T-Cells Flashcards

Question

what happens when a thymocyte passes selection?

Answer 1

- the remaining 5% of lymphocytes express TCR with low affinity for self MHC can recognize self and aren't auto-reactive - this contains an individuals unique t-cell repertoire and is highly diverse - now they are ready to be activated and detect invading pathogens --> all have the potential to be useful but only few are actually useful to things in body (i.e some may be effective to things found in fish so it'll never be used)

Answer 2

- a single pathogen can be recognized by many t-cells, which each one targeting different parts (epitopes) of the pathogen - it is not a 1:1 relationship between a pathogen epitope and TCR - TCRs have varying binding strengths (affinities) for epitopes of a pathogen (stronger = more effective response) this is important because it ensures the immune system can build a robust and diverse response to a pathogen. it also increases the chances of eliminating a pathogen even if not all TCRs bind strongly to the epitope of the pathogen

Answer 3

- helper t-cells = express accessory molecule CD4 which binds to MHC class II - cytotoxic (killer) t-cells = express accessory molecule CD8 which binds to MHC class I - Tregs = regulatory t-cells that suppress the activity of CD4 and CD8 t-cells and control immune responses --> they all work in tandem and know what to do because of cytokines (communication)

Answer 4

- t-cells are only activated in the presence of antigen-presenting cells (APCs) such as dendritic cells, macrophages or B-cells - the APCs internalize and digest pathogens into small antigen fragments, which are loaded into their MHC class I or MHC class II molecules on the surface - it can then be recognized by t-cells, leading to activation

Answer 5

- dendritic cells exist within tissues in an immature state - immature dendritic cells have the high ability to internalize antigens, such as pathogens - dendritic cells drain from the tissue to the lymph nodes at a steady rate, particularly increasing during inflammation or infection - as the dendritic cells migrate to the lymph nodes, they mature and cannot pick up any more antigens; they can only present them - mature dendritic cells exist in the lymph nodes - in the lymph nodes, mature dendritic cells present processed antigens using MHC (Class I and class II) to T-cells, leading to activation and a target immune response

Answer 6

- dendritic cells are part of the innate immune system, but they also bridge the gap to the adaptive immune system by activating T-cells - this antigen presentation process occurs at high rates during infection, helping to initiate an immune response. if no dendritic cell present = no t-cell activation = no adaptive immune response = PROBLEM

Answer 7

- called the major histocompatibility complex (MHC) --> called a 'complex' because all the MHC genes are found in a single location on this chromosome - MHC molecules are essentially peptide receptors because they bind to peptides (short chains of amino acids) in order to present them to t-cells - these peptides are derived from pathogen or host-derived proteins that have bene broken down by antigen-presenting cells

Answer 8

1) class I MHC = comprised of alpha chain non-covalently attached to a beta-2 macroglobulin 2) class II MHC = comprised of an alpha and beta chain --> both MHC have a peptide binding groove --> however, MHC class I and class II have different pathways for loading peptides into their peptide-binding grooves

Answer 9

- in humans, the genes that code for MHC is known as HLA (human leukocyte antigens) --> genes coding for class I MHC are HLA-A, HLA-B HLA-C --> genes coding for class II MHC are HLA-DR, HLA-DP, HLR-DQ - MHC molecules are co-dominantly expressed, meaning that both maternal and paternal genes are expressed simultaneously in the same cells --> each cell in your body expresses 2 copies of HLA-A, HLA-B, HLA-C resulting in 6 different classes of class I MHC --> specialized APCs express 2 copies of HLA-DR alpha/beta, 2 copies of HLA-DP alpha/beta, 2 copies of HLA-DQ alpha/beta = 12 classes of MHC class II

Answer 10

- polymorphic means that there are many different alleles (versions) of the same gene found within the population --> for MHC genes, this means that the gene exists in many different forms among people, creating a great deal of genetic diversity - MHC genes are the most polymorphic genes in the human population = the chance you have the same MHC genotype as someone else is extremely rare unless you're twins

Answer 11

- the polymorphic region is the peptide binding groove (most diversity occurs here) - different MHC alleles can bind to different sets of peptides (small parts of pathogens like viruses or bacteria). - the more different MHC alleles you have, the broader the range of peptides (from various pathogens) your immune system can present. - the diversity in MHC molecules means that each individual can present a unique set of pathogen-derived peptides, allowing for a wide-ranging and more effective immune response.

