BIOL 2402 A&P II                              Lecture Notes                                      Immune

Immunity :: the ability to resist organisms/toxins that tend to damage to cells and tissues.

Immune System :: Overview

     Properties :

            Protects the body from pathogens

            Removes dead or damaged tissue and cells

            Recognizes and removes abnormal cells

     Anatomy:

            Primary and secondary lymphoid tissues

                        Primary lymphoid tissue            = bone marrow and thymus

                        Secondary lymphoid tissue        =

                                    Encapsulated à LN, spleen

                                    Nonencapsulated à Tonsils, Galt, Malt

                                    Immune cells à leukocytes

     Immune Responses:

            1) Detection and Identification

            2) Communication (Antibodies and Hormones called Cytokines)

            3) Recruitment and Coordination

            4) Destruction and suppression

            5) Tolerance

            Note:  Substances that trigger an immune response are called Antigens

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     Divisions:

General defense process --> Nonspecific defenses, inherited, innate, native protection

Specific defense process --> must be exposed to antigen before it can respond/protect with specific defenses, acquire specificity; also known as the adaptive immune system.

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Immune System:: Detail

I. Nonspecific defenses:: first and second line of  Body defenses which are in place at birth

A. Mechanical barriers --> first line of defense

B. Inflammation/Fever/Cells/ Proteins  -->  Second line of body defenses

                        Inflammatory chemicals released into ECF :

                                    histamine, kinins, prostaglandins, heparin, lymphokines, compliment

Two pathways involved ::  Classical and Alternate

Classical Pathway for compliment activation ::

This binding of antibody to antigen on the pathogen will expose reactive sites in the constant heavy region on the antibody.  C1 binding sites are exposed to bind and activate C1 compliment protein.  This activation process is called Compliment Fixation.  This initial activation will create a positive feedback cascade to activate the other compliment proteins, C2+C4 +C3 àC3ab à C5abàC6+C7+C8+C9

Alternate Pathway for compliment activation ::

Involves C3 and Factors B, D, and P.  The factors will bind with the pathogen's cell membrane polysaccharides (carbohydrates) and activate C3 to C3ab and then continues as mentioned earlier and more specifically  below.

All pathways go to common terminal pathway involving C3 which then splits into C3a and C3b

C3a   stimulates mast cells to release histamine and cause vasodilation resulting in INFLAMMATION

C3b Activates phagocytes (MO, neutrophils) to engulf pathogens and helps put a "handle" on the pathogen membrane.  This is called OPSONIZATION and involves a (+) charged protein coat over a (-) charged pathogen membrane.  The (-) charged WBC can then be attracted to the now (+) coated  pathogen and attack.

C3b also activates C5-C9 to create MAC (membrane attack complex)   that will punch holes in the pathogen membrane to create hydrophilic channels to let ions and water in.  This results in CELL LYSIS

Compliment must be carefully regulated, for if uncontrolled can create problems such as:

Interferon :: proteins secreted by virus infected cells

Interferon are one of the hormones of the immune system and belong to a group of immunohormones called CYTOKINES.

These proteins will stimulate the synthesis of other proteins (PKR antiviral proteins) in other normal cells to inhibit (interfere) with viral replication if invaded.

Types are classified based on the cell that secretes them ::

Alpha interferon will activate the Macrophages and NKC (natural killer cells) to help with infected cells (viral, cancer)

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SPECIFIC IMMUNITY  ::  3rd line of body defenses

Review of Lympocyte Origins:

            Recall that lymphocytes develop from a red bone marrow stem cell called the hematocytoblast or pluripotent hematopoietic stem cell (PHSC) via the lymphoid cell line to become lymphoblasts à prolymphocytes à lymphocytes.  These lymphocytes then have one of three pathways to become EITHER a Natural Killer cell (NK), OR a Thymic Lymphocyte (T cell) OR a Bursal lymphocyte (B cell). 

