Immunology Flashcards

Question

How does the structure of the Peyer's patch differ during an immune response?

Answer 1

The germinal centres can be seen during an immune response

Answer 2

Lymphocytes which have not yet encountered an antigen and are constantly circulating the blood and secondary lymphoid organs

Answer 3

T-lymphocytes are in the blood and can enter lymph nodes at the HEV (high endothelial venule) Chemokines are bound to HEV which causes the T-cell to bind weakly to it (due to selectins) Once integrins are present, T-cells bind strongly to ICAM 1 (intracellular adhesion molecule 1) T-cell is immobilised and moves into lymph node

Answer 4

Naive lymphocytes circulate from the blood to secondary lymoid organs such as lymph nodes until they die or become activated. Activated = antigen detected, proliferation and differentiate IN THE LYMPHOID TISSUE

Answer 5

B and T lymphocytes can not be differentiated under the microscope as they both have agranular cytoplasm and a large nucleus They can be differentiated due to their cell surface molecules; seperated into clusters using monoclonal antibodies CD markers = internationally recognised, more than 350

Answer 6

B LYMPHOCYTES: * Function = produce antibodies * Expresses CD19 and CD20 * Expresses MHC Class II * Recognises a free, intact antigen in body fluids * Antigen receptor - cell surface antibody T LYMPHOCYTES: * Function = CD4+ secrete cytokines, CD8+ lyse infected cells and secrete cytokines * Expresses CD3, 2/3 CD4 (T helper and regulatory T) and 1/3 CD8 (cytotoxic T) * Only recognise an antigen presented on the surface of another cell via an MHC molecule

Answer 7

Dendritic cells= widely spread in skin and mucosal tissue ► T-cells Follicular Dendritic cells= lymph node follicles ► B-cells B-cells= lymphoid tissue ► T-cells Activated macrophages= lymphoid tissue ►T-cells

Answer 8

A polymorphonuclear leukocyte short lived circulates in the blood and migrates into tissues first at site of infection/tissue damage highly phagocytic cells and kills them after

Answer 9

Usually antigen uptake is more effective after opsonisation opsonisation = coating the microorganism with proteins to aid phagocytosis; opsonins bind to both the antigen and phagocytes

Answer 10

Two mechanisms 1. Oxygen-independent * using lysozymes and hydrolytic enzymes 2. Oxygen-dependent * using toxic metabolites e.g. nitric oxide, hydrogen peroxide

Answer 11

monocytes = bloodstream macrophages = tissues Act as signals of infection by releasing cytokines such as interleukins (IL-1, IL-6 and IL-8) Engulf and kill invading organisms

Answer 12

Small secreted proteins which are involved in cell to cell communication. They have low concentrations and act locally on cells. They function by binding to specific cell surface receptors.

Answer 13

1. interleukins = between leukocytes 2. interferons = anti-viral effects 3. chemokines = chemotaxis and movement of cells to particular sites 4. growth factors = development of cells in the immune system 5. cytotoxic = can induce cell death e.g. tumor necrosis factor

Answer 14

1. IL-1 = alarm cytokine (fever) 2. TNF-alpha = alarm cytokine 3. IL-6 = burns/ tissue damage, liver 4. IL-8 = signal for the movement of neutrophils (chemotaxis) 5. IL-12 = directs adaptive immunity and activates natural killer cells

Answer 15

Complements the activing of a specific antibody A complex series of proteins in serum and tissues which cause an enzyme cascade which leads to: * opsonisation of microorganisms * direct killing of microorganisms * promotion of inflammation * recruitment of leukocytes

Answer 16

Roughly 30 proteins and glycoproteins - in serum (high conc) Mostly precursors to enzymes which once activated cause a cascade Thus a highly amplified and rapid response occurs

Answer 17

Three ways 1. Classical = intiated by antigen-antibody complexes 2. Alternative = direct activation by pathogen surface 3. Lectin = activation via lectins which bind to carbohydrates only found on pathogens

Answer 18

The classical, lectin and alternative pathways converge at C3 C3 (a complement component) leads to a common pathway in which the MAC (membrane attack complex) is formed causing cell lysis.

