TBL 9 Intro to Immunology Flashcards
The primary organs of the immune system include the ________ and the ________.
bone marrow and thymus
The secondary organs of the immune system include:
Tonsils, lymph nodes, spleen and peyer’s patches
The bone marrow contains ___________ stem cells, which will differentiate into _______ progenitor cells and _______ progenitor cells.
Hematopoietic stem cells which will differentiate into myeloid progenitor cells and lymphoid progenitor cells
The _________ mature in the bone marrow, whereas the ________ mature in the thymus.
B lymphocytes mature in the bone marrow; T lymphocytes mature in the thymus
The ______ progenitor cell lineage gives rise to red blood cells, platelets, neutrophils, eosinophils, basophils, monocytes and macrophages.
myeloid
The ________ progenitor cell lineage gives rise to T lymphocytes, B lymphocytes and natural killer cells.
lymphoid
Neutrophils are phagocytes, and they account for 50-70 of circulating WBCs. They circulate in the ______.
blood
T-lymphocytes can give rise to three main types of T-cells.
1) Cytotoxic T cells
2) Helper T cells
3) Regulatory T cells
________ cells are part of the lymphoid progenitor lineage, and function to identify and kill virus-infected cells and tumor cells.
NK cells
_______ are Y-shaped proteins, produced mainly by plasma cells. They function to neutralise pathogens.
Antibodies
The ________ system involves a series of enzymes that are sequentially activated to result in the lysis of infected cells and bacteria.
complement
_______ are small secreted proteins produced by cells that have specific effects on cell-cell interactions, cellular communications or on cell behavior.
Cytokines
The first line of defense involve exterior barriers such as the ____, _______ and secretions.
skin, mucous membranes and secretions
The ______ of the skin forms a shield against invaders and secrete chemicals that can kill potential invaders.
epidermis
Foreign particles that are inhaled will be stuck in ______ and hair-like structures known as ____ will sweep this into the throat for coughing or swallowing.
stuck in mucus; hair-like structures known as cilia will sweep the mucus
The second line of defense involves ______ immunity, through the functions of (cells).
innate immunity through phagocytes and other myeloid cells
Virus-infected body cells will release ________ when an invasion occurs. This is a chemical that interferes with the ability of viruses to attack other body cells.
interferons
________, a chemical, will cause the capillaries to dilate, pyrogens to be released, pain receptors to be activated and WBCs to flock to the infected area. (i.e. inflammatory response)
Histamine
The third line of defense in the immune system involves ________ immunity.
adaptive immunity
Under adaptive immunity, T-lymphocytes will trigger __________ immune response, by recognising the peptide antigen on APCs and differentiating into effector cells that are able to kill infected cells.
cell-mediated immune response
Under adaptive immunity, B-lymphocytes mediate the _______ immune response. This is coupled with the antibodies, that eliminates extracellular microbes and their toxins.
Humoral immune response
Innate immunity depends on pre-formed cells, while adaptive immunity depends on _________.
clonal selection and proliferation
Innate immunity starts (faster/slower) than adaptive/acquired immunity.
faster
Granulocytes include _______, _______ and ______.
Neutrophils, eosinophils and basophils
________ have a multi-lobed nucleus.
Neutrophils
_______ have a kidney-shaped nucleus and is agranulated.
Macrophages
While the innate immunity is not specific to the type of pathogen, pathogens are recognised by receptors of immune cells using __________.
PAMPs (Pathogen-associated molecular patterns)
Primary lymphoid organs (i.e. bone marrow and thymus) are sites of _______.
lymphopoiesis (production of B and T lymphocytes)
Secondary lymphoid organs are sites of lymphocytic interactions with antigens and other lymphocytes.
-
Mature B lymphocytes are passed from the _________ into the (blood/lymph/both), and recirculation will occur between the peripheral lymphoid organs and the vessels.
passed from the bone marrow into the blood
Mature T lymphocytes are passed from the ________ into the (blood/lymph/both), and recirculation will occur between the peripheral lymphoid organs and the vessels.
passed from the thymus into both the blood and lymph
The _____ of the thymus is the outer region of the lobule. It is the site of earliest events in thymocyte development, including the T-cell receptor gene rearrangement and positive selection.