Answer 12

- polymorphic = many different alleles (for the same gene) within a population - oligomorphic = few different alleles found within a population - monomorphic = only one allele found within a population

Answer 13

A haplotype refers to the combination of all MHC genes (HLA alleles in humans) inherited from each parent - these genes are co-dominantly expressed, meaning that alleles from both maternal and paternal chromosomes are present on the individual’s cells - although your haplotypes are inherited from your parents, recombination during meiosis (cell division creating sex cells) can shuffle the MHC genes, creating unique haplotypes in offspring. - this results in variation across generations and among siblings = genetic diversity in immune responses

Answer 14

- an individuals MHC haplotypes dictates what peptides your MHC can bind best to --> this means that some cells MHC may be great at presenting some antigens to your T-cells and others will be bad at presenting other antigens to your T-cells

Answer 15

1) allelic advantage - some alleles are better at presenting antigens, making them more effective at protecting against specific pathogens. 2) heterozygotic advantage - individuals who are heterozygous (having different MHC alleles from each parent) have a greater diversity in the MHC molecules they express - increased diversity in MHC molecules gives individuals a better ability to bind to and present a wide variety of peptides = better immune response 3) mate selection - people are often attracted to those with different MHC haplotypes. - this pairing results in offspring with greater MHC diversity, benefiting from the heterozygotic advantage and a stronger immune system

Answer 16

- heterozygotes (inherited diverse alleles from both parents) will have more diversity of MHC and be able to form a larger repertoire of presented antigens (Ag) compared to homozygotes - homozygotes (inherited same alleles from both parents) would have more overlap in their MHC alleles, resulting in less diversity and less effective immune system - the divergence of haplotypes matter: --> if they are very different = wide variety of antigens can bind --> if they are closely related = you will bind more antigens (Ags) than a monozygote, but fewer than if you had divergent haplotypes the overall idea is that greater diversity in MHC alleles = more antigens presented = increased likelihood of an immune response

Answer 17

- MHC is also responsible for defining "self" and is enforced by MHC restriction --> T-cells learn to recognize self-MHC in the thymus; positive selection only allows t-cells that bind self-MHC with moderate affinity to survive - defining self ensures that t-cells can recognize whether a "self" or "foreign" peptide is being presented in MHC --> can either start immune response or prevent autoimmunity from attacking own cells

Answer 18

the concept that a TCR will only recognize and bind to its specific matching antigen that is presented by its own HLA allotype (specific version of self-MHC) -the TCR will not bind to the same antigen if it is presented by a different HLA allotype (a different version of MHC). - the TCR will not bind a different antigens even if presented by the same allotype (same MHC) - the combo needs to be perfect!

Answer 19

when t-cells interact with antigen-presenting cells (APCs), they need to check 2 things: 1) does my receptor bind the ligand 2) is the MHC self-MHC? - mismatch haplotype = t-cell doesn't recognize MHC - mismatch antigen affinity = t-cell will not recognize antigen because theres insufficient binding affinity even if MHC is correct - MHC haplotype and antigen affinity must match

Answer 20

- MHC allorecognition is the process by which the immune system recognizes differences in the major histocompatibility complex (MHC) molecules between donor and recipient cells - T-cells can detect 'self' vs 'non self' by binding to MHC - recognizing non-self MHC will lead to T-cell activation against the non-self MHC = principle behind transplant rejection

Answer 21

1) direct allorecognition - t-cell is activated by an intact MHC molecule of donor cells 2) indirect allorecognition - t-cells recognize donor peptides processed and presented by recipient APCs

