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POM > Lymphocytes > Flashcards

Lymphocytes Flashcards

1
Q

What makes up the adaptive immune system?

A

Made up of lymphocytes

They come from the common lymphoid progenitor

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2
Q

What does the adaptive immune system do?

A

Improves the efficacy of the innate immune response
Focuses response on the site of infection and organism responsible
Has memory
Needs time to develop

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3
Q

What is an epitome?

A

the portion of an antigen that makes contact with a particular antibody or T cell receptor

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4
Q

What are the 2 types of adaptive immune responses?

A

T cells: kill infected cells (CD8), produce cytokine (CD4)

B cells: the humoral response, produce antibodies

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5
Q

How do B and T cells respond to antigens?

A

T cell recognises linear epitopes in context of MHC- recognise primary structure

B cell recognises structural epitopes- 3D structure of antigen in space- recognised tertiary structure

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6
Q

What is clonal expansion?

A

Each lymphocyte has a single, unique receptor
Interactions between foreign antigen and receptor leads to activation and clonal expansion (multiple copies of the same cell)

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7
Q

How is the adaptive immune response specific?

A

Each antibody or T-cell receptor recognises one antigen only

Thi means we need a large pool of cells with specific receptors that can recognise a huge array of antigens

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8
Q

How do we deal with antigen diversity?

A

10^15 antibodies can be generated but for this we would need this many genes which would be impossible to incode
Therefor functional genes for antigen receptors don’t exist until they are generated during lymphocyte development

Immunoglobulin gene rearrangement: in B cell maturation gene segments are rearranged and brought together to form BCR

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9
Q

What are T helper cells?

A

Have CD4 markers
Activated when they come into contact with antigen presenting cell
Secrete cytokines - Th1, Th2, Tfh, Th17, Treg (Th0)

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10
Q

What cytokines do T helper cells secrete?

A

Th1- proinflammatory, boost cellular immune response, secrete IFN gamma, IL-12, TNF

Th2- proallergic, boost multicellular response- IL-4, IL-5, IL-13

Tfh- Pro-antibody- IL-21

Th17- proinflammatory, control bacterial and fungal infection- IL-17, IL-23, IL-6

Treg (Th0) (CD25, CD4+, FOXP3) - anti- inflammatory, limits immune response- IL-10, TGF beta

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11
Q

What are cytotoxic T cells?

A

Have CD8 markers
Kill infected cell or tumour cells by increasing apoptosis through 3 major mechanisms:

  1. Secrete IFN gamma and TNF
  2. Production and release of cytotoxic granules
  3. FAS-FAS ligand interactions
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12
Q

What’s the effect of Tc cells secreting IFN gamma and TNF?

A

Have antitumor and antiviral microbial effects

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13
Q

What happens when Tc cells produce and release cytotoxic granules?

A

Cytotoxic granules contain 2 families of proteins- perforin and granzymes

  1. Perforin forms pore in membrane of target cell similar to MAC of compliment
  2. Pore allows granzymes in granules to enter infected or malignant cells
  3. Granzymes have serine proteases which cleave proteins inside cells shutting down production of viral proteins and causing apoptosis of target cell
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14
Q

What happens during a Fas/ Fas ligand interaction?

A
  1. Activated CD8+ cells express Fas ligand which binds to Fas receptor on surface of target cell
  2. This binding causes Fas molecules on surface of target cells to form a trimer which pulls together signalling molecules
  3. These signalling molecules lead to activation of a caspase cascade which leads to apoptosis

CD8+ cells carry both Fas/ FasL so can kill each other with this mechanism

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15
Q

What is a T cell receptor?

A

Has 2 Fab regions each made of one heavy (alpha) and one light chain (beta)
Has 1 Fc region made of 2 heavy chains
Has a variable region made by gene reassortment
All TCRs are associated with a CD3 complex (important is signal transduction)
They recognise antigens on APCs
Antigens are presented on the MHC
TCRs have coreceptors e.g. CD4, CD8 which stabilize MHC-TCR complex

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16
Q

What is the major histocompatibility complex (MHC)?

A

Plays a central role in defining self and non-self
Its encoded by HLA genes in humans
It presents antigens to T cells
Its polygenic (has many genes) and polymorphic (has many alleles)
Different genes combine to form different classes (several class I and class II loci)
Lots of different alleles mean MHC can recognise different pathogens

17
Q

What are the 2 families of MHC molecules?

A

MHC class I and MHC class 2

18
Q

What does MHC class I do?

