Immunology And Infection Flashcards

Question

What are fungi

Answer 1

Unicellular eukaryotes

Answer 2

Macroscopic Multicellular eukaryotes

Answer 3

ABPA (allergic bronchopulmonary aspergillosis)

Answer 4

Bud/divide (unicellular fungi like yeast) Or using their filaments/hyphae - cross wall and septa, spreading them into neighbouring cells and fragment and divide this way

Answer 5

Superficial (on surface of skin) Cutaneous Subcutaneous Deep/systemic

Answer 6

``` Cell wall (human cells have no cell wall) Cell membrane (fungal cells use egosterol to stabilise membrane whilst human cells use cholesterol) DNA replication (fungi activate certain molecules involved) ```

Answer 7

Candida albicans (a fungi)

Answer 8

1) Tape worm 2) Flat worm (fluke) eg causes schistosomiasis- vector is a snail, helminths burrows into soles of feet and enters blood stream, resides in liver causing fibrosis and cirrhosis (liver hardening) 3) round worm eg Ascaris

Answer 9

There is treatment but no vaccine

Answer 10

Faecal oral - lay their eggs in gut so eggs are present in faeces - contaminates water

Answer 11

Alternative pathway

Answer 12

Large number of proteins react with one another to Opsonise pathogens Or Directly kill pathogens using MAC (membrane attack complex)

Answer 13

Liver Macrophages Monocytes

Answer 14

1) classical pathway - antibodies and antigens 2) MBL (mannan binding lectin aka mannose binding protein) pathway - MBL binds to pathogens surfaces to initiate complement cascade and is produced in liver 3) alternative pathway - uses no antibodies, instead uses bacterial surface to initiate complement cascade

Answer 15

1) initiation 2) production of C3 convertase 3) production of C5 convertase 4) MAC formation

Answer 16

Inhibit complement convertases Inhibit complement proteins Degrade/cleave complement proteins Activate host-derived regulators

Answer 17

1) produces SCIN protein which binds to C3bBb and prevents formation of C3 convertase and C5 convertase. This prevents C3b deposition, C3a formation and C5a formation 2) produces Efb protein which binds to C3d part of C3 and induces a conformational change in C3. This prevents factor B binding to C3 and C3dg binding CR2 3) produces SSL7 which binds to C5 and prevents formation of MAC

Answer 18

1) proteases cleave complement components 2) acquired host derived complement regulators Eg - C3 is inactivated by fH on bacterial surface - C4BP is associated with fI and degrades C2a from C3 convertases

Answer 19

Evade opsonisation Evade complement Evade actions of neutrophils - evade chemotaxis - evade phagocytosis - kill neutrophils

Answer 20

Commensal bacteria living in the nose of 30% of population Is opportunistic - can become harmful Is gram positive

Answer 21

Opsonins (could be antibodies or complements) bind/tag bacterial antigens This allows 1) deposition of complement in the classical complement pathway 2) neutrophils and other phagocytes to detect invading microbes

Answer 22

1) expression of capsule -stops opsonins binding by hiding antigens 2) inhibits antibody opsonisation - SpA (staph aureus surface protein) binds to Fc region of IgG antibodies 3) inhibits detection of antibody - releases SSL10 which binds to Fc region of IgG antibody that is opsonising the bacteria and stops it being detected by neutrophils

Answer 23

Hide antigens Disrupt function of antibodies Prevent detection of antibodies Degrade antibodies - produce proteases to cleave AB’s Modify antigenicity - can switch antigen expression to a different variation

Answer 24

TLR receptors - bind to conserved microbial structures CLEC receptors - bind to microbial carbohydrates FPR receptors bind to formylated peptides (residues that come off bacteria)

Answer 25

1) Fc receptors - bind to antibody opsonised microbes | 2) complement receptors - bind to complement opsonised microbes

Answer 26

Some are activatory (enhance immune cell activity) some are inhibitory (suppress immune cell activity) Eg Cytokine recpetors - TNFR/ ILR/ IFNR (tumour necrosis factor receptors, interleukin receptors, interferon receptors) Chemoattractant receptors - chemoattractants (C5aR, PAFR, BLT1, BLT2) LILR receptors SIGLEC receptors LAIR receptors CEACAM receptors

Answer 27

1) evade chemotaxis: produce CHIPs which bind to C5aR and FPR on neutrophil to prevent them binding to C5a and FMLP (formylated proteins). This prevents activation of neutrophils and their migration to site of infection 2) evade phagocytosis: produce FILPr which binds to Fc gamma receptors on neutrophil, preventing IgG binding to neutrophil Produce SSL5 which binds to Fc alpha receptors on neutrophil, preventing IgA binding to neutrophil. This prevents detection of IgG and IgA opsonised bacteria by neutrophils therefore reduces antibody mediated phagocytosis of S aureus 3) killing neutrophils by producing toxins 4) inhibiting function of neutrophil receptors by producing neutrophil receptor antagonists

Answer 28

Bind inhibitory receptors Modify intracellular signalling Modify bacterial surface Inhibit effects of anti microbials

Answer 29

How do we know if a particular organism causes disease? 1) found in large numbers in diseased but not healthy individuals 2) can be isolated from the diseased individual and cultured outside 3) if re-injected into a healthy person, it should cause the same disease 4) isolate from this new individual and compare to first strain - they should be identical

Answer 30

1) non enveloped —> symmetrical protein capsid Eg adenovirus, calicivirus, picornavirus 2) enveloped —> lipid envelope derived from host cell membrane Can be Pleiomorphic (can change shape): measles virus Have a typical shape: Ebola virus 3) combination of capsid and envelope Eg Herpes virus

Answer 31

Attachment of protein to host cell via specific protein or glycoprotein receptors Entry of virus Capsid falls away, exposing the genome Formation of early regulatory proteins Formation of late structural proteins Formation of virion Exocytosis by budding or cytolysis (host cell explodes, releasing all newly formed viruses)

Answer 32

gp120 on HIV binds to CD4 receptor on host T helper cell and then to co receptors CCR5 or CXR4 HIV enters by fusion with membrane, instead of endocytosis Capsid falls away, exposing genome Reverse transcriptase converts HIV RNA to doubled stranded DNA Integrase inserts it into the hosts DNA Formation of viral proteins by host Leave by budding

Answer 33

Influenza virus has haemagglutinin spike which attaches to sialic acid receptor on host cells Virus enters cell by endocytosis Capsid falls away, exposing the 8 segments of the negative sense RNA genome of Influenza The RNA is converted to mRNA using RNA dependent RNA polymerase Viral proteins are made use host ribosomes Cytolytic release (cell breaks) of virions using neuramindase (cleaves the bind between haemagluttinin and host cell receptor, releasing the virus molecule)

Answer 34

Amantadines block the uncoating of the virus by blocking M2 channels RNA polymerisation Neuraminidase inhibitors (leave virus bound to sialic acid)

Answer 35

Detection of ``` Viral genome - PCR Viral antigens - ELISA Viral particles - electron microscope Viral antibodies - serology Cytopathic effect - isolate suspect virus and place onto cultured cells - see if produces cytopathic effect ```

Answer 36

Cell dies due to infection with virus Due to either the virus trying to stop the host cell synthesis proteins Or excessive production and accumulation of new virus particles (causes cell to burst open - cytolysis)

Answer 37

Lysis occurs due to shutdown of protein synthesis or virus particles using cytolytic exit Death of cells causes formation of plaques (clear areas on a layer of cells where the virus killed of the cells) - serial dilutions can be done of viral solutions and the number of plaques each dilution forms can be recorded - can quantify initial viral conc —> “plaque assay” Or instead of dying, the virus can cause the cells can fuse together forming syncytia. A syncitia assay can also be done to measure how many virus particles you have. Syncitia develop with HIV infection

Answer 38

