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Antigens
Antigens are microbes or microbe parts that provoke an immune response
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Antibodies
Proteins made against antigens
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The antigen that provokes the best immune response is a
- Protein
- Carbs provoke a little response and lipids a very poor response
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Haptens
- Less than 10000 molecular weight, so no immune response
- We don't build antibodies to haptens
- Can attach to something else to provoke an immune response
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Antigenic determinants
- Epitopes
- Protein receptors on B and T cells recognize discrete regions of the antigen called epitopes
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Haptens
- Non immunogenic molecules that don't stimulate the immune system by themselves, but when they are linked to proteins in the body, the larger combination may be recognized as nonself.
- Specific immunologic tolerance
- An example is penicillin
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Immunological memory
The ability to remember past pathogen exposures
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Immunocompetent
- Refers to lymphocytes capable of reacting with a specific epitope
- B and T cells are waiting in the wings to respond to an antigen
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Clonal selection
Exposure to an antigen only activates those naive B and T cells with receptors recognizing specific epitopes on the antigen.
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Autoantigens
Body attacks self
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Immune deficiency
The loss of the body's ability to respond to antigens and epitopes
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Regulatory T cells prevent
Other T cells from attacking "self" cells
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Autoimmune diseases occur when
Self-tolerance breaks down
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If nonimmunogenic molecules (haptens) are linked to proteins,
- They may not be recognized as "self"
- Thus they might provoke an immune response (allergies)
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Immunological memory
- The ability to "remember" past pathogen exposures
- The body fights off any subsequent infections
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The humoral immune response involves
- Activation of B cells
- Production of antibodies against the identified antigen
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T lymphocytes (T cells) provide resistance through
Lysis of infected or abnormal cells
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If the microbes enter cells
Antibodies are useless
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Then the cell mediated immune response (T cells) is activated to
Eliminate "nonself" cells
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B lymphocytes (B cells)
- Involved in producing antibodies against epitopes
- Humoral immunity
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T lymphocytes (T cells)
Cell mediated immunity
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Where are B cells and T cells found?
In the lymph nodes and spleen
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When are B & T cells activated?
When an antigen is detected
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B cells
- React quickly when activated
- Memory cells
- Plasma cells
- Each B cell can produce only one type of antibody
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Plasma cells
- Produced from B cell clones
- Synthesize and secrete antibodies against the invading pathogen
- B cells that make antibodies
- Makes about 2000/second
- Live about 4 days
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Memory cells
- Are long lived B and T cells capable of dividing on short notice to produce more effctor cells and additional memory cells in an immune response
- Can live for decades
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Effector cells
- Target the pathogen
- B and T cells contain activated lymphocytes that will develop into effector cells and memory cells.
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Hematopoietic stem cells
- Lymphocytes originate from these cells in the yolk sac, but end up in the bone marrow
- Develop into myeloid and lymphoid progenitors
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Myeloid progenitors
- Developed from Hematopoietic stem cells
- Become red blood cells and most of the white blood cells
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Lymphoid progenitors
Become lymphocytes of the immune system
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Antigen binding site
- The variable domains in a light and heavy chain forma highly specific, three-dimensional structure
- It is this region on the antibody that binds to the antigen with epitopes
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Antigen exposure activates
Only T and B cells with receptors that recognize specific epitopes on that antigen
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B and T cell clones contain lymphocytes that develop into
- Effector cells that which target pathogens
- Memory cells are long-lived B and T cells
- They are capable of division on short notice
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The immune system originates from
- Groups of stem cells
- Hematopoietic stem cells
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In the fetus, lymphocytes arise from
Hematopoietic stem cells in the yolk sac and bone marrow
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T lymphocytes are formed in
The thymus
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B cells are formed in
The bone marrow
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Antibodies are of a class of proteins called
- Immunoglobulins, (Ig)
- Hooked together with a disulfide bond
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Antibodies comprise
17 % of protein in serum
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Epitope recognition requires antibodies to have a special structure of
- 2 identical heavy (H) chains
- 2 identical light (L) chains
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The humoral immune response
- Immunoglobulins
- Results in the activation of B cells and the production of antibodies that recognize epitopes on the identified antigen in the blood or lymphatic fluids
- The response is so specific that the body can generate antibodies to just about any antigen or epitope it encounters.
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Immunoglobulin constant region
Determines the destination (body location) and functional class of the antibody
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Immunoglobulin variable region
- Contains different amino acids for the many antibodies produced
- Binds to antigen
- Each variable region can bind to two antibodies
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Each immunoglobulin light and heavy chain has:
- A constant region, which determines the location and functional class of the antibody
- A variable region, which contains different amino acids for the many antibodies produced
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Immunoglobulin variability allows
Formation of the specific antigen binding site
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The Fab fragment of an antibody combines with
The Epitope
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The Fc fragment performs functions in
Opsonization
- Able to be crystalized
- It can combine with phagocytes, activate the complement system or attach to certain cells in allergic reactions
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How many know Immunoglobulin classes are there?
