DCs MHC TCR CS individual Flashcards
what is a point of having immune system
to protect us against pathogen
immune system distinguish btn sel and non-self
what is a characteristic of innate immune system
-it doesn’t create memory ( problem)
- rapid response
- many cells have similar identical receptors
what is a characteristic of adaptive immune system
- have ability to recognize many pathogen
- potential of creating memory cells
- each cells have unique receptor
how does T cells recognize antigen
- antigen is presented on TCR (T cell receptor) by APC(antigen presenting cell)
- TCR is able to recognize linear/peptide antigen only
- T cells have many identical receptor on their surfaces
how does APC be able to present antigen on T cell
by using MHC (major histocompatibility complex) to which peptide (antigen) is binding
mechanism of how T cell recognize antigen
APC carry MHC on its surface to which antigen (peptide) is binding. then MHC meets TCR attached to T cells and then antigen is presented
what is TCR
- is membrane bound receptor on the surface of T cell
- f(X): is to signal T cell activation
TCR structure
- heterodimer; beta alpha TCR and gama delta TCR
majority T cells carry alpha beta TCR and gama delta TCR are few.both they have similar structure but different recognition properties. - extracellular portion of each chain: variable (variable amino acid sequence) and constant (constant amino acid sequence).
- stalk segment : connect V and C domains to the membrane
- membrane region: contains transmembrane of both chain (alpha and beta) and is positive charged (create balance on the surface of cell)
-disulfide bond : connect two chain
what is gama delta T cells
T cells that have TCR that binds to gama delta chain
what is the importance of having specificity in TCR
is due to CDRs
what is CDRs
-elements that allows TCR to interact with the MHC and peptide (antigen)
- CDR1 and 2 binds to the MHC, CDR3 binds to the peptide antigen
how doe cell get signal when antigen bound to TCR
-TCR can not signal into the cell
- TCR is composed of antigen-binding alpha and beta heterodimer that are associated with signalling chain CD3 and homodimer (ITAM)
where does signalling of T cells start
it start from ITAMs
what are two T cells subsets
ThCD4+: T helper cell and
Tc CD8+ T cytotoxic Cell
-both ate associated with surface of either CD4 marker or CD8
what is the function of CD4 and CD8
interact with MHC and make effective response to antigen
TCR diversity
is ability of T cell to recognize huge number of different antigen
How can the TCR recognize the huge number of different potential antigens
its recognize antigen through its 4 gene which are α, β, γ, δ by performing gene rearrangement
which way does TCR use to diversify
- somatic recombination
- conjunction diversity
-combination of different V and C segments
different btn TCR diversity and antibody
TCR does have somatic hypermutation and effector function
where does TCR diversity take place
in Thymus
what does effector function depends on for T and B cells
B cells depends on secreted antibody
T cells depends on cell-cell contact
what does effector cell do
- effector cells are the relatively short-lived activated cells that defend the body in an immune response.
-Effector B cells are called plasma cells and secrete antibodies, and activated T cells include cytotoxic T cells and helper T cells, which carry out cell-mediated responses.
what is MHC
glycoprotein that display antigen i form of peptide on the surface of T cells
what are the two type of MHC
-MHC class I
-MHC class II
MHC class I molecule
- MHC I present antigen to CD8+ ( T cytotoxic cell)
- ## it structure has 2 polypeptide chain: 2 alfa chain and 1 beta microglobulin
what is the different between beta and alpha chain of MHC I
only alpha chain spans membrane
what is the role of peptide binding cleft
-form polymorphic: influence which peptide (8-10 aa length) has to bind which defines the specificity of the antigen presented to T cell
what is the MHC I capable of
is able to stably bind to wide range of different peptide due to anchor residue which make it stable
what happens of peptide are not bound ti MHC I stably
-means MHC I molecule is not stable too.