``` CASS Cost - needs to be affordable Administration - easy to administer Safety - most important Strains - does it deal with all the strains ```

Answer 39

Bacteria are prokaryotes so are completely different to human cells so abs can just target these differences Viruses however, enter host cells and replicate there using host machinery - so need to be v selective to damage as few of our own cells as possible

Answer 40

Antiviral for influenza Sits in and blocks the tetrameric M2 proton channel which would usually have protons passing through as part of the process to uncoat the virus and allow it to enter the cell Developed by random screening Is functionally useless now as a single point mutation in the influenza virus gives it resistance. This mutation also doesn’t affect the virus’ fitness so it is rapidly spread through viral populations. Almost every modern flu strand is no resistant to amantadine

Answer 41

Antivirals for influenza Developed by rational dug design - ie using knowledge of structure of influenza virus Developed to be the shape of sialic acid - hold the neuraminidase so the virus is stuck into the old cell and can’t move onto and infect a new one Examples Relenza and Tamiflu Baloxavir - binds to and inhibits PA endonuclease (subunit of influenza viral RNA polymerase)

Answer 42

It is a nucleoside analogue antiviral Used to treat HSV 1 (cold sores) It lacks a 3 hydroxy group and so, when inserted into the viral genome, it prevents formation of phosphodiester bond and acts as a chain terminator Very specific - given in the unphosphorylated form but needs to be in the tri phosphorylated form to work. Only virus infected cells have the thymidine kinase needed to phosphorylate it Further specificity comes from the fact that acyclovir tri phosphate has a higher affinity for viral RNA polymerase Resistance is very rare, as the mutation for viruses not to produce thymidine kinase makes them less fit, so it’s not easily spread in the population - poor selection pressure

Answer 43

Analogue of adenosine Causes chain termination 3 nucleotides downstream of where it was incorporated Developed for use against Hep C Tested against Ebola but didn’t meet endpoint Being tested against Covid

Answer 44

HAART - highly active anti retroviral therapy Combination therapy of multiple (3) antivirals - incase your infection develops resistance to one of them PrEP - pre exposure prophylaxis Taken by people who have sexual relationships with HIV positive individuals to prevent infection with HIV the drug used for PrEP is Truvada - a combination of two NRTI’s (nucleoside reverse transcriptase inhibitors) AZT Is a nucleoside analogue Worked to start with but then became ineffective due to resistance - as used only as a single drug

Answer 45

If the person is infected, they may have a lot of HIV virus in their body already PrEP is a combination of only 2 drugs instead of 3, so could lead to selection of resistance more easily

Answer 46

Passive immunotherapy Antibodies taken from recovered individuals or produced from immortalised B cells (Always end in “mab”) Eg palivizumab against RSV for infants - a humanised monoclonal antibody against the F protein

Answer 47

The chemistry of relenza means it more readily acquires resistance

Answer 48

It inhibits the neuraminidase enzyme that removes sialic acid from the infected cell surface and allows onwards spread of the new virus particles

Answer 49

Human rhinovirus

Answer 50

Because there are hundreds of different serotypes which are all antigenically distinct

Answer 51

It exists as multiple different classes/ quazi-species

Answer 52

They secrete surface antigens out of them which bind to and mop up antibodies so the antibodies can no longer bind to the virus or to infected cells

Answer 53

Has 4 serotypes and carries out antibody dependent enhancement (binding of viruses to suboptimal antibodies enhances their entry into host cells) This leads to dengue haemorrhagic fever when you are infected with 2 serotypes (second virus serotypes notes cells via antibodies to first virus serotype)