Cortex
The _______ of the thymus is the central region of the lobule. It is the site of later events in thymocyte development.
medulla
The Hassall’s corpusules is in the ______ of the thymus, and contains ________ (cell) involved in the development of regulatory T lymphocytes.
The Hassall’s corpusules is in the medulla of the thymus, and contains fibroblasts involved in the development of regulatory T lymphocytes.
The lymph nodes are encapsulated kidney-shaped organs. The outer area, known as the _______, is made up of B-cells which stick together to form lymphoid ______.
The outer area is known as the cortex. It is made up of B-cells that stick together to form lymphoid follicles.
When an antigen has been captured, the lymphoid follicle enlarges, containing a ________, which is a massive proliferation of B cells as a result of clonal expansion.
germinal center
The deeper parafollicular cortex (in between the medulla and the cortex of the lymph node) contain ___ cells, where they interact with dendritic cells.
T-cells
The ____________ allows for B and T cells to leave circulation in the blood and enter the lymph node.
high endothelial venule (HEV)
The spleen consists of the ____ pulp and the _____ pulp.
red pulp and white pulp
The ___ pulp of the spleen removes old RBCs and holds a reserve of blood. It also contains _______ (cell) for the opsonisation of any antigens found.
red pulp; macrophages
The ____ pulp of the spleen synthesises antibodies, and removes antibody-coated bacteria. It contains the (cell) and immediately surrounds the splenic arteries.
white pulp; T and B lymphocytes
The white pulp consists of the ________, which holds T-cells. It also consists of the _______, containing B cells.
white pulp:
1) primary follicles (B cell area)
2) Periarterial lymphatic sheath (T-cell area)
_________ are areas of aggregated lymphocytes present in the gut-associated lymphoid tissue (GALT).
Peyer’s patches
The GALT where most lymphocytes are found, feed into the ______ lymph node.
mesenteric lymph node
______ (Cell) are found above the Peyer’s patches, taking up antigens from the intestinal lumen and passed into the Peyer’s patch below to initiate the immune response if required.
Microfold (M cells)
The cutaneous immune system in the skin is made up of epidermal ________ cells and _________ lymphocytes.
cutaneous immune system: epidermal Langerhans cells and intraepidermal lymphocytes
In the villi of the gut, _______ lymphocytes are found.
intraepithelial lymphocytes
The ______ of the skin contain T lymphocytes, resident macrophages and dermal dendritic cells.
dermis of skin
________ of lymphocytes in the body is important as it increases the chances of a lymphocyte meeting its specific antigen.
Recirculation
When the resident dendritic cell in the tissue takes up the pathogenic antigen, it will migrate to the draining lymph to the regional lymph node, and present the antigens to the __ cells present in the node. T-cells arrive in the lymph nodes via recirculation, and keep on circulating in their blood and lymph until they meet their specific antigen and becomes activated lymphocytes.
T-cells
________ of naive T-cells refers to the process by which T-cells leave the high endothelial venule of blood vessels to the lymph nodes during recirculation.
Extravasation
________ present on the endothelial cell of the blood vessels can be recognised by the receptors on the T-cell. This increases the affinity of _______ on T-cell for the molecules on the endothelial cell, leading to increased adhesion. Trans-endothelial migration occurs, where T-cells can squeeze through the endothelium into the lymph nodes.
Chemokines present on the endothelial cell of the blood vessels can be recognised by the receptors on the T-cell. This increases the affinity of integrins on T-cell for the molecules on the endothelial cell, leading to increased adhesion. Trans-endothelial migration occurs, where T-cells can squeeze through the endothelium into the lymph nodes.
Chemokine signals present on the endothelial cells are governed by ______ on the surface of these cells.
selectins
All T-lymphocytes express the marker ____.
CD3
Two classes of TCRs are expressed:
1) _____
2) _____
1) aB receptor (more common)
2) yd receptor (less common)
____ T-lymphocytes are known as T helper cells or regulatory cells. They mainly function to secrete cytokines.
CD4
____ T-lymphocytes are known as cytotoxic T-cells, which mainly function to lyse infected cells and secrete cytokines.
CD8
The reason why elderly finds it more difficult to survive new infections is because:
Thymic output of T-cells declines with age, causing the production of new T-cells to decline. There is therefore slower adaptive immune response.
