Quail_Innate Immunity Flashcards

Question

What is the difference between the interaction of Leukocytes with the endothelium and the interaction of lymphocytes with the endothelium?

Answer 1

Leukocyte - Endothelium: Sialyl lewis + X glycan + epitope - E-/P-Selectin Lymphocytes - Endothelium: L-Selectin - Sialyl lewis + X glycan + epitope *Selectin is on the endothelium for leukocytes, but on the lymphocytes

Answer 2

- Irritation of nerves when inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain - Fluid influx into the tissue with increased vascular permeability causes increase in pressure

Answer 3

1. Pathogen is encountered   2. Recognized by PRRs (e.g.  NOD-like receptors, Toll-like  receptors)   3. Intracellular signalling  cascade is initiated   4. Three consequences:  1. Production of pro- inflammatory cytokines 2. Presentation of antigen  3. Initiation of co-stimulation 5. This engages the adaptive  immune system, and stimulates an immune response against the pathogen

Answer 4

1. Adipocytes become large, and undergo hypertrophy. 2. Hypertropic adipocytes release DAMPs into the microenvironment (when they dye, they spill their contents) 3. Causes recruitment of macrophages and formation of « Crown-Like Structures » (highly inflammatory) 4. CLS produce pro-inflammatory cytokines, creating chronic inflammation in obese individuals. *Obesity-Associated inflammation leads to adverse health conditions (e.g. cancer)

Answer 5

Viral genome entering the cells → disruption in ion balance and other factors → engage different sets of PRRs Chronic inflammation → higher baseline levels of pro-inflammatory cytokines already present in the cells (IL-1b) When caspase-1 is activated, many more pro-domains are present which induces a stronger response when all these cytokines are activated *higher levels of IL-1b are associated with severe COVID

Answer 6

GRAFT side: 1. Transplantation → cell lysis → release of DAMPs 2. DAMPs → inflammation and activation of TLRs 3. Inflammation → Changes in vasculature (adhesion molecules) 4. Inflammation → Activation of DCs 5. Inflammation → Cytokine production HOST side: - Activated DCs from the host → host T cell activation in the Lymph nodes - Cytokines from the graft donor → inflammation amplification in the host Can lead to increase risks of graft rejection

Answer 7

Vaccines contain virus or virus particles (PAMPs), or more recently, mRNA encoding parts of a virus. These are recognized by innate immune cells at the site of injection, which undergo pyroptosis. Spilling of the cell contents releases more PAMPs and DAMPs into the microenvironment to amplify the innate immune response. Interactions with PRRs on innate immune cells leads to 3 signals: production of pro-inflammatory cytokines, antigen presentation, and co-stimulation. This stimulates T cells, which interact with B cells to stimulate production of antibodies specific to the viral antigen → MEMORY *The insertion of a needle also creates tissue dammage (DAMPs) Innate immune cells undergo some for of trained immunity following a vaccine as well as the memory effect

Answer 8

1. Pattern recognition 2. Antigen presentation 3. Complement

Answer 9

- Enhances the ability of the immune system to clear pathogens and damaged cells - Plays a role in both innate and adaptative Pathogen exposure for the 1st time = Complement is activated by the pathogen in a non-specific manner Repeated pathogen exposure = Complement is activated by Ab-Ag complexes (recognizes Ab-Ag complexes)

Answer 10

The complement system is made up of a large number of different plasma proteins that interact with one another to opsonize pathogens and to induce inflammation. *Found in the fluid that comes into the tissue Complement proteins are produced by the liver as pro-enzymes. Exist as inactive enzymes in the blood and interstitial fluid at all times, and need to be cleaved in order to become activated. These cleavage events potentiate an immune response. Cleavage → a and b components - a component will lead to an anaphylaxic reaction - b component will continue to potentiate the complement cascade

Answer 11

C5a and C5b are key components of the complement system, each with distinct roles in immune responses. C5a → Anaphylatoxins, Chemotaxis - Inflammatory mediator, chemoattractant C5b → Continue to potentiate the pathway - Initiates MAC formation

Answer 12

The core complement proteins are named C1 to C9 and function as part of the complement cascade: 1) C1 complex – Composed of C1q, C1r, and C1s, which initiate the classical pathway. 2) C2, C3, C4 – Key components in all pathways. - C3 is the central protein of the system, with C3b playing a major role in opsonization. 3) C5, C6, C7, C8, C9 – These contribute to forming the membrane attack complex (MAC), leading to direct cell lysis.