  A. Innate Immunity ::  genetically determined, no prior exposure

  For lymphocytes, this involves the NK cells which make up ~10% of circulating large granular lymphocytes and part of native immunity.  Natural killer cells are preprogrammed with the genetic, innate information about body defenses. They do not undergo specialization because they are already programmed to recognize the correct numbers of the self antigen (MHC*HLA) found on all normal cells via their receptors. If a cell has an abnormal number of self antigen (too low) this triggers a response.
This lack of self antigen does not engage the turn-off (inhibitory) NK receptors and thus, those cells NOT expressing normal numbers of self antigen (such as in viral / cancerous infected cells) will be killed via a perforin protein that disrupts the  plasma membrane to cause cell lysis.
Besides recognizing abnormal numbers of MHC*HLA, NK cells can also respond to IL-12 produced by macrophages that are presenting antigen to Tcells. In response, the NK cells can secrete IFN-gamma.

  B. Acquired (Adaptive) Immunity ::

             Antigen specific immunity

             May require 1-2 weeks to be fully active after the FIRST exposure to an antigen

            1. Humoral-Antibody  Mediated  Immunity

            2. Cell-Mediated Immunity

Specific Immune system involves cells: Lymphocytes and how MO tie nonspecific with specific

10%     B- lymphocytes (B-cells) are for humoral immunity, secrete antibody

80%     T- lymphocytes for cell-mediated immunity.  Various subpopulations

T-Helper Cells  (Th)    55%      secrete cytokines

T-Cytoxic Cells (Tc)    25%    kill cells expressing foreign antigen

Macrophages   for help in phagocytosis and PRESENTING antigen to Th cells.

Macrophages can also present antigen to B cells.

NOTE: Antigen presenting cells are called APCs.

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T and B Lymphocytes arise from the hemocytoblast (PHSC) lymphoid line in the bone marrow.   Becomes

TOLERANT and immunocompetent depending on where they mature.  During this processing of selection the lymphocytes develop functional receptors and begin to first accept fetal tissue as normal and those that react to "self" are eliminated.  The final selection process and maturation  involves recognizing foreign antigen or "non-self". 

The receptors on the lymphocytes are determined by genetic information (DNA).

Specific lymphocytes will have their own unique receptor (TCR or BCR), a group of Cluster determinate proteins (CD) and the normal self antigen protein MHC-HLA. There will be other cluster determinant proteins as well as ligands that aid in recognizing and responding to the signal (cytokines) to activate.

1. T- Lymphocytes  ....start as immature lymphocytes from the bone marrow and then migrate to the thymus.  Will divide and mature under hormonal influence (Thymosins from endothelial cells in the thymus) and have self-tolerance and I.D. foreign antigen.

When mature, they will have T-cell receptors (TCR that consists of two protein chains either alpha/beta or gamma delta) on their membrane T cells have other protein markers (i.e. CD 4 or CD8) to help with binding to MHC regions to provide a second costimulatory signal and to provide stabilization.

********T cells ONLY recognize processed (digested) antigen via their TCR + CD proteins which are presented (shown) to them on the MHC-HLA antigen regions. Usually antigen presenting cells [APCs] such as dendritic cells, macrophages, and even B cells are involved with the processing of antigen for the T-cells.

 

2. B-Lymphocytes...arise from fetal liver and bone marrow.  Will mature in bone marrow and have a B-cell receptor (IgD) on its membrane surface to bind to specific antigen in its native (non-digested/processed) form.

Recognition of foreign antigen is done by forming noncovalent bonds (hydrogen bonds) of high affinity to portions of the molecule.  This bond is a close one and the distribution of electrostatic charges (+/-) will also help in bond formation. 

The lymphocyte receptors responsible for bond formation are coded by the DNA and there are many diverse receptor genes due to various genetic rearrangement, nucleotide changes, errors in replication or repair, and a combinational diversity as the receptor chains are assembled and folded.  All receptors have various segments :  V, D, J, C.  and each of these has various versions. 

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Specific Lymphocytes are selected by the hormones in the primary lymphoid tissues: the Thymus or Bone Marrow

1. Hormones promote the expression of functional receptors:: IgD or IgM for B-cells,   TCR for T cells

2. Lymphocytes reactive against self (fetal) antigens are eliminated via apoptosis
Remember, in the fetus all antigens are considered self during this immune selection and discrimination process and results in TOLERANCE.

