What are the 3 levels of protection against disease?
1) anatomical and physical barriers (ex. skin), 2) Innate (non-specific) immunity and 3) Adaptive (specific) immunity
Where do WBC come from?
Bone marrow - hematopoietic stem cells
Hematopoietic Stem Cells
are blood formation cells
Where do T-cells develop? B-Cells?
T-Cells = Thymus
B-Cells= Bone marrow
A highly specialized B-Cell is
a Plasma Cell
Which WBC make up majority of WBC population? And how much does it make up?
Neutrophils make up 65% of WBC
neutrophils and mast cells (also eosinophils)
T Cells and B Cells
Hematopoietic Stem Cells
How can HSCs can be isolated?
distinguishing between the unique combination of proteins that each express on their cell surface
HSCs are successfully used to treat?
cancers of immune systems, immunodeficiencies and genetic diseases
How can HSCs be used to treat hematopoietic malignancies?
HSCs coming from a close relative, after they have received a drug that will cause HSCs to migrate out of bone marrow and into peripheral blood.
How can HSCs be used to treat immunodeficiencies?
Same as hematopoietic malignancies OR from HSCs found normally in umbillical cord or bone marrow
How can HSCs be used to treat gene defects?
usually Gene therapy
taking patient's own HSCs and culturing them in the lab in order to correct the gene and then re-infuse it back into the patient.
is a separate but connected system to the circulatory system - contains lymph which is fluid lacking RBC, this fluid drains from tissues into the lymphatic cappilaries and then into the lymph nodes.
Where are the lymphatic and circulatory system connected?
via thoracic duct - subclavian vein
What are Primary Lymphoid organs? Provide examples.
are organs where the lymphocytes develop and mature. Thymus and Bone Marrow
What are Secondary Lymphoid Organs? Provide examples.
Where lymphocytes encounter foreign pathogens and molecules. Such as the capillaries, and other lymph vessels and lymph nodes.
What is the Spleen?
is the largest lymphoid organ - it is a secondary lymphoid organ.
Major function of the Spleen
bring blood into contact with lymphocytes so that any blood borne disease organisms come into contact with the lymphocytes.
What happens if Spleen is gone?
Bone marrow and liver will take over its main function. Its other functions are not as relevant and so the body can manage without them.
What are the anatomical and physical barriers?
First line of Defense: Skin, mucous membranes, body temperature, low stomach pH, lysozymes (enzymes) in tears and saliva, Defensins and complement
is the second line of defense: Innate and Adaptive Immunity
are biologically active factors (proteins) usually secreted by one cell so as to influence activity of another cell. Relevent in immune system.
Most important immunological cytokines
Interleukins - because they are proteins responsible for communication between WBCs
are Cluster of Differentiation - proteins expressed on the surface of the leukocytes
How are CD molecules and ILs named?
They are numerical sequentially labelled based on discovery.
Main functions/mechanism of Innate Immunity
opsonization, activation of complement, chemotaxis, phagocytosis, stimulate release of proinflammatory cytokines
How do innate cells detect pathogens?
PAMPs - Molecular structures of the pathogen - not found in multicellular hosts, present on numerous groups of pathogens, do not undergo frequent mutation
pathogen associated molecular pattern
Examples of PAMPs on bacteria
flagellin protein from flagella bacteria, peptidoglycan (polysaccharide) of gram+ bacteria, lipopolysaccharide (LPS) from membrane of Gram - bacteria
Pattern recognition receptors
receive a signal from a pathogen - causing a cascade of reactions to occur resulting in a response from the cell - which is usually the production of a protein (ex. Transcription of cytokines)
PAMP binding initiates intracellular signals which result in cytokine release and initiation
transcription factors the transcribe cytokines
Types of PRRs
Soluble proteins which circulate, Cell associated phagocytosis and TLRs
is a conserved family of receptors initially found in fruit flies
share a common intracellular and extracellular domains as Toll
How many TLRs have been found to date in mice/humans?