Answer 54

``` Mutation - antigenic drift (over time, accumulation of mutations) Antigenic shift (sudden recombination - happens with zoonotic infections) ```

Answer 55

Small proteins released by virus infected cells Initiate the antiviral state in infected cells and surrounding cells - protein kinase R, 2’5’ oligoandenylate synthase, activate NK cells Types: Type I = IFN Alpha and beta Type II = IFN gamma Type III = IFN lambda

Answer 56

Hep B : inhibits IFN transcription | Influenza : produces NS1 protein which counters RNA sensing and prevents poly A processing

Answer 57

Are antigen presenting Produce interferons and cytokines Initiate and determine the nature of CD4/8 T cell response

Answer 58

Nucleoside analogue reverse transcriptase inhibitors

Answer 59

PBP 2a (gene which encodes beta lactamase)

Answer 60

Molecules, mostly proteins, which are recognised by highly specialised lymphocyte receptors and act to induce an adaptive immune response

Answer 61

Antigens (corresponding to a pathogen) encountering B or T lymphocytes which have receptors with specific reactivity

Answer 62

Immunological memory Long lasting protection Highly specific

Answer 63

Immunoglobulin gene rearrangement | During B cell maturation in bone marrow, the gene segments are rearranged

Answer 64

Possibility of generating receptors which react against self antigens - autoimmunity

Answer 65

T cells mature in thymus, B cells in bone marrow T cells are inside lymph nodes, B cells stay outside lymph nodes T cells must respond to antigen presentation (antigen + MHC of antigen presenting cells), B cells can respond directly to antigens that have drained into the lymph nodes T cells are to do with killing things, B cells are to do with antibodies

Answer 66

Antigen binds to T cell receptor - cell proliferates and divides into 1) Cytotoxic T cells: kill infected cells or intracellular pathogens 2) Helper T cells: provide signals, often in the form of specific cytokines, that activate the function of other cells eg B cells to produce antibodies, macrophages to kill engulfed pathogens 3) Regulatory T cells: suppress activity of other lymphocytes, help to limit possible damage of immune responses

Answer 67

CD4 receptor = T helper cell | CD8 receptor = T killer cell

Answer 68

Macrophages, inflammation, B cell class switching Produce IFN gamma, TNF, IL12 Act against microbes which can survive or replicate inside macrophages - recognise bacterial antigens on surface of macrophage and release IFN gamma which further activates the macrophage and enables it to destroy the intracellular pathogen more efficiently Pro inflammatory Promotes B cell class switching that favours IgG production

Answer 69

Allergies and worms ``` Produce IL4/5/13 Help control infections from extra cellular parasites such as helminths by promoting responses involving eosinophils, mast cells and IgE Cytokines produced by secondary response are required for B cell class switching to produce IgE - fights parasitic infections and allergies ```

Answer 70

Neutrophils, bacteria, fungi Produce IL 6/17/23 Induces in response to extra cellular bacteria and fungi Amplify neutrophilic responses to these

Answer 71

B cell support Produce IL21 Interact with B cells to regulate antibody production

Answer 72

no immune response Produce IL10 and TGF beta Anti inflammatory Limit immune/T cell response

Answer 73

Effector T cells express surface molecules and cytokines that help B cells differentiate into plasma cells or memory cells ``` The interaction of the antigen stimulated B cell with the T helper cell determines the fine tuning of the antibody response (increasing affinity of antibody for antigen) and class switching to most immunoglobulin classes other than IgM - B cells that haven’t been stimulated by binding to T helper cells can only produce IgM (IgM is not very specific, so T cell biding is v important) ```

Answer 74

Apoptosis (programmed cell death) by fragmentation of nuclear DNA Initiate lysis through pore creation: Store perforin, granzymes, granulysin in cytotoxic granules Release granules after target recognition Perforin molecules polymerise and form pores in the pathogen/infected cell Granzymes then travel through pores and stimulate the apoptosis inside the cell

Answer 75

Top = variable region Bottom = constant region Part that inserts into T cell = cytoplasmic tail

Answer 76

Small portion of the antigens structure which is recognised by the antigen receptor or antibody (Has MHC on it)

Answer 77

MHC I present on all nucleated cells (SO NOT RBCs) Has a single variable alpha chain and a common beta micro globulin MHC II Only on professional antigen presenting cells Has 2 chains - an alpha and a beta chain

Answer 78

Glycoprotein

Answer 79

Dendritic cells Macrophages B lymphocytes

Answer 80

Antigen from the pathogen/target (infected) cell is presented on MHC I to CD8 T cell - saying that it needs to be killed Antigen from professional antigen presenting cell is presented on MHC II to CD4 T cell - to get it activate and initiate the immune response

Answer 81

Scan cells, looking for MHC I showing non self (in uninflected cells, MHC I shows self peptides) - antigens derived from viruses or bacteria replicating inside of an infected cell are displayed on the cells surface by MHC I

Answer 82

Recognise antigens presented by MHC II proteins (expressed by antigen presenting cells: dendritic cells, macrophages, B cells) - recognise antigens taken up by phagocytosis from extra cellular environment

Answer 83

Co dominant - both maternal and paternal genes are expressed

Answer 84

Cells from transplanted organ are very likely to have different MHC a than your self cells So your immune system recognises them as non self and will attack the transplanted organ

Answer 85

MHC is 1) polygenic: there are several different MHC I and II genes 2) highly polymorphic: there are multiple alleles/variants of each gene

Answer 86

Surface bound antibodies

Answer 87

Thymus dependent pathway: - BCR recognises thymus dependent antigen - antigen is internalised and degraded and expressed with MHC II on surface - antigen MHC II complex is recognised and bound by CD4 T helper cell - B cell is activated and produces antibodies (B cell undergoes class switching, produces IgG antibodies rather than IgM) Thymus independent pathway: - induces antibody production in the absence of helper T cells - first signal from thymus independent antigens: highly repetitive molecules eg polysaccharides of bacterial cell walls - second signal from microbial PAMPs eg LPS (activate TLR signalling in B cell) - only leads to IgM production and no memory *note that thymus dependent actually has nothing to do with your thymus, it really means T cell dependent

Answer 88

Clonal selection (of specific B cell to that antigen) and clonal expansion

Answer 89

``` There are 5 types IgM IgD IgG IgA IgE And 5 classes of each type - the classes are denoted by lower case Greek letters and are defined by the structure of the antibody’s heavy chain Mu Delta Gamma Alpha Epsilon ```

Answer 90

IgM (it’s the first antibody produced)