3. CD (cluster determinants/designation) proteins are then expressed. For example 

4. Lymphocytes are then allowed to mature and tested to see if they can recognize foreign antigen (by binding to it with their receptors and CD proteins)

After preprocessing for immunocompetence, the naive lymphocytes will go to secondary lymphoid organs (lymph node, spleen, tonsils, etc.).  75 % of the T cells will be in the blood circulation and are normally the lymphocytes seen on a stained blood smear. It is in these tissues that they are tested to become true mature lymphocytes for the 3rd line Specific Defenses.

Resting (naïve) specific lymphocytes must receive 2 signals:

            a) binding of the receptor (TCR or BCR + CD protein) to an antigen = sensitized

            b) Costimulatory signal (cytokines, B-7 protein) received via other CD proteins = activated

Summary of Stimulatory Signals for Lymphocytes ::

Primary signal is antigen binding by B and T cell receptors and specific CD proteins

Secondary signal is a costimulatory signal through the cell membrane. 

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Because macrophages are an important connection between the specific and nonspecific immune divisions and are very important in helping to sensitize and activate T lymphocytes, it is important to know where they are found. Macrophages will be distributed to lymphoid organs and other areas such as::

Macrophage main function is to engulf foreign particles and clean up debris/ dead /damaged cells.

This helps control inflammation and promote healing of tissues.

They also PRESENT ANTIGEN, & secrete proteins (Interleukins) that help activate T cells, which in turn help activate the B-cells and other immune cells (NK).

SO WHY do we have a specific immune system ????  ::   For adaptable antigen recognition !!!!

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ANTIGEN ::

            (Ag) are large, rigid, and complex substances that can be easily degraded. 

            This then makes this substance capable of promoting an immune response.

            There are two types of foreign antigen :: complete  antigens or incomplete antigens.

1) Complete antigens will stimulate antibody production & react with antibodies and therefore considered to be antigenic.  These are large substances with at least two sites for antibodies to bind. They can also be degraded by APCs and presented to T lymphocytes.

2) Incomplete antigens called HAPTANS are low molecular weight and only have one site for antibodies to bind.  Therefore, they are NOT antigenic (capable of stimulating antibody production).
Examples of haptans are  :: drugs, and allergy related substances --> pollen, dust, mold, dander etc

 If bound to body's protein carriers, will cause an antibody production and response because the binding sites have increased and it will be recognized as a foreign substance

To summarize :: certain portions on the antigen will become the antigenic determinants--> the sites where antibodies will bind.  Can have several sites with several different  structures and therefore provoke a response from many different lymphocytes.

The number of the antigenic determinants on an antigen is called the VALENCE.

The actual binding site of the antigen that is recognized by the lymphocytes is called the EPITOPE.  Remember that strength of binding is determined by electrostatic charges and hydrogen bonds and the number of bonds involved. A strong immune response is the result of good bonding with all binding sites. A weaker response is the result of fewer bonds or weaker bonds.

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IMMUNOLOGICAL MEMORY  -->

a. Primary Immune Response ::

            cells proliferate and differentiate. 

            Takes 5-7 days for onset, lasts about 10 days. 

            Weak potency, short duration.

b. Second Immune Response ::

             faster 3-5 days

             more prolonged

             more potent. 

            System already primed with sensitized memory cells.

Occurs for HUMORAL and CELL-MEDIATED Immunity.

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***************** Humoral response ***********************************

Antibodies (Ab) produced by B-lymphocytes response to antigen.  The antibodies then help promote a fluid (humoral) defense by:

Process ::  B cells are sensitized when antigens bind to specific antibody (Ig D or IgM) receptors and their CD79 proteins.

Most B cells (T cell dependent B cells) need helper T cells to activate them via cytokines at their CD 19 and CD21 proteins. This gives the sensitized B cell permission and causes a stimulation of B cell growth and division into clone cells (B cells with the same antigenic receptor complexes). Clone cells can become plasma cells that secrete the specific antibody [Ab].  These plasma cells live about 5 days.

