T and Th cells Flashcards
What is a T cell and how does it recognise AG? Describe the structure, associated proteins and classes of TCR?
T Cells recognise intracellular pathogens and help regulate the immune system-sees using TCR, but requires presentation of MHC TCR is 1 alpha and 1beta chain identical to Fab arm of an AB-with Variable, constant, light, heavy, CDR, etc-but small TM region-associated with CD3 gammaepsilon that transmit the signal of AG binding 2 main classes of T cells are determined by their TCR CD4-T helper cells-associate with MHC class II-secrete helping cytokines to regulate immune system CD8-CTL-associate with MHC class I-kill target cell with chemicals (can also signal)
Describe the maturation process of T cells in the thymus. Explain VDJ recombination for TCR, and how T cells are selected for action.
T cells starts CD4-8–> start by developing preTCR (surrogate aTCR, normal bTCR)-then become CD4+8+TCR+, and finally move to medulla and specify into CD4 or CD8
Similar to AB, VDJ recombination creates the variety, then as a and b come together-can be different->creates increases variety
Finally, chain is verified for functionality-does it bind MHC at all?, does it bind it too strongly? too weakly? -need to hit sweet spot or apoptosis/deactivation
Describe the strcture of MHC I, its target and the special characteristics of its binding
Main self receptor-actor in transplant rejection
has Long alpha chain (a1, a2, a3), and small microglobulin beta1. a chain transmembrane and with cytoplasmic tail-
In simple terms-long a chain goes around, small b chain just size of a1 -immunoglobulin family. a2 and 3 bind peptide
MHC I shows processed self AG, and the piece of AG does not go all the way to the edges (anchored tho)
Describe the strcture of MHC II, its target and the special characteristics of its binding
MHC class II has 2 about identical chains-with top binding region and bottom IgLike. 2 TM domains->2 signalling The processed AG can sit and go all the way to the edge (even a bit beyond)
Explain the role of MHC in transplant, human HLA, where MHC is expressed and MHC polymorphism
MHC class I, showing self AG-makes transplant rejection, as host recognises tissue as different HLA is the name for human MHC, and there are more than 1 genes. 12 HLA gene-different genes for alpha and beta chain for MHC I and II. several classes exist-and are co-dominant. MHC I is expessed on every cell, while MHC II is only on APC Many different alleles for HLA genes, found in populaton =>why people have different immune responsiveness. 9000 alleles exist, but some very rare. England has a lot of A1/B8 -> but remember, alleles are not randomly generated (population and stuff matters)
List the main APC and describe their usual location. What AG does each MHC present
Activated macrophages (lymphoid tissue, present to T cells), Dendritic cells (found in nearlty all peripheral tissue (skin), and present to T cells) and B cells (lymphoid tissue-present to t cells) MHC I presents endogenous AG (present within the cell), while MHC II present exogenous AG, which can present to T cells to activate them
Describe the way MHC I and II take AG and present it
Class I are present in everycell-and present AG. Proteins are taken from the cell, and taken into the proteasome and into the RER->where MHC I is. The peptide is added to MHC, and both are transported to golgi then to the cell wall (if virus infects and produce own proteins, then they are presented instead and recognise as non self
Class II take exogenous AG-When in the golgi, an invariant chain takes the place of the AG. The MHC is transported out of the RER, to the golgi and then in a vescile, where CLIP enzyme processed the invariable chain. The AG is processed and added to MHC II in the vescile, which is then presented for T cells to recgonise
Why is a cell mediated immunity needed on top of the humoral immunity?
AB are not enough, as some pathogens are intracellular (HIV), or organism has evolved to escape AB recognition-either by changing shape or producing decoy AG.