T-cells only recognise _______ antigens i.e. antigens presented by MHC molecule in APCs
processed
B-lymphocytes all express 2 types of markers.
CD19 and CD20
B-lymphocytes express _____ MHC molecule, allowing them to act as APC to T-cells.
Class II
________ cells are antigen presenting cells that are widely spread in skin and mucosal tissues. They capture intact antigens and process them to present to _____.
Dendritic cells; present to T-cells
_________ cells are present in lymph node follicles, and they capture intact antigens to present to ______.
Follicular dendritic cells; B-cells
Monocytes is the largest type of leukocyte, which can differentiate into ________ and ________.
macrophages and dendritic cells
Phagocytic cells (include _______ and _______) engulf the microorganism by extending their ________.
Macrophages and neutrophils; extend their pseudopodia
Neutrophils are circulating in the ______ whereas macrophages are dispersed throughout the _______.
Neutrophils - blood; macrophages - tissues
Neutrophils move into tissues from the bloodstream by ______ and ______. (processes)
diapedesis and chemotaxis
Neutrophils move into tissues by diapdesis and chemotaxis.
- Pathogens secrete PAMPs which affect the ______ of the blood vessel, causing it to express certain ligands recognised by the neutrophil.
PAMPs affect the endothelium of the blood vessel
Neutrophils movement by diapdesis and chemotaxis:
- When ______ on the neutrophils is activated by chemokines, they switch to high affinity state. This causes neutrophils to stop rolling along the endothelium, and bind to ______.
integrins on neutrophils are activated by the chemokines produced by the endothelium –> cause neutrophils to bind to selectin
________ is the process where neutrophils squeeze through the endothelium and into the tissue.
It follows the concentration gradient of chemokines in the tissue. This is known as ______, which directs neutrophils to the site of infection.
Diapdesis; chemotaxis
When many neutrophils become activated, an abscess filled with ___ may form. This is a form of inflammation.
pus
_______ refers to the coating of micro-organisms with proteins to facilitate phagocytosis. Neutrophil activity is much more efficient this way.
Opsonisation
Micro-organisms to be phagocytosed are opsonised and marked with an _______.
antibody
Phagocytes have ______ and ______ receptors on their surface, allowing them to bind closely to the opsonised pathogen.
complement and antibody receptors
Neutrophils kill by either oxygen-independent or oxygen-dependent mechanisms.
Oxygen-independent includes ______ or antimicrobial peptides.
Oxygen-dependent includes respiratory burst toxic metabolites and reactive nitrogen intermediates.
enzymes (oxygen-independent)
Macrophages function to signal infection whenever it occurs by secreting soluble mediators known as ______.
cytokines
Macrophages express different types of receptors known as ________ (PRRs). These include NOD-like receptors and ______ receptors.
PAMPs recognition receptors
e.g. toll-like receptors
PAMPs are characteristic to microorganisms. Examples include ______ and ______.
liposaccharide and flagella
Bacteria or pathogen binding to macrophage receptors initiates a response to release cytokines, which then signal to other immune cells that an infection is occuring. Macrophages can then phagocytose the bacteria.
-
Cytokines exert (short-lived/long-lasting) effects and are generally localised within the tissue. It is initiated at (very low/high) concentrations.
short-lived; very low concentrations
There are 5 different classes of cytokines.
Interferons, interleukins, growth factors, cytotoxic and chemokines
_______ (cytokine) are secreted by virus-infected cells and have anti-viral effects by interfering with viral replication.
Interferons
_______ (cytokines) act as messenger molecules between leukocytes.
Interleukins
_______ (cytokine) is involved in chemotaxis and movement of immune cells.
Chemokines
_________ (cytokine) is involved in growth and proliferation of immune cells.
growth factors
Macrophages secrete 5 different important types of cytokines.
IL-1, IL-6, IL-8, IL-12 and TNF-a
___ (cytokine) secreted by macrophages serves as an alarm cytokine that eventually results in fever response.
IL-1
____ (cytokine) secreted by macrophages serves as acute phase inflammatory proteins in the liver. It therefore exerts an (autocrine/endocrine/paracrine) effect.
