-helper cells. Binds to MHC II.
c. CD8: The antigen cluster associated with the T cell receptor on the surface of T-cytotoxic cells. Binds to MHC I.
d. Epitope: A single antigenic site or epitope on a complex antigenic molecule or particle. Also called antigenic
determinant.
e. Fc receptor (FcR): A receptor on a cell surface with specific binding affinity for the Fc portion of an antibody
molecule. Fc receptors are found on many types of cells.
f. Major histocompatibility complex (MHC): A cluster of genes on chromosome 6 in humans, encoding cell
surface molecules that are polymorphic and that code for antigens which lead to rapid graft rejection between
members of a single species which differ at these loci. Several classes of protein such as MHC class I and II
proteins are encoded in this region. These in humans, are known as 'Human leukocyte antigens' (HLA).
g. MHC class I molecule: A molecule encoded to genes of the MHC which participates in antigen presentation to
cytotoxic T (CD8+) cells.
h. MHC class II molecule: A molecule encoded by genes of the MHC which participates in antigen presentation to
helper T (CD4+) cells.
IV. [S4] Key Terms
a. MHC restriction: The ability of T lymphocytes to respond only when they 'see' the appropriate antigen in
association with "self" MHC class I or class II proteins on the antigen presenting cells.
b. NK cell: Naturally occurring, large, granular, lymphocyte-like killer cells that kill various tumor cells; they may
play a role in resistance to tumors. Also, they participate in ADCC. They do not exhibit antigenic specificity, and
their number does not increase by immunization.
c. Null cells: An early population of lymphocytes bearing neither T-cell nor B-cell differentiation antigens.
d. Primary lymphoid organs: Organs in which the maturation of T and B lymphocytes take place and antigenspecific receptors are first acquired.
e. Secondary lymphoid organs: Organs in which antigen-driven proliferation and differentiation of B and T
lymphocytes takes place.
f. T cell: A lymphocyte which undergoes a developmental stage in the thymus.
g. T-dependent antigen: An immunogen that is able to induce antibody synthesis only in the presence of
lymphokines released by helper T cells.
h. T-independent antigen: An immunogen which induces antibody synthesis in the absence of lymphokines
released by T cells; the antibodies are generally only of the IgM isotype.
V. [S5] Overview
a. Function
b. Components
c. Cells
d. Molecules
e. Lymphoid Organs
VI. [S6] Function
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Scribe: Dylan Vaught
Tuesday, October 20, 2009
Proof: Sally Hamissou
Dr. Zsuzsa Bebők
Immune System #1
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a. Immunis (Latin) = exempt.
b. The main function of the immune system is to provide protection from intruders such as infectious diseases and
foreign substances (antigens)
VII. [S7] Components
a. Innate Immunity
i. Born with these
b. Adaptive (specific) immunity
i. Our system is learning to react against the infectious agents and the foreign substances.
VIII. [S8] Innate Immunity
a. Anatomic barriers(skin, mucous membranes)
b. Physiologic barriers (temperature, low pH, chemical mediators secreted by cells)
c. Phagocytic/endocytic barriers (non-specific endocytosis and breakdown of different material, by specific cells
such as monocytes, neutrophils, tissue macrophages that digest, WBC’s that secrete toxic materials)
d. Inflammatory barriers (leakage of vascular fluid containing antibacterial molecules and influx of phagocytic cells
into the affected area)
i. This is where the connection between the innate and adaptive immunity occurs because the fluid may
contain immunoglobulins
e. Four cardinal signs of inflammation (Celsus): rubor, tumor, calor, dolor (Galenus added: “functio laesa” or loss of
function)
IX. [S9] Example: Phagocytosis of bacteria
a. This is how we get rid of bacteria (via macrophage)
i. Attachment
ii. Ingestion into intercellular vesicles
iii. Fusion with lysosomes
iv. Enzymes of the lysosomes digests the bacteria
v. Cell excretes or releases the digested agents
X. [S10] Inflammatory response
a. This is what happens when infectious agent gets into the system by the surface of the skin.
