Immunology

Question 1

Define immunology

Answer 1

The study of the physiological mechanisms that we use to defend our bodies against invasion by other organism

Question 2

Hypervariable regions

Answer 2

Antibodies have 3 and these determine the complementary fit between the antigen and the antigen binding site of the antibody

Question 3

CDR’s

Answer 3

Complementary determining regions (part of the antibody and align with the loops at the end of the variable domain) which interact with the antigen and give the antibody specificity

Question 4

Antigen binding

Answer 4

Bind to the antigen binding site of the antibody by non covalent forces (hydrogen, ionic, VDWs and hydrophobic)=weak bonds so a large number is required to ensure the 2 parts bind together

Question 5

Antibody affinity

Answer 5

Strength of the total non-covalent interactions with a single antigen binding site on the antibody and a single epitope on the antigen

Question 6

Antibody avidity

Answer 6

Overall strength of multiple interactions between an antibody with multiple antigen binding sites and a complex antigen with multiple epitopes

Question 7

Antibody cross-reactivity

Answer 7

Antibody with an antigen binding site complementary to a specific antigen can also recognise different antigens with a similar structure

Question 8

IgG

Answer 8

• Gamma heavy chain
• Must abundant immunoglobulin
• Found in the blood and extracellular fluid
• Variability of the heavy chain at the hinge region gives rise to 4 different subclasses which have subtly different functions
• Activates the classical complement pathway
• Can be actively transported across the placenta to give the foetus passive immunity and therefore protect it

Question 9

IgA

Answer 9

• alpha heavy chain
• Variation of the heavy chain at the hinge region gives rise to 2 different subclasses which have subtly different functions
• found in breast milk
• multimeric due to formation of J chains, but IgA in the blood is monomeric
• monomer in the blood and dimer in secretion
• Secretion protects mucosal surfaces
• Secretory component of antibody protects it from degradation

Question 10

IgM

Answer 10

• mu heavy chain
• first immunoglobulin synthesised from infection in the primary immune response
• 5 monomers joined and held together by J chains=multimeric
• activates agglutination and the complement pathway
• multiple binding sites allow for agglutination and to compensate for the low affinity
• mainly found in the blood

Question 11

IgE

Answer 11

• epsilon heavy chain
• produced to defend against parasitic infections and allergic reactions
• binds to the high affinity Fc receptors on the mast cells and basophils which are complementary to this specific antibody
• the cross linking by antigen triggers the mast cell activation, degranulation and hence histamine and other inflammatory mediator release
• found at low concentrations/levels within the blood serum

Question 12

IgD

Answer 12

• sigma heavy chain
• very low blood serum concentration
• Involved in the B cell development and activation

Question 13

Light chains

Answer 13

Can be either both kappa or both lambda (cannot be one of each because the antibody molecule is symmetrical)

Question 14

Antibody roles

Answer 14

Roles in medicine, laboratory science and in defence

Question 15

Laboratory science antibody roles

Answer 15

vast range of diagnostic and research applications

Question 16

Medicine antibody roles

Answer 16

• Monoclonal antibody therapy for cancer treatment
• Antibody levels can help diagnose disease and monitor disease progress
• Pooled antibodies for passive immunity/therapy

Question 17

Defence antibody roles

Answer 17

• Neutralisation of toxins by antibodies binding to antigens/toxin molecules
• Passive immunity in newborns with the antibodies gained from the mother
• Opsonisation=coating of the pathogens with antibodies (proteins) to promote phagocytosis, aiding the phagocytes
• Agglutination=antibodies can clump the pathogens together due to their multiple antigen binding sites
• Complement activation via the classical pathway

Question 18

Where are the B cells produced and mature?

Answer 18

Produced by haematopoietic stem cells in the bone marrow and mature here also before being released into the bloodstream/circulation as naïve B lymphocytes

Question 19

Role of B lymphocytes

Answer 19

Occur in humoral immunity and if complementary antigen to binding site is encountered, cell proliferation occurs by clonal selection and antibodies of the same specificity will be synthesised

Question 20

Antigen epitope

Answer 20

The specific part of the antigen to which the receptor binds. Antigens have multiple epitopes so a single antigen can be targeted by multiple antibodies

Question 21

B cell receptor

Answer 21

Membrane bound antibody which binds to the epitope of antigens. Also consists of a di-sulfate linked heterodimer with an IgA and IgB component

Question 22

Di-sulfate linked heterodimer

Answer 22

Cytoplasmic tail is long enough to interact with the intracellular components and trigger a cascade

Question 23

Immunoglobulin gene rearrangement

Answer 23

• Accounts for multiple B cell receptors
• Occurs in bone marrow when progenitor B cells are converted to mature B cells
• Immature B cells begin with germline DNA
• Heavy chain has 3 gene segments=V,D and J regions
• Regions are composed of many segments and a singular segment is selected from each region to join to the constant region
• VDJ regions formed from recombination with addition/removal of DNA, then transcription and splicing
• light chain is V and J=no D
• 3 enzymes involved=kappa, lambda, all heavy