Answer 19

MBL = mannanose-binding lectin CRP = C-reactive protein

Answer 20

* Constant changing of components * Dilution of components in biological fluids * Regulatory proteins * circulating; C1-inhibitor, Factor I * membrane bound; CD59, DAF

Answer 21

Microorganisms undergo: 1. lysis 2. opsonization 3. activation of inflammatory response 4. clearance of immune complexes

Answer 22

Tissue damage \> bacteria enter Recognised by macrophages which are activated, secrete cytokines Affects local vascular permeability Neutrophils move towards site of infection leave circulation 2nd exposure = antibodies present will bind to bacteria (classical pathway activates complement) Or then alternative pathway activates complement Degrades mast cells – releases histamine Lymphocytes and monocytes also move towards site of infection

Answer 23

Activated if the pathogen is not cleared after the local inflammatory response \> systemic respose required Usually after 1-2 days Fever occurs Induced by cytokines e.g. interleukins

Answer 24

* C-reactive protein (activates complement, levels may increase 1000X) * Mannose binding lectin (activates complement, opsonin for monocytes) * Complement * Fibrinogen (clotting)

Answer 25

Lymphocytes which have large granules Cytotoxic- lyse target cells and secrete interferon gamma Expresses activating and inhibiting receptors; determines if NK is activated or not Receptors can binf to antibody-coated cells Used in defence against tumour cells and viral infection

Answer 26

Activating receptors bind to stress-induced molecules and thus the cell is targeted to kill

Answer 27

Fab = antigen binding site (equal amount of light and heavy chains; hinge region provides flexibility to bind to antigens; binding comes from non-covalent interactions) Fc= constant region (stays the same as doesn't bind to antigens; can change conformation when bound to an antigen to perform effector functions such as activating complement)

Answer 28

Where antigen binds to antibody Surface is predominantly flat with 3 hypervariable regions forming the complementarity determining regions (CDRs); light chain also has a variable region Non-covalent forces involved: * hydrogen bonds * ionic bonds * hydrophobic interactions * van der Waals interactions Individually weak but collectively create a strong force

Answer 29

A measure of the strength of binding between a SINGLE binding site of an antibody and its epitope on the antigen

Answer 30

The overall strength of binding between an antibody with MULTIPLE binding sites and antigen with MULTIPLE epitopes

Answer 31

Ig: * A * D * E * M * G All have either 2 kappa or 2 lambda light chains; differences arise in the heavy chain

Answer 32

Heavy chain: gamma with 3 domains Most abundant antibody and has 4 different subclasses (differ in hinge region and effector function) In general IgG = neutralises toxins and viruses Actively transported across the placenta = long half life so provides a baby with approx 3 month protection Classical complement is activated by IgG1 and IgG3

Answer 33

Alpha heavy chain with 3 domains Has 2 subclasses and also second most abundant Can exist as monomers (blood- IgA1) and as dimers (secretions- IgA2) Dimer of IgA = with a joining and secretory component (major secretory immunoglobulin) Provides protection of mucosal surfaces from bacteria, viruses and protozoa

Answer 34

mu heavy chain with 4 domains A pentameric molecule = 5 monomers joined by J chain (10 antigen binding sites) Usually found in the blood First Ig synthesised after exposure to an antigen 10 antigen binding sites allows for strong binding and agglutination Can also activate complement

Answer 35

E heavy chain with 4 domains Very low concentration Produced in response to parasitic infection and allergic reactions Binds to mast cells (cross-links cause histamine release) and basophils

Answer 36

Delta heavy chain with 3 domains Low serum concentration Expressed in early B-cell development (on surface) Involved in B-cell development and activation

Answer 37

B-lymphocytes originate from stem cells in the bone marrow where is also where they mature - in the absence of antigen They can migrate into cirulation (blood and lymph) and also into lymphoid tissue Immature B-cells express IgM; mature B-cells express IgD Mature B-lymphocytes are for a specific antigen, brought about by the B-cell receptor (BCR) for antigen