The Ab circulates in various body fluids and will bind with its specific antigen to MARK THE CELL FOR DESTRUCTION.

Clone cells that do not become plasma cells become MEMORY B CELLS.

If exposed again to that specific antigen, will have a quicker response since they already were sensitized.

***************ANTIBODIES***(Ab)*******************************************

Immunoglobulins --> abbreviated  Ig........are gamma globulins of the blood proteins

(about 20% of plasma proteins identified on blood chemistries or on a refractometer)

These are the soluble proteins secreted by activated B cells and plasma cells in response to antigen.  The secreted antibody will bind to that antigen marking it for destruction.

Immunoglobulins are grouped into 5 classes that have slightly different structure

Basic Structure::

The heavy chains have a flexible hinge in the middle so that their shape takes on a "Y" appearance.  This Y shaped molecule is called an antibody monomer.

On the arms of the monomer, there are two regions: One constant region and one variable region for both the heavy and light chains. In antibodies of a given class, (its istoype)  the constant region has the same amino acid sequence. This determines characteristics related to membrane solubility, & adherence to antibody & compliment complex

Variable regions:: the sequence of amino acids is variable in this section of the protein. The variable light chain and the variable heavy chain form antigen binding sites for each arm. These two sites fit specific antigen binding sites and will be different for each antibody.  The variable region determines the Ab's antigen specificity.

Antibody Classes: five classes based on constant regions in their heavy chains :: IgDelta, IgMu, IgGamma, IgAlpha, IgEpsilon.

  Each class plays a different role in the immune response.

IgE :: ~ 00.2% of Ab. Involved with allergies/parasites. Secreted by plasma cells in the skin, gi, tonsils, respiratory.  IgE will bind to mast cells and basophils to cause degranulation an release of histamine.  (a very potent vasodilator).

IgG :: ~ 76% of Ab, therefore the most abundant, crosses placental barrier to protect human newborns for 3-6 months [other animals would be in terms of 3-6 weeks], and fixes compliment due to C-1 binding site.

IgA :: ~ 155 of Ab. Found in mucus and glandular secretions such as tears, saliva, milk, respiratory, reproductive. Prevents pathogens from entering or binding to mucosal surfaces.

IgM :: ~ 8% of Ab. First antibody released by plasma cells.  Can be free in plasma as a pentamer or membrane bound as a monomer to form a Bcell receptor. Fixes compliment due to C-1 binding site for classical complement pathway activation.

IgD :: ~ 1% of Ab. Attached to Bcell to function as a receptor along with CD proteins.

  Gene segments code for Heavy and Light chains.  Located on the same gene, but separate so that the two chains are separate.  The mixing of these segments creates the diversity and there can be mutations in the gene to cause a hyper-variable region. Antibody molecules are also flexible: Fc wag; Fab rotation; Fab arm wave; Fab elbow bend.

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ANTIBODY FUNCTION :: to inactivate antigen and target (mark) pathogen for destruction. Ab DOES NOT "Kill". Other cells [macrophages] and proteins [complement MAC] have that responsibility.

Ab+Ag ==> forms Ag|Ab immune complexes to cause::

1) neutralization.......blocks toxic sites on virus/bacteria to pathogens can't bind to tissues to cause injury.                      

2) Agglutination ..... cross-linked clumping of cell bound antigen of cells. (seen with RBC)

3) Precipitation....cross-linked Ag|Ab are formed into large complexes and settle out of solution.  Immune complexes result when antigen is soluble and therefore can be brought out of solution.

4) FIXES AND ACTIVATES COMPLIMENT.....the chief way used. 

Antigen binding to antibody (IgG and IgM) changes shape and exposes compliment C1 fixation to antigenic cell surface to cause cell lysis as well as promoting phagocytosis by opsonization  and causing inflammation.

Monoclonal AB :: Ab prepared for research, treatment, tests.

Descendants of a single cell that is pure and specific.