Answer 22

MHC class I presents intracellular peptides approx. 9 amino acids long --> since MHC class I presents to CD8+ t-cells, you want to present intracellular peptides to tell killer t-cell its infected

Answer 23

intracellular pathogens are broken down by peptides in the cytoplasm of the infected cell: - proteasome is always present in the cell, breaks down damaged, mis-folded and unneeded proteins - immunoproteasome is produced by APCs and some infected cells, which preferentially degrades proteins to produce MHC class I compatible peptides (not every peptide will fit)

Answer 24

- TAP is the channels mediating transport from the cytosol into the endoplasmic reticulum (ER) - a 9 amino acid peptide chain is actively transported into the ER by the Transporter associated with Antigen Processing (TAP) - TAP is essential for peptide delivery so they can be loaded onto MHC class I molecules

Answer 25

1) Within the rough endoplasmic reticulum (RER), the MHC class I alpha chain binds to calnexin (a chaperone) and ERp57, ensuring proper folding and stabilization. 2) The binding of beta-2-microglobulin to the alpha chain displaces calnexin. This enables the MHC class I molecule to interact with other chaperones like calreticulin and tapasin, which is connected to the peptide transporter TAP (Transporter Associated with Antigen Processing). 3) Meanwhile, immunoproteasome is actively cleaving and breaking down intracellular proteins into peptides that will be transported into the ER by TAP 4) The association of calreticulin, tapasin, and TAP forms the protein loading complex (PLC), which promotes the binding of antigenic peptides to the MHC class I molecule. 5) Antigenic peptides transported into the RER by TAP can be further trimmed and modified by ERAP to optimize their length for binding to MHC class I molecules. 6) The binding of a suitable antigenic peptide stabilizes the MHC class I molecule-peptide complex, allowing it to exit the RER and be transported to the plasma membrane for presentation to cytotoxic T cells (CD8+ T cells).

Answer 26

- w/o MHC class I = we'd have no CD8+ t-cells - w/o chaperone (calnexin) proteins = MHC wouldn't fold properly or be held together - w/o TAP = there'd be no peptide loading = no MHC class I presentation - w/o ERAP = less effective/slower loading of peptides

Answer 27

1) calnexin = a chaperone protein that assists in the folding of MHC class I alpha chain 2) peptide loading complex: - tapasin = brings MHC class I to TAP and bends MHC so it is close to TAP for effective antigen binding - calreticulin = a chaperone protein that stabilizes the MHC class I complex - ERp57 = acts as a stabilizer for the complex, ensuring proper assembly 3) ERAP = trims peptides so they fit better into the MHC class I peptide binding groove 4) TAP = transports peptides into ER to be loaded onto MHC class I

Answer 28

- a strong-binding antigen that fits well into the peptide binding groove induces a conformational change in MHC class I - this change releases MHC from tapasin, leaving the peptide-loading complex (PLC) - MHC class I exits the RER after antigen loading - it passes through the golgi apparatus where it is glycosylated - MHC then travels to the plasma membrane to present the antigen to CD8+ T-cells

Answer 29

REMEMBER: all cells present MHC class I - under normal, uninfected conditions, MHC class I molecules present self peptides (fragments of proteins naturally produced by the cell) which signal to the immune system that the cell is healthy - when a cell is infected (i.e virus), the pathogen proteins are processed and chopped by the proteosome inside the cell, which are loaded and presented on MHC class I molecules - the immune system recognizes these foreign peptides as "non-self" and activates CD8+ t-cells to target and destroy the cell to control infection

Answer 30

- MHC class II binds extracellular peptides approx. 22-24 amino acids long - extracellular peptides are derived from pathogens that are engulfed by APCs (macrophages, dendritic cells) - then they're presented on the surface of the APC to CD4+ t-cells --> makes sense because CD4+ t-cell help with b-cell activation which produce antibodies = key in defending against extracellular infections

