Innate immunity Flashcards

Question

C3 convertase

Answer 1

C4b2a (C4b + C2a, covalently bind together) C3bBb (noncovalently bond together)

Answer 2

3 pathway start with diffferent initiator generate C3 convertase can lead to 3 main outcomes

Answer 3

Triggered by soluble proteins known as lectins Expression of lectins increase during infection These PRRs can bind surface of pathogens (PAMPs), changes the confirmation of MASPs, cleave the complement protein, triggers signaling cascade on pathogen surface C3 convertase is generated (C4b2a), C3 cleaved → C3a and C3b

Answer 4

(PRRs circulating in blood) - Mannose-binding lectin (or MBL) - Ficolins

Answer 5

**C1q**: bind pathogen surface - Can bind pathogen directly - Can bind antibodies (from B cells) that are bound to pathogen surface (connect adaptive to innate) once C1q bind, C1r2s2 switch on and cleave the complement protein, generate C4b2a cleave C3

Answer 6

C3a: Involved in enhancing inflammation C3b: Involved in Opsonization, and is a C5 convertase → C5a and C5b C5a: inflammation C5b: formation of MAC

Answer 7

**first pathway**: once C3b has been produced by the other two pathway, C3b bind with factor B, then factor B cleave to Bb by factor D form C3bBb, then cleave to generate more C3b **Second pathway**: high concentration of C3, C3 can undergo spontaneous hydrolysis C3(H2O)bind with factor B, allowing to be cleaved by factor D into Ba and Bb C3(H2O)Bb is a C3 convertase C3bBb is very unstable: properdin (factor P) secreted by neutrophils can stabilize C3 convertase by binding to some microbial sufaces

Answer 8

**inflammation**: 1. additional signaling results in cleavage of other complement molecules (C3a and C5a are the mainly ones promoting inflammation) 2. large amount C3a and C5a can lead to anaphylactic shock 3. C3aR(receptor)/C5aR on granulocytes bind with C3a and C5a ➢Stimulates release of proinflammatory cytokines and granule components from basophils, eosinophils, neutrophils, mast cells **increased phagocytosis** 1. Phagocytes have receptors for C3b 2. Opsonization of pathogen → more readily taken up by phagocytosis **pathogen lysis** 1.membrane-attack complex (MAC) formation lead to cell lysis 2. C5 and C3 involved (C5b directly, C3b indirectly--cleave C5)

Answer 9

Complement-regulatory proteins in plasma or cell surfaces prevent complement activation from proceeding under normal/basal conditions: - Prevent appearance of C3 convertase - Promote disappearance of C3 convertase ex. inhibiting MAC formation via CD59 (Protectin)

Answer 10

Damage-Associated Molecular Patterns

Answer 11

All types of **myeloid white blood cells** Subset of the lymphoid cells: **T cells, B cells, NK cells** PRRs are also expressed by some other cell types (**commonly exposed to infectious agents**, ex.Epithelial cells of the skin and mucosal tissues and endothelial cells)

Answer 12

Cytosolic sensors of viral nucleic acids are expressed by most if not all cells in the body

Answer 13

cell surface intracellular secreted

Answer 14

Toll-like receptors (TLRs) NOD-like receptors (NLRs) RIG-I-like-receptors (RLRs) C-type lectin receptors (CLRs) Ficolins, MBL, C1q Others

Answer 15

signaling pathways are activated, contributing to innate/inflammatory responses

Answer 16

**Toll-like receptors** intracellular and extracellular always membrane bond homodimer or heterodimer different TLRs recruit different adaptor proteins (and they will link different protein-binding partners together and facilitate large signaling complex, leading to down stream effect) -**NF-kB**: trascription factor activation -**IRF**: interferon regulating factor pathways -MAP kinase pathway downstream transcription factors (**AP-1**) **all these three are transcription factors** the signaling activate the TF and lead to transcription of innate immune/pro-inflammatory genes, the gene expressed have specific impact

Answer 17

TLR bind with ligand trigger the cascade phosphorylation: activate proteins (transcription factors) TF translocate into nucleus to activate gene gene express as cytokines, chemokines, antimicrobials key molecules: adaptor proteins: MyD88, TRIF transcription factors: IRF3/7, NF-kB, AP-1

Answer 18

1. ligand bind to receptor: might induce receptor dimerization 2. recruitment and activation of kinases and adaptors 3. secondary messenger activated (usually through phosphorylation) 4. activation and translocation of TF 5. change in gene expression 6. post transcriptional or post translational modifications 7. functional response then secrete out of the cell