There are five immunoglobulin classes
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IgM
- Is the first (but short-lived) Ig to appear in circulation after B cell stimulation
- Primary antibody response
- Largest Ab in circulation
- Doesn't cross the placenta
- 5 chains
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IgG (gamma globulin)
- Is the major circulating antibody
- It provides immunity to the fetus and newborn. Crosses the placenta
- 1st discovered. Classical
- 80% of all Ig's in the blood
- A little slow, takes 24-48 hours
- Secondary Ab response
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Memory cells
IgG memory cells provide long term resistance
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IgA
- Provides resistance in the respiratory and gastrointestinal tracts
- It is found in colostrum & tears
- 2 chains hooked together J chain
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IgE
Plays a role in allergic reactions
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A primary antibody response occurs
- The first time the body encounters a pathogen
- B cells are activated and effector cells, the plasma cells, start producing and secreting antibody
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A secondary antibody response is
- More powerful and longer lasting
- It occurs with a subsequent infection by the same pathogen
- Due to the presence of memory cells, a rapid response to antigen leads to the production of IgG principle antibody.
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Antibody diversity is a result of
Gene arrangements
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Somatic recombination
- A random mix and match of gene segments to form unique antibody genes
- This accounts for the large number of unique antibodies encoded by immune system genes
- The information encoded by these genes is expressed in the surface receptor proteins of B cells and in the antibodies later expressed by the stimulated clone of plasma cells.
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How many Immunoglobulin genes exist?
- 300 Variable
- 50 diversity
- 4 joiner
- 8 constant regions
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Viral inhibition
Antibodies react with molecules at the viral surface and prevent the viral attachment to cells
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Membrane attack complex
Forms pores in the bacterial cell membrane increasing cell membrane permeability and inducing the cell to undergo lysis through the unregulated flow of salts and water
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Major histocompatibility complex
Proteins that define the uniqueness of the individual and play a role in the immune response
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Antigen presenting cells
- MHC-II molecules fold to form a pocket in which small antigen (peptide fragments can bind)
- APCs present antigen fragments to CD4 T cells which will bind them with their TCR/CD4 receptor complex
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MHC-1
- Molecules that are found on all nucleated cells of the body
- Fold so that they can bind a small antigen fragment from an infecting virus
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Interleukin 1
A cytokine which binds with naive T cells and stimulates T-cell activation
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Helper T cells
- T2: Help in the activation of humoral immunity
- T1: Recognize and bind to infected APC displaying the appropriate MCH-1 peptide
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Perforin
- Toxic proteins that insert into the membrane of the infected cell forming cylindrical pores in the membrane
- This releases ions, fluids, and cell structures
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Granzymes
Cytotoxic cells release granzymes that enter the target cell and trigger apoptosis.
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Toxin neutralization
Antibodies called antitoxins combine with toxins and neutralize them and prevent toxin attachment to cells
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Opsonization
Antibodies coat bacterial cells and prevent bacterial attachment to cells
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Aggluntination
Antibodies combine with antigens on the cell surface and bind the cells together or restrict movement.
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Precipitation
- Antibodies combine with dissolved antigens to form lattice like arrangement that precipitate out of solution.
- Each Antibody attaches to two antigens.
- Deals with something smaller than a cell
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Phagocytosis
The Fc portion on antibodies encourages phagocytosis by forming a bridge between antigen and receptor sites on the phagocyte.
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Five types of antigen-antibody complexes
- Antitoxins
- Agglutination
- Precipitation
- Opsonization
- The complement system
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Formation of antigen-antibody complexes result in the antigen
- Death
- Inactivation
- Increased susceptibility
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Four Types of T Cells
- Cytotoxic T cells
- Delayed hypersensitivity T cells
- Naive cells, (Helper T cells)
- Suppressor T cells
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Cytotoxic T cells
- Killer T cells
- The marines
- Cytotoxic T cells have T-cell receptors (TCRs) and CD8 coreceptor proteins
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Naive cells, (Helper T cells)
- Stimulates B cells and cytotoxin cells
- Makes other cells not lazy
- Have TCRs and CD4 coreceptor proteins
- Formerly known as helper T cells can help with both humoral and cell mediated immunity
- HIV attaches to the CD4 receptor and infects the cell
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Suppressor T cells
Keeps other T cells from getting too active so they don't attack self
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The Cell Mediated Immune Response
- Cytotoxic T cells
- Naive T cells
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Naive T Cells Mature into
Effector T Cells
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