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What is the 3rd line of defense?
- Adaptive immunity - acquired
- - specific response to Ag with a Ab and lymphocytes
What is an Ag?
substance (protein or polysaccarides) that causes the body to produce Ag or sensitized T cells
- Ab = a protein made in response to an Ag
- specific Ab that can only combine with that Ag
Abs are a globulin class of protein (protein with globular form) so Ab are called immunoglobulins (Ig)
2 branches of the specific immune response?
- 1. Cell mediated response (T cells)
- 2. Humoral response or antibody mediated - B cells & plasma cells (Abs)
What is the B lymphocyte
Memory B cell?
- B cells = bursa derived (bursa of checken, not human)
- B cells arise from pluripotent cells that are produced and mature in the red bone marrow
B cell has specific Ag on it surface - when stimulated by matching Ag - it becomes a plasma
cell - makes ↑# Abs (identical to Ab on B cell surface)
A plasma cell is a mature stimulated B cell that makes Abs
- Memory cells do not attack invaders - they remain in the system as
- clones (thousands) after a specific immune response - they speed up
- immune response is same Ag is encountered again in the future
What is a T cell?
What does it make?
- T cell = thymus derived
- - made in red bone marrow
- - mature in thymus (lymph tissue
Each has specific T cell receptor
that binds to specific Ag - when Ag binds T cell is stimulated and produces cytokins
→ immune repsonse
What is a hapten?
Hapten = an small Ag molecule (too small to register respone) that contains an epitope - needs to be combined with a carrier protein to cause an immune response
2nd encounter - hapten alone will trigger immune response
4 Types of T cells
- a. Cytotoxic T cells - CD8 (co-receptor)
- - activated by cytokins - cause apoptosis
- b. Helper T cells - CD4 (co-receptor)
- - release cytokins → activate dendritic cells (APCs), macrophages, cytotoxic T cells, B cells (plasma cells)
- c. Memory T cells - CD4 & CD8 (co-receptors)
- d. Regulatory T cells - turn off specific immune response
What is an epitope?
Epitope = the part of an Ag that binds to the Ab and starts the immune response - also called an antigenic determinant
Step in cell mediated immunity -
Exogenous and Endogenous processing
- CD4 T cells: -Exogenous Processing (MCH II/ Ag)
- 1. APC presents Ag to CD4 lymphocyte - Ag binds at TCR (T cell receptor) and CD4 is the coreceptor
- 2. Costimulant (such as IL-2) causes cell to become activated
- 3. CD4 T cells make active helper T cells - (they secrete cytokins (IL-2) and memory T cells - not active until next contact with Ag
- CD8 T cell - Endogenous processing (MCH I/ Ag)
- 1. APC presents Ag - Binds at TCR and CD8 is the coreceptor
- 2. Costimulator (possibly IL-2 secreted by activated CD4 cells) causes cell to be activated
- 3. Cell makes clones of active cytotoxic T cells - (attack invaders) and memory cytotoxic T cells - (can quickly activate and make active and
- memory cytotoxic T cells at next meeting of Ab)
What binds to the heavy chains?
What is the valence?
- Complement and macrophages bind to the heavy chains on compliment.
- Ab monomer has a valence of 2
What are the 5 classes of Abs?
% = % of all Abs in serum
- 1. IgG (80%) - most abundant in blood - able to leave blood & migrate into tissue during immune response
- - monomer
- -triggers compliment when bound to Ag
- - increases phagocytosis (opsonization)
- - kills viruses & toxins
- - crosses placenta - innate immunity in fetus
- 2. IgM (7%) - large pentamer (M=macro)
- -1st Ab involved in immune respone -short life
- - triggers compliment
- -causes aggregation (valence 10)
- - serves as Ag receptor on surface of B cells - also found in blood in lymph
- 3. IgA (10%) - most abundant in body (not serum)
- - in secreations - mucous membranes - salvia, mucus, tears, milk
- - blocks adherance to membranes
- - dimer
4. IgD (.2%) - monomer - unknown function
- 5. IgE (.002%) - monomer -
- -serves as Ab receptor on Mast cells, basophils, eosinophils
- - particiapes in allergic reaction - in presence of allergen IgE stimulates the mast cell to release histamine
- - large #s during allergic reacion
- - involved in extracellular killing of large parasites
Which Ab crosses the placenta?
Which Ab is a pentamer, 1st to respond to an Ag, and cannot fit out of a blood vessel?
Which Ab is on the surface of a B cell?
Where is IgA found?
In secreations - saliva, milk, tears, mucus
Do you have a lot of IgE in your serum? When do you?
What cells binds it? What does this cell release?
- No unless having an allergic reaction - then lots
- Bound to Mast cells, basophuils, eosinophils that relase histomine in presence of allergen
What is an Antibody Reaction?
What are the responses?