Answer 19

**C-type lectin receptors** only membrane bond bind **carbohydrates** on pathogens and some **allergens** (peanut and dust mite proteins) Activated **tyrosine kinases** trigger signaling cascades: -**CARD adaptor protein -IRF5 activation -MAPK pathways** activation resulting in activation of **AP-1 and NF-kB** -Induce the expression of **inflammatory cytokines**

Answer 20

**RIG-I-like receptors** **cytosolic PRRs** Recognize **viral double-stranded RNAs and certain structured single-stranded RNA** RIG bind to its PAMPs, providing signals to associated protein called **MAVS**: mitochondrial antiviral signaling protein MAVS will activate: IRFs (transcription factors) NF-κB (transcription factor) they tranlocate into nucleus and then express the gene for cytokines, chemokines and antimicrobials ## Footnote RIG has RIG-I filament, they both associated with adaptor protein CARD, and CARD filaments bind with MAVS protein

Answer 21

**NOD-like receptors** Nucleotide oligomerization domain (NOD) **cytosolic PRRs** (floating or anchor in endosome in a vesicle) Recognize **peptidoglycan from bacterial cell wall** (processed cell wall that already enter the cytosol) Can trigger **NF-kB, AP-1 and IRF signaling** Activates **caspase-1 protease** -Caspase-1 cleaves pro IL-1beta/IL-18 into active forms (IL-1beta/IL-18) for release (pro-inflammatory cytokines) **This is a post translational modification**

Answer 22

1.Cytokine production 2.Chemokine production CC chemokines (CCL2) CXC chemokines (CXCL 8, IL-8) 区别是location of the two cysteine residues 3.increase expression of costimulatory molecules -B7.1 (CD80) & B7.2 (CD86) signal 2 for T cell activation 4.enhance migration to regional, secondary lymphoid organ -upregulation of specific adhesion molecules

Answer 23

IL-1, IL-6, IL-18, TNF-alpha, IL-12

Answer 24

Type I IFN (IFN-alpha, IFN-beta) IFN bind to receptors on surrounding cells, trigger more signaling, leading to more transcription (生成可以影响viral life cycle or replication的东西), halt or slow down virus infeciton

Answer 25

Chemokine receptors are an example of G-protein-coupled receptors -Transduce signals via interactions with GTP/GDP-binding G protein -Many receptors can bind to more than one chemokine; several chemokines are able to bind to more than one receptor *Chemokines direct leukocyte migration →**chemotaxis** -Signaling through chemokine receptors helps cells move to different areas **1.Change in cell adhesiveness 2.Changes in cell’s cytoskeleton 3.Induce movement of leukocytes up a chemokine concentration gradien

Answer 26

1.rolling adhesion 2.tight binding 3.diapedesis 4.migration diapedesis: cell crosses from lumen of a vessel into the surrounding tissue go through between endothelial Migration: direction of higher chemokine concentrations

Answer 27

Pathogens enter the cell PRR binding to PAMPs Induce phagocytosis Produce cytokine and chemokine Innate immune cells recruit to the site (vasodilation of blood vessels allow cells to pass) Production of other proteins Leads to 4 hallmarks of inflammation

Answer 28

Heat Redness Swelling Pain Normal inflammation is acute Severe or chronic inflammation will lead to arthritis or loss of function

Answer 29

adhesion anchor on endothelial change confromation pass through the endothelial migrate into surrounding tissue differenciate to functional immune cells at the site of infection monocyte (differentiate to macrophages), nuetrophils, other leukocytes

Answer 30

1.Selectins 2.Integrins 3.Immunoglobulin superfamily Different tissue distribution Some adhesion molecules are expressed at baseline expression up regulate expressed when there is an infection

Answer 31

Small (~25kD), heterogeneous glycoproteins Mostly soluble (some have membrane-bound forms) cytokine production is tightly regulated (post trancription/translation modification) provide cellular commmunication

Answer 32

distant cells: endocrine nearby cell: paracrine itself (the producing cell): autocrine

Answer 33

Activation proliferation differentiation survival (or death) of target cell **Cascade induction**: the action of one cytokine on one target cell induces that cell to produce one or more additional cytokines ex. change expression of adhesion molecles and chemokine receptors on target cell Increase or decrease activity of particular enzymes-->Change transcriptional program (type I IFN)

Answer 34

**Interleukins (IL)**: from 1 to 37 so far **Interferons (IFN)**: Type I (IFN-alpha, beta) and Type II (IFN-gama) **Tumor necrosis factors (TNF)**: alpha and beta **Hematopeoitins or growth factors**: e.x. GM-CSF, G-CSF **Chemokines**

