Intro to pathology Flashcards

Question

Viral infected cells

Answer 1

PRoduce IFN alpha IFN beta Causes resistance to viral replication Increase expression of ligands recognised by NK Activate NK cells

Answer 2

Release perforin to form pores in membrane Releas granzymes to induce apoptosis Antibody Dependent Cell Cytotoxicity (ADCC) Recognise Fc part of antibodies, needs multiple antibodies Macrophage activation Make CXCL8, IL-12 & IL-15 which activates NK cells make IFNgamma which increase killing capactity of macrohphage

Answer 3

amplify signals produced during innate recognition ILC1s protect against viruses and intracellular pathogens ILC2s assist mucosal and barrier immunity against parasite and helminths infection ILC3s protect against extracellular bacteria and fungi

Answer 4

Secreted soluble proteins BInd to recptors to conteol activity of immune cells Autocrine,paracrine,endocrin Redundancy, several different cytokines may have the same function * Pleiotropism, a single cytokine may have a variety of different effects * Antagonism, one cytokine blocks the action of another * Synergy, multiple cytokines work together to achieve an effect that is greater than the additive effect of each alone Use JAK/STAT pathway Interluekins INterferons TNF-Tumour necrosis factor

Answer 5

IL-6 stimulates hepatocytes to release acute phase proteins C-reactive protein (opsonin and complement activation) and Fibrinogen (fibrin clot formation) Denfensins disrupt microbe membranes Pentraxins bind to pathogens and phagocytes liek antibody

Answer 6

potent inflammatory mediators such as prostaglandins and leukotrienes Prostoglandins vascular permeability vascular dilation neutrophil chemotaxis leukotrienes back up for histamine, longer stronger response bronchial smooth muscle contraction neutrophil chemotaxis Slow Reacting Substance of Anaphylaxis (SRS-A)

Answer 7

cells move towrads it down gradient CXCL8

Answer 8

Bradykinin which increases vascular permeability, vasodilatation Activates complement

Answer 9

Nod like recpeote NLRP3 forms inflammsome Recognise peptideoglycan, bacterial DNA, ATP, toxins, ds-RNA induce inflammation by causing caspase-1 to activate IL-1b

Answer 10

dilate blood vessels to increase blood flow. * increase permeability of the vessel wall to allow a protein rich fluid into the tissues. A fibrin web forms and complement and CRP are recruited. Recruit neutrophils and others like monocytes-macrophages lymphocyte, eosinophil

Answer 11

Induce fever IL-1beta TNF-alpha IL-6 Secreted by activated macrophages

Answer 12

Selectins like P/E selectin bind to glycoprotein ligands present on the neutrophil integrin family adhesion molecules (LFA-1) on cell bind Intercellular Adhesion Molecules) on the endothelium tightly Diapedesis, squeeze through the gaps between endothelial cells (extravasation) elastase to degrade membrane Migration using CXCL8 grad LFA-1 deficiency stops neutrophil recruitment Leukocyte adhesion deficiency (LAD) Monocytes are recruited later because the endothelial adhesion molecule (VCAM-1) is made slower

Answer 13

Sepsis occurs when pathogens enter the blood stream. TNF=alpha secreted by macrophages vasodilation and movement of fluid into the tissues causes loss of blood pressure Septic shock Also triggers clotting in small vessels disseminated intravascular coagulation)

Answer 14

Short half lives and degrade quickly When apoptic neutrophils engulfed by macrophage, anti-inflammatory lipoxin made Makes anti inflammatory cytokines such as IL-10 and TGF-b to stop inflam

Answer 15

repair is called granulation tissue recruitment of endothelial cells to form new blood vessels and fibroblasts to lay down extracellular matrix (ECM) Macrophages phagocytose debris kill microbes with ROS recruit fibroblasts FGF recruit endothelial cells VEGF secrete metalloproteinases to allow remodelling of ECM

Answer 16

stimulated by cytokines produced by macrophages (e.g. VEGF). drives preexisting vessels to send out capillary sprouts into the area of damage.

Answer 17

causative agent is endogenous: e.g. stomach acid (peptic ulcer) non-degradable: e.g. silica evade host defences: e.g. tuberculosis autoimmunity): e.g. rheumatoid arthritis

Answer 18

multinucleate giant cell area of necrosis Surrounded by T cells walled off as can't remove infectous agent

Answer 19

Activation of inflammation Opsonisation of microbes Lysis of target cells C3 has an internal thioester bond. When cleaved to C3a and C3b, C3b can bind to phagocyte surfaces C3a anaphylatoxin and stimulates local inflammation by activating mast cells

Answer 20

CR1 binds directly to C3b and once C5a binds trigger phagocytosis C3b is an opsonin

Answer 21

C3 spontaneously reacts with H20 C3H20 bind factor B and factor D cleaves B into Ba which leaves and Bb C3H20Bb fluid phase C3 convertase Cleaves C3 into C3b and C3a similarly surface bound C3b bind factor B and D so C3bBb alternative pathway C3 convertase cleaves even more C3 so more C3b binds

Answer 22

C3bBb binds C3b to form (C3b)2Bb the alternative C5 convertase cleaves C5 into C5a and C5b C5b binds C6 which binds C7 C7 inserts into membrane C8 binds and causes polymerisation of C9 to form a membrane pore

Answer 23

Mannose binding lectin (MBL) is a PRR that binds f mannose residues that are found on microbial surfaces MBL is bound to MASP 1 and 2 MBL-associated serine protease which when MBL binds cleaves C4 into C4b and C4a C4b binds to pathogen surface C2 binds and is cleaved into C2a/b, C2a binds to C4b C4bC2a, the Classical C3 Convertase cleaves C3

Answer 24

antibody or C-reactive protein (CRP) made in liver due to Il-6 release by macrophage C1q can bind multiple antibodies or CRP C1s then cleaves C4 so C4b binds then like lectin C2 binds, C2a remains forming C4bC2a which cleaves C3 C4bC2aC3b can form a classical pathway C5 convertase.