Answer 31

1) newly synthesized MHC class II alpha and beta chains bind to protein called invariant chain while still in the endoplasmic reticulum (ER) --> the invariant chain (li) prevents intracellular peptides from entering and bindings MHC class II prematurely/by mistake 2) meanwhile, extracellular pathogens/antigens are taken into the cell via phagocytosis or endocytosis by antigen-presenting cells (APCs) 3) as the antigen travels away from the surface, the phagosome/endosome acidifies, merges with lysosomes, and the pathogen is degraded into peptides 4) the MHC class II + li complex goes through the golgi and will eventually merge with a late endosome 5) the invariant chain (li) is degraded by proteases inside the vesicle, leaving a small portion remaining in the MHC class II peptide groove, called CLIP (class II associated invariant chain peptide) 6) HLA-DM catalyzes and mediates the release of CLIP from the peptide binding groove which is replaced by a pathogen-derived/antigenic peptide --> HLA-DO acts a negative regulator of this pathway, binding HLA-DM and blocking its function 7) the MHC class II peptide complex is then transported to the plasma membrane where it is presented to CD4+ t-cells

Answer 32

HLA-DM function: - HLA-DM is a non-classical MHC class II molecule that catalyzes that facilitates the exchange of CLIP (fragment of invariant chain) for pathogen-derived peptides in the peptide-binding groove HLA-DO function: - HLA-DO, also a non-classical MHC class II molecule, acts as a negative regulator in this pathway which binds to HLA-DM and blocks its function - it prevents the release of CLIP and the binding of pathogen-derived peptides. Outcome: - HLA-DM and HLA-DO can up-regulate or down-regulate as a mechanism of control - this regulation ensures that only properly processed peptides are presented on the surface of antigen-presenting cells, allowing for an accurate immune response. --> More HLA-DM enhances the exchange of CLIP for antigenic peptides, effectively up-regulating the presentation of pathogen-derived peptides --> More HLA-DO down-regulates the activity of HLA-DM, inhibiting the release of CLIP and preventing the binding of antigenic peptides

Answer 33

naive CD4+ t-cells are cells that haven't encountered their matching antigen - they become activated when they recognize extracellular antigen/peptides presented on MHC class II molecules by APCs like dendritic cells, macrophages or b-cells - after activation, they differentiate into helper t-cell subsets

Answer 34

- naïve CD8+ T cells are cells that have never encountered their matching antigen and need activation - in order to become activated, they recognize extracellular pathogen-derived peptides presented on MHC class I (they cannot be activated by seeing MHC class I on healthy cells) - however, naive CD8+ T cells primarily reside in lymph nodes and do not encounter pathogens directly there (not infected), so they require additional support by dendritic cells to bring the antigen to them --> therefore, naive CD8+ t-cells use CROSS PRESENTATION where APCs take up extracellular pathogens and present peptides on MHC class I to activate t-cells *yes, APCs traditionally present antigens to CD4+ T cells via MHC class II, but they can do both*

Answer 35

- cross presentation is the ability of antigen-presenting cells (APCs) to take up, process and present extracellular antigens using MHC class I molecules to CD8+ t-cells - cross-presentation by APCs is essential for the activation of naive CD8+ t-cells - after activation, CD8+ t-cells are able to recognize and kill cells infected by intracellular pathogens *traditionally, APCs present extracellular antigens using MHC class II molecules to activate CD4+ T cells*

Answer 36

- dendritic cells are unique in that they can present both MHC class I and MHC class II molecules - This allows them to activate both CD8+ T cells (via MHC class I) and CD4+ T cells (via MHC class II). - in order for dendritic cells to crosspresent to CD8+ t-cells, they must be "licensed" --> licenscing occurs when the dendritic cell presents antigen on MHC class II and activates CD4+ t-cells --> the CD4+ returns the favour and "activates" the dendritic cells, allowing them to present antigens on MHC class I to activate CD8+ t-cells