TLR2 and 6
recognizes LPS (best characterized interaction)
recognizes bacterial DNA
Inflammatory Response: Recognition of Danger
Bacteria are immediately recognized by resident tissue macrophages by LPS-induced activation of TLR4 -this results in activation of transcription factor NFkB
transcription factor that when activated moves to the nucleus and stimulates the transcription of "alarm" cytokines
Alarm Cytokine examples
tumor necrosis factor alpha (TNF-a), Interleukin-1 (IL1), interleukin-6 (IL6)
Inflammatory response: pain, swelling and cell recruitment
"alarm" cytokines act on blood vessels causing them to dilate, also nearby mast cells release histamines to also dilate blood vessels also increases the permeability of blood vessels
are small inflammatory molecules that help in the inflammatory response
Blood vessel dilation in inflammatory response
increases blood flow which allows more white blood cells to come to the damaged site. Causing redness and heat
TNF-alpha function in inflammation response
is to initiate the expression of the adhesion molecules to the surfaces of the endothelial cells lining the blood vessels
Adhesion molecules in inflammation response
allow leukocytes (neutrophils and monocytes) to attach to the blood vessels and because of the increased blood vessel permeability the WBC squeeze through the spaces and they migrate to the damaged tissue
is the stop, roll and squeeze out of blood vessel and into damaged tissue done by leukocytes
Inflammatory response: phagocytosis
neutrophils and moncytes (matured in macrophages) are recruited to damage site to perform phagocytosis on bacteria
are short lived leukocytes that ingest the bacteria in a process known as phagocytosis
is the membrane that the bacteria are engulfed into by the macrphage/neutrophil - they become acidified which kills most pathogens
are membrane bound granules that contain lysozyme and other enzymes that break down pathogens
is the fusion of lysomes and phagosomes which contain nitric oxide (NO), superperoxide anion (O2-), hydrogen peroxide (H2O2), defensins and proteasesthat kill bacteria and degrade it into smaller fragments
are cationic peptides
1. bacteria is engulfed, 2. takin into phagosome, 3. (doesnt always occur) phagosome fuses with lysosome, 4. low pH, H2O2, lysozyme and proteases kill bacteria, 5. Large fragments are released by exocytosis
Inflammatory response: clotting
the sealing of the wound and immobilizing of the bacteria resulting in skin repair
Inflammatory response: Pus
an aggregation of macrophages, neutrophils, live and dead skin cells, dead and dying bacteria and plasma
complete and rapid elimination of pathogen by neutrophils (mostly) with little to no damage to the host
pathogen is not eliminated, WBC persistence results in activation of adaptive immunity - long term inflammation results in tissue damage due to the continual release of toxic metabolites
What are the toxic metabolites the are continually released in inflammatory response?
Nitric Oxide (NO) and proteases -such as what causes TB and rheumatoid arthritis
is a set of plasma proteins that act together to attack extracellular pathogens - are either numbered of labelled as factors
Activation of complement proteins
Classical and alternate pathways
is antibody dependent - part of the adaptive response
is part of the innate response
Result of both the alternate and classical pathway?
The production of C3 convertase
Function of C3 Convertase
to cleave complement protein 3 (C3) into C3a and C3b
Functions of Complement
Inflammation, Opsonization and direct pathogen killing by MAC formation
small fragments of complements bind to receptors and stimulate inflammation, which undergoes dilation and increasing permeability of blood vessel, phagocytosis, histamine release, and leukocytes recruitment
when C3b binds to pathogen surfaces they function as an opsonin which is like signalling factor that facilitates phagocytosis.
Membrane attack complexes
Direct pathogen killing by MAC formation
when complement proteins work together (C3b and C5-C9) to create a membrane attack complex (MAC) which directly attacks pathogens
Adaptive immune response
last line of defense after innate fails, but works with innate response
Cells that allow communication between innate and adaptive responses?
are also known as ANTIGEN PRESENT CELLS: macorphages and dendritic cells after being activated by PRRs
Weapons of the adaptive immune response?
Tcells (directly fight pathogens), and B-cells which make antibodies (indirect)
differentiate from monocytes, are similar to macrophages as they are activated by PRRs and they are also phagocytes. They link innate and adaptive immunity.
Difference between dendritic cells (DCs) and macrophages
is that after they "eat" pathogens - they traffic into the lymphatic system and to the lymph nodes where they interact and stimulate T-cells
Key features of the adaptive response
Diversity, Specificity, Inducibility, Memory and Tolerance
Adaptive response: Diversity
adaptive response have about 10-100 million antibodies, and millions of different kinds of T-cells to combat a diverse kinds of pathogens
Adaptive response: Specificity
only specific peptides (antigens) are recognized - a specific pathogen is targeted
Adaptive response: Inducibility
the primary immune response it takes time for a full adaptive immune response to occur because it doesnt have the necessary specific "weaponry" yet.