Answer 91

Consists of 2 heavy chains and 2 light chains The heavy chains are joined to each other by disulphide bridges and each heavy chain is joined to a light chain by a disulphide bridge Their is a variable region (Fab region) and a constant region (Fc region) There are glycosylation sites on the Fc region There are 2 identical antigen binding sites Two types of light chains in antibodies (lambda and kappa) - will never have both in the same antibody

Answer 92

Opsonisation - for bacteria in extra cellular space: antibodies coat a bacterium to better enable phagocytosis by macrophage or neutrophil. Fc receptor on phagocytic cell binds to Fc region on antibodies and ingests the complex Neutralisation - for bacterial toxins: antibodies bind to viruses/bacterial toxins and block their entry into cells - preventing infection and destruction of other cells, this complex is then ingested by macrophages Complement activation - for bacteria in plasma: antibodies coat bacterial cell . This stimulates complement proteins and therefore stimulates complement receptors on macrophages. Bacterium is lysed by MAC and ingested by macrophage

Answer 93

Treg (decrease immune response, this is needed when the immune system is overactive)

Answer 94

``` Class switching (Producing IgM due to thymus independent activation - by antigens going straight into the lymph nodes. Dendritic cells then present antigens to the T cells, activating the T cells. These activated T cells then cause thymus dependent activation of the B cells, which causes class switching) ```

Answer 95

Immunoglobulin gene rearrangement

Answer 96

Artificial active

Answer 97

``` Safe Cheap Easy to administer Single dose, needle free Stable Active against all variants Life long protection ```

Answer 98

The more immune individuals there are, the less likely it is that a susceptible person will come into contact with someone who has the disease (to do with reducing the R0 number)

Answer 99

The number of people an infected person goes on to infect R0 < 1 : the infection will die out in the long run R0 = 1 : each infected person passes disease to one person R0 > 1 : disease spreads exponentially in population Aim is to reduce it to below 1

Answer 100

Antigens : stimulate the immune response to the target disease Adjuvant (normally alum) : enhance and modulate immune response (by replicating the danger signals needed to stimulate dendritic cells) Excipients : inactive vehicle or medium for the vaccine - buffer, salts, saccharides and proteins - maintain pH and osmolarity - preservatives - water

Answer 101

Inactivated protein : tetanus toxoid Dead pathogen : Split Flu vaccine , Hep A Live attenuated pathogen : OPV(Polio) / BCG / LAIV(influenza) / chickenpox / MMR Recombinant protein : Hep B Carbohydrate : S pneumoniae Carbohydrate is a carb that the pathogen specifically produces Recombinant protein is made synthetically to replicate pathogen

Answer 102

Live attenuated pathogen

Answer 103

Inactivated protein

Answer 104

Carbohydrate

Answer 105

Chemically inactivated form of toxin | Induces antibody, antibody binds to toxin and blocks it from binding nerves

Answer 106

``` Pros Cheap and simple to make Relatively safe High protective efficacy Highly immunogenic - stimulates immune response v well ``` Cons Not all pathogens produce toxins Need a good understanding of the toxin produced Toxin may not be fully inactivated

Answer 107

Contain a mutation which prevents them from causing disease but can still replicate and be recognised by host immune system as foreign

Answer 108

Pros Replicate so a small dose is needed Strong immune response - life long immunity Induce a strong local immune response in the site where the particular infection is most likely to occur ``` Cons May lose key antigens on attenuation May develop virulent factors Can infect immunocompromised Can be outcompeted by other infections ```

Answer 109

Pathogen is killed either chemically (phenol or formaldehyde) or by heating Antigenic components are still intact so can initiate B or T cell response

Answer 110

Pros Effective in stimulating an immune response Cheap Simple Cons Antigen can be altered or destroyed in inactivation Need to grow live pathogen which can contaminate the vaccine - risk of vaccine induced pathogenicity

Answer 111

Immune system generates neutralising antibodies against the antigens

Answer 112

``` Pros Pure Safe Good immune response Low strain variation ``` Cons Expensive Protein structure may not be exactly the same

Answer 113

Same as carbohydrate vaccines Polysaccharide coat component is coupled to an immunogenicity carrier This protein stimulates a T cell response via CD4 which improves B cell immune response

Answer 114

Pros Improves immunogenicity Highly effective against infections by encapsulated bacteria Cons Expensive Strain specific Carrier protein may interfere with immune response

Answer 115

Substances used in combination with a specific antigen that provide a more robust immune response than using the antigen alone

Answer 116

Activate dendritic cells, which then present the antigens to T cells Extra info: not that important (Potentate immune response by interacting with PAMPs and DAMPs which causes the cell to release inflammatory mediators. These are recognised by pattern recognition receptors on T cells)

Answer 117

``` Changing age demographics Changing environments (disease moving to different parts of the world) Antibiotic resistance New viruses Old diseases we still can’t fix ```

Answer 118

Scientific challenges Infection safety Logistics Development issues - time / cost of vaccine development / cost of product Public expectation of a risk free vaccine

Answer 119

Herd immunity

Answer 120

The sites where new lymphocytes are made - lymophopoesis

Answer 121

B, T and NK cells All derived from common lymphoid progenitor cells Which are derived from HSCs - multi potent haematopoietic stem cells

Answer 122

Bone marrow and thymus (B and T cell populations originate in bone marrow. B cells complete most of development there but T cells migrate to the thymus, where they complete development)

Answer 123

B cells | Bone marrow has yellow centre (fat) and red around that where haematopoiesis occurs

Answer 124

Foetus Liver Spleen All bones Adult Mostly flat bones: iliac bones, vertebrae, ribs

Answer 125

Positive selection: testing if the T cell receptor can signal/respond to an MHC (does it work positively ?) Negative selection: testing if the T cell reacts against our own body (making sure it doesn’t work negatively) (This is Central T cell tolerance!!)

Answer 126

Thymic output declines with age Thymus itself degenerates - thymic involution occurs (shrinking and structural change of thymus with age) and functional tissue is replaced with fat

Answer 127

Remains the same Number of peripheral T cells is maintained by the division of mature T cells outside the central/primary lymphoid organs But this means you get less variety as fewer cells come from new lineages - so older people are more vulnerable to a new strain of pathogen

Answer 128

1) no change to thymus (because this isn’t where the lymphocytes are interacting with the antigens) 2) increased white cell production Most changes will happen in secondary lymphoid tissues

Answer 129

Where lymphocytes can interact with antigens and other lymphocytes

Answer 130