i. Vasodilatation
ii. Edema
iii. Migration out of the cell, diapedesis, chemotaxis
XI. [S11] Adaptive (Specific) Immunity Characteristics
a. Antigenic specificity means that there are molecules in cells which are able to distinguish between minimal
differences that are presented by these infectious agents or molecules that enter our system. Recognize small
changes and proliferate and transfer information to other cells to aid in destroying infectious agents.
b. Diversity means that very small fractions of the infectious agents are recognized by specific molecules. Can
recognize many different antigens.
c. Immunologic Memory – once cells meet infectious agent, they can move around and go back in the system and
even in resting stage, (if the infectious agent effects the cells a second time) the cells are able to respond very
quickly and mount a more effective response
d. Self/non-self recognition – the system has to learn how to attack foreign antigens without destroying self
molecules because there are certain proteins on our own cells that are similar to antigen cells, so our system
has to learn how to recognize them. Autoimmune diseases happen when this system is breaks down.
XII. [S12] Cells of the Immune System
a. Lymphocytes – main cells of the immune system
i. B cells or B lymphocytes
ii. T cells or T lymphocytes
iii. Null cells or Natural Killer cells
1. These are lymphocytes structurally, but do not carry the characteristics of the B and T cells on their
surface
b. Accessory cells
i. The functions of these cells are to activate and help lymphocytes, or to remove the infectious agents. They
are called effector cells because they are able to lyse which were labeled and recognized by the specific
cells here. These are the granulocytes and macrophages which are phagocytizing the foreign material.
XIII. [S13] B Cells
a. Small round cells with round nucleus and bluish colored crescent shaped cytoplasm.
b. Main function of the B cells is to present Ig on the surface (aka antigen receptors)
i. Ig are able to recognize the antigen without presentation
c. Two types
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Scribe: Dylan Vaught
Tuesday, October 20, 2009
Proof: Sally Hamissou
Dr. Zsuzsa Bebők
Immune System #1
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i. Following activation they can turn into plasma cells which are the Effector cells
1. Effector cells become factories of Ig and secrete Ig into the tissue spaces where the plasma cells are
located. (GI tract, lamina propria, etc.). Ig don’t require any additional helper cells to recognize
foreign antigens (as opposed to T cell helper cells)
ii. Memory cells
1. Some of the B cells that met the antigen can move around the immune system and when the same
infectious agent comes in these memory cells can respond quickly.
XIV.
[S14] T Cells
a. Structurally the same as B cells. The way we differentiate the two is by the TCR.
b. Present membrane receptor for antigen.
c. Recognize antigens presented with MHC molecules on the surface of cells (APC, virus infected cells).
d. Require a helper
i. Effector cells
1. T helper (TH, CD4+, cytokines)- help the induction and proliferation of T cells
2. T cytotoxic (TC, CD8+, CTL)- bind to oncongenes that are presented on our own cells and can
destroy those cells
3. CD4 and CD8 are the main effectors cells
ii. Memory cells
XV. [S15] Natural Killer Cells (NK)
a. Have many Fc receptors that bind Ig (Y shaped molecule) produced/secreted by plasma cells.
b. Lack B or T cell specific markers
c. Lack of specific antigenic receptors
d. Recognize altered cells tagged by antibodies (tumor, virus infection)
e. Recognize Ig constant region (Fc receptor, CD16)
f. ADCC (antibody dependent cell-mediated cytotoxicity)
g. Chediak-Higashi syndrome (NK cell, neutrophils and macrophage deficit and increased incidence of
lymphomas)
XVI.
[S16] ADCC
a. Killing mechanisms are different depending on which cell you are talking about.
XVII. [S17] Accessory Cells
a. Monocytes (blood)
b. Macrophages (tissues)
XVIII. [S18] Granulocytes
a. Neutrophils – phagocytosis
b. Eosinophils – phagocytosis
c. Basophils – allergy
d. Mast cells – allergy
XIX.