             Done by exposing lymphocytes to tumor cells to create hybridoma cells.

            Cells that produce the desirable Ab are then cultured.

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Key Words used in 3rd Line defenses:

Progenitor lymphocyte : a future T or B cell that is formed in the red bone marrow

Pre-T or Pre-B cell: one that is undergoing immunocompetency processing in the bone marrow or thymus

Naive T or B cell: one that has accepted the "rules" via + and - selection processing

Mature T or B cell: one that is being challenged in the secondary lymphoid tissues/organs

Sensitized T or B cell: one that has bound Ag to its receptors and CD proteins

Activated T or B cell: a sensitized cell that is now being stimulated by cytokines via other CD and ligand proteins

Effector T or B cell : the result of clonal expansion of an activate T or B cell. Will have unique name to help identify it in the immune response (i.e. Plasma Cell, Killer T cell, T-H1 orT-H2 ).

Memory T or B cell: progeny that will be used for future immune responses, duplicate of parent cell.

***************Cell Mediated Immune Response **********************************

Three types of T lymphocytes (T cells) :

T cells respond to processed (digested) antigens presented by boAPCs or body cells

            Usually macrophages, that are infected with bacteria/virus/cancer that break down pathogen and incorporate foreign antigen on their MHC*HLA self marking proteins. Once antigen has been processed, the macrophages will also secrete various interleukins. IL-1 will activate T cells to produce clone cells for the immediate immune response and memory cells for further responses.

Chemical mediators (immune hormones) involved with T cells :: are called Cytokines

Cytokine examples:

Recognition and Activation of T cells occurs by binding of antigen to lymphocyte surface of

T cell receptors  ::  TCR (looks like lower 2 of AB) and are designated as either an alpha/beta or a gamma/delta with the Cluster determinate (CD) that gives the T cell it's unique ID. [CD4+ or CD8+]. Remember that there are other CD proteins and ligands that are used for adherence to the foreign antigen and for signal transduction to create secondary messengers.

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To recognize self, there are membrane glycoproteins on most all cell surfaces that are coded for by genes in a region of the DNA called the

MAJOR HISTOCOMPATABILITY COMPLEX (MHC). 

Two types of glycoprotein classes are Class I MHC and Class II MHC marker proteins

1. Class I MHC are glycoproteins found on the surface of all nucleated cells and are called HLA-1  (Human Leukocyte Antigen -1) and have alpha chains 1, 2, 3. Are bound to the cell surface by only one of the chains. They are created when endogenous antigen is picked up and then are used to help display it on the surface. This is usually the case when normal tissue cells are exposed to viruses or are undergoing cancerous changes. The foreign proteins are being created within and are then incorporated into the HLA structure, which makes it "abnormal" to the other WBCs and mark it for destruction when recognized.

2. Class II MHC are glycoproteins found on the surface of macrophages and T and B lymphocytes.  Therefore, they can recognize one another. These marker proteins are called HLA-2 (Human Leukocyte Antigen-2) and consist of alpha 1, alpha 2, beta 1 and beta 2 protein chains. These class II MHC*HLA are bound to the cell surface by two of the chains and are created when exogenous antigen is engulfed and then are used to display it at the surface of the cell. This is usually the case of APCs such as Macrophages, dendritic cells, and Bcells when they present antigen.

The MHC regions of the DNA code for these proteins that are specific for each species:

Effector Mechanisms ::                         

So then what happens..............well, cells can process and present antigen to help activate T cells

Class I changes in MHC regions will then allow the binding to T-cytotoxic cells with their TCR + CD 8 proteins

Class II changes in MHC regions will then allow binding to T-helper cells with their TCR + CD 4 proteins

 

Class I MHC cells that process, bind, and present endogenous antigen will help activate cytotoxic T cells, and suppresser T cells.  T cell activation by a change in Class I MHC HLA-1 protein is done endogenously & tends to result from viral infections.

Class II MHC cells that process, bind, and present exogenous antigen will help activate helper T cells.  T cell activation by changes in the Class II MHC HLA-2 protein is usually done exogenously and tends to result from bacterial infections.