IL-6; endocrine (distant organ)
____ (cytokine) secreted by macrophages serve as a chemokine for neutrophils.
IL-8
____ (cytokine) secreted by macrophages directs adaptive immunity and activates NK cells.
IL-12
___________ is when there is systemic infection of bacteria around the entire body, due to massive release of TNF-a and IL-1 by activated macrophages (alarm cytokines) caused by bacterial endotoxins.
Bacterial septic shock
The complement system is part of the innate ________ immunity.
humoral (soluble)
The complement system is temperature-specific. At higher temperatures, the activity of complement is halted, so bacteria cannot be lysed.
-
The complement system complements the activity of _______ to cause the lysis of ____.
antibodies; bacteria
The complement system works as a triggered ______ cascade system that produces a rapid, highly amplified response.
enzyme cascade
Components are produced mainly in the ____, but also by monocytes and macrophages. They are produced as inactive precursors, and have to be activated to mount an immune response.
liver
There are 3 pathways to activate the complement system, and they all converge at ___ leading to the final common pathway, ending with the formation of a _________ complex that leads to cell lysis.
converge at precursor C3b which can finally lead to formation of membrane-attack complex (MAC)
The Classical pathway for activation of complement system is initiated by _________.
antigen-antibody complexes
The alternative pathway involves the direct activation of _______.
pathogen surfaces
The mannan-binding lectin pathway involves antibody-independent activation of the Classical Pathway by lectins that bind to _______ on the pathogens.
carbohydrates
In the lectin pathway, the two types of lectins which bind to the bacterial surface are ______ and _______.
MBL (mannose-binding lectin) and CRP (C-reactive proteins)
The MAC will be inserted into the (organelle) of the bacteria, contributing to their death by lysis.
outer cell membrane
Complement system is controlled by 3 factors.
1) Lability of component (quick turnover rate - effect not long-lasting)
2) Dilution of component (low concentration)
3) Specific regulatory proteins
The cleavage of precursors in the complement activation pathway results in the formation of ________ molecules.
pro-inflammatory
____ cell secretes histamine and other inflammatory mediators like cytokines.
Mast cells
Mucosal mast cells are found in the ____, whereas ________ mast cells are found in the skin and peritoneal cavity near blood vessels.
Mucosal mast cells - lungs
connective tissue mast cells - skin
Mast cells can recognise, phagocytose and kill bacteria, and are activated by complement products called _________.
anaphylatoxins
An inflammatory response typically results in (vasoconstriction/vasodilation) and (increased/decreased vascular permeability).
vasodilation; increased vascular permeability
The Mannan-binding lectin can also serve as ______ for monocytes.
opsonin
______ cells are large granulated lymphocytes which are cytotoxic in nature.
Natural killer (NK) cells
NK cells secrete _________, which is a cytokine that has anti-viral properties.
Interferon-y
NK cells do not possess antigen-specific receptors, but it expresses both ________ and _________ receptors which will help NK cells recognise the type of cell they are binding to.
activating and inhibitory receptors
(Activating/inhibiting) receptors on NK cells will lead to NK cell activation and lysis of target cell,
Activating
___________ is important in the defence against tumor cells and viral infections. NK cells possess receptors to bind to antibody-coated cells so that they can lyse cells that have been infected.
Antibody-dependent cellular cytotoxicity (ADCC)
The main function of T lymphocytes is the destruction of (intracellular/extracellular) pathogens.
intracellular
____ polypeptides are associated with all TCR molecules on the cell surface, and it functions to deliver signals from the TCR which will activate the T lymphocyte.
CD3
CD4 T cells use CD4 co-receptors and they recognise peptide antigens presented on MHC Class __.
Class II (i.e. they are class II restricted.)
CD8 T-cells recognise peptide presented on MHC Class __.
Class I
In T cells, the ___ binds directly to the antigen-MHC complex, while the CD4/CD8 co-receptors binds to the ______.
TCR binds to antigen-MHC complex; CD4/CD8 co-receptors bind to MHC class molecules.
CD4/CD8 co-receptors directly binds relevant MHCs to increase the avidity of T-cell target cell interaction, which is important in signalling.