Adaptive response: Memory
immune system "remembers" pathogens its "fought" before so that when they re-encounter the response is more rapid and effective - secondary immune response
Adaptive response: Tolerance
immune system can distinguish between self and non-self antigens and also can differentiate between harmful and non-harmful foreign antigens
Why is tolerance important?
It helps understand how allergies and autoimmune systems arise
Dendritic Cells maturity
its activated by PAMP/PRRs and they mature into cells with dendritic processes thus the name dendritic cells
How does adaptive immunity recognize antigens (short peptides)?
by the work of MHC (Major Histocompatibility)
MHC vs. HLA
MHC is a general term for all kinds of species, but HLA (human leukocyte antigen) is only for humans.
Major Histocompatibility are proteins are split into two different classes: Class I and II.
MHC Class I
proteins expressed on cell surfaces of ALL nucleated cells (thus does not include RBC or platelets)
MHC Class II
proteins expressed on cell surfaces of antigen presenting cells (APCs)
Name the Antigen Presenting Cells
Dendritic Cells, macrophages, and B cells
Describe the MHC Class I protein
its a transmembrane protein with an alpha chain covalently bonded to a soluble Beta2 microglobulin
Describe the MHC Class II Protein
is a heterodimer of 2 transmembrane chains (alpha and beta)
What has to happen to MHC before it can be expressed?
MHC proteins have to be bound to a peptide = Peptide loading
MHC Class I peptide loading
antigens/peptides are loaded in the endoplasmic recticulum
MHC Class II peptide loading
peptides are loaded by vesicle fusion -vesicles containing class II fuses with one containing antigens/peptides
How does MHC provide diversity to adpative immunity?
There are 6 different types of MHC proteins (3 MHC Class I and 3 MHC Class II) and each type has 2 alleles (on from dad and one from mom) so there are 12 different MHC proteins in one person
Alleles with MHC Proteins
in our population there are many different alleles for each MHC for example there are atleast 50 versions of HLA-B
Expression of MHC Proteins
they are codominantly expressed so there are 6 gene loci and 12 MHC alleles and all 12 are expressed. thus there is a high degree of polymorphism
Why is high degree of polymorphism important with MHC?
It maximizes the probability of being able to bind to a peptide of an antigen - makes it more diverse in attacking more antigens- variability means it can act on multiple antigens
is the particular combo of 12 HLAs that a person has
Why is tissue type key in transplantation?
This is important because if it doesnt match than tolerance within the body cannot be achieved and immune response will start to target self cells
MHC Primary role
is to bind and present peptides derived from any protein - thus an adaptive response cannot be made without a peptide bound to MHC proteins
What is the problem with inbred populations in terms of MHC proteins?
these populations will have less diversity thus it will be more susceptible to more pathogens because their peptides cannot attach to MHC to be presented to adaptive immunity
are any substance (mostly proteins) which can be recognizes by antibodies or when bound to T cell receptor. They bind on epitopes to recognize the protein.
is a protein portion that the Antigens and TCRs can recognize - they can only recognize short peptides.
T cell receptors
it can only recognize short peptides when bound to MHC on the surface of an antigen presenting cell.
is the degradation of proteins into peptides
is the binding and display of the antigen as a peptide fragment bound to MHC on the surface of a cell
Processing of proteins by MHC Class I? MHC Class II? (how proteins and MHC meet)
MHC I - proteins are made inside the cell via a viral attack (virus inserts itself into cell and produces its viral proteins).