[S19] Tissue Macrophages
a. Most of the macrophages phagocytize the material and excrete
b. Functions are similar/same but named different because of where they were when they were discovered.
c. Alveolar macrophages
d. Histiocytes (connective tissues)
e. Kupffer cells (liver)
f. Mesangial cells (kidney)
g. Microglial cells (brain)
h. Osteoclasts (bone)
i. Langerhans cells (skin)
XX. [S20] Antigen presenting cells
a. Crucial to the systemic immune response
b. All have phagocytic activity
c. Attach a fragment of the digested antigen to MHC-2 and present it on their surface (this is important)
d. T cells recognize this and are activated.
e. Answer to an inaudible student question: These are accessory cells because they are not T cells or B cells.
Most of the time they look like macrophages in tissues. Not all macrophages are APCs. All APCs can
phagocytose. That is the difference.
f. Another response to an inaudible student question: These (APCs) are part of the adaptive immune system.
There are no APCs in the innate immune system. There are phagocytic cells in the innate immune system, but
they cannot present the antigen. It is definitely a component of the adaptive immune system.
XXI.
[S21] Dendritic Cells
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Scribe: Dylan Vaught
Tuesday, October 20, 2009
Proof: Sally Hamissou
Dr. Zsuzsa Bebők
Immune System #1
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a. Presents antigens to TH cells
i. Can hold the antigen on their surface for long periods of time. They are staying somewhere in tissue and
the T cell that migrates through the system will meet the presented antigen and once the T cell is the one
that can recognize that particular antigen and bind to it then it gets activated. Complicated/interesting
process that we don’t have time to talk about.
b. Long membrane extensions
c. Named differently by location
i. Langerhans cells – in epidermis and mucous
ii. Interstitial dendritic cells – heart, lungs, liver, kidney, GI tract
iii. Interdigitating dendritic cells – T cell areas of secondary lymphoid tissues, thymus
iv. Circulating dendritic cells – present in the blood or circulating lymph
XXII. [S22] Molecules involved in immune responses
a. Antibodies
b. T-cell receptor
c. MHC molecules
d. CD markers on surface of T cells
e. Cytokines
i. Small peptides which are secreted by components of the immune system. Effects need to be activated in
the immune organs
XXIII. [S23] Antibodies or Immunoglobulins
a. Antigen-binding regions (2)
b. Heavy chains (2)
c. Light chains (2)
i. Hyper variable region is genetically encoded for every single antigen (10^12 possibilities)
XXIV. [S24] Antibody Functions
a. Function is to bind to the antigen after the plasma cell secreted them out – opsonization
XXV. [S25] T Cell Receptor
a. Recognizes the antigen but requires the help of the CD molecule because it can only recognize the presented
antigen presented by the APC
XXVI. [S26] MHC molecules
a. MHC-II molecule is secreted with antigen and presented on the surface of the APC
XXVII. [S27] Role of MHC molecules
a. MHC-2 molecule presents the antigen to the T H cell and is only present on surface of APC’s in our system
b. MHC-1 molecules are present on every cell in our system
c. Some viral molecules bind to MHC-1 molecule and change the structure of the MHC-1 molecule that was
already on the cell. There was no antigen. T cells will not recognize it as a self molecule anymore.
d. Example. If the foreign molecule is presented by the MHC-1 then the CD-8 molecule can bind to MHC-1
molecule and TCR can bind to the particle itself. Then the cytotoxic T cell can bind and destroy the virus
infected cell.
XXVIII. [S28] CD Markers
a. 100’s of them. They come from clusters of differentiation. Just know the following two.
i. CD4
ii. CD8
XXIX. [S29] Other important molecules
a. Accessory molecules secreted by cells of the immune system that will help the elimination of the infectious
agent.
b. Complement: A series of serum proteins involved in the mediation of immune reactions. The complement
cascade is triggered classically by the interaction of antibody with specific antigen.
c. Complement receptor: A structure found on erythrocytes, lymphocytes, neutrophils, monocytes and
macrophages that binds C3 fragments.