Question 24

VDJ recombinase

Answer 24

Discards unwanted loops of DNA

-Includes enzymes RAG 1 and RAG 2

Question 25

Alternative RNA splicing

Answer 25

IgD and IgM are co-expressed

Question 26

Plasma B cell

Answer 26

produces antibodies | -requires an accessory signal from microbial constituents or activation from a T cell

Question 27

Memory B cell

Answer 27

prepares for future infections=subsequent infections with the same antigen

Question 28

Somatic hypermutation and affinity maturation

Answer 28

improves antibody quality

Question 29

IgM BCRs

Answer 29

only immunoglobulin receptor which can recognise PAMPs

Question 30

Activation by T helper cells

Answer 30

- Antigen binds to BCR and is internalised by B cell - degraded into peptides on presented on membrane via MHC class 2 receptors - dendritic cell also has antigen presented in MHC class 2 - dendritic antigen recognised by CD4 T helper cell - T cell migrates to lymph nodes and encounters B cell with the same antigen=activates - B cell proliferates and divides

Question 31

Ig class switching

Answer 31

- Gene segment rearrangement in the constant region | - Secreted cytokines switches class

Question 32

Somatic hypermutation and affinity maturation

Answer 32

- more specialised BCR - once bound to antigen, AID enzyme alters variable region in B cell DNA=introducing point mutations to AT - Point mutations change the antibody structure helping the antibody bind more strongly to the antigen - weaker binding antibodies are selected against and don't survive - leads to improvement of antibody quality

Question 33

Primary antibody response

Answer 33

Involves IgM=not very protective

Question 34

Secondary antibody response

Answer 34

Class switch so memory cells change from IgM to IgG

Question 35

Cytokines

Answer 35

- secreted by immune cells | - small secreted proteins

Question 36

Type 1 interferons

Answer 36

Activates natural killers and anti viral defence

Question 37

Type 2 interferons

Answer 37

Produced by T cells usually and proinflammatory

Question 38

Pre-infection body defences

Answer 38

Mechanical, chemical and microbiological

Question 39

Cytokine storm

Answer 39

Overproduction of cytokines leading to accumulation of immune system cells=can lead to death

Question 40

Defence against bacteria

Answer 40

- Surface defences - fever - phagocytosis - antibody opsonisation - complement activation via the alternative pathway - release of inflammatory mediators and acute phase proteins

Question 41

Defence against viruses

Answer 41

-surface defences -interferons -Natural killer cells -release of inflammatory mediators and acute phase proteins -T cells mainly resolving infection antibody, complement, ADCC

Question 42

Gram positive

Answer 42

Violet, 1 cytoplasmic membrane, staph aureus not e coli (gram negative)

Question 43

Immune system function

Answer 43

Prevent infections by non self molecules - too much=immune hyper-activation autoimmunity - too little=infections

Question 44

Pathogen recognition

Answer 44

- bacteria enter body - PRR's recognise PAMPs - trigger innate response - APC's process and present antigen peptides to adaptive immunity

Question 45

MHC class 2

Answer 45

- APC's | - presents exogenous peptides on CD4 helper T cells

Question 46

MHC class 1

Answer 46

- all nucleated cells | - endogenous peptides on CD8 cytotoxic T cells

Question 47

MHC

Answer 47

- highly polymorphic | - presents processed antigens to T lymphocytes

Question 48

MHC class 2

Answer 48

heterodimer of 2 alpha 2 beta

Question 49

MHC class 1

Answer 49

heterodimer of 3 alpha 1 beta microglobulin

Question 50

cytotoxic

Answer 50

- direct killing - membrane perforation - fas to fasL induced apoptosis

Question 51

T cell pathway

Answer 51

- precursor in bone marrow - mature with markers in thymus - gene rearrangement in cortex and survival of T cells with useful TCR which binds to antigens - medulla sees elimination of T cells which bind too strongly to MHC - MHC bound peptide then co-stimulation then cytokine stimulation

Question 52

Helper

Answer 52

- response modulation - secrete cytokines - recruit other immune cells

Question 53

Cytotoxic T cells

Answer 53

-virally infected or transformed cells

Question 54

Th1

Answer 54

intracellular infection=macrophage activation

Question 55

Th2

Answer 55

allergy

Question 56

Th17

Answer 56

inflammation, bacterial and fungal infection

Question 57

Treg

Answer 57

- regulation of effector T cell function=regulation of immune response - switch off naïve or activated effector T cells - anergy (absence of normal immune response), deletion or regulation - regulation=T cell not exposed to the antigen or there is insufficient amount of antigen to activate it

Question 58

Role of Treg

Answer 58

-prevents excessive tissue damage (healthy tissue damage)

Question 59

Lymphocytes

Answer 59

- regulation by cytokines - prevent responses against self. central tolerance (thymus) and peripheral tolerance (anergy, deletion, regulation and ignorance) and prevents responses to also avoid tissue damage (lymphocytes apoptose after infection is cleared)