- in simple words MHC molecule lacking a bound peptide is unstable
what is anchor residue
- is the one which hold peptide in the cleft
- they defines specificity holding of peptide
MHC class II molecule
- present antigen to T helper cells (CD4+)
difference between MHC I and MHC II
- MHC I, present antigen on CD8+ (cytotoxic T cells). have 3 alpha chain and one beta microglobulin. only alpha chain span the membrane. small peptide binding cleft, binding peptide of 8-10. the peptide tightly bind to the end of cleft coz they are short
- MHC II, present antigen on CD4+ (helper T cells). has 2 alpha chain and 2 beta chains and they both span the membrane. wider peptide binding cleft, binding peptide of 13-17. they are more flexible and able to bind more peptide and the end of peptide don’t tightly bind to the cleft.
similarity between MHC I and MHC II
-both have peptide binding cleft
-both has high polymorphic
- anchor residues
- both can bind wide range of different peptide
which class of MHC do we have in brain
MHC I is positive
MHC II is negative
in mouse MHC II is negative
where can we find MHC I and MHCII
MHC I can be found in any nucleated cells and MHC II can be found in antigen presenting cells
what are two properties of MHC gene which enable it to kill pathogen
- polygenic : contains several different MHC I and II genes and all have different peptide binding property. so that they can ensure production of number of MHC molecules individual.
*in few words: if for example we have 3 genes they all encode different class I protein. - chromosome here are homozygote means one allele per gene and only 3 protein variants is produced here.
*can create one variant of the gene because it is homozygote - no multiple variants of genes
- polymorphic: they are multiple variation of each gene. they ensure diversity.
- multiple variants of each gene
- chromosome pairs show heterozygote means two different alleles per gene
- two protein variant per gene
*can create two variants of gens because it is heterozygote
which property of MHC found highly in the both classes
polymorphic property is found highly in both MHC I and II class
how do you call human MHC and mouse MHC
human MHC: is called HLA (human leukocytes antigen) complex
mouse MHC. is called H-2 complex
what are three class I alpha chain gene for HLA (NOT IN EXAM)
HLA-A,B and C
what are three pairs of class II alpha, beta chain gene for HLA ((NOT IN EXAM))
HLA-DR, DP and DQ
how does MHC polymorphic affect T cell recognizing antigen
- it influence peptide (antigen) binding
- influence contact between TCR and MHC molecules
how does MHC affect transplantation
when the MHC alleles of donor and recipient are different body will recognize it as foreign substance and denies it.
which MHC class is APC express on
- APC express on MHC class II
- all other nucleated cells are expressed on MHC class I example B cells, macrophage and dendritic cells
how does three different APC type differ
- antigen uptake: DR and Macrophage use phagocytosis
-MHC expression: DR are few in tissue-resident but high in lymphoid tissue. Macrophage is activated by bacteria and cytokines.
-location : DR all body and macro lymphoid tissue or body cavity
-effect: DR result in activation of naive T cells. macro result in activation of macro
what is the process of antigen epitopes being recognized on by T cells
first, antigen is broken down into peptide fragments
and epitope peptide will bind to the MHC molecule
then TCR will bind to the complex of MHC molecule and epitope peptide
what are two processes involved in APCs
- Antigen processing: it occurs within the cell and lead to display of antigen on APCs surface
- Antigen presentation: APC display antigen on its surface in the way T cells can see it
what are three main type of professional antigen presenting cells
dendritic cells, B cells, Macrophage
where in lymph node are APCs located
- DR are in cortex in T cells zone
-Macrophage are in marginal zone sinus
-B cells are in follicles
what role does DR cells do in adaptive immune response
- it initiate adaptive immune response
- activate T cells by presenting antigen to it
what are immature dendritic cells
are one that hasn’t account antigen before and they reside in peripheral tissues.