Answer 38

Diversity =\> rearrangement of the immunoglobulin gene During B-cell maturation gene segments for the BCR chain are rearranged and brought together Light Chain = V and J segments Heavy Chain = V, D and J segments V=variable, D=diversity and J=joining

Answer 39

The principle for gene rearrangement remains the same for both the heavy chain and the light chain 1. Germline DNA rearragned * only some V/D/J components used 2. Forms B-cell DNA 3. Transcripted into pre-mRNA 4. Alternative splicing to produce mature mRNA * some V/D/J components are removed along with introns 5. Translation into polypeptide (heavy/light)

Answer 40

1. Plasma cell = producing antibodies 2. Memory cell = prepares for future infections 3. Enters somatic hypermutation and affinity maturation = improves quality of antibody

Answer 41

* via a T-helper cell * produces all forms of Ig- protein based antigens 1. BCR recognises antigen 2. Antigen is internalised and degraded into peptides 3. Peptides associate with "self" MHC class II and is expressed at the surface 4. Complex recognised by CD4+ T helper cell 5. T helper cells secrete lymphokines 6. Causes B-cell to undergo mass cloning with identical BCRs

Answer 42

* Recognised by microbial constituents * Ony produces IgM 1. Polysaccharide has repeating units 2. Binds to many BCR on same cell (cross-linking) 3. Secondary signal from the microbe is needed e.g. LPS

Answer 43

T-cells can release cytokines which can cause Ig's to switch class via a different combination of V, D and J gene segments resulting in different constant region

Answer 44

The B-cell must be intitally activated via thymus dependency. Memory follicular T helper cells detect the activated B-cell; there is binding between the TCR and MHC class II peptide Enters germinal centre where differentiation into a memory cell can occur

Answer 45

OCCURS IN THE GERMINAL CENTRE TO IMPROVE A SECONDARY RESPONSE Somatic hypermutation = production of centroblasts- class switching may occur here Affinity maturation = activated B-cells produce antibodies with an increased affinity; repeated exposure will result in increased affinities

Answer 46

PRIMARY RESPONSE Slower as longer time taken for antibody production; mainly consists of IgM SECONDARY RESPONSE Faster and greater reponse due to memory B-cells; more IgG rather than IgM

Answer 47

Detects and destroys intracellular pathogens using the TCR (T-cell receptor). The TCR only recognises processed antigens which are presented by MHC moleucles (a small peptide fragment of the pathogen along with self MHC)

Answer 48

1. CD8+ * cytotoxic T-lymphocytes = kill target cells * recognises peptide antigen presented by MHC I * secrete cytokines * may induce apoptosis in target cell 2. CD4+ * T-helper cells * recognises peptide antigen presented by MHC II * secretion of cytokines to help activate macrophages and amplify B-cell and CD8+ cell responses

Answer 49

T-cells origniate at the bone marrow. However they then develop in the thymus. Move from the outer cortex to inner medulla as they develop. TCR formation = mature T-cell 1. Germline DNA rearranged (gene segment rearrangement) 2. Cells express TCR and both CD4 and CD8 3. Cells undergo selection; only those chosen if TCR recognises self MHC (not too strongly) 4. Mature cells express TCR and either CD4 (Th1/2) or CD8

Answer 50

MHC = Major Histocompatibility Complex MHC molecules are displayed on the cell surface and are markers of "self" which indicate the "health" of cells and can be recognised by T-cells.