- When an Ab/ Ag complex form Ab tabs microbe for death by:
- 1. aggluatination - clumping
- 2. opsonization - ↑ phagocytosis
- 3. activates compliment
- 4. cell mediated death (eosinophils → lytic enzymes)
- 5. neutralization of microbe - cant adhere
Is IgA a monomer?
No it is a dimer
What 3 cells are capable of phagocytosis?
- 1. macrophages (A monocyte matures into a macrophage in tissue (not in blood stream)
- 2. neutrophils (PMNs)
- 3 .APCs - dendritic cells
What is microbe agglutination?
In agglutination (also called aggregation) Ab cause Ag to clump together. IgM is very good at this becuase it has a valence of 10
What is the B cell response?
T-independent & T-dependent responses
- Ab mediated immune response occurs in the lymphoid tissue. T dependent Ags:
- 1. B cell eats Ag and is broken down into peptide fragments (combined with MHC-II) and moved to B cell plasma membrane
- 2. Helper T cell binds to B cell and costimulates - B cell divides into: Plasma cells & Memory B cells
- a. Specific B cell receptor (BCR) binds with an Ag
- b. The cell is now actived and undergoes clonal selection - plasma cells that secrete Ab and memory B cells for next encounter
- c. Plasma cells release thousands of Abs that travel in the lymph to site of infections
- T-independent Ags:
- Ags stimulate B cell directly-
- - provokes a weaker immune response
- - response is primarily IgM
- - no B membory cells are generated
What is self tolerance?
Body dosent make Abs against itself
- all body cells (except RBCs) are tagged with MHC Ags
- -also called HLA Ags - Human leukocyte Ags
- - your body ignores there Ags
- After organ transplants the patient must take medication that inhibits
- immune response becuase the Ag on the new organ are foreign - the body
- will try to attack it. This is also a factor in autoimmune diseases
- where lymphocytes attack the bodys cells. However, it is not an issue
- in blood transfusion becuase the RBC do not carry MHC Ags - they only
- carry blood type Ags
What is clonal selcetion?
Clonal selection = creating memory cells that are responsible for an enhanced secondary response to an Ag
Clonal deletion = removing all clones of B and T cells that are capable of damaging "self Ags"
Autoimmune diseases are those where cells arise that do not recogine "self Ags" are are able to damage body cells.
What is a dendritic cell?
- A dendritic cell is a type of APC -it is nonspecific
- It is an agranulocyte derived from a moncyte
- -primary APC - engulf invader and take to T cells in the lymph
What do regulatory T cells do?
- Supress and inhibit other T cells
- - combat autoimmune disease by inhibiting T cells that escape deletion in the thymus
- - turn cell mediated immune reactions off using cytokins
- APC - Antigen Presenting Cell
- Dendritic Cells & Macrophages
- 1. They eat (phagocytosis) invaders
- 2. Attach a peptide fragment to their plasma membrane via MHC (major histocompatibility complex)
- 3. Travel to lymphatic tissue to present the antigen to T cells
What is a natural killer cell?
- Natural killer cells (NK) are nonspecific lymphocytes -
- they can also attack parasite and tumors
How do cytotoxic T cells kill mocrobes?
Cytotoxic T cells leave lymphatic tissue and travel to infection - bind to cells with specific microbial Ags
- kills cell by one of several options:
- 1. can release granzymes - protein -digesting enzyme that trigger apoptosis (progranned cell death)
- 2. can release Perforin and granulysin
- - perforn makes hole in cell membrane (cell lysis) and granulysin enters cell through hole and kills microbe by creating holes in it cell membrane.
- 3. can release lymphotixin - activates enzymes in the target cell that cause the cells DNA to fragment (cell dies)
What are the functions of cytokins
- Proteins- they mediate immune responses - produced by all cells of immune system in response to a stimulus
- -can stimulate or inhibit it
- -activate macrophages
- - transform B to plasma cells
- - transform B and T to memory cells
In Humoral response (B cell - Ab) - Helper T cell binds to B cell and releases cytokins to make B cell proliferate faster → plasma cells + memory B
- IL (interleukins), interferons, TNF tumor necrosis factor
What 2 things can activate a macrophage?
What is ADCC?
Antibody-dependent cell-mediated cytotoxicity
- specific reaction Ab/Ag
- Extracellular killing - invaders that are too large to be phagotized - parasites
- 1. Parasite is coated with Ab
- 2. Macrophages attach to C regions of IgE & IgE can bind to eosinophil cell membrane
- Ag/IgE binding → enzymes released that digest parasite
Primary & Seconday immune response
- Ab titer - relative amt of Ab in the serum
- IgM - first Ab produced
- IgG - second Ab produced
Natural passive immunity
Natrual active immunity
Artificial active immunity
Artificial Passive immunity
- Natural passive immunity - mother to fetus
- Natrual active immunity - infection Ab/Ag reaction
- Artificial active immunity - vaccination - inject Ag
- Artificial Passive immunity - inject Ab
- Blood serum with Ab against a certain Ags
- Injection can give immediate passive protection against the disease (that produced the Ags) - it does not last long (about 3 weeks)