immature DR as soon as they account with antigen they migrate through lymphatic vessels to lymph node region where they will meet naive T cells and activate T cells
when does dendritic cells become mature
when they account antigen
what is the different btn immature and mature DR cells
immature DR: specialized in antigen recognition and uptake, they express low level of MHC
mature DR: specialized in antigen presentation, they express high level of MHC, they develop dendrites, regulate antigen receptor
what are two different type of DR cells
- plasmacytoid DR cells: express CD123, sensing viral infection (large amount of interferon is produced)
-conventional DR cells: express CD11c, activator of naive T cell
what are 3 different ways of antigen uptakes
- phagocytosis : uptake of large particle, complement receptor
-macropinocytosis : uptake of small particle, Fc receptor
-endocytosis: uptake of soluble particle, receptor independent
which molecule are used to present antigen on surface of APCs
- MHC molecule
-and there is different molecule in each class
-and each of their genes are polymorphic with many variant in the population
how does MHC I and II deliver peptide
they deliver peptide through two intracellular compartment which are:
MHC I deliver peptide through cytosol
MHC II deliver peptide through vesicular compartments
what type of antigen associated in MHC I and II
-virus and bacteria are replicated in cytosol so in MHC I and presented on effector CD8 leading to cell death
-other bacteria and some parasite are associated in MHC II and presented on effector CD4 leading to
what are two pathways of antigen processing and presentation
cytosolic and endocytic.
-endogenous antigen are processed in cytosolic pathway and presented on MHC I
- exogenous antigen are presented on endocytic pathwat and are presented on MHC II
what are MHC restriction
MHC restricts the ability of T cells to recognize the antigen.
WHY: because when MHC genotype is different from what T cells was presented then they will be restriction on MHC and antigen will not be able to be recognized by T cells
what are two ways of MHC restriction
- directly: this is when MHC is different (change) so TCR wont be able to recognize it so that it can bind on it
-indirectly: is when peptide bind to MHC change and TCR wont be able to recognize it so that it can bind on it
When and where does antigen presentation
and T cell activation take place?
in secondary lymphoid organs: spleen, lymph node, and tonsil. where T cells can meet antigen and are activated
antigen are transported actively or passively to secondary lymphatic organs through lymphoid system
how does T cells inter and leave the lymph node
-enters though the blood via HEV
-leave cortical sinuses when they are not activated by dendritic cells
why does activated T cells doesn’t leave lymph node
because they are activated they start to proliferate and they lose their ability to exit the lymph node. after they differentiate into effector T cells and they exit lymph node
How do the T cells migrate
they use chemokines and adhesions molecules
Can all T cells recognize both MHC I and MHC II?
-Cytotoxic T cells carry cell surface CD8 and recognize peptide on MHC I
-Helper T cells carry cell surface CD4 and recognize peptide on MHC II
what is cross presentation
is process by which dendritic cells take up extracellular protein and can give rise to peptide presented on MHC class I molecule
is process that enables antigen in class of extracellular source to be presented by MHC class I molecule and activate CD8 T cells
what are 3 signal needed for naive T cell activation
- activation: antigen specification signal, binding of peptide through CD4 and CD8 , TCR and MHC class II
- survival: costimulatory signal through CD28
- differentiation through cytokines
what is the importance of 3 signals
- if only one signal occurs maybe they will not be activation and differentiation of T cells
- allow self-tolerance expressed on tissue cells to induce tolerance
what activated naive T cells can differentiate into ?
naive T cells they can differentiate into effector T cells or long lived memory T cells.
some effector T cells can become memory T cells
what are the groups of memory T cells
- central memory that express CCR7. they remain in lymphoid tissue
- effectoR memory that don’t express CCR7. the migrate to tissues.
why do we need Memory T cells
-because they more easily to stimulate than naive T cells
- they respond more quickly
what are different type of effector T cells
- CD8 cytotoxic T cells: which kill virus infected cells
-CD4 helper T cells: kill pathogens and bacteria
different type of T cells and their function
- CD4 Th1 cells: activate macrophage
- CD4 Th2 cells: kill parasite
- CD4 Th 17 cells: control early phage of infection
- T fh cells: produce cytokines
-CD4 regulatory T cells: suppress T cells activity
what are the important of CD4 Th1,2,fh B cells
they help B cells for production of ntibody
what is anergy
mechanism that protect our body from being attached by T cells recognizing self-antigen