-
In the case of _____ cells (a type of T cell), the TCR binds to the antigen-MHC complex directly on an antigen-specific B-cell, as it functions to help B cells produce antibodies.
TH2
_______ T-cells directly lyse target cells and secrete cytokines. It induces apoptosis in the target cell.
CD8 Cytotoxic T cells
_______ cells kill cells by secreting cytokines. They recruit effector cells of innate immunity to remove pathogens and activate macrophages to clear pathogens. They also amplify and help with cytotoxic T cell and B cell responses.
CD4 T helper cells
Development of T lymphocytes occurs in the _________, after being produced in the ________.
Development/maturation of T lymphocytes occurs in the thymus, after the precursors are being produced by the bone marrow.
When precursor T cells first arrive at the thymus and are held at the (cortex/medulla), they are __________ cells. This means that they express neither CD4 or CD8 co-receptors.
first held at the cortex (outer region);
double-negative cells
In the outer cortex, the genes coding for TCR begin to rearrange, forming a pre-TCR.
-
After forming a pre-TCR for T cells in the cortex of the thymus, the cell pre-TCRs are tested on ___ molecules to see if they can recognise them.
MHC
If the pre-TCR T cells pass the MHC checkpoint in the cortex, they will express both CD4 AND CD8 co-receptors. This is known as __________ T-cell. This occurs in the _____ of the thymus.
double-positive; occurs in the cortex of the thymus
Further maturation and selection of double-positive T-cells will occur in the ________ of the thymus, where it results in the formation of mature T-cells either expressing CD4 OR CD8 coreceptors. These are known as ________ cells.
occur in the inner medulla of the thymus; forming single-positive T-cells.
Genetic rearrangement of TCR a and B gene chains to generate new TCRs occur in the _____ of the thymus.
cortex of the thymus
In the alpha chain of the TCR gene, there are 2 segments for recombination
V and J
In the beta chain of the TCR gene, there are 3 segments for recombination.
V, D and J
Upon genetic rearrangement of the TCR genes, pre-TCR are checked for functionality and reactivity.
_______ selection refers to TCRs which recognise MHC relatively weakly, and it’ll receive a signal to survive.
________ selection refers to TCRs which strongly recognises self-antigens, and will receive signal to die by apoptosis.
Positive selection - TCRs recognises weakly
Negative selection - TCRs recognises self-antigens strongly
_____ genes are the most important segments controlling transplant acceptance or rejection.
MHC
MHC Class __ are the transplantation antigens.
Class I
MHC Class __ are the immune response genes, which control the ability to mount an antibody response.
Class II
MHC Class I molecules consist of two separate polypeptide chains - a (large/small) alpha chain and a (large/small) B chain.
1 large alpha chain;
1 smaller beta chain
The large alpha chain of the MHC class I molecule is divided into 3 domains, whereas the smaller B chain only has one domain.
The ___ and ___ domains are the antigen-binding and presentation segments.
The __ and __ domains are immunoglobulin-like regions.
a1 and a2 domains - antigen binding and presentation
b1 and a3 - immunoglobulin-like regions
MHC Class II molecules consist of two equally-sized polypeptide chains, each divided into 2 domains.
The __ and __ domains are the peptide binding and presentation segments.
a1 and B1 domains - antigen binding and presentation
TCRs recognise the peptide binding regions of each MHC class, whereas co-receptors of T-cells recognise ___ domain in class I and ___ domain in class II.
Co-receptors recognise the a3 in class I and B2 in class II
MHC Class I is expressed in (what type) of cells. Its expression is altered during infection by cytokines. (e.g. Interferons that induce class I production to present viral antigens)
all nucleated cells
MHC Class II is expressed only on ______ cells. Its expression is strongly influenced and regulated by cytokines.
professional APCs (dendritic cells, macrophages and B cells)
(Endogenous/Exogenous) antigens are antigens that are synthesised inside cells, and are recognised by _______ T-cells and MHC ____).
Endogenous (inside cells);
recognised by CD8 cytotoxic T-cells and MHC Class I.
(Endogenous/exogenous) antigens are antigens captured from outside cells via phagocytosis, and is recognised by ____ T-cells and MHC ____
Exogenous; recognised by CD4 T-helper cells and MHC class II.
