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Blood and defence > Antibodies and complement > Flashcards

Antibodies and complement Flashcards

1
Q

What is an antigen?

A

Substance that triggers the adaptive immune response

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2
Q

What two things can happen to an antigen receptor?

A

Secreted or cell associated

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3
Q

Describe T cell receptor location

A

Only associated to cell (no secreted form)

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4
Q

What produces antibodies?

A

Plasma cells (clonally selected B-cells)

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5
Q

Describe where T cells are made, where they travel and their response to an antigen.

A

Generated in bone marrow (primary lymphoid organ) then circulate through lymph system
T cell encounters antigen presenting cell in secondary lymphoid organs
Here immune reactions generate more lymphocytes

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6
Q

Where are plasma cells sites of immunoglobulin synthesis?

A

Gut, Mammary glands, lymphoid organs, bone marrow

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7
Q

What does the adaptive immune system require before maximal response?

A

Stimulation and clonal expansion

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8
Q

What generates diversity of responses to antigens?

A

Somatic rearrangements of genes encoding antibody and T cell receptors

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9
Q

What happens after membrane bound antibody binds non self antigen?

A

B cells undergo clonal selection and expansion. Differentiate to plasma cells which secrete soluble antibodies to eliminate antigen

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10
Q

What are the roles of antibodies

A

Bind to microorganism and prevent their entry into body cells

Binds to phagocytes (assist phagocytes i.e. oponisation) and activates phagocytes to neutralise bacterial toxins)

Bind antigen and activate complement and induce inflammation

Membrane bound antibodies are receptor for antigen on B cells

Neutralise toxins or viruses

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11
Q

Describe the basic structure of Ig

A

2 light chains, 2 heavy chains with interchain and intrachain disulphide bonds holding them together

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12
Q

What lies within each variable domain?

A

3 hypervariable regions (complementarirty determining region) which form specific antigen binding site

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13
Q

What is the benefit of flexibility at the hinge region?

A

Allows 2 antigen binding sites to interact with antigens on a large surface

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14
Q

What is the underlying protein structure of an immunoglobin?

A

Beta sheets joined by loops

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15
Q

How are Fab and Fc produced and what do they consist of?

A

Cleavage at hinge region. Fab (antibody binding region with heavy and light chain)
Fc (crystallizable, heavy chains)

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16
Q

What chain determines biological activity, what is this activity?

A

Half life, heavy chain determines this

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17
Q

What are the roles of Fc binding?

A

Complement activation

Binds to receptors on different cells e.g to marcophages and neutrophils to trigger phagocytosis (opsonisaiton)

Binds to mast cell (IgE) triggers degranulation

Binds to epithelial cells for trans epithelial secretion (e.g. IgA into tears, saliva, gut. IgG across placenta)

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18
Q

What sort of molecule are Ig?

A

Glycoproteins

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19
Q

Describe the order of abundance of Ig isotypes?

A

IgG, IgA, IgM, IgD, IgE

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20
Q

Describe locations of different antibody isotypes

A 
IgG: intra/extra vascular
IgM: intravascular
IgA: secretions/intravascular
IgD: B cell surface
IgE: mast cells, basophils, secretions.
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21
Q

What are the different structures of antibodies and thus how many binding sites?

A 
IgG: Monomeric, 2
IgM: pentameric, 10
IgA: dimeric, 4
IgD: monomeric, 2
IgE: monomeric, 2
22
Q

What is avidity?

A

Accumulated strength of multiple affinities of individual non-covalent binding interactions.

23
Q

Which antibody can either be monomeric or pentameric, how come?

A

IgM, normally pentameric but monomeric when acting as B cell receptor for antigen

24
Q

What function do low affinity Fc regions have?

A

Not normally occupied Fc receptor, the receptors only become occupied after the antibody has become complexed with the antigen (useful in phagocytosis).

25
Q

What function do high affinity Fc regions have?