Answer 35

**Pleiotropy** one cytokine produces multiple effects **Redundancy** more than one cytokine induces the same effect **Synergy** two (or more) cytokines work together to induce an effect **Antagonism** one cytokine can inactivate the effect of another

Answer 36

cytokines impact the differentiation of T cells (signal 3) then these cells produced other cytokines

Answer 37

normally mix but one response can dominate cytokines can determine the type of adaptive immune response we get

Answer 38

Mostly directed to -Viral infections -Intracellular pathogens -Some extracellular pathogens Characterized by: -T helper cells →Innate immune cell activation -Cytotoxic T lymphocyte (CTL) activation

Answer 39

Mostly directed to -Extracellular bacteria/pathogens– Characterized by predominant: -B cell activation -Antibody production

Answer 40

Proinflammatory cytokine, induce /trigger inflammation mainly secreted by macrophages stimulates migration of innate cells dilates blood vessels, increasing clotting (preventing pathogen from entering the bloodstream) involved in many autoimmune disease Therapy targeting TNF-alpha used to treat Rheumatoid Arthritis and Crohn’s Disease

Answer 41

normal inflammation local migration of cells, clear pathogen

Answer 42

caused by multiple site infection or pathogen enter the blood stream lead to a lot of vasodilation can cause multiple organ failure, collasping of blood vessel, septic shock sepsis: systemic infection and inflammation

Answer 43

A change in the proteins present in the blood that occurs during the early phases of an infection **Induced by proinflammatory cytokines (IL-1 beta, TNF-α, and IL-6)** (from macrophages in this example) Acute phase response involves: **Increased synthesis/secretion of antimicrobial proteins from the liver (known as acute phase proteins)** 1.Mannose-binding lectin (MBL) 2.Complement components 3.C-reactive protein →can opsonize bacteria and trigger classical complement cascade by binding to C1q Liver acute phase proteins activate other processes that help eliminate pathogens

Answer 44

IL-1beta, IL-6, TNF-alpha= key pro-inflamcytokines liver: acute-phase protein bone marrow: neutrophil mobilization hypothalamus, fat, muscle: increase body temperature dendritic cell: TNF-alpha stimulates migration to lymph node Acute effect on different tissues/cell types cause: acute-phase response, mobilizing cells, fever contributes to response angaist pathogen

Answer 45

NK cells are innate lymphoid cells (ILCs) Share a progenitor (common lymphoid progenitor) with B and T cells but are innate immune cells not specific as B and T cells

Answer 46

not antigen specific 3 tyeps of ILCs cytokines can influence which ILC to generate into ILC1, ILC2, ILC3

Answer 47

Tend to reside in tissues –important role in mucosal immunity contribute to defense against specific pathogens but ILC2 in circulation

Answer 48

NK cells can be found in tissues or circulation Can directly kill cells Different inducing cytokines lead to differentiation into different ILCs, which secrete different cytokines

Answer 49

All types of **myeloid white blood cells** Subset of the lymphoid cells: **T cells, B cells, NK cells** PRRs are also expressed by some other cell types: Those commonly exposed to infectious agents (eg. **Epithelial cells**of the skin and mucosal tissues and **endothelial cells** that line the blood vessels, leading to production of antimicrobial susbtances) Cytosolic sensors of viral nucleic acids are expressed by most if not all cells in the body **ILC I II III don't have PRR**

Answer 50

Act in tissues (here in gut mucosa) Activated by cytokines produced by DCs or other cells (ex. epithelial cells) (don't have PRRs bind with PAMPs) Secrete cytokines that contribute to pathogen killing

Answer 51

NK cells are lymphoid cells with innate immune functions Express receptors for self proteins that can be induced by: **-Infections -Malignant transformations (Cancer) -Other stresses** Activated NK cells can: -Kill the altered self cell →due to infection or Tumor cells -Produce cytokines (help differentiate T cells) that induce adaptive responses against the altered self cell

Answer 52

Germline encoded –don’t change Activating receptors AND inhibitory receptors Recognize MHC class I molecules or MHC class I-like molecules MHC I molecules are expressed on all nucleated cells

Answer 53

NK cell receives activating and inhibitory signal →inhibitory signal prevents activation of NK cell inhibite > activate

Answer 54

Altered self cell doesn’t trigger inhibitory receptor →NK cell only receives activating signal →NK cells kills target cells via granules that trigger apoptosis (cell death)

Innate immunity Flashcards

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