T lymphocytes meet their antigens in _________ during recirculation.
secondary lymphoid organs
Antigens need to be transported to the secondary lymphoid organs from the site of infection to meet with the lymphocytes. _________ cells resident at the tissue picks up the antigen and travel via (afferent/efferent) lymphatic venules to the lymph nodes.
Antigen-presenting cells (APCs) e.g. dendritic cells pick up the antigen and travel via the afferent lymphatic venules to lymph nodes.
There are 3 signals needed for T-cell activation.
1a. [Antigen] Antigen binds to complementary TCR on T-cells.
1b. Constant region of MHC Class molecule binds to co-receptors CD4/CD8 on T-cells.
- [Costimulation] CD__ on T-cells bind to CD__ and CD__ on the antigen-presenting cells.
- APC secretes programming _____ to T-cells, to direct the differentiation of T-cells into the various subtypes according to the type of infection in the tissue.
- CD28 on T-cells bind to CD80 or CD86 on APCs.
3. APC secretes programming cytokines to direct differentiation of T-cells into the various subtypes.
Upon antigen recognition and co-stimulation, the T cell begins expression of the ___ (cytokine) receptors. They will then start secreting their own (cytokine) which act on their own receptors, inducing vigorous proliferation of selected cells.
IL-2
In infected tissues, T-cells have to meet their specific antigen again (known as restimulation), to exert their effector functions.
-
The T-helper cells can differentiate into 5 different specialised subtypes upon activation.
1) TH1
2) TH2
3) T regulatory cell
4) TH17
5) TFH (Follicular)
The TH1 cell is characterised by the production of _______ (cytokine), to hyperactivate macrophages to phagocytose bacteria that are hard to kill.
interferon-y
The TH1 cells will secrete 6 different cytokines.
1) Interferon-y (hyperactivate macrophages)
2) fas ligand (apoptosis)
3) IL-2 (proliferation)
4) IL-3 (macrophage differentiation)
5) TNF-a (induce diapdesis of macrophages)
6) CXCL2 (chemotaxis to cause macrophages to accumulate at the site of infection)
For bacterium that are very resistant to macrophage killing, TH1 cells then resort to containing the bacteria within _____ rather than killing them.
granulomas
hyperactivated macrophages fuse together to form multi-nucleated giant cells, which recruit TH1 cells
The formation of _______ when bacteria is resistant to macrophage killing functions to reduce immune activation and prevent the destruction of body tissue.
granulomas
The formation of granulomas is an (active/passive) process. It constantly recruits new T cells and macrophages.
active process
The centre of granulomas often contains necrotic cells due to the lack of vascularisation, and this forms a _______ necrosis.
caseous
Activated TH2 cells contribute to immune response mainly against ______ which are too large to be phagocytosed.
parasites
TH2 secretes cytokines IL-4, IL-3 and IL-5.
IL-4 and IL-3 bind to B cells to induce ____ (antibody) secretion, which can bind to parasites and mast cells.
IL-5 acts on progenitor cells in the bone marrow to induce _________ (cell) differentiation.
IL3/4: IgE;
IL-5: eosinophils
IL-5 secreted by ____ T-cells will induce eosinophils. differentiation. Eosinophils will move into the tissues and bind with (antibody) bound to the parasite, releasing enzymes and toxic proteins to kill the parasite.
TH2 cells; bind with IgE
(T-cell subtype) is involved in the pathology of allergy.
TH2
TH17 cells secrete ____ cytokines which act on fibroblasts or epithelial cells which secrete _______, to recruit neutrophils to the site of infection.
IL-17
TH17 cells which secrete IL17 might also induce the production of _______, which are small antimicrobial peptides, which will integrate into and lyse the bacterial cell membrane.
defensins
(T-cell subtype) contribute to immunoglobulin class switching and production of antibodies. It is defined mainly by tissue location - within _______ of secondary lymphoid organs, where they act on B lymphocytes.
TFH (Follicular Th cells);
germinal centers of secondary lymphoid organs
In the case of TFH cells, _________ act as the APCs when they present a processed antigen to the T-cell.