A

Often pre-bound to receptor and waits for antigen to bind to Fab end. (i.e. IgE on mast cells)

26
Q

What does membrane bound IgM do?

A

Binds non self antigen so B cell activation i.e. proliferation and differentiation into plasma cells

27
Q

Which 2 antibody subtypes activate complement, which one’s better?

A

IgG and IgM

IgM better (only one needed)

28
Q

What is main function of IgG?

A

Placental passage in pregnancy as fetus can’t make own antibodies,
Neutralises toxins, opsonisation

29
Q

What is the role of IgM?

A

Initial antibody produced by B cells (main antibody of primary response).

Activates complement

30
Q

What does IgA do?

A

Triggers eosinophil degranulation

Enhances phagocytosis (low affinity phagocyte binidng)

31
Q

Where is IgA found?

A

Tears, saliva, mucus, colostrum, respiratory system, intestine

32
Q

What is main function of IgD?

A

B cell receptor

33
Q

What is the role of IgE?

A

Antibody of allergy (binds to mast cell/basophil to trigger degranulation and histamine release)

Antiparasitic activity

34
Q

Describe affinity and avidity of IgM

A

Low affinity, high avidity

I.e. many binding sites but interaction at each one is low affinity

35
Q

Which region of antibody varies between Ig isotypes?

A

Fc region

36
Q

What is opsonization?

A

Complement proteins “flag” the microorganism for phagocytosis thus enhancing phagocytosis.

Can cover pathogen in IgG (opsonize) to increase phagocytic appetite for pathogen.

37
Q

What sort of immune response is the complement system part of?

A

Innate immune response

38
Q

What is complement?

A

Proteolytic cascade of over 30 sequentially activated serine proteases (secreted into plasma by liver/macrophages) example of feedforward amplification

39
Q

What does complement enhance?

A

Phagocyotsis of opsonised bacteria

Chemotaxis of leucocyte to site of infection, acts as chemoattractant

Can lead to cell death via MAC attack

40
Q

Describe how size of antibodies relates to their distribution in body fluids

A

IgG are smallests and are thus intra and extravascular - can ass through placenta
IgM are biggest and thus remain intravascular
IgA are small - found in secretions

41
Q

Where do T and B cells mature?

A

Primary lymphoid organs
T cell: thymus
B cell: bone marrow

42
Q

What molecule digests the Fab and Fc fragments?

A

Papain

43
Q

Which antibody is secreted first in response to antigen re-exposure?

A

IgG

44
Q

What are the three biochemical pathways that initiate complement?

A

Alternative - Activated by C3
Lectin - Activated by mannose binding lectin
Classical - Activated by IgG or IgM

45
Q

Describe the classical pathway

A

A single pentameric IgM can initiate the pathway, while several, ideally six, IgGs are needed. It activates the C1 complex.

Controlled by the C1 complex consisting of C1q binds to antibody antigen complexes, C1q protein associated with 2xC1r and 2xC1s.

C1q binding causes C1r to cleave C1s to an active form.

Then C1s cleaves C4 and C2 to generate C4b and C2b

C4b2b is an active C3 convertase which promotes cleavage of C3 into C3a and C3b.

46
Q

What structure underlies the hypervariable region?

A

Loops between beta sheets

47
Q

What is the role of MHC class 1 ?

A

Display peptide fragments of proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen

48
Q

Do MHC class 1 show limited diversity?

A

Yes

49
Q

What forms hybridomas, what is their function?

A

Antibody producing B-cells are fused with immortal B cell cancer cells, a myeloma, to produce a hybrid cell line.

Rapidly divides and produces large amounts of Ig.

50
Q

A particular monoclonal antibody is always of a single subclass of Ig?

A

True

51
Q

The WBC involved in acute allergic reactions?

A

Basophil

52
Q

The major antibody secreted in breast milk in humans is?

A

IgA

Blood and defence (5 decks)

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