Adaptive immunity

Question 1

Humoral immunity…

Answer 1

Defence against extracellular bacteria and secondary viral infections.

AB binds to BCR on B lymphocytes and turns them into plasma cells which produce soluble AB.

Question 2

Antibodies

Answer 2

Unique Y-shape
Label materials to kill

Question 3

Describe the basic Ab structure

Answer 3

Soluble glycoproteins - Immunoglobulins.

Fab
Fc
Hinge

Question 4

How does structure of the AB reflects its dual role?

Answer 4

AG recognition:

Fab regions (variable in sequence) bind different AGs.

AG elimination:

Fc region - constant in sequence. Bind to complement proteins, FcR on phagocytes and NK cells.

Question 5

The constant regions are

Answer 5

Same for ABs of a given H chain class or L chain type.

Question 6

The variable and constant regions encoded…

Answer 6

By separate exons.

Question 7

What brings about the high diversity in Abs?

Answer 7

Multiple variable region exons in the genome -> RECOMBINE and MUTATE during B cell differentiation -> different AB specificities.

Question 8

What are the five classes of Immunoglobulins?

Answer 8

M
A
D
G
E

Question 9

IgG

Answer 9

Main class in serum and tissues.

Important in secondary/memory responses.

It can cross the placenta.

Question 10

IgM

Answer 10

Important in primary response.

Question 11

IgA

Answer 11

In serum and in secretions - protection of mucosal surfaces.

Question 12

IgD

Answer 12

Unknown

Question 13

IgE

Answer 13

Present at very low levels - involved in allergy and response to parasitic infections.

Question 14

What are the two light chain types?

Answer 14

Kappa or lambda.

Question 15

Are the light chain types class restricted?

Answer 15

No - it can either be IgG-kappa or IgG-lambda.

Question 16

In primary response

Answer 16

IgM and IgG.

Question 17

In secondary response

Answer 17

IgM and much higher IgG.
Can also include IgA and IgE.

Question 18

How ABs protect against infection?

Answer 18

Specific binding/Multivalency (Fab):

Neutralise (toxins) IgG;IgA

Immobilise motile microbes IgM

Prevent binding to and infection of host cells.

Form complexes.

Enhance innate mechanisms (Fc)

Activate complement (IgG;IgM)

Bind to FcR:
Phagoctytes (IgG;IgA) enhance
Mast cells (IgE) release inflamm. mediators
NK cells (IgG) enhance killing of infected cells.

Question 19

ABs can be used in research, diagnostics and therapy

Answer 19

Identify and label molecules in complexes.

Serotype pathogens.

Identify cell types

Humanised AB in therapy.

Her-2 Breast CA -> Herceptin

Question 20

Cell-mediated immunity

Answer 20

T-cell in thymus

Bind to AG via TCR -> produce CKs; specifically kill infected host cells.

Question 21

What are the major subpopulations of T-cells?

Answer 21

T helpers (CD4 +ve)
- Help B cells make AB
- Activate macrophages and NK cells
- Help development of Tcytotoxic

T cytotoxic (CD8 +ve)
- Recognise and kill infected host cells.

T regulatory cells (CD4 +ve)
Suppress immune response

Question 22

TCRs

Answer 22

2 alpha and 2 beta chains.
Multiple V region exons in the genome which recombine during T cell differentiation and give different specificities.

Question 23

How do T cells recognise AGs?

Answer 23

Via MHC molecules.

Question 24

What is the MHC?

Answer 24

On Cr. 6
Important in graft rejection
HLA-A, HLA-B, HLA-C
Most polymorphic proteins in man. (1400 alleles of HLA-B locus)

Question 25

MCH I

Answer 25

HLA-A, HLA-B, HLA-C On all nucleated cells AG to CD8 +ve (cytotoxic) T cells

Question 26

MHC II

Answer 26

HLA-DR, HLA-DP, HLA-DQ On macrophages, dendritic cells and B cells. AG to CD4 +ve (helper) T cells.

Question 27

TCR and MHC I

Answer 27

Cytotoxic T cell recognises peptide bound to MHC I. Virus-infected cell (viral proteins broken down in cytosol - peptides to ER and bind to MHC I - expressed on surface). Activated T cells induce apoptosis.

Question 28

TCR and MHC II

Answer 28

T helper cells recognise this. Macrophage/dendritic cell/B cell internalise and break down foreign material. Peptides bind to MHC II in endosome -> cell surface. Helps B cells make Ab, produce CK that activate/regulate other leucocytes.

Question 29

What are cytokines?

Answer 29

Small secreted proteins involved in communication between the cells of the immune system. Produced and act locally. Bind to cytokine receptors on target cells.

Question 30

What are the main groups of CKs?

Answer 30

ILs - usually made by T cells IFNs viral infection alpha and beta, cells activation gamma Chemokines - cell movement or chemotaxis. CSF - leukocyte production

Question 31

IL-1

Answer 31

Source: macrophages, endothelial and epithelial cells.. Induces inflammation, fever and activation of leukocytes.

Question 32

IL-2

Answer 32

T cells Stimulates T, B and NK cell growth.

Question 33

IL-4

Answer 33

TH2 cells and mast cells. Induces IgE prod. Promotes Th2 differentiation

Question 34

IL-8

Answer 34

Macrophages, endothelium, fibroblasts, keratinocytes Induces neutrophil chemotaxis

Question 35

IL-10

Answer 35

Monocytes, Th2 Cells Downregulates Th1 cytokines, MHC II expression

Question 36

IFN gamma

Answer 36

Th1 cells and NK cells Activates macrophages and NK cells, increases MCH II expression

Question 37

TNF alpha

Answer 37

T cells, macrophages and NK cells Activates neutrophils, endothelial cells, induces cachexia=wasting

Question 38

Th1 subset produces what?

Answer 38

IL-2, IFN gamma and TNF beta. Activate macrophages -> inflammation. Promotes production of cytotoxic T cells. Induce B cells to make IgG. Important in intracellular infections.

Question 39

Th2 subset produces what?

Answer 39

IL-4, -5,-6,-10,-13 activate eosinophils and mast cells. Induce B cells to make IgE - promotes release of inflammatory mediators (histamine) Important in helminth infections and allergy.

Question 40

Tregs produce what?

Answer 40

IL-10, TFG beta - downregulate other T cells subsets

Question 41

The hygiene hypothesis

Answer 41

Insufficient exposure to certain types of infection (dirt) skews TH1/TH2 balance towards TH2? But -ve correlation between helminth infections and allergic disease.

Question 42

Counter regulation hypothesis

Answer 42

Infection protects against allergy by promoting IL-10 and TFG-beta production (upregulates Treg, downregulates TH1 and TH2)

Question 43

Activation of adaptive immunity in the draining lymph node

Answer 43

Bacterium picked up by macrophages and dendritic cells. Lymph drain from the infected tissue via afferent lymphatic vessels. Afferent artery brings blood with naive T cells. Follicular dendritic cells activate T cells. Plasma cells produce AB. Efferent vessels carry ABs and effector T cells.

Question 44

What are the two main lineages of haemtopoiesis?

Answer 44

Myeloid and lymphoid cells.