``` Lymph nodes Spleen Epithelial barriers Gut associated lymphoid tissue Tonsils ```

Answer 131

At the point of convergence of vessels of the lymphatic system

Answer 132

Collects antigens from blood and is involved in immune response to blood borne pathogens Lymphocytes enter and leave spleen via blood vessels

Answer 133

Majority of the spleen is red pulp - where haemopoiesis occurs Arterioles run through the spleen and lymphocytes surround these arterioles, forming white pulp This sheath of lymphocytes around an arteriole is called the periarteriolar lymphoid sheath (PALS) and contains mainly T cells Lymphoid follicles occur at intervals along the sheath, containing mainly B cells

Answer 134

Epithelial/mucosal surfaces eg skin Protected by secondary lymphoid tissues - MALTs ( mucosa - associated lymphoid tissues Skin can have cutaneous immune system

Answer 135

Gut associated lymphoid tissues | Includes tonsils, adenoids, appendix, peyers patches (in small intestine)

Answer 136

A peyers patch contains numerous B cell follicles which contain germinal centres T cells occupy the areas between the B cell follicles Antigens are collected directly from the gut by specialised elithelial cells - M cells Dendritic cells in the peyers patch present the antigens to T cells Effector lymphocytes generated within the peyers patch travel through lymphatic system and into blood stream They are disseminated (spread) back into mucosal tissues to carry out their effector actions

Answer 137

``` Langerhans cells (type of dendritic cell) Keratinocytes Intraepidermal lymphocytes T lymphocytes Tissue resident macrophages ```

Answer 138

``` Lingual tonsil (on bottom behind tongue) Palatine tonsil (on sides) Tubular tonsil Pharyngeal tonsil (on top) ``` All form the Waldeyer’s ring

Answer 139

Trap antigens and antigen presenting cells from infected areas and present them to small lymphocytes to initiate adaptive immune response

Answer 140

Enter the blood stream and continuously circulate peripheral lymphoid tissues Eg lymph nodes Spleen Mucosal lymphoid tissue of gut, nasal, resp, urogenital tracts

Answer 141

Increased size

Answer 142

Cost of production | Ease of administration

Answer 143

Inactivated protein vaccine

Answer 144

B and T cells

Answer 145

Clonal expansion and Clonal selection

Answer 146

Lymph node (or any secondary lymphoid tissue eg spleen)

Answer 147

No he cannot be forced | He has bodily autonomy

Answer 148

Highly attached to the arterial circulation via the splenic artery So it can filter blood rapidly and in large numbers

Answer 149

Thymus Bone marrow Foetal liver

Answer 150

An anatomically restricted site where B cells undergo maturation and selection to generate high affinity antibodies

Answer 151

Selectin binding | Integrin binding

Answer 152

1) rolling along endothelial surface of HEVs (High endothelial venules) Mediated by L selectin and CD34 (selectins) 2) activation of integrins Mediated by CCL21(chemokine) 3) firm adhesion Mediated by LFA-1 and ICAM-1(integrins) 4) Diapedesis into paracortical areas/ T zones Mediated by CCL21 and CXL12 (chemokines)

Answer 153

The display of peptides on MHC I or MHC II proteins such that the T cell receptor can attempt to bind them

Answer 154

Professional antigen presenting cells - dendritic cells Or Flow of antigens by themselves into lymphatic system

Answer 155

Activation of dendritic cells’ PRRs (pattern recognition receptors) by PAMPs at the site of infection stimulates the dendritic cells in the tissues to engulf the pathogen and degrade it intracellularly They also take up extra cellular material eg virus particles and bacteria - “macropinocytosis”

Answer 156

Free antigens and antigen presenting dendritic cells travel from site of infection through afferent lymphatic vessels into the draining lymph nodes Here, activated T cells undergo proliferation and differentiation and leave via efferent lymphatic vessels This carries them to the blood stream and towards the tissues where they will act

Answer 157

Detection of tissue damage - DAMPs (damage associated molecular patterns) eg DNA outside of cell Detection of pathogenic structures - PAMPs (pathogen associated molecular patterns) eg peptidoglycan from bacterial cell wall This initiates the innate / non specific immune response These cells than communicate with adaptive immune cells After some time, adaptive immune response is initiated

Answer 158

After a pathogen is cleared, some of the immune cells undergo apoptosis due to reduced signals to them Therefore there is reduced production of inflammatory cytokines The cell population “contracts” (ie shrinks in size) and some of the remaining cells form memory cells Tissue repair and remodelling occurs

Answer 159

All cells of one lineage have the same receptors

Answer 160

Physical barriers - skin - mucous - epithelial cells Humoral barriers - mediated by liver - lectins: bind to specific bacterial carbohydrates, neutralise and opsonise pathogens for destruction - iron chelation proteins: prevent formation of favourable environment for bacteria - complement system : Anaphylatoxins (increase vascular permeability) Chemokines (attract immune cells to site of infection through conc gradients) Opsonisation (by complement or antibodies, sets a pathogen up for phagocytosis) Membrane attack complex - MAC ``` Cellular barriers - granulocytes: Neutrophils Basophils Eosinophils Mast cells Monocytes Macrophages NK cells (only innate lymphocytes) Dendritic cells ```

Answer 161

Neutrophils | Followed by macrophages

Answer 162

Inactive cells | Haven’t yet come into contact with pathogen/antigen for which they have a specific receptor

Answer 163

Are either tissue resident or circulatory

Answer 164

From monocytes - monocytes circulate in the blood for a few days and then go back into tissues and become macrophages