Once activated by binding to MHC with Ag, the T cells enlarges & proliferates to form clone cells some of which become memory T cells to maintain immunological memory.

T cell proliferation also affected by cytokines ::

So lets see what happens....

Macrophages that have phagocytized a foreign antigen will presents Ag on their Class II MHC, and release various interleukins, the most important one being Il-1 to call T-H cells to them.

Helper T cells binds via their TCR+CD4 to the macrophage at its MHC*HLA-2 bound with foreign Ag and is affected by Il-1 (it receives its co-stimulation) and then the T-H cell releases Il-2 via a seondary messenger system [transcription factors on the DNA of the cell then create the interleukin to be secreted] to create a positive feedback cycle that causes additional co-stimulation to ::

T cell function ::

Helper T cells -->

Th-1 cells stimulate  other T-h cells to secrete cytokines and activate T-c and macrophages

Th-2 cells

      How the T helper cells work ::

Cytotoxix (who become Killer) T Cells main targets are viral infected cells, but can also attack cancer cells, transplants, and intracellular bacteria.

They work the following way ::

Cells with Class I MHC + Ag will cause Cytotoxic T cells to bind.

             This activates the CT cell to become either a memory cell or a killer cell.

Killer cells can destroy the target one of two ways :

SOOO, ultimately their function involves cell lysis.        

Remember that Interleukin-2 from T cells can also activate cytotoxic T cells to become killer cells.

Suppressor T cells ::

            can release lymphokines and suppress the activity of T and B cells.

Their function is to stop the immune system and prevent an autoimmune reaction.

Their actual existence is still in debate, since they have the CD8 marker like T-c
Perhaps they are just a "turned off" T-Cytotoxic cell.

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TO SUMMARIZE ::

B cell makes up 10% of lymphocytes. 

            They respond to Ag by plasma cells producing AB (one of 5 classes). 

            Ab will protect by inactivating or promoting and helping other immune cells to eliminate the pathogen. 

            Most B cells are dependent on T cells for their second costimulatory signal (the Interleukin signal).

T-helper cells make up 55% of lymphocytes and function to ::

there are two subsets of T helper cells

T-cytotoxic cells make up 25% of lymphocytes and respond to foreign antigen by killing the infected cell by one of two methods ::  perforin or FAS

Natural Killer Cells make up 10% of lymphocytes.  They function in our native (born) defense mechanism to mainly control virus and cancer cells.  They will kill if that cell FAILS to express normal self antigens.  Their activity is greatly increased by Ag|Ab binding, interferons, and some cytokines.

Memory T and B cells are clones that will recognize Antigen at subsequent exposures.  Easily activated. May be short lived or life long.  Depends on how many cells are created and how strongly antigenic (causing an immune response) the original antigen was.

Normal :  when other Cells MHC-HLA proteins don't match [fit] those of the immune system cells

Abnormal :  when antigen is presented at MHC-HLA regions

        when there is a different MHC-HLA protein on the cell membrane and the lymphocyte receptor and CD proteins match up or fit like a lock and key mechanism.

Immune system Applications :

ACTIVE AND PASSIVE IMMUNITY ::

Active, naturally acquired -->

            Form Antibody and cells needed for defense

            from exposure to bacterial/virus. 

            Will have symptoms of the disease

.

Active, artificially acquired -->

             vaccines. Will prime the immune system to create Ab and cells need for defense

  Vaccines are attenuated (changed) to spare symptoms of the disease but still function as antigenic determinants to stimulate immunological memory.  Can have vaccines --> killed, modified-live, and live.

Passive, naturally acquired -->

            antibodies or cells from mother to fetus through placenta or colostrums milk

Passive, artificially acquired -->

            artificially produced gamma globulins (Ab) or cells.

             Given for diseases that need immediate protection such as Hepatitis, antivenoms, botulism, rabies, tetanus

  *** Passive immunity ..........antibodies and cells already made by someone else’s immune system or in a lab. Therefore B cells and T cells are NOT challenged and therefore NO memory cells are produced. Protection is borrowed (passive).  Passive immunity will provide immediate protection, but short lived (2-3 weeks) as antibody and cells are removed.