Answer 51

MHC class I = classical transplantation antigens and are expressed by all cells (at different levels) MHC class II = regulatory, control the ability to mount to immune responses, only expressed by APCs (antigen presenting cells; dendritic cells, macrophages and B-lymphocytes)

Answer 52

A range of peptides must be able to bind to MHC but a degree of specificity must also be maintained. Achieved via specific binding pockets only allowing side chains with the correct amino acid to bind (anchor residue)

Answer 53

HLA = Human Leukocyte Antigen (human MHC) Class I: HLA a/b/c Class II: HLA dp/dq/dr HLA genes are highly polymorphic (large number of alleles) expression is co-dominant. Inherit 2 MHC haplotypes (group of MHC alleles tightly linked on one chromosome) determines immune responsiveness. Diversity at the population level not within an individual

Answer 54

An antigen synthesised in the cytoplasm; presented by MHC class I to CD8 T-cells

Answer 55

An antigen captured from the external environment (usually a pathogen) which is presented by MHC class II to CD4 T-cells

Answer 56

Protein sythesised in cytoplasm Proteasome cleaves proteins to form peptides Peptides enter ER via TAP (transporter associated with antigen processing) Class 1 MHC molecule folds with the help chaperone proteins Binding of heavy chain, peptide and beta 2 microglobulin The complex then moves through the Golgi complex to the cell surface

Answer 57

Class II MHC molecule in RER binds to invariant chain Movement through Golgi complex; invariant chain digested to only leave a small part CLIP (class II associated invariant chain peptide) Exogenous antigen enters cytoplasm via endocytosis Antigenic peptide exchanged with CLIP MHC class II molecule and antigenic peptide presented at cell surface

Answer 58

B-lymphocytes = directly recognises an intact, extracellular antigen T-lymphocytes = only recognises processed antigens presented by MHC molecules; Class I = CD8+ and Class II = CD4+

Answer 59

T-cells only mature once they detect and antigen presented via MHC molecules by APCs such as dendritic cells (DC) They must also be co-stimulated CD28 meets with CD80/86 This causes a naive T-cell to become an effector and performs its function Some effector cells can then become memory T-cells When T-cells are in circulation if they present the correct chemokine receptor they can follow the chemokine gradient and addressins and integrins allow T-cells to move out of the vessels

Answer 60

T-cell mediated immunity is required for: * detection and elimination of pathogens which can live intracellularly * eliminate altered cells such as tumour cells

Answer 61

Cytotoxic T-cells (CTL) kill target cells (those which present MHC class I with virus peptides) via apoptosis i.e. fragmenting nuclear DNA CTL have stores of perforin, grazymes and granulysin in granules which are released after target recognition. Perforin = polymerises and forms pores in the target cell membrane If Fas is present on the target cell it can interact with FasL to induce cell death Cytokines may also be released

Answer 62

Th1 effector cells activate macrophages to promote the killing of intracellular pathogens (mycobacterium and leishmania) activated macrophages = increase in CD40 and TNF-alpha receptors (pro-inflammatory molecules)

Answer 63

DTH is associated with allergic reactions. Sensitisation = primary exposure to antigen and then Effector = second exposure causes a severe response to be triggered CD4+ Th1 cells release inflammatory cytokines which can recruit and activate macrophages - takes a few days to develop

Answer 64

* Th1 * produces interferon-gamma, interleukin-2 and tumor necrosis factor-alpha * boosts intracellular immune response * activates macrophages * Th2 * produces IL4,5,13 * aid B-cell differentiation into antibody secreting plasma cells * Tfh * allows for class switching * secretes IL-21 * Th17 * secreted IL-17 in autoimmune diseases such as arthritis * Treg * inhibit activation of naive and effector T-cells by contact-dependent mechanisms or secreted cytokines

Answer 65

There are 3 signals by which T and B cells collaborate: 1. ANTIGEN; B-cell presents antigen and T-cell has the MHC 2. CO-STIMULATION; link between CD40 on B-cell and CD40L on the T-cell along with CD28 which binds to B7 on the B-cell 3. CYTOKINES; IL-4, IFN-gamma and IL-21 released by T-cells Release of cytokines can cause class switching in B-cells and also the activation of B-cells to produce antibodies

Answer 66

T helper cells produce cytokines which can have a wide range of effects across many cells e.g. Treg, B-cells and macrophages Usually cytokines activate these cells to increase the immune response