Answer 13

- C1 and C6-9 are NOT cleaved - C6-9 are not enzymes *These are the end points of the complement cascade, make the whole thing relevant

Answer 14

C5b → initiates MAC formation → causes recruitment of C6 → assembles and causes recruitment of C7 → assembles and causes recruitment of C8 → goes into the plasma membrane → all the C9s form a ring The active MAC is made up of: 4 complement proteins, including C5b, C6, C7 and C8. These bind to the outisde of the plasma membrane. Multiple copies of C9, which form a ring like structure within the plasma membrane. - Hydrophobic external face to facilitate association with the plasma membrane. - Hydrophilic internal face to allow fluid to pass through. - C6 - C9 are all NOT cleaved - b subunit of C5 potentiates the response by engaging additional proteins, while C5a is free to act as a chemoattractant - contents of the cells getting out of the cell causes an inflammatory response

Answer 15

The MAC creates pores in the plasma membrane of an invading pathogen. This leads to exchange of fluids between the cell and the extracellular space - this is cytotoxic to the cell. This spills the contents of the cell into the microenvironment to potentiate the innate immune response (inflammatory response as the contents are full of PAMPs/DAMPs).

Answer 16

C3 The most important event is C3 activation (cleaved from pro-enzyme → C3a + C3b)

Answer 17

There are three complement pathways, which are are named based on how C3 cleavage is triggered (i.e. they are not fully distinct pathways). All complement pathways converge on C3 cleavage and the events that follow are common to all pathways. 1. Classical pathway (Antigen:Ab complexes) 2. Mb-lectin pathway (Lectin binding to pathogen surface) 3. Alternative pathway (pathogen surface) *ALL 3 cause C3 activation → C3 activation leads to the following (common to the 3 pathways) 1. Recruitment of inflammatory cells 2. Opsonization of pathogens 3. Killing of pathogens *After C3 everything is the same!!

Answer 18

Complement proteins patrol the blood and the tissues as inactive pro- enzymes. They become activated when they encounter a pathogen. → 3 pathways of complement activation 1. Classical pathway (Antigen:Ab complexes) 2. Mb-lectin pathway (Lectin binding to pathogen surface) 3. Alternative pathway (pathogen surface)

Answer 19

1. When a pathogen is encountered, C3 that is surveilling the tissue becomes activated (cleaved). 2. C3b binds/is deposited to the cell surface (starts opsinising the pathogen) of the pathogen —> flags to the rest of the body that this is a pthogen 3. Along with another factor called Bb, they form C3bBb = C3 convertase. 4. This cleaves more C3, providing more C3b. **C3bBbC3b = C5 convertase. 5. C5 convertase cleaves C5 into C5a and C5b. 6. C5b initiates formation of the membrane attack complex in the pathogen C3b will also facilitate clearance through a process called opsonization. - This basically ‘flags’ the pathogen for phagocytosis by innate immune cells such as macrophages, which express complement receptors (help PRRs!)

Answer 20

These are anaphylatoxins!! 2 functions: 1. Activation of mast cells, to release histamine through degranulation - This causes the bronchioles to constrict, and the endothelium to open up. 2. Attraction of neutrophils and other immune cells to the site of infection

Answer 21

C3bBb = C3 convertase C3bBbC3b = C5 convertase.

Answer 22

Most pathogens have mannose on their surfaces. This is bound by mannose binding lectin (MBL). Activation of the MBL occurs through binding with mannose, and associated proteins (MASPs) Activation of this structure causes cleavage: - C4 into C4a and C4b. C4b attaches to the cell surface of the pathogen - C2 into C2a and C2b. C2a binds to C4b.  The C4bC2a complex is another C3 convertase. This activates C3 cleavage *C3b feeds into the amplification loop to generate C5 convertase, and initiate the membrane attack complex

Answer 23

It is a complex formed in the Lectin pathway of complement activation C3 convertase → activates C3 cleavage → C3b feeds into the amplification loop to generate C5 convertase, and initiate the membrane attack complex

Answer 24

The classical pathway involves adaptive immunity(!!). After prolonged infection, the body starts to develop antibodies against specific antigens. When Ab bind Ag, complement proteins can help expedite the response. → The C1 complex binds to Ab-Ag pairs - this causes activation Initiated by the binding of the C1 complex (C1q, C1r and C1s) to bound antibody. C1r activates C1s which first cleaves C4 and then cleaves C2 leading to the formation of the classical pathway C3 convertase (C4bC2a).

Answer 25

- C4 into C4a and C4b. C4b attaches to the cell surface of pathogen (ex: bacterial surface) - C2 into C2a and C2b. C2a binds to C4b The C4bC2a complex is another C3 convertase. This activates C3 cleavage. *C3b feeds into the amplification loop to generate C5 convertase, and C5 initiate the membrane attack complex

Answer 26

The complement pathways have different names based on how C3 cleavage is triggered (i.e. they are not fully distinct pathways). - Alternative pathway: C3 is cleaved in response to the pathogen. - Lectin pathway: C3 is cleaved in response to upstream events that follow MBL-  mannose interactions. - Classical pathway: C3 is cleaved in response to upstream events that follow Ab-  Ag interactions.  