Answer 37

1) activation of CD4+ t-cell - the dendritic cell (typically residing in tissues) phagocytoses extracellular pathogens and processes them into smaller peptides - as it migrates to the lymph node, they mature and presents these processed pieces on MHC class II to activate CD4+ t-cells 2) dendritic cell licensing by the CD4+ t-cells - the activation of CD4+ t-cell leads to the release of IL-2 - IL-2 contributes to the activation of CD8+ t-cells - IL-2 also triggers dendritic cells through proper signalling to begin cross presentation, which is the process of presenting extracellular antigens on MHC class I molecules 3) activation of CD8+ t-cells - CD8+ t-cells with TCRs that match the antigen presented in MHC class I become activated - activated CD8+ t-cell leave the lymph node and travel to infected tissue, where they bind infected cells by MHC class I

Answer 38

- without cross presentation, the CD8+ t-cell would never get activated - cross-presentation allows dendritic cells (APCs) to present extracellular pathogen-derived peptides on MHC class I molecules --> this is crucial because naive CD8+ T-cells, which normally recognize intracellular pathogens, do not have access to infected tissues directly - it also links the immune response to extracellular pathogens with the response to intracellular pathogens

Answer 39

Activation: CD8+ T-cells are activated by extracellular pathogens through cross-presentation by dendritic cells. Function: Once activated, CD8+ T-cells kill cells infected by intracellular pathogens (e.g., viruses) or tumour cells.

Answer 40

- the first step to induce adaptive immune responses is the activation of CD4+ (helper) t-cells - this occurs in secondary lymphoid organs (lymph nodes, spleen, peyers patches) - the most potent APC that can activate naive t-cells are dendritic cells (most dominant, best) - there are 3 signals requires to activate a helper t-cell which are provided by the APC --> w/o the signals, we can't activate t-cells

Answer 41

1) activation site - naive t-cells are activated in secondary lymphoid organs such as lymph nodes, spleen and peyers patches 2) activation requirements - receptor-ligand interactions occur between T-cell receptors (TCR) and MHC molecules on dendritic cell - lots of cytokine signals are provided by the dendritic cell and other supportive immune cells 3) outcome of activation - effector and memory t-cells are produced - CD4+ t-cells differentiate into helper t-cells that secrete cytokines to amplify activity of other immune cells - CD8+ t-cells differentiate into cytotoxic t-cells that kill infected cells - memory t-cells "remember" the pathogen for a quicker response upon reinfection

Answer 42

1st signal: - the T-cell receptor (TCR) must recognize and bind a specific peptide antigen presented by the MHC molecule on the antigen-presenting cell (APC). the MHC must be recognized as self. 2nd signal: - a co-stimulatory signal is also required for activation -together these trigger a signalling cascade that results in production of cytokines 3rd signal: - cytokines trigger t-cell proliferation (IL-2) and differentiation into functional subtypes (polarizing cytokines)

Answer 43

when APCs detect pathogens (PAMPS) using PRRs, they increase expression of co-stimulatory molecules CD80/CD86 - this recognition signals the APC to up-regulate the expression of CD80/CD86, making the APC ready to activate T cells --> T-cells express CD28 protein on their surface --> APCs present CD80 or CD86 co-stimualtory molecule on their surface --> the CD28-CD80/CD86 interaction provides the second signal for activation - only mature dendritic cells, activated macrophages, and B cells can express CD80 and CD86

Answer 44

- APCs present both pathogen-derived peptides which are recognized by T-cell receptors (TCRs) on the surface of T-cells. - a t-cell with a TCR that matches with the antigen will bind their CD28 to APCs CD80/86 co-stimualtory molecule - cytokines present in the microenvironment contribute to t-cell activation, proliferation and polarization

Answer 45

signal 1: antigen recognition - specific binding of a TCR to an appropriate MHC/peptide complex - Co-receptor (CD4 or CD8) bind to MHC class II or class I respectively signal 2: co-stimulation - CD28 present on the t-cell binds to the CD80/86 on the APC - this binding activates an intracellular signaling cascade within the T-cell. - this ultimately leads to production of transcription factors that move to the nucleus - the transcription factors will initiate the expression of genes responsible for T-cell survival, proliferation, and effector function