MHC II -antigen proteins are engulfed into the cell by phagocytosis/endocytosis
is the enzyme inside a cell that cleaves/degrades viral proteins inside the cell. It cuts it into about 8 -11 amino acids long which is the perfect fit for MHC I
TAP Transporter Proteins
are on the surface of the endoplasmic reticulum - they transport peptides from cytoplasm (after cleaved by proteosome) and into the lumen of ER where they bind to MHC I
Loading MHC I
proteosome cleave viral proteins, TAP transporter takes these proteins from cytoplasm to the ER, there they bind to MHC I proteins, and MHC I gets released to the surface of the cell
are enzymes in the pahgosomes that have antigens and they cleave/degrade the antigens into short peptides
Loading MHC II
engulf the antigen via phagocytosis into a phagosome, phagosome fuses with lysozome to form phagolysozome which has proteases that break down antigen, MHC II leaves ER in vesicle, vesicle fusion of MCH II and phagolysozome. MHC II binds to short peptide and is taken to the surface of APC
cytokines that help cells resist viral infection - ex IFN alpha, beta, gamma
programmed cell death, where the cell activates an internal death program - it is an active program requiring energy.
levels of expression can go up or down (variant)
T Cell development
occurs in thymus, thymocytes proliferate and mature into TCells
T cell receptor
are heterodimer (TCR alpha and TCR beta) proteins that ALL Tcells express
T Cells are so diverese because?
Of T Cell Receptor Rearrangement. they have a variable region of DNA which they splice and rearrange at random in a single cell.
TCRs main function
is to recognize peptides presented by MHC
How do T cells express Specificity
they can produce about 100,000 identical TCRs on their surface which only recognizes one antigen
Where is the peptide binding groove of the MHC Class I?
its WITHIN the alpha chains
Where is the peptide binding groove of the MHC Class II?
its BETWEEN the alpha and beta chains
is a complex of accessory molecules that help TCR - because the TCR isn't completely transmembrane, thus the accessory molecules (CD3) help transmit the signal from out of the cell to in
Special loading for MHC Class I
"cross presentation" - special case where the MHC Class I is loaded extracellularly
What goes on in the Thymus?
Positive and Negative Selection for thymocyte maturation into Tcells
only thymocytes that can bind (preferrably with low affinity) to self MHC survive, as they get the survival signal, if not they don't receive the signal and thus die of neglect
only thymocytes that bind to BOTH MHC cells and self-peptides (bind strongly) die by apoptosis
Success rate of Selection in the thymus?
is VERY LOW. >98% fail to be positively selected
Purpose of Positive/Negative Selection? What is this process called altogether?
Positive selection ensures that T cells can bind to self MHC with foreign peptides. Negative selection ensures that T cells don't attack to SELF antigens. This entire process is called CLONAL Selection or Deletion b/c each T cell is a clone
How do Antigens from organ-specific or developmental proteins get into the Thymus?
thymic epithelial cells express a transcription protein known as AIRE which allows the expression of as many genes in the thymus as possible
What happens if Clonal selection fails? What's another way this negative effect could occur?
T cells cannot distinguish between self and foreign and would attack self cells causing an AUTOIMMUNE disease - genetic mutation/defect occurs on AIRE
arises because the selection process of T cells is not perfect. it is a second line of defense if T cell selection fails so that we don't develop autoimmune disease
Generally how are T cells activated?
when their TCR binds to a particular combination of MHC + peptide (antigen)
Division of T cells
CD4+ and CD8+ = this difference is based on the expression of Co-receptors of the T cell
CD4 and CD8 recognize
a certain theme in MHC and helps to strengthen the interaction between the T cell and APC
can ONLY BIND to MHC class I and function as a cytotoxic cell
can ONLY BIND to MHC class II and function as a helper T cell
What are the other names/labels for CD8+
Cytotoxic, Tc, CTL, CTLp
What are the other names/labels for CD4+
Two signal model
T cells need two signals in order to be fully activated.
Signal 1 and Signal 2. - it costimulates and signals the effector cell to turn naive cells into active cells (memory/effector/both)
TCR properly binds to MHC and and antigen
Signal 2 for T cell activation
CD28 found on the T cell binds to B7 (which is actually CD80/86) on the APC
is a state of unresponsiveness- this is due to the lack of the second signal - it just receives Signal 1; this is not cell death
What makes an APC "professional" ?
they express MHC II and co-receptors
Inflammation activates what in APCs? Importance?
they upregulate expression of MHC and CD80/86 - this is important because it starts the activation of the adaptive immunity
Why are dendritic cells the best APCs?
they activate both CD4+ and CD8+, they traffic through the body like macrophages to sites of inflammation, HIGHLY responsive to PAMP signals and mature. Once they have Ag they traffic back to lymph nodes to stimulate T cells
What is the difference between Dendritic cells and macrophages?
they are the only APCs that can activate naive T cells b/c of their high expression of MHC and costimulating molecules and cytokines, especially when activated by PAMPs, and they are able to traffic back to Lymph nodes.
