Chapter 3 part 2 Flashcards
sections 3-7
Within Dendritic Cells
peptides from the pathogen are bound by glycoprotiens of host origin called MHC molecules
Major Histocompatibility complex
genes that encode for MHC molecles
Dendritic cell Peptide
in the DC the peptide from the pathogen is loaded onto a MHC molecule and placed on the DC’s surface (Antigen presentation) (figure 3.7)
antigen presentation
the loading of the pathogen peptide, via the MHC molecule, and placing on the DC surface
peptide (from pathogen)
MHC molecules interact with TCR that is specific for that peptide Antigen
Dendritic Cells
are very important and very effective antigen presenting cells as they are the cells that start off a primary T cell Immune response
Steps of DC presentation
5 steps
- dendrictic cells takes up pathogen for degradation
- pathogen is taken apart (degraded) inside the dendritic cell to release pathogen protein
- pathogen proteins are unfolded and cut into small pieces
- (pathogen proteins aka) peptides bind to MHC molecules and the complexes go to the cells surface (aka loading)
- T -cell receptors bind to peptide: MHC complexes on dendritic cell surface to form a dimer
2 types of MHC
MHC Class I (pirate look peg leg) MHC class II (normal legs) different alleles for each of these MHC classes (most people have at least two aleles for each MHC class i.e. are heterozyous for these MHC alleles)
Individual expression of MHC
each individual can express a few different types of MHC molecules -MHC class I or II
Each MHC molecule
has the ability to bind many type of Antigen peptides.(however there are binding limitations in terms of peptide size)
MHC genes are highly polymorphic
This is the basis of tissue typing and for most transplants. This forces the physicians to look for a donor with a compatible MHC match (i.e. kidney compatablity)
* if the transplanted tissue is not well- matched then the recipients immune system recognizes it as foreign and rejects the tissue
Reason that MHC molecules are highly polymorphic
they are polymorphic within the human population for survival of the species.
* since everyon in the population will likely present the pathogen’s antigen in a different way (dur to differeing MHC molecules among the individuals in the population)there is more chance someone in the population will survive b/c of their Antigen presentation was favorable to the immune response
What classes of MHC do Nucleated cells present What are these nucleated cells Where is this class present
ClassI T and B cell Marphages dendritic cells Neutrophils in the Thymaic epithelium Liver hepatocytes Kidney epithelium Brain
lymph cells present the majority of
What are these cells
Where is this class present
class II few T cells most B cells some macrophages most Dendritc cells All in Thymic epithelium
MHC class I molecules
present Antigens of intracellular pathogens -due to loading of cytosolic degraded antigen onto MHC class I molecules in ER
MHC class II molecules
present antigen of Extracellular pathogens
-due to laoding of MHC Class II molecules with Antigen degrated in the endosome
CD
clusters of differentiation
CD#
the fact that there are molecules of a certian type expressed on a cell’s surface
Two major classes of T cells
CD8 cells and CD4 cells
mature T cells
are either CD8 or CD4 (of the t-cells circulating 1/3 are CD8 cells and 2/3 are CD4 cells
the most abundant type of CD cells present in body
CD4
CD8 cells
cytotoxic t cells *have a CD8 co-receptor on their surface binds to MHC class I from Antigen Presenting Cell
CD4 cells
- helper T cells
* have a CD4 co-receptor on their surface (, binds to MHC class II from Antigen Presenting Cell
MHC class I molecules
- cytotoxic T Cells (CD 8 cells) recognize Antigen presented by MHC class I molecules
- This is insred b/c CD8 T cells have a CD 8 co receptor that ONLY interacts with MHC class I
MHC Class II molecules
- helper T cells (CD4 cells) recognize Antigen presented by MHC class II molecules
- this is insured b/c CD4 T cells have a CD4 co-receptor that only interacts with MHC class II molecules
MHC class I reacts only with _____
CD8 cells (cytotoxic cells)