Answer 46

t-cell activation needs to be turned off eventually because it uses energy and resources. - as infection in the body resolves, t-cells start to express CTLA-4 on their surface --> CTLA-4 is an inhibitory co-stimulatory molecule that has higher affinity for CD80/86 on the APC than CD28, which leads to inactivation of the t-cell --> PD-1 is another inhibitory receptor expressed by the t-cell to inactivate it - CTLA-4 inactivates the T cell and blocks antigen presentation, effectively turning off the immune response and preventing further activation - when there is insufficient co-stimulation (after CTLA-4 or PD-1 engagement), the t-cell enters an anergic state - anergy refers to the state when t-cells are alive but not responsive to further stimuli (zombie cell)

Answer 47

- when a T cell receives Signal 1 (binding of its TCR to the MHC/peptide complex on the APC), it recognizes the antigen. - if the T cell does not receive Signal 2 (the co-stimulation from CD28 binding to CD80/86), the T cell becomes anergic. --> anergy means that the T cell is alive but not responsive to further stimuli. --> the T-cell does not die; it simply becomes unresponsive to activation signals, which helps to prevent excessive or inappropriate immune responses. key takeaway: signal 2 is crucial for full T cell activation. without it, even if the T-cell encounters its antigen (Signal 1), it will enter a state of anergy and won't respond effectively.

Answer 48

1) primary immune response - pathogens cross physical barriers (i.e skin, membranes), releasing antigens into the body - the innate immune system attempts to control the infection initially using macrophages and neutrophils - if the infection persists, the adaptive immune system is activated 2) antigen capture & presentation - dendritic cells are key antigen-presenting cells (APCs) that initiate t-cell response - dendritic cells take up the antigens via phagocytosis, present in MHC (class II to begin with) and migrate to the t-cell zone of the lymph node (centralized hub) 3) t-cell activation - in the lymph nodes, naive CD4+ and CD8+ exist within concentrated regions - the dendritic cells bind to the fibroblastic reticular cell (FRC) network and are scanned by naïve CD4+ and CD8+ T cells - if the TCR on a CD4+ t-cell matches the antigen in MHC class II on APC then a synapse forms between the naive CD4+ T cell and the APC - If the TCR matches the antigen (signal 1) and the T cell is recognizing the correct MHC AND there are co-stimulatory molecules (signal 2) THEN the T cell starts to activate 4) cytokine influence - signal 3 is when cytokines produced by the APC and other immune cells dictate how the CD4+ t-cell will differentiate

Answer 49

signals 1 and 2 are responsible for PROLIFERATION - signals 1 and 2 cause an increase in survival signals and increased production of IL-2 and IL-2 receptor - this causes robust proliferation, producing lots of clones of the original activated t-cell with the same TCR (who will recognize the antigen in the infection) - daughter cells can become memory cells that can self renew (live for month) OR terminally differentiated effector cells (live for weeks)

Answer 50

CYTOKINES are the 3rd signal and are responsible for the type of CD4+ t-cell it will become - PRRs on the surface of the APC and other cells will sense PAMPs from the pathogen - this PRR/PAMP binding triggers cytokine production - the cytokines produced depends on which PRRs are activated - cytokines are sensed by the CD4+ t-cells and will change how the t-cell responds to infection

Answer 51

- cytokines are small signalling protein that are released from cells to communicate within the immune system - they act by binding to specific receptors on target cells, triggering signaling pathways that regulate immune cell behaviour and determine their function. - there are many subtypes of helper T cells, so cytokines in the surrounding environment tell the cell what to become

Answer 52

polarizing cytokines: - are proteins from the surrounding environment that influence t-cell differentiation - they guide the naïve T cell to become a specific helper T cell subtype by activating particular transcription factors, which regulate gene expression. and tell them what helper cell to become by activating certain transcription factor that regulate expression --> determine what type of helper T cell a naïve T cell will become effector cytokines: - are the cytokines produced by differentiated t helper cells - responsible for executing the immune response (i.e promote inflammation) --> are the active molecules that carry out the immune response once the T cell has differentiated.