Macrophages usually stay in the tissue and phagocytose dying/infected cells and can only active memory/effector T cells
Memory/Effector T cells activation
don't need such a strong signal, and can be activated by either non-professional or professional APCs, except for CD4+ cells which can only be activated by professional APCs
depending on the Cytokine present, CD4s can differentiation even further into Th1 and Th2 cells
What cytokines are needed to differentiate into Th1? how about a Th2?
Th1 = IL12 and IL18
Th2= IL2 and IL4
What do Th1s produce? Th2s?
Th1 produces: IL2, IFN gamma, and TNF alpha.
Th2 produces: IL4, IL5, IL10, IL13
What controls which Th is prevalent?
The type of infection that occurs
When does differentiation into Th1 dominate?
IL12 and IFN gamma predominate in response to bacterial and viral infections.
When does differentiation into Th2 dominate?
IL4 predominates in response to parasites and extracellular pathogens
Th1 cell function
it increases Cell-mediated immunity - by activating macrophages and phagocytosis
Th2 cell function
help B cells produce antibodies and activate mast cells and eosinophils via Humoral Activity
If all body cells express MHC I then are professional APCs only important for CD4+?
No, b/c in order to be activated the first time a naive CD8+ T cell needs to encounter Ag on a Dendritic Cell, which expresses all the co-stimulatory receptors
is the "schooling" of the T cells - the process of both negative and positive selection
CD4+ Th1 cells help CD8+ cells by producing IL2 which is an essential T cell growth factor. Th1 also produce cytokines which activate macrophages and phagocytosis -induce immune response to rely on CELLS to destroy intracellular pathogens
humoral=fluid -as antibodies are soluble proteins which circulate in our blood. Th2 produces cytokines which help T cells make antibodies which are used for clearing extracellular pathogens/infections such as parasites
Why do CD8+ need help from CD4+Th1 cells?
They are not very good at making their own IL2 (growth factor) so they need a 3rd signal in addition to costimulation from APC that allow them to gain exogenous IL2 from neighbouring CD4 via APC that express both MHC I and II
when activated they secrete and express proteins which kill target cells (pathogens).
CD8+ secreted/expressed proteins
perforin, granzymes, FAS ligand
CD8+ protein that makes holes in cell membranes
CD8+ protein - it is a serine esterases which causes apoptosis.
CD8+ protein that kills cells by starting apoptosis
Phases of T cell immune response
activation, clonal expansion (cell division) of memory OR effector cells. Effector cells than either turn into memory cells OR die
Where do Bcells differentiate?
in the bone marrow - originally lymphoid precursors
Development of B cells
as they mature they begin to express immature forms of the B cell receptor (BCR)/immunoglobulin (Ig)/Antibody
BCR is composed of
two identical heavy chains and two identical light chains
B-Cell Receptor which is composed of the immunoglobulin and the co-receptors Ig-alpha and Ig-beta
membrane bound immunoglobulin of a B-Cell
the secreted immunoglobulin of a B-Cell
are Ig-alpha and Ig-beta
How are BCR diverse?
they are highly polymorphic like T-Cells due to their extensive gene rearrangement that they do (similar to T-cells)
is the maturing stage of B-cells. it's where they learn to recognize and bind to self-peptides in order to be able to mature.
Regions of a BCR
there are two regions: a constant region and a variable region.
Antigen binding pocket is composed
of the heavy and light chain variable region - this is where the antigen comes to bind- it is variable so that it can recognize multiple kinds of antigens - it is a 3D pocket, shape is determined by the sequence of amino acids in the hypervariable region
B-Cell activation requires
3 signals to activate the B-Cell
Signal 1 B-Cell activation
a) binding of antigen to mIg. b) cross-linking when several mIgs bind to Ag, resulting in initiation of the intracellular signal from Ig-alpha and Ig-beta. c) the activated B-Cell then upregulates MHC II and CD80/86 turning it into an APC for a T-Cell
Signal 2 B-Cell Activation
a bind/ interaction occurs between T-Cell and B-Cell. where the activated Th cell's CD40 ligand binds to the CD 40 of the B-Cell.