MHC class 2 reacts only with
CD4 Cells (helper cells)
Antigen interaction between MHC class I and CD8 cells from infection of DC to apoptosis of infected cells *8 steps
1.Infected DC travels to draining LN
2.as infection progresses in DC, viral proteins are produced on ribosomes of DC are degraded by cytosolic proteases
3.These peptides are Transported to Endoplasmic Reticulum where they bind MHC class I molecules
4 antigen MHC class I leaves Endoplasmic Reticulum travels to golgi apparatus and then to the plasma membrane
5. it is now accessable to be presented to naive T cells that are circulating in LN
6. CD8 Tcells with a TCR specific for the Antigen being presented engage the DC and the T cell becomes activated
7. the T cells then proliferate(stick together to produce cytokines) which leads to clonal expansion occurs and differentiation into cytotoxic T cells leave LN to lygate infected (MHC I displaying) cells
8.TCR and CD8 bind to these MHC I molecules of infected cell CD8 cell stimulates the production of toxic chemicals that induces apoptosis in infected cells
Cytosolic proteases
within infected DC that degrade viral proteins in prep for binding with MHC class I
Cells that can express MHC class I
since most cells can be infected by some sort of virus most can express MHC class I but not RBC
Infected cell MHC class I presentation 5 Steps
1virus infects cell
2 viral proteins synthesized in cytoplasm
3 the peptide fragments of viral proteins bound by MHC class I in ER
4 bound peptides transported by MHC Class I to cell surface
5 Cytotoxic T cell recognizes comples of viral peptide with MHC class I and induces apoptosis in infected cell
differentiation into Effector T-cells (helper T-cells)
when naive CD4 cells encounter their antigen (MHC class II complex)
effector CD4 cells
following differentiation of CD4 T-cells into effector/ helper T cells the CD 4 cells secrete cytokines and “help” augment the activity of the other immune cells
what cells do CD4 cell cytokines activate
B cells and macrophages
MHC class II development and movement
- DC’s take up tathogens by endocytosis,
- then degrade their proteins and load these onto the MHC class II molecules located on the endosome inner membrane surface(MHC made in ER and then transported to endocytic vesicles)
- the Ag: MHC classII molecule moves to the DC surface while DC moves to draining LN
- in LN TCR of CD4 Tcell interacts iwth its specific Ag MHC class II molecule complex and the co- receptor interact
- CD4 T cell is activated and becomes one of several types of helper T cells
some activated CD4 T cells produce cytokines to
help neutrophils
monocytes and
macrophages
to be more efficient in phagocytosis
once activated CD4 helper T cells do 2 things
- some of these travle to infected tissue and produce cytokines to help neutrophils, monocytes and macrophages to be more efficient
- some stay in LN and help activate B cells to antibody production
B cell activation
Helped by helper T cell, B cell proliferates and differentiates into a plasma cell
Plasma cell
differentiated / mature B cell that only produces antibodies, these antibodies are of the same specificity as the Ig (BCR) present on the B cell
MHC class II molecules present on what types of cells
cells of the immunesystem
macrophages, B cells, DC
not somatic cells
Activation of macrophage(immune cells) by MHC class II molecule steps
- macrophage in infected tissue engulfs and degrades bacterium, producing peptides
- bacterial peptides bound by MHC classII in vesicels
- Bound peptides transpored by MHC class II to the cell surface
- Helper T cell recognizes complex of peptide antigen with MHC class II and activates macrophage
Some B cell receptors and antibodies recognize..(other ways of recognizing pathogen, 2)
- parts of native structure of molecules on the outer surface of the pathogen
- bind extracellular toxins released by pathogen
DC in tissue ___
carry pathogens with them into LN or pathogen enters via lymph
protiens on pathogens
can interact with BCR of circulating naive B cells
Those B cells with specific BCRs for the pathogen bind it and stay in LN while those not specific to the protien leave.