d. Cytokines: IL
XXX. [S30] Organs of the Immune System
a. Primary lymphoid organs
i. Bone Marrow – responsible for development of B cells
ii. Thymus – responsible for development of T cells
b. Secondary lymphoid organs
i. Discussed next lecture
XXXI. [S31] Primary Lymphoid Organs
a. Main Function – development and maturation of lymphocytes into mature, immunocompetent cells
H&E: 2:00-3:00
Scribe: Dylan Vaught
Tuesday, October 20, 2009
Proof: Sally Hamissou
Dr. Zsuzsa Bebők
Immune System #1
Page 5 of 5
i. B cells have Ig on surface
ii. T cells have TCR on surface.
iii. The primary lymphoid organs are sheltered from the antigens. The antigens are not going into the primary
lymphoid organs because these cells have to develop WITHOUT meeting the antigen into the stage where
they are competent to meet the antigen
XXXII. [S32] Bone Marrow
a. If you look at the structure of the bone marrow you don’t know what is what. You can only see that there are a
bunch of cells at different levels of development. If you stain using an antibody system you can differentiate
between the stages of cellular development.
b. [S33] B cells develop in the bone marrow in the absence of the antigen and they decide to come out of the bone
marrow as a little small lymphocyte with surface antigen. One cell will only express one type of antigen
XXXIII. [S34] B cell development
a. Stromal cells are important for the development of the lymphocyte. Cells move along the bone marrow stromal
cell and acquire different signals from these cells and from the developing granulocytes. They will reach this
point where they have the surface Ig on their surface and each cell will have different specificity depending on
which type of signal they got. Specificity is based on rearrangement of the gene.
XXXIV. [S35] Thymus
a. Small organ located on the front of the trachea in the upper part of the chest right behind the sternum.
b. Responsible for development of T cells
XXXV. [S36] Function of the Thymus
a. To develop mature T helper and T cytotoxic cells. They come out of the thymus with the TCR on their surface
and with their CD receptor and then move to the secondary lymphoid organs.
XXXVI. [S37] T lymphocyte maturation
a. All the cells that bind with strong affinity to the stromal cells of the thymus will be eliminated and die out to
apoptosis. Most of the cells are eliminated this way
b. Only the cells that have a certain binding affinity to the surface of the stromal cells will be allowed to migrate out
of the thymus.
XXXVII. [S38] Structure
a. The thymus is an epithelial reticular organ
b. In the openings you can see the stages of development of the T cells.
c. Nursing cells engulf the T cells in the cytoplasm. It is not fully understood what happens exactly, but what
happens is that the thymocytes are thought to mature in the outer part and move toward the center and enter
the lymphoid vessels as they progress in their development. Only the cells which are not self-reactive will move
down to the area where they can be secreted into the blood stream/lymphoid circulation.
XXXVIII.
[S39] Thymic lobule
a. The thymus is an epithelial reticular organ (repeated to stress the importance).
b. This is different from lymph nodes because lymph nodes have reticular base or stroma, but those are not
epithelial cells. They are reticular cells that do not have epithelial connection between them.
c. The thymic lobule are epithelial cells with desmosomal connections
d. Tiny globule with connective tissue around it. Dark dots are lots of T cells in the network / cortex
e. Light pink area is the medulla of the thymic lobule
XXXIX. [S40] Hassall’s Corpuscles
a. Function still not known. These are epithelial reticular cells rolled up into and this is how they are destroyed.
This is how the thymus degenerates with age. Those cells show up as keratinized globules that stain usually in
the center of the medulla of the thymus. These grow by age.
XL. [S41] Epithelio-reticular cells
a. To distinguish between the different cells
i. Darker nuclei here are the T cells
ii. Lighter cells are ERCs and have larger nuclei and we don’t see the connections to the others, but there are
supposed to be desmosomes @ the connections
XLI.
[S42] Summary
a. The primary lymphoid organs (BM, Thymus) are responsible for the development of immunocompetent B and T
cells in the absence of antigen
b. Stromal cells play an important role in the maturation process
c. Immunocompetent cells once matured in the primary lymphoid organs are delivered to the secondary lymphoid
organs by lymph and blood
d. Activation of both B and T cells in the presence of antigen takes place in the peripheral (secondary) lymphoid
organs
e. [END 54:03]