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*******************FYI and Problems*******************************************

Immune system and organ transplants :: to prevent reaction,  blood type , cross match so that  MHC antigens determined.  Mediated by helper and cytotoxic T cells.  T-Helper cells are involved in the initial reaction, while cytoxic T cells accelerate the reaction.

Treatment involves immunosuppression with corticosteroids, radiation, azathioprine, and cyclosporine to inhibit lymphokine production and suppressed helper T cells.

Immune Disorders :

1. Immunodeficiency --> abnormal production or function of immune cells, phagocytes, or compliment.

Can be congenital or acquired.

Congenital -->

Acquired Immunodeficiency-->

    1. AIDS.......interferes with helper T cells due to destruction by the HIV virus. This RNA virus can fit the CD4 receptor and invade the helper T cell and therefore will decrease cell mediated immunity.

    2. Immunosuppressive drugs

    3. Radiation treatments

 

2. Autoimmune disease -->

When the individual's immune system ceases to tolerate self-antigens and mounts a response to that antigen.  Usually occurs after a microbial infection. 

Causes ::

The immune system will now target normal cells and creates auto-antibodies.

Other mechanisms can also occur :: 

 Sensitization of  cytotoxic T cells caused by altered body proteins from antibody damage or tissue antigen change due to disease. Also can involve antigens not previously exposed to the immune system such as the self antigens of the thyroid gland, lens of the eye, and sperm.  Cross reactions can occur if antibodies made for foreign antigen react with self antigens

            Autoimmune disease Examples :: glomerulonephritis, rheumatic fever, Grave's disease,  lupus erythematosus, myasthenia gravis, rheumatoid arthritis, MS, DM (juvenile)

3. HYPERSENSITIVIES :: allergies

the antigen is termed the allergen.  Different types of hypersensitivies depending on the amount of time and the cells involved.

I. Type I Hypersensativities

Local reactions in

Systemic --> Anaphylactic shock

Atopy --> allergies to environmental antigens due to genetic causes of large amounts of IgE

 

2. Subacute Hypersensitivity 1-3 hours ::

a. Type II Hypersensitivites --> AgAb reaction (Ig M primarily, sometimes Ig G) [agglutination reaction]

             as those seen in blood transfusion  reactions (RBCs), platelets, drug reactions

b. Type III Hypersensitivities --> AgAb (Ig G) immune complex  [precipitation reaction]

            (seen in most autoimmune diseases such as arthritis)

 

3. Delayed Hypersensitivities

1-3 days, involves activated T cells (cytotoxic & helper)

examples are contact dermatitis, poison ivy.

Clinical usage involves TB (tuberculosis testing)

Specific MOA (mechanisms of action)

            T-h1 à MO à TB

            T-h2 à Eosinophils -à chronic allergies, asthma

            T-c à cells à contact dermatitis

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Other problems :

            Genetic Defects

                        * MHC class I deficiency

                        * MHC class II deficiency

                        * Agammaglobulinemia

                        * Leukocyte adhesion deficiency

Aging problems :: decreased efficacy (effectiveness)

                 decreased number of cells

so therefore have decrease in the response of the immune system

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FYI SUMMARY OF LYMPHOKINES ::

   those secreted by helper T cells are Interleukins (Il):

Il-2 --> stimulates growth & proliferation of Cytotoxic/Suppressor/Helper  T cells

Il-3 --> promotes growth & stimulation of all different types of hematopoietic stem cells

Il-4, 5, 6 --> Bcell stimulation and growth

 Other Interleukins ::

Activated macrophages due to a response from inflammation, will secrete : 

IL-1 --> stimulates T and B cells to undergo proliferation if sensitized

TNF (tumor necrosis factor) and CSF (colony stimulating factor)

Il-6       mediates inflammation

Il- 8      activates neutrophils

Il-12     also involved in T-helper cell activation  (along with Il-2)