Receptor-mediated endocytosis
caused by the binding of BCR and pathogen, The pathogen is killed inside of the B cell and proteins are degraded in the endosome there the MHC class II molecule is loaded with peptided of pathogen and is then presented on the surface of the B cell (figure 3.13)
Following presentation of MHC class II peptide by B cell
MHC class II complex presents to CD4 cells (helper t cells) that are specific for this peptide (this CD4 cell has already been activated by the peptide from DCs)
B cell + T cell interaction of MHC class II and CD4 results in
CD4 secretion of cytokines
activation of B cell
Steps of B cell MHC class II presentation
1 Cell-surfacej immunoglobulin of B cell binds bacteria; the cell engulf and degrades them, producing peptides (antigens of pathogen present to and warn other cells) 2 baterial peptides bound by MHC class II in endocytic vesicles 3 bound peptides trasported by MHC class II to the cell surface 4 helper T cell recognizes complex of peptide antigen with MHC class II and activates B cell (B and T cell are specific for the same pathogen but receptors are often interacting with different components of the same pathogen)
Immunity due to Ab is called humoral immunity
know each and job description
there are Five classes (isotypes ) of antibodies produced by B cells and plasma cells IgG IgM IgA IgD IgE
All anti-bodys within a class share
similar constant regions on their heavy chains each class has certain functions and at times this and this constant region even determines the antibodies location
antibodies found in blood,lymph and intercellular fluid
IgM, IgA, IgG,
Most abundant antibody in blood, lymph and intercellular fluid
IgG
What Antibodiy can be transported across the placenta
IgG
What antibody is found in mother’s breast milk?
IgA
What antibody is produced within the baby
IgM it is evidence of an interuteral infection the baby experienced
first antibody made during the primary reaction
IgM
C3b deposition
is deposited and binds with IgM and then facilitates the phagocytic uptake
Important opsonins to assist in phagocytic uptake
IgG
Antibody transported transplacentally
IgG
Anti toxin, defends against toxin
IgG
can activate complement
IgG
can enter extracellular spaces
IgG
selectively transported onto mucus membrane
IgA (and is in a high abundance)
Antibody In breast milk and decreases rates of Gi tract and Resporitory diseases
IgA
mother’s antibody found in baby to protect baby
no phagocytic receptors for this antibody for the Fc region
IgM
excellent activator of complement
IgM
requires C3b deposition on antibody prior to phagocytic uptake to occur
IgM
First class of antibody to be made during a primary reaction
IgM
Too large to enter extracellular spaces easily
IgM
Related to allergic reactions
IgE
important in parasitic defense
IgE
Binds to mast cells sensitizing them to antigens
IgE (causes allergic reactions)
important as a developmental marker for B cells as as it is present on naive circulating B cells
IgD
IgM too but not freely floating instead membrane bound
Mechanism by which Ab combats infection
specific antibody-> bacterial toxins or bacteria in extracellular space->either neutralizes bacterial toxins or opsinzation by binding and marking bacterial cells-> the neutralized bacterial toxin or bacterial cell is then ingested and destroyed by phagocyte
quality of antibody __________ during the course of an Immune response
Improves
inital Dominant class of antibody in Immune Response
IgM
aspects of antibodies change as IR proceeds due to _____,_______
somatic hypermutation
isotype switching
IgM somatic hypermutation to IgG
- IgM is the first antibody made against infecting pathogen
- Somatic hypermutation selects for antibodies that bind more tightly to the pathogen
- Switching antibody isotype to IgGallows delivery of the pathogen to phagocytes
Somatic hypermutation
addition or subtraction of nucleotides in variable of Heavy and Light chains
purpose for somatic hypermutation
creates/transforms ig into “new” Ig which bind to pathogen better
B cells that do this and are successful become plasma cells
the “new” Ig that bind poorly war B cells that are not chosen to be plasma cells
another name for Isotype Switching
class switch recombination)
isotype Switching
genes for another class are chosen to be transcribed example gamma heavy chain gene is selected instead of Mu heavy chain (this doesnt alter Variable region)
anther name for Variable region
Antigen binding region
isotype Switching ________ alter the variable region
does not!