Answer 27

The initial triggering event depends entirely on the composition of the cell surface of the pathogen. The alternative pathway is always active, and constantly deposits C3b onto all cell surfaces. Host cells deactivate these C3b molecules to avoid complement-mediated destruction (“don’t eat me” signal). However, there are also “eat me” signals (i.e. MBL-mannose or Ab-Ag, for the lectin and classical pathways, respectively). These pathways are only activated when those specific patterns are detected on the cell surface of the target cell. Ex: CD47 - Expressed on cells that are ‘self’ - Elevated in cancer - Not expressed once the cell dies

Answer 28

1. Lysis (membrane attack complex) 2. Opsonization (binding to pathogen surface to help phagocytes) 3. Activation of inflammatory response (Chemoattraction + Anaphylaxis) 4. Clearance of immune complexes(assist with adaptative immunity)

Answer 29

- Histamine release - Bronchiole constriction - Vasodilation *Part of the activatio of inflammatory response

Answer 30

1. Activation of the complement classical pathway 2. Mediates T cell activation in response to Pattern Recognition

Answer 31

In peripheral tissue: 1. Immature DCs recognizes PAMPs and beocme activated 2. TLR signaling indces CCR7 and enhances processing of pathogen-derived antigens In Lymph Nodes 3. DCs migrate to the draining lymph nnodes via CCR7 4. DCs present antigenic peptides on MHC to naive T cells in the lymph node *3 signals are required

Answer 32

Major Histocompatibility Complex (MHC) molecules → determine compatibility between individuals. - Peptide-binding glycoprotein molecules - Interaction via the TCR Expressed on the cell surface: - Class I = expressed by all cells except RBCs - Class II = expressed by ‘professional’ APCs *Class II expression is induced by Pattern Recognition Receptors

Answer 33

1. Antigen processing (need to phagocytose it) 2. Antigen presentation (via MHC)

Answer 34

Class I: Glycoproteins expressed on the surface of nearly all nucleated cells. Major function is to present endogenous (intracellular) antigens to cytotoxic T cells (CD8+) Class II: glycoproteins expressed primarily on APC (Dendritic cells, Macrophages and B cells). Major function is to present exogenous (extracellular, phagocytosed) antigens to helper T cells (CD4+). Class III: proteins that have immune functions including components of complement (C2, C4) and inflammation

Answer 35

HLA (Human Leukocyte Antigens): HLA-A, HLA-B, HLA-C (found on all nucleated cells) - Intracellular antigens are processed for presentation by MHC-I (in the cytosol) *location of the antigen matters for what type of MHC will present it

Answer 36

1.MHC will encounter an antigen in the ER where MHC it is synthesized and held open by calnexin 2. Antigen is brought to the ER (from cytosol) via TAP 3. MHC-Antigen complexe are transporter via a secretory vesicle from the ER to the plasma membrane

Answer 37

They do so through a transporter (TAP1) which delivers cytosolic proteins to the ER TAP = Transporter associated with antigen processing

Answer 38

MHC-II is only expressed on professional APCs (ex: DCs) MHC-I = intracellular antigens MHC-II = Extracellular antigens → internalized/phagocytosed and processed for presentation by MHC-II Meanwhile, MHCII is synthesized in the ER. Class II-associated invariant chain peptide (CLIP) binds MHCII and remains bound until it is exchanged for Ag. This prevents binding of self-Ag Unlike MHCI, MHCII encounters the antigen in the lysosome (not the ER, APCs degradepathogens within lysosomes). After Ag binding, they are transported to the plasma membrane to present antigen to CD4+ T cells (not CD8+ T cells)

Answer 39

MHC-I = alpha 1, apha 2, alpha 3, b2 - alpha 3 = single TM domain - alpha 1 and alpha 2 = peptide-binding cleft MHC-II = alpha 1, alpha 2, beta 1 beta 2 - 2x TM domains = alpha2 + beta2 - peptide-binding cleft = alpha1 + beta1

Answer 40

In humans, the HLAs corresponding to MHCII are HLA- DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, HLA-DR.

Answer 41

1. What type of cell they are? (if they aren't a professional APC, they have no other choice than MHC-I) - If professional APC, have both options 2. Where is the pathogen encountered? Intracellular → MHC-I Extracellualr → MHC-II 3. Exceptions → cross presentation of exogenous antigens when you get phagocytosis, but that pathogen gets into the cytoplasm and presented by MHC-I to naive CD8+ T cells

Answer 42

Pro-enzymes that are cleaved into an a and a b component. Generally, the a component causes a « allergic »-like reaction and the b component potentiates complement cascade ultimately leading to cleavage of C5 and formation of the MAC

Answer 43

gram+ bacteria → Peptidoglycans gram- bacteria → LPS

Quail_Innate Immunity Flashcards

(67 cards)