Signal 3 B-Cell Activation
is when cytokines release from the Th to signal the B-Cell to produce antibodies. Specific cytokines cause the production of an equally specific antibody.
respond rapidly to 2nd response by recognizing the pathogen/antigen quickly
are effective B-cells as they produce the necessary antibodies. - they have lots of endoplasmic reticulum to make them
Epitopes of T-Cells vs. Epitopes of B-Cells
TCR epitopes have to be linear fragments of the original Ag as they are shown/recognized on MHC proteins. Whereas the B-Cell can recognize portions of a WHOLE 3D Ag and attach to those places (epitopes) that can be linear or conformational and usually on the surface of the cell. B-Cells can bind to more to two epitopes at a time.
each Ab has 2 identical heavy chains and 2 identical light chains it is BIVALENT - where the antigen can bind to the antibody allowing close contact (like lock and key)so hydrogen bonds can occur which in turn results in ionic and hydrophobic interactions to happen
Antibodies protect against pathogens in what ways?
neutralization, opsinization and activation of classical complement
antibodies bind to bacteria and viruses preventing them from entering the cells.
What is Opsonization? And what structures do this?
alteration of the surface of a pathogen/Ag so that it can be ingested by a phagocyte. Done by complements and Ab
Types of Opsonization
Agglutination and Precipitation
When Ags and Abs clump together they make it easier for macrophages to "eat" them.
pre-antigen molecules are dissolved in blood/body fluid
Types of B-Cell constant regions?
There are 5 types: IgA (alpha), IgD (delta), IgG (gamma), IgM (mu) and IgE (epsilon)
What type of constant regions are on Naive B-Cells?
IgM or IgD and it will be exposed on the cell surface
Immunoglobulins on the same cell can have ____ C-regions and V-Regions are ____
C-Regions can be DIFFERENT on the same cell, but they have IDENTICAL variable regions.
What are the types of light chain on B-Cells?
Kappa and Lambda
Heavy and Light Chain pairings on B-cells
each heavy chain can only bind to one Light chain - either kappa or lambda never both
Isotypes of antibody
are the different constant regions of the Ab - IgA, IgD, IgE, IgG, IgM
Secreted IgM structure
is secreted as a single unit, but extracellularly it becomes a pentamer consisting of 5 IgMs joined together by disulfide bonds which are connected by J (joining) chains.
Single IgM vs. Pentamer IgM
a single IgM has LOW affinity for Ag, but on a pentamer IgM there are more binding sites (2x5=10)available for Ags they have a HIGH avidity for Ag (still a low affinity though just more desire to have Ag occupancy)
it is dominant type of Ab in primary immune response -w/ its main function is to kill bacteria by complement mediated lysis
major class of Ab during secondary immune response, with a good neutralizing capability, and opsonization and has the ability to cross the placenta
IgG and opsonization
phagocytes ingest bacteria coated in IgG more readily as the a sequence in the constant region binds to FcR (constant region receptors) on the surface phagocytes (neutrophils and macrophages)
Secreted IgA structure
in serum it is a single structure, but in bodily fluids it forms a dimer joined together by a J-chain (same that links IgM), it is associated with a peptide known as secretory piece
Secretory piece and IgA
Secretory piece is a peptide that associates with the IgA to help it be able to cross layers of the epithelial cells
it prevents attachment of pathogens to host surfaces (neutralization)
Secreted IgE location
it is secreted into the serum but it is most always bound to mast cells or basophils on a receptor known as Fc(epsilon)R1
is the receptor that IgE binds to basophils or mast cells
the anitbody responsible for triggering allergic reactions, when IgE binds to Ag, it triggers mast cells and basophils to degranulate release histamines, and also the main class of Ab in response to worms (intestinal worms)
What is the cause of the allergic reactions?
Histamine release from mast cells/ basophils - initiated by IgE
Compare 2 human the same antibody
their heavy and light chain variable regions have different amino acid sequences.
their heavy and light chain constant regions are the same
Compare a human and a different species same antibody type.
both their heavy and light chain variable and constant regions are different
What is an important conclusion between species and antibody structure?
Constant regions of the anitbodies are region specific, that is one species type has the same constant region but different with a different species
When are situations where another species Abs are necessary?