Isotype switching within Lymph node and spleen(blood)
from IgM to IgG
isotype switching within the peyer’s patches(gut)
IgM to IgA
isotype switching in parasitic infections
IgM to IgE (the Fc region of IgE can be bound by mast cells basophils and esionphils this is a pathogen specific response)
Fc region of IgE can bind to
mast cells
basophils
eosinophils
Results of somatic hypermutation
Better antibodies (secreted Antibodies bind to pathogen more tightly)
Class switching
antibody that can be delivered to site of infection due to properties of its class
Immunological memory
clonal expansion not only provides B and T effector cells it also creates memory cells
Memory cells
long lived and allow for rapid secondary response if same pathogen should attack person againThey are activated more quickly then naive cells
What advantage in preventing infection do memory cells have in second encounter with pathogen?
There is now an abundance of memory cells specific to pathogen as compared with time of first attack when only some naive cells were specific to pathogen
Memory T cells
patrol non-lypmphoid tissues so they can detect infections at an earlier time. unlike naive T lymphocytes
memory B cells
make higher affinity antibody then newly activated B cells since memory cells are a result of somatic hypermutation and class switching
activation of naive lyphocytes is shut down when______ is resent
memory cells
Cost to achieve diversity in producing theoreticall one B or T cell specific for every Antigen
there is a possibility of generating self-reactive receptors by this random process
thus we must have a selection process that will eliminate these self reactive cells before they cause self harm
Clonal selection/deletion is a method of preventing these self reactive cells from succeeding
Clonal Deletion
result of selection due to self reactive change in antibody that causes the orignal to be deleted
Immune tolerance
is usually achieved in most people
Self Immune Tolerance
is inpart achieved during lymphocyte development in the thymus where immature developing T cells undergo positive or negitive selection
Immuno intolerance
when one reacts to won immune sysem and own immune system attacks self
Negitive selection for immunotolerance
IDs T cells that are binding too strongly to self-MHC and are thus eliminated by inducing apoptosis(they are self reactive) this is autoimmunit
positive selection for Immunotolerance
Selects T Cells with TCR’s that interact with host MHC molecules on epithelial cells in the thymus cortex. these are given survival signals. is not signaled survival then cell dies via communication with immune cells
_________ Selection occurs in Cortex of the thymus
Positive
how many types of different MHC types do most people have out of the 1000 possible variations
20
thus many cells die
this is a result of Positive selection via self restricting group T cells
_________ selection occurs in the medula of the thymus
negative
What % of cells survive negative selection process
< 1%
Result of negative selection
self-tolerant pool of circulating T cells that are non reactive aka autoimmune
Where does positive and negative selection of immature developing B cells occur
Bone marrow
What to B cells require to become activated?
B cells require help from a self-reactive T cell to activate a self reactive B cell.
Selection for B cells
similar process to positive and negative selection in T cells but occurs in bone marrow
Apoptosis
Cell suicide aka programmed cell death
mechanism by which auto reactive lymphocytes are eliminated
non mess way to die and doesnt harm neighboring cells (unlike necrosis)
necrosis
messy cell death in which cell contents are spilled on and damage neighboring cells
Central tolerance
a way to fix auto-reactivity
occcurring in primary lymphoid tissues of bone marrow and thymus
Peripheral tolerance
a way to fix auto reactivity which occurs in secondary lymphoid tissue
an example of this involves regulator T cells which suppress auto-rxn in periphery
Autoimmune disease
a by product of protection against a pathogen cross self rxn . in which an effective antibody against an antigen that was encountered at a young age is produced to fight infection but this specific antibody also reacts/binds to MHC on self cells thus killing them as well. mistake when regulation of IR is not controlled
Hypersensitivity
allergy in which harmless substances (pollen) are attacked. often involves IgE and mast cells
this is immunologically abnormal.mistake when regulation of IR is not controlled
hygiene Hypothesis
and increase in hypersenstitivity diseases and autoimmune diseases in richer countries as compared to poorer countires could this be do to hygiene vaccines and antibiotices since IgE are not being used find other antigens to react with?