Answer 165

``` Enhanced: Phagocytosis and migration Cytokine/chemokine production Expression of cell surface molecules Anti microbial activity Antigen presentation and T cell activation ```

Answer 166

Interferons are secreted by immune cells and non immune cells (infected cells) in response to intracellular infection - ie by viruses or gram negative bacteria The interferons signal surrounding cells to produce proteins which stop the immune infection Eg type 1 and 3 interferons promote antiviral responses type 2 interferons promote anti bacterial response

Answer 167

Nucleases Inhibitors of viral entry and exit Inhibitors of viral uncoating and replication Inhibitors of protein translation

Answer 168

Virus and cancer cells can evade detection by MHC I - could stop host cell producing it So NK cells will kill all cells that do not express MHC I as the reason for this could be a viral infection or cancer

Answer 169

Humoral immunity: - antibodies - complement (stimulated by antibodies via classical pathway) Cellular immunity: - cytotoxic T cells - T helper cells - T regulatory cell - B lymphocytes - Plasma cells

Answer 170

TCR BCR (which is basically a surface bound IgM receptor) There are millions of variations of these but they need to be tested against self antigens first to make sure they don’t cause autoimmunity The selected ones will undergo Clonal expansion and all cells of the same clonal lineage will have the same receptor

Answer 171

In lymphoid tissues - lymph nodes/ spleen/ GI mucosa/ mucosal epithelia/ bone marrow And In the circulation - memory T cells can constantly migrate to and from lymphoid tissues - memory B cells can differentiate into plasma cells which secrete abs into blood

Answer 172

MHC II + antigen complex from professional APC

Answer 173

When APCs bind to T cells they activate them by producing cytokines eg IL-12 which causes T cell replication In response to this, T cells produce cytokines that activate the APCs eg IFN-gamma which upregulates MHC-II expression for antigen presentation

Answer 174

Activate phagocytes: T helper cells Activate B cells: Follicular T helper cells Directly kill infected cells: cytotoxic T cells Regulate immune response: T helper cells

Answer 175

Can function as APCs - present soluble antigens to T cells | Produce antibodies by differentiating into plasma cells

Answer 176

Th1: macrophages - macrophage activation against intracellular pathogens Th2: eosinophils - eosinophil and mast cell activation against helminths Th17: neutrophils - neutrophil activation against extracellular bacteria and fungi

Answer 177

Naive T cell - hasn’t encountered its particular antigen Effector T cell - during the infection Memory T cell - after the infection

Answer 178

Level of Naive T cells goes down Level of memory T cells goes up Because as someone ages they get thymic involution and the thymus stops producing naive T cells And also as you age and encounter more pathogens, more of the remaining naive T cells will change into effector and then memory T cells

Answer 179

Innate immune cells recognise that there is a pathogen and become activated They secrete cytokines (to recruit adaptive immune system) and phagocytosis the pathogens The APCs travel into secondary lymphoid tissues where they encounter naive lymphocytes and activate them The lymphocytes proliferate and differentiate into a specific type (type is based on the specific cytokines secreted by the phagocytes) The activated lymphocytes can then start the cellular and humoral respond of the adaptive immune system

Answer 180

Because after RE-exposure, the plasma cells will continue to secrete protective serum antibodies - so the antibody level in the serum after the second infection will be higher than after the first infection - after first infection, level of antibodies returns back to normal level

Answer 181

False | MHC I can be read by cytotoxic T cells whilst MHC II can be read by T helper cells

Answer 182

False | MHC I can also show pathogen peptides if the cell has been infected

Answer 183

False | MHC I is on all NUCLEATED cells

Answer 184

Yes but it’s not their main function | APCs are mostly macrophages and dendritic cells

Answer 185

Reduced removal of pathogens/ unwanted cells Opportunistic infections Cancer - cancerous cells will evade immune response and apoptosis

Answer 186

Can cause hypersensitivity- immune system attacks own tissues Can be triggered by - infection - environmental factors - female predisposition - genetic factors - hygiene hypothesis (we have such good hygiene nowadays that our immune system encounters much less pathogens than it used to, so instead it reverts to attacking our own tissues)

Answer 187

Immune system causes damage to self tissues Damage to tissues produces more of the signals/antigens that recruit immune cells This drives an even stronger immune response

Answer 188

Sepsis - immune cells enter the wrong compartment of the body, causing organ dysfunction there Hypercytokinaemia (cytokine storm) - body produces too many cytokines, can cause organ dysfunction and sepsis Organ dysfunction- can be due to cytokine storm and sepsis or can be directly due to autoimmune diseases eg type 1 diabetes, Hashimotos Fatal damage to tissues - eg in MS, ALS (autoimmune diseases of nervous system)

Answer 189

Licensing of the immune response

Answer 190

Antigen (which they are specific to, on MHC I for cytotoxic or II for helper) Costimulation (via receptors on APCs) Cytokines (from immune or infected cells)

Answer 191

Apoptosis - prevents auto immunity The problem is that antigens from damaged self tissue will remain in the body for a long time, until the tissue from which they are derived is completely destroyed. So the immune system needs to have a way to limit the immune response to these persistent antigens (break the positive feedback loop) - basis of immune tolerance

Answer 192

The specific unresponsiveness to an antigen that is induced by the exposure of lymphocytes to that antigen

Answer 193

Could treat auto immune or allergic diseases | Could make organ transplants more successful

Answer 194

Central tolerance - destroys self specific T and B cells before lymphocytes enter circulation. B cells destroyed in bone marrow, T cells destroyed in thymus Peripheral tolerance - after lymphocytes enter circulation

Answer 195

If the IgM antibodies on the surface of B cells produced in the bone marrow bind to and react with antigens on the stromal cells of the bone marrow, they undergo apoptosis as they are auto reactive

Answer 196

T cells shouldn’t bind to MHC when there is no antigen presented or when the antigen presented is not one that they are specific to So T cell tolerance has 2 stages 1) positive selection: does T cell bind to MHC at all. If not, apoptosis 2) negative selection: does T cell react to self antigens and MHC too strongly. If yes, apoptosis

Answer 197

Thymic cells express a transcription factor called AIRE | This allows them to express antigens found on cells that aren’t in the thymus

Answer 198

It is a very severe systemic autoimmune disease due to mutations in the AIRE gene So T cells aren’t exposed to antigens from other parts of the body during their development, thus affects the negative selection process so some auto reactive T cells can be released

Answer 199

Peripheral tolerance

Answer 200

B cells undergo somatic hyper mutation - “affinity maturation” When a B cell is activated and selected it will undergo clinal expansion by mitosis. The mitosis/replication of the variable/Fab region of the antibody/receptor on the B cells is made to be prone to mistakes This is to allow for receptors with higher affinity to the antigens to be made (as well as those with lower affinity) Only those with higher affinity will survive This allows for B cells with higher affinity to the antigen to be produced A problem with this is that some pathogenic antigens are very similar structures to self antigens So affinity maturation could produce B cells which could be auto reactive against self tissues and cause systemic immune response These need to be inactivated by peripheral tolerance

Answer 201

Anti ‘streptococcus pyogenes’ antibodies can cross react with heart muscle and cause infective endocarditis

Answer 202

During positive selection If they bind more strongly to MHC I, they become CD4 T helper cells If they bind more strongly to MHC II, they become CD8 cytotoxic T cells

Answer 203

Anergy Ignorance Deletion/AICD (antigen induced cell death) Regulation

Answer 204

Anergy is when a T cell can encounter it’s specific antigen but without co stimulation - “unresponsiveness to self antigens” These cells, esp naive T cells, became anergic, ie they become less and less responsive, even if a later antigen with costimulation is encountered Also occurs at the end of an immune response

Answer 205

Can happen in 2 ways 1) T cells that encounter antigen in levels lower than the threshold response, will eventually either become anergic or undergo apoptosis 2) Naive T cells, that could potentially be self reactive, are kept out of important “immunopriveliged” sites eg in brain/eye/ genitalia (where you don’t want an auto reactive inflammatory response) This is either by - “compartmentalisation”: anatomical barriers preventing migration Eg in testes Or - Anti inflammatory cytokines and apoptotic signals Eg in brain Also occurs at the end of an immune response

Answer 206

T cell binds to APC, but instead of being activated by this, it is signalled to undergo apoptosis This is induced by “Fas ligand” (FasL) This reduces the number of auto reactive T cell This also occurs at the end of an immune response to normally to T cells that are normally functioning, but you want to get rid of them after an infection

Answer 207

Carried out by regulatory T cells Reg T cells bind to self antigen but don’t kill them as a response They upregulate transcription factor Fox P3 which helps them develops into mature Treg cells

Answer 208

Develop IPEX syndrome: | - immune disregulation/ polyendocrinopathy, enteropathy X-linked IPEX

Answer 209

During pregnancy, mothers are exposed to their foetus’ cells which have a different MHC I But their immune system must make sure they don’t launch an immune response against the foetal cells Treg cells control this

Answer 210

Natural regulatory T cells (nTreg) - develop in thymus, reside in periphery Inducible regulatory T cells (iTreg) - develop during T cell immune response

Answer 211

1) inhibit APC receptor expression - affects costimulation etc 2) release anti inflammatory cytokines (IL-10, IL-35, TGF beta) - blocks release of pro inflammatory cytokines - stimulates expression of inhibitory ligands on APCs so cells that come into contact with the APCs become inactivated 3) mop up inflammatory cytokines

Answer 212

Master regulatory cytokine Is pleiotrophic ie has many functions Inhibits production of pro inflammatory IL6/8, IFN gamma, TNF Inhibits macrophage function Some viruses will mimic IL10 in order to escape the immune system

Answer 213

Once T helper cells have developed into different subtypes, they secrete specific cytokines These cytokines drive more production of the T helper cell subtype that released them, but down regulate/ have inhibitory effects on the formation of other T helper cell subtypes

Answer 214

They provide the link between the cellular and humoral immune response by activating naive B cells to become plasma cells, through interaction between TCRs and MHC II

Answer 215

B cell internalise antigen and presents it on MHC II to Tfh Costimulatory binding of CD40 on Tfh to CD40L on B cell - activate the B cell Costimulatory binding of CD28 on Tfh to B7 on B cell - activate the T cell Tfh then starts to secrete IL21 which amplifies B cell activation

Answer 216

The interleukins secreted by the particular T helper cell

Answer 217

Different antibody classes (eg IgE vs IgA) have different constant regions

Answer 218