Answer 53

master regulators are transcription factors that, once activated, control protein synthesis within the T-cell and determine the t-cell's function by regulating the expression of specific genes. --> different cytokines can activate different master regulators, which then guide the differentiation of T-cells into distinct subtypes

Answer 54

Th1 and Th2 CD4+ helper cells have opposing roles in the immune system - the immune system will prefer to develop Th1 or Th2 responses based on the pathogen; usually one dominates --> Th1 promotes immunity against intracellular pathogens and produce IFN-gamma which suppresses Th2 development --> Th2 are involved in defence against extracellular pathogens and produce IL-10 which suppresses Th1 development The ability of Th1 to suppress Th2 and Th2 to suppress Th1 ensures a balanced immune response, preventing excessive inflammation or inadequate defence.

Answer 55

Th1 response combats intracellular pathogens by inducing cell-mediated immune responses (i.e activating phagocyte) and activating CD8+ t-cells for killing infected cells - PAMPs from intracellular pathogens are detected by PRRs on APCs, triggering production of polarizing cytokines like IL-12 - the APC presents the pathogen's antigen on its MHC class II molecule, and co-stimulatory molecules (CD80/86) on the APC binds to CD28 on the CD4+ T cell, leading to activation. - upon activation, the APC releases Th1-polarizing cytokines such as IL-12, which acts as Signal 3 in T cell activation. This ensures that the CD4+ T cell will proliferate and differentiate into a Th1 helper T cell - the Th1 CD4+ T cell produces IFN-gamma and TNF, which have several important effects such as activating CD8+ t-cells and promoting inflammation (macrophages)

Answer 56

Th2 response combats extracellular pathogens by recruit and activate inflammatory cells (i.e. mast cells, basophils) - extracellular pathogens (PAMPS) are sensed by PRRs on the surface of the APC, triggering production of polarizing cytokines like IL-4 - The APC presents the pathogen’s antigen on its MHC class II molecule, and co-stimulatory signals (CD80/86 binding to CD28) activate the CD4+ T cell. - upon activation, the APC releases Th1-polarizing cytokines such as IL-4, which acts as Signal 3 in T cell activation. This ensures that the CD4+ T cell will proliferate and differentiate into a Th2 helper T cell. - Th2 CD4+ T cells produce IL-4, IL-5 and IL-13 which encourages production of IgE antibodies from b-cells (basophils and mast cells) all helpful to control worm infections

Answer 57

Th1 CD4+ T cell produces effector cytokines that: - Encourage cross-presentation of antigens in MHC class I = allowing CD8+ T cells to recognize antigens - Can provide co-stimulatory molecules (CD40L) to bind CD40 on CD8+ T cells to help with CD8+ T cell activation = provide 2nd signal to promote activation - Produce IL-2 to cause CD8+ proliferation - Produce IFN-gamma that aids in CD8+ T cell differentiation into cytotoxic T cells *CD8+ t-cell can activate in the absence of CD4 helper cell, but efficiency would be dramatically reduced

Answer 58

- activated killer t-cells (CD8+) will leave the lymph node and circulate through the body and go to the site of infection/tissue to do their job - activated helper t-cells (CD4+) move to where they are needed, depending on the type of helper cell, to help mediate the immune response

Answer 59

- memory t-cells react faster and mount a stronger immune response than naive t-cells if the body is re-exposed to a pathogen - memory cells are positioned at locations where they were most useful in the past - once re-exposed to the same pathogen, memory T cells are re-activated = a faster and more efficient immune response. - their ability to "remember" past infections provides long-term immunity and forms the basis for vaccination

Answer 60

- after activation of a t-cell, there is rapid clonal expansion and production of effector cells that contribute to controlling the infection - after the pathogne is cleared from the body, approx. 90-95% of t-cells die by apoptosis --> if they all stayed, it would be a waste of resources and cause damage to the body - the remaining 5% of effector cells remain as antigen-specific memory t-cells - these cells persist long after the infection is gone and are key to immune memory.