A

CD8 cells work with MHC I
MHC I is found on surface of all nucleated cells
Has 1 transmembrane protein
Accommodates shorter polypeptides

Presents intracellular antigens:

  1. protein from intracellular pathogen digested by proteasome
  2. Antigen peptides transported via TAP (transporter associated with antigen presentation)
  3. MHC Class I synthesized in ER
  4. In ER, MHC 1- antigen complex forms
  5. complex transported to and expressed on cell surface
19
Q

What does MHC class II do?

A

CD4 works with MHC II
Has 2 transmembrane proteins
Present in professional antigen presenting cells only (DC, macrophages, B Cells)
Accommodates longer polypeptides

Presents extracellular antigens:

  1. Extracellular antigen phagocytosed into an endosome
  2. Endosome fuses with lysosome and antigen is digested
  3. MHC II synthesised in ER- an invariant chain blocks peptide binding groove
  4. Vesicle containing MHC II buds from ER and fuses with lysosome
  5. MCH II- antigen complex formed
  6. Complex transported to and expressed at cell surface
20
Q

What are the different HLAs corresponding to MHC Class I?

A

HLA-A, HLA-B, HLA-C

21
Q

What are the different HLAs corresponding to MHC Class II?

A

HLA-DP, HLA-DQ, HLA-DR

22
Q

What are the 3 functions of antibodies?

A

Neutralisation- antibody prevents bacterial adherence

Opsonization- antibody promotes phagocytosis

Complement activation- antibody activates complement which enhances opsonization and lyses some bacteria

23
Q

How is an antibody structures?

A

Has 4 protein chains- 2 heavy and 2 light
Made of Fab and Fc regions
Each heavy chain has a variable and constant region:

Constant region- identical in all antibodies of same class/isotype but differs in different isotypes

Variable region- differs depending on B cell that produces it but is same for all antibodies produced by single B cell or B cell clone

24
Q

What are the different classes of antibodies?

A

IgG (most common), IgA (dimer), IgM, IgE (parameter), IgD

25
Q

What is IgG?

A

Most prevalent antibody in serum
Able to cross placenta to allow maternal protection for newborn
Important in cell-mediated cytotoxicity, fighting viruses and toxins
Highest opsonization and neutralisation
Made by B cells by T helper cells

26
Q

What is IgA?

A

Main Ig in secretions (saliva, breast milk, tears) and mucosal epithelia
Forms dimers after secretions- consists of 2x IgA molecules, J chain and a molecule of secretory component which protects molecule from proteolytic attack and facilitates its transfer across epithelial cells into secretions

27
Q

What is IgM?

A

Main antibody in early immune response
Has a pentametric structure- 5 Ig units held together by J chain and disulphide bonds
10 potential antigen binding sites so very efficient at agglutination of bacteria and activation of complement pathway

Made by B cells by microbial constituents

28
Q

What is IgE?

A

Involved in allergy and protection against parasitic infections
Binding of antigen to IgE coupled with Fc receptor on mast cells and basophils triggers an allergic reaction by activation of mast cells and release of mediators such as histamine

29
Q

What is IgD?

A

Found mainly on surface of B cells as receptor molecules

Involved in B cell activation

30
Q

Where do antibodies come from?

A

White blood cells
Lymphocytes
Effector cells of humoral immunity
Memory B cells

31
Q

How are B cells produced to have different antibodies?

A

Somatic recombination- Gene segment rearrangement that occurs to create repertoire of antigen receptors

VDJ (variety, diversity, joining) and VJ recombinases are responsible for looping and cleavage of immunoglobulin gene- also randomly add or remove nucleotides to create variable joint between DNA fragments:
- Heavy chain undergoes VDJ rearrangement first
-Then light chain undergoes VJ rearrangement
VDJ recombinase cuts extra genes we dont want and splices together 2 wanted genes

32
Q

What is SCID and what causes it?

A

Severe Combined Immunodeficiency Disease

Due to mutations in genes coding for VDJ/VJ recombinase

33
Q

How is diversity of B cells achieved?

A
  1. Germline diversity
  2. Combinational diversity
  3. Junctional diversity
  4. Heavy and light chain diversity
  5. somatic hypermutation chain diversity- antigen induces point mutations in variable regions
34
Q

What is a B cell receptor?

A

Membrane bound antibody with accessory immunoglobulin heterodimer to enhance signal transduction

35
Q

How are B cells activated by T helper cells?

A
  1. Membrane bound BCR recognises antigen
  2. Receptor- bound antigen is internalised and degraded into peptides
  3. peptide associated with “self” molecules (MHC class II) and is expressed at cell surface
  4. complex is recognised by matched CD4 T helper cell
  5. B-cell activated

POM (48 decks)

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