``` 2 The interleukins, secreted by the T helper cell that regulates the whole response, determines the antibody class produced ```

Answer 219

Skin prick test, checking for wheal and flare reaction to specific known allergens

Answer 220

Immediate and mediated by IgE against environmental allergens Two phases 1) sensitisation Early phase (within minutes): Leads to formation of Th2 cells (which recruit eosinophils) and follicular T helper cells specific to the allergen The Tfh cells secret IL4 and 13 which causes B cells specific to the allergen switching from IgM to IgE production IgE is immediately taken up and loaded onto cell membranes of mast cells and basophils through their Fc epsilon receptors When the allergen is encountered again and a second antibody binds to the mast cell/ The 2 IgE antibodies cells cross link and this causes the mast cells/basophils to degranulate as they have been sensitised to the antigen 2) re exposure leading to anaphylaxis They release inflammatory mediators, causing the hypersensitivity reaction at much lower antigen conc than normal immune reactions Later response (within a few hours) : Recruitment of neutrophils Late response (within 3-4 days): Eosinophils are recruited and Th2 cells are present

Answer 221

Histamine: vascular permeability and smooth muscle constriction Cytokines: recruit and mediate immune response Leukotrienes and prostaglandins: vascular permeability and smooth muscle constriction Proteases: break down ECM

Answer 222

One of the inflammatory mediators released is proteases which break down ECM, constant breaking down and building up can cause cancer

Answer 223

Adrenaline injection - because histamine released during the hypersensitivity causes increased vascular permeability and decreased blood pressure, adrenaline counteracts thus by causing vasoconstriction Antihistamine Put patients feet up - maintain blood perfusion