B-lymphocytes
When B cells present antigens to TFH, CD___ ligand binds to CD__ receptor on the B-cell, to give signal to B and T-cells to secrete cytokines which act on the B-cell.
CD40
_________ T-cells are involved in the suppression or reduction of immune reactions.
Regulatory T-cells
There are two types of regulatory T-cells, classified according to the locations that they are induced.
1) Thymus Treg - induced in the thymus to act against self-antigens, reducing immunity of other T-cells and minimising autoimmunity.
2) Peripheral Treg - induced in tissues during chronic inflammatory conditions, to reduce inflammation in these tissues.
Function of regulatory T-cells is dependent on the transcription factor ____.
FoxP3
______ (condition) may result from dysfunctional FoxP3. (no regulatory T cells)
They have strong autoimmune responses.
IPEX
Regulatory T cells can act on all the other types of T cells as well as dendritic cells.
It secretes cytokine _______ which binds to CD80 and CD86 molecules on dendritic cells, downregulating the expression of CD80 and CD86 by dendritic cells. This causes dendritic cells to no longer be able to bind to CD__ on T-cells.
cytokine CTLA-4 secreted by T regulatory cells, which binds to CD80 and CD86 on dendritic cells.
prevents CD28 on T-cells from binding, preventing T-cell activation
________ T-cells mainly kill virus-infected cells in the body.
Cytotoxic
When the cytotoxic T-cell meets the specific antigen, it uses _________ to attach to the target cell. The cytotoxic granules become focused near the interface and are released at the region of cell contact, acting only on the target cell
cytoskeleton redistribution to focus the granules
_______ is a protein which polymerise to form pores in the cell membrane of target cells. It is one of the effector molecules present in the cytotoxic granules released by cytotoxic T-cells.
Perforins
Perforins function to lyse the bacterial cell, and also allow _________ and ________ to enter the cytoplasm of target cells to exert their effects.
granzymes and granulysin
Granzymes include Granzyme A and B.
They are serine _______ (enzyme) which activate protease-inducing caspases, that in turn induce _______ in target cell.
They are serine proteases which activate protease-inducing caspases, that in turn induce apoptosis in target cell.
Granulysin induces apoptosis in the target cell. It has antimicrobial functions, and also acts as a _____ to recruit other T lymphocytes, monocytes and inflammatory cells.
Granulysin - acts as chemokine to recruit other immune cells
There are two independent pathways to target cell death by cytotoxic T-cells.
1) Granule exocytosis pathway
2) Fas-FasL pathway
In the Fas-FasL pathway, most cells express a molecule known as Fas. When Fas molecule meets its ligand, it induces a caspase to ultimately lead to apoptosis.
Fas ligand is expressed in activated cytotoxic T cells.
-
CD___ is much more abundant on memory T-cells compared to naive T-cells.
This is involved in the transmission of signals from the TCR and CD3 receptor to the interior of the cell.
CD45
CD__ and LFA-1 are adhesion molecules that anchor the memory T-cell to the APC, and transmit signals into the cell.
CD2 and LFA-1
Memory T-cells and naive T-cells differ in their composition.
Extracellular:
CD2, LFA-1, CD45
Intracellular: Lck and Bcl2
___ is a tyrosine phosphate, which floats around in naive T-cell. When it becomes activated, the __ molecule will bind to the CD4/8 molecules. In memory cells, these molecules are already associated, with higher expression of ____ and ____ (same signalling cascade as Lck) which activate transcription factors that lead to rapid transcription of genes.
Lck molecule
ERK1 and ERK2
Memory cells also express the anti-apoptotic protein ____ that enables them to survive for very long periods of time.
Bcl2
Central memory T-cells circulate through ________ (location), whereas effector memory T-cells and tissue-resident memory T-cells circulate through _______.
Central memory T-cells: secondary lymphoid organs
Tissue-resident memory T-cells: peripheral tissues (inflammation)
In central memory T-cells, there is expression of adhesion molecule ________ and the chemokine receptor ___.
L-selectin and CCR7
In tissue-resident memory T-cells, there is expression of other adhesion molecules like ________ and chemokine receptors ______ and ______.
adhesion molecules integrins;
chemokine receptors CXCR3 and CCR5