Cell mediated immunity can help digestion by innate immune system (by targetting them to the pathogen), or by killing themselved (CD8)
Recall and explain why APC are so important to T cells. Explain how they circulate to find AG
T cell TCR can only recognise processed AG, and need co stimulation to activate-need to bind AG presented on MHC. CD4 cells bind MHC II, while CD8 cells bind MHC I
T cells circulate in the blood and lymph, from node to node, until they die or find AG (uses HEV to enter, then sit and/or leave)
What are the 3 phases of cell immunity? How is that regulated by the 3 signal model?
1st step is DC/APC cell that collect and uptake antigen from the zone of infection. Bring it to the lymph nodes-MHC peptide interaction activates T cell-from naive to effector (clonal expansion)-and then goes do its effects. Finally, effector pool retracts and some become memory cells
Activation cannot only be dont by AG-need co stimulation by the APC that confirms the attack. At the same time, the right cytokines have to be present around the T cell
Describe CD8 cell, their function, mode of action, and the main advantages/disatvantages. give an exemple of CD8 important
CD8 cells recognise MHC I and can differentiate self vs non self (CD8 is co stimulator). CD8 can recognise when an infected cell presents a foreign protein, a result of the virus producing its own proteins within the cell
When it find non self MHC I (or lack of self MHC AG), it degranulates. the granules have perforin and granzyme-perforin forms a pore in the target cell, and granzymes come in and lead to apoptosis. CD8 cells can also activate Fas mediated apoptosis
The main advantage is the specific recognition of non self AG, and the fast action. Can also kill several cells per CD8 cells-whereas macrophages can really only ingest 1
CD8 with the HLAB75 mutation are resistant to HIV-and not only cant get infected, but also causes the virus to lose fitness in the patient (as soon as change, gain fitness back)
Describe CD4 cells, their variety (and how they are categorised) their activation
CD4 cells are some of the most important ones, as they modulate the response, increase, decrease and target the immune system
CD4 can be T helper cells-and there are many-usually determined by the cytokines they produce and what transcrption factors cause them to change
Th1 cells produce INF gamma -usually intracellular response vs viruses (TF STAT5)
Th2 cells produce IL4, 5, 13, and boost anti-multicellular (parasite) response (TF STAT6)
Th17 produce IL17-activate anti bacterial (innate)
Th0 (Treg)-help inhibit and reduce the response (TF Foxp3)
Describe the 4 main functions of T helper cells
1) Macrophage activation-inflamatory Th1 activate macrophages to promote killing of cells-Macros produce CD40 and TNFa receptors (to get activated more), and secrete TNFa and INFy which leads to antimicrobial response
2) delayed type hypersensitivty-primary role is defence vs intracellular pathogens by degranulation of innate cells (eosinophils). If pathogen not cleared-chronic inflamation, if AG not a microbobe (cross activation)-allergy
Usually mechanism of activation are Th1 or th2 specific to an AG that activate eosinophils or macrophages-cytokines cause the inflamation as defence-but can go wront. CAlled delay becaused ALWAYS need sensitivation before reaction (effector phase)-cannot be allergic to an AG only seen once)
3) B cell activation-as before, B cell can act as APC, and Th can activate them to plasma cells-B cell brings AG on MHCII to the node, looks for t cell with same AG-once found, activates t cell, which then produces cytokines to activate the T cell
What is T cell memory? how does it arise? What are different types of T cell memory How can it go wrong?
T cell memory happens after an infection, when the effectors T cell pool contracts and a few are selected for memory-can confer life long immunity, and the memory cells lie dormant until activation-can activate much faster and stonger than before (qualitative difference between naive and memory)-and unlike B cells, no other pathway (affinity maturation or isotype switch)
some memory t cells exit circulation and enter tissue where they sit until they are presented AG-faster response
Some memories are bad-such as allergies, but also against self AG-AI, or in excess (immunopathology)
What is T cell exhaustion?
As infections last, the levels of CD8 cells contracts-to limit damage-which is what happens in HIV-> leaves the patient immunocompromised and can be dangerous
T cells can also exhaust with age, as the thymus produces less, less cells capable of binding new AG appear-why flu is dangerous in the elderly