Answer 224

They could get a second anaphylaxis reaction even after they are stable - called “biphasic anaphylaxis”

Answer 225

IgG or IgM mediated cytotoxicity reactions against either self antigens (self reactive B cells are activated by self reactive T helper cells) or foreign/extrinsic antigens bound to cell membranes In Type 2, the antibodies are tissue specific, rather than systemic Antibodies can cause disease by 1) ADCC - antibody dependent cell-mediated cytotoxicity This can happen by 4 cytotoxic mechanisms, the first 3 use the classical complement pathway Cytotoxic Mechanism 1 - antibodies bind to antigen on cell membrane and induce classical complement pathway - this recruits neutrophils to the site - the neutrophils degranulate, killing the cell Cytotoxic Mechanism 2 - antibodies bind to antigens on the cell membrane and induce the classical complement pathway - this leads to the formation of MAC which kills the cell by creating pores and inducing apoptosis by osmotic overload Cytotoxic Mechanism 3 - antibodies bind to antigens on the cell membrane and induce the classical complement pathway leading to the formation of C3b - C3b binds to Fc portion and acts as an opsonin around the cell - cell is now opsonised by ABs and C3b - macrophages in the spleen phagocytose the opsonised cell Cytotoxic Mechanism 4 - antibodies bind to antigens on the cell membrane - NK cells recognise the Fc portion of the antibody and release toxic granules containing perforin and granzymes + granulysin The perforin creates pores like MAC The granzymes + granulysin induce apoptosis 2) Anti receptor activity (non cytotoxic mechanism) Antibodies bind to antigens bound to cell membrane and either block the receptor so other substances can’t bind (eg in Myasthenia Gravis, abs bind to Ach receptor) Or abs activate the receptor themselves, leading to over activation (eg in Graves’ disease, abs bind to receptor on thyroid causing hyperthyroidism)

Answer 226

In type 2, self reactive antibodies bind to antigens on cell surfaces In type 3, the antigens are soluble and are just floating around by themselves in the circulation In type 3, complement is used more than in type 2

Answer 227

Usually auto antibodies (but can in some cases be against foreig; antigens) For auto antibodies: Self reactive B cells are stimulated by self reactive T cells to switch from IgM to IgG production The antibodies bind to soluble antigens in the circulation and from immune complexes Large immune complexes are quickly removed from blood by spleen but smaller ones are not - they are “less immunogenic” These small immune complexes then deposit in blood vessel walls, kidney glomeruli (due to blood filtration there) and joints (synovial fluid is filtered from the blood), causing inflammation and damage where they deposit eg to the blood vessel wall This leads to 2 problems 1) activation of complement system 2) activation of neutrophil degranulation The complement is activated, leading to -MAC formation - which leads to oedema by anaphylatoxins - which leads to neutrophil recruitment, the neutrophils are attracted to the site by chemokines - the neutrophils bind to Fc portion of ABs and try to oahgocytose the immune complexes but are usually unsuccesful - so instead, the neutrophils degranulate and release: Lysosomal enzymes Reactive oxygen species (can change DNA and cause nuclear damage ) Example: systemic lupus erythematosus (SLE) - auto antibodies against DNA and nuclear proteins Or could be against foreign antigens Example: serum sickness (when a person received antibody therapy for venom treatment, body produces antibodies against the foreign anti-venom antibodies. If the person is re exposed to the antivenom antibodies, they will mount a type 3 hypersensitivity response against the antibodies, leading to inflammation due to deposition in their vessel walls)

Answer 228

Delayed-type hypersensitivity | Because it is mediated by T cells and the recruitment of T cells takes time

Answer 229

Mediated by T cells instead of antibodies Damage can occur through CD4+ T helper cells or CD8+ cytotoxic T cells Reaction occurs in 2 phases 1) sensitisation phase Exposure to haptens leads to dendritic cell uptake Dendritic cells present to naive T cells in the lymph node and cause differentiation into Th1 cells which can then form memory cells 2) re exposure and immune response During re exposure, the specific memory T cells induce inflammation in the tissue by secreting IL2 and INF gamma which leads to Th1 cell expansion This causes macrophage activation (macrophages secrete TNF, IL1, IL6) These cause increased vascular permeability and swelling and redness Other types of T cells can also be involved, depending on the signal received from macrophages - Th17 can secrete IL17 which recruits neutrophils which can degranulate and kill the cell - CD8+ self reactive cytotoxic T cells can directly kill the cells with the antigens

Answer 230

Small proteins that function as antigens when bound to other proteins

Answer 231

Poison ivy infection Many autoimmune diseases - type 1 diabetes - Hashimoto’s thyroiditis - transplant rejection

Answer 232

Type 4 Sees if someone has been infected with TB Inject a small amount of tuberculin (antigen from TB) into the skin, if they have been infected their immune system has been sensitised, so this is a re exposure which will cause type 4 reaction You leave it for a few days and come back and if the6 have been infected, you will see an induration of the skin (hardness caused by swelling)

Answer 233

type 4 Th1 cells damage myelin around nerve fibres Th1 cells cause inflammation of intestinal lining

Answer 234

Histamine | Cause increased vascular permeability and vasodilation - leads to oedema

Answer 235

Causes vasoconstriction in the peripheral areas - increases blood pressure

Answer 236

Mast cell (more in the skin than basophils)

Answer 237

Adrenaline - cause peripheral vaso interaction and increases BP Anti histamine - reduces inflammatory response Corticosteroids- reduce inflammatory response

Answer 238

eukaryotes: well defined cytoskeleton prokaryotes: poorly defined cytoskeleton

Answer 239

rapid progression septic shock severe inflammatory response

Answer 240

cutaneous mucosal systemic mycoses

Answer 241

metazoa with eukaryotic cells | replicate sexually

Answer 242

``` egg miracidium (develops within small intermediate host) cercaria adult ```

Immunology And Infection Flashcards

(278 cards)