Answer 25

Short half life Properdin (Factor P) stabilises C3bBb and the C5 convertase complex Factor I degrades C3b and C4b Membrane cofactor protein (MCP) on host cells breaks down C3 convertases Also cleaves C3b/C4b with factor I Factor H attaches to sialic acid present on host membranes but not bacteria and causes dissociation of C3bBb and cleavage by I Decay accelerating factor (DAF) dissociates C3 convertases Protectin stops C9 recruitment

Answer 26

C1, C2, C4 Immune-complex disease, infection C3 Infection with encapsulated bacteria as C3 important opsonin C5-C9 Susceptibility to Neisseria infections as complement mediated lysis is best defence Factor D,Properdin Susceptibility to pyogenic bactera Factor I, Factor H uncontrolled AP activation resulting in C3 depletion, Susceptibility to infection with pyogenic bacteria DAF, Protectin Autoimmune-like conditions as red blood cells are lysed

Answer 27

Staphylococcus aureus. polysaccharide capsule Staphylococcus Complement Inhibitor (SCIN) on surface to inactivate C3 secretes proteins that bind or degrade and inactivate C3 protein A binds the Fc region of IgG blocking complement recruitment and activation. Clumping factor A recruits factor I to the bacterial surface Chemotaxis Inhibitory Protein blocks the C5a chemotactic receptor on neutrophils limiting recruitment to sites of infection.

Answer 28

Bind small epitopes on antigens variable regions that interact with antigen COnstant region that recurits effector Neutralization- binding toxin to stop it from binding Opsonisation- IgG bind to Fcg recptors on macrophages and neutrophil to enchance phagocytosis Complement activation classical pathway by C1q

Answer 29

cytotoxic T cells CD8 MHC class 1 kill virus/tumour cells T helper CD4 MHC class II Activate B cells, macrophages and cytotoxic T cells MHC class II found on professional antigen presenters like dendritic, macrophage, b cells

Answer 30

MHC I oresents peptides from inside of cell MHC II presents peptides from molcules that enter via the endocytic pathway. Survey external environ

Answer 31

dendritic cell PRR binds PAMP becomes professional antigen presenting cell (pAPC) Presents on MHC I and II Signal 1 from recognition of MHC and peptide Need costimulation from B7 on dendrite to bind CD28 on T cell, Both signal needed Cytokines can change which T helper cell Cytotoxic T cells need both signals but also somtimes need TH1 to make IL-2

Answer 32

TH1 cells help activate macrophages IL-12 and IFN-g TH2 helps parasite infections IL-4 TH17 cells help promote neutrophil control of extracellular bacterial and fungal infections .IL-6, TGF-b and IL-23 TFH cells help B cells become activated IL-6 and IL-21 Treg cells suppress the activity of other effector T-cell populations TGF-b

Answer 33

dendritic cells enter and activate T cell follicular dendritic cells (FDCs) trap peptide fro long times so B cell with highest affinity matures Affinity maturation

Answer 34

pairs of heavy and light chains held together by covalent (disulphide bridges) Variable region and contstant region IgA, IgD, IgE, IgG and IgM depends on heavy constant region Has hinge to be flexible antigen binding site is formed by interaction between heavy and light chain variable domains complementarity determining regions with CDR3 most variable

Answer 35

VDJ- variable, diversity, junctional gene segment DJ first the V joins DJ for heavy chain 2 copies of VDj from parents so 2 tries for rearrangement Light chains no D, diversity segment only VJ Make K chain first then lamda so 4 tries RAG1 and RAG2 recombinase Further junctional diversity by addtition or loss of nucleotides by P or N addition

Answer 36

deamination of cytosine to uracil by the enzyme Activation Induced (Cytidine) Deaminase or AID to add point mutation Antibodies with increased affinity are selected by affinity maturation

Answer 37

Can swap from IgM and IgD to IgG, IgA or IgE

Answer 38

low and high affinity and bind single or mutliple to give different levels of antigen senstivity

Answer 39

Can cause degranulation of eosinophils MAst cells have prebound antiobodies bind to antigen to cause degranulation IgA in gut protects mucosla surfaces, in breast milk IgG moves across placenta Antibody immune complexes can bind BCR and terminate them to stop response

Answer 40

Affinity is the strength of 1 anitbody binding site Antibodies have multiple binding sites IgG has 10 so though low affinity high avidity

Answer 41

Class I all cells except red blood cells alpha 1 and 2 Beta 1 and 2 alpha 1, beta 1 peptide binding Class II Alpha 1,2,3 Beta 2 recognised by CD4 alpha 1,2 peptide binding Bind a broad range of peptides

Answer 42

Human MHC 3 copies A,B,C from each parent so 6 total High polymorphism Inherited together and codominantly expressed. Variability in peptide binding and T cell receptor binding part Depedning on the amino acid in important anchor position in the peptide binding region changes what is bound

Answer 43

Chicken only 1 MHC either fastidious binds few peptides or promiscuous binds many After infection promiscuous favoured

Answer 44

Protein into peptide by proteosome Transporter associated with Antigen Processing (TAP) sends peptide into ER Loaded onto MHC class I and sent by golgi to surface

Answer 45

class II will bind peptide in cell when in ER so to avoid this it has an invariant chain to block peptide groove class II is sen into a vesicle where it fuses with an endosome containing antigens and is loaded with the help of HLA-DM