Answer 61

cytotoxic T lymphocytes (CTLs) are CD8+ T-cells that can specifically recognize and kill virus infected cells - the only way to eliminate a virus infection is to kill all the virus infected cells! - CTLs represent the third wave of antiviral responses within the body

Answer 62

1) type 1 IFNs 2) NK cells 3) CD8+ CTLs

Answer 63

1) activation 2) recognition 3) killing

Answer 64

1) type 1 IFNs are produced within minutes to hours after infection = FASTEST - production of interferon stimulated genes (ISGs) produce an antiviral state - they also recruit NK cells 2) NK cells recognize virus infected cells and kill by apoptosis (capable of killing low level infection) - NK cells control the virus until cytotoxic t lymphocytes (CTLs) are generated. *Virus infections can be managed by IFNs and NK cells alone in some cases, without CTLs*

Answer 65

- sequential - simultaneous

Answer 66

1) The CD4+ (helper) T cell binds to the APC first, which licenses (activates) the APC to cross present antigens in MHC class I for CD8+ T cell recognition. 2) The APC then binds to the naive CD8+ T cell, providing: - antigen in MHC class I for the TCR binding (Signal 1) - CD80/86 binding to CD28 for co-stimulation (Signal 2) - Cytokines to support activation (Signal 3) 3) The activated CD8+ T cell undergoes clonal expansion (rapid mitosis) and differentiates into a mature CTL or memory cell

Answer 67

1) CD4+ t-cell and naive CD8+ t-cell bind to the APC at the same time - The CD4+ T cell is not directly stimulated by the APC at this point. Instead, it assists in the activation of the CD8+ T cell 2) CD4+ T cell licenses the APC to present antigens in MHC class I via the release of cytokines. the remaining 2 signals occur: - CD80/86 binding to CD28 for co-stimulation (Signal 2) - the CD4+ T cell releases IL-2 (signal 3) 3) the CD8+ t-cell undergoes clonal expansion (rapid mitosis) and differentiates into a mature CTL or memory cell *APCs can express multiple MHC (class I and class II) and can interact with various immune cells at the same time*

Answer 68

- once activated, the mature effector CD8+ t-cells (CTLs) leave secondary lymphoid organs and circulate through the bloodstream - they enter inflamed tissues through chemokine gradients produced by resident cells at the site of infection or inflammation - inside the tissue, CTLs continuously scan for infected or abnormal cells by checking for specific antigens displayed on their MHC class I molecules - If a CTL encounters a cell displaying an antigen that matches their TCR, it forms a synapse with that cell --> CTLs do not need 3 signals to activate to kill, 1 signal (MHC class I with Ag binding TCR) is sufficient as its already soooo specific

Answer 69

Before killing, the CTL forms a tight synapse with the target cell through a process known as the "kiss of death", where the CTL and target cell make close contact, ensuring that killing happens specifically at the right site (one at a time) 1) Granule Exocytosis: - CTLs release perforin and granzymes into the synapse. - Perforin creates pores in the target cell membrane. - Granzymes enter the target cell through these pores and activate the caspase cascade, leading to apoptosis (programmed cell death). 2) Receptor-Mediated Apoptosis: - target cells express death receptors (such as Fas) that can trigger apoptosis when activated. - CTLs express death ligands (like FasL) that bind to the target cell’s death receptor. - the binding between the death receptor and death ligand triggers the apoptotic pathway, causing the target cell to undergo programmed cell death.

Answer 70

- important because cells may have mechanisms that resist one form of killing --> i.e remove death receptors --> i.e prevent perforin from poking holes - some pathogens can evolve strategies to evade immune response so multiple killing pathways makes it harder to develop resistance - if one pathway is compromised than the other pathway can still function

Answer 71

- CTLs make cytokines, such as IFN-Gamma - IFN gamma will stimulate macrophage activation and inflammation - macrophages will phagocytose apoptotic bodies and promote repair/healing following CTL killing of virally infected cells