A venomous bite -anti-venom is necessary and comes from the horse. Same with rabies from an animal with immunity, and also in trial stages Cancer
Antibodies with the different isotypes can...
recognize the SAME antigen
Basic concepts of Primary immunity
pathogen presence a) danger signals recruit APCs, b)DCs present antigen to naive Tcells in lymph nodes, c) Ags bind to BCR activating naive B-cells d) activated T cells help B cells to divide. e) Some B cells turn into plasma cells secreting Abs. f) other B-cells become memory cells to help secondary immunity
Basic Concepts of Secondary immunity
pathogen appears again (one thats already been encountered): a) memory B-cells proliferate (on their own) and produce Ab once they encounter Ag. b) memory T cells also proliferate and ultimately enhance the immune response
is the rapid response that occurs when the same pathogen is encountered by the immune response again. more memory B and T cells are produced.
Immunoglobulin Class Switching and how it is done
is the switching of the Constant regions of immunoglobulins - only the constant regions - the specificity of the variable regions stays the same - requires the help of T cells (CD40/CD40L and cytokines) - class is determined by the cytokines the T cells release
What is the fundamental basis of vaccination and boosters?
Immunological memory -where vaccinations/boosters give adaptive immunity Ags so that they can build memory cells so that if you encounter the pathogen for real a fast and big secondary response can be mounted to defend your body
How long can T-cells and B-cells remember?
plasma cells continue to secrete Abs thus they have a longer half-life than T cells who have a lower half life - CD4>CD8 half life but only by a little
is when the immune system is actively stimulated by a pathogen mounting a response by the adaptive immune system - your own body produces this response
occurs when pre-formed Abs from an already immune donor are transferred to an non-immune donor -to provide temporary immunity (a few weeks)
Example of passive immunity
From mother to baby - IgG crosses placenta during pregnancy. and IgA passes through in milk after birth.
Anti-toxin for emergencies like snake bites or rabies.
the total Ig from other people infused to immunodeficient people
How do bits of bacteria in the skin get to the lymph nodes?
DC called Langerhan cell live in the skin, engulfs bacteria and processes and presents bacterial proteins. Langerhans cells can then migrate to lymph nodes
Antibodies main defense against?
T-Cells main defense against?
viral infections and bacterial pathogens that cause intracellular infection.
Cleavage products of complement
C3a, C4a, C5a - they initiate inflammatory response
are C3a, C4a, C5a - cleavage products that can cause inflammation but too much of it would shut down circulatory and cause anaphylactic shock
C3a and C5a can cause
increased permeability, increased adhesion molecules, increased histamine and TNF-alpha release. C5a is also a powerful chemoattractant for phagocytes
are antigens that can activate Bcells w/o T cells - they cause crosslinking of mIg which may be enough for it to secrete IgM
Downside to mitogenic Bcell activation?
Lack sophistication and does not generate memory Bcells
Delayed Type Hypersensitivity only observed during? Why?
Secondary Immune response. -b/c during primary response little inflammation is produced due to weak response -not many macrophages are activated
Delayed Type Hypersensitivity is mediated by?
Activated Th1 cells and is also known as Th1-mediated inflammation
is the clumping if RBCs because of antibodies binding to the same antigen but on different RBCs brings them closer =clumps
are antibodies produced for no apparent antigenic stimulation
fluorescent activated cell sorter
How to fuse a plasma cell with a myeloma cell to make plasma cell immortal?
Use chemical called polyethylene glycol
enzyme linked immunoadsorbent assay
is from an immunized animal that has produced an antibody against the antibody of another species - used to detect the presence of said antibody
a special of T-cell which can stop other T cells from being activated, dividing and making cytokines - can be either CD8 or CD4
Function of Treg
inhibit CD8and 4 activation, proliferation and cytokine production, inhibit Antigen-processing and presentation, inhibit antibody production to over all decrease of inflammation and immune response
Signals to activate Treg
Signal 1 - MHC -complex binding (apc and Tcell)
Signal 3 -B7 binding with CTLA4 on Tcell AND PD1L and PD1 on Tcell
Tregs in the thymus arise from
characterized by expression of CD25 which is part of the IL2 receptor. and transcription factor called FOXP3
Tregs in the periphery arise from
when MHC-Ag complex does not give off enough "danger" signals it may develop into T reg cells which allows for generation of specific Tregs for antigens that arent self-antigen but safe