Recognition Of Extracellular Pathogens

Question 1

Innate recognition mechanisms

Answer 1

Infection induces the production of inflammatory mediators for macrophages - cytokine interleukin-6 (IL-6);
IL-6 induces the liver to produce large quantities of acute phase proteins that include the important pattern recognition molecules C-reactive protein (CRP) and mannan-binding lectin (MBL) that bind to PAMPs on microbial surfaces;

Leukocytes express a range of PRRs - PRRs expressed by macrophages include mannose receptor and scavenger receptor;

Toll-like receptors (TLRs) are PRRs expressed by macrophages, dendritic cells and various other cell types - interacts with PAMPs leading to cellular stimulation and generation of immune activity. Components of bacteria, viruses, fungi and Protozoa interact with TLRs and include lipopolysaccharides, lipoproteins, carbs, proteins and nucleic acids;

Question 2

Antigen

Answer 2

Any molecule that is recognised specifically by a lymphocyte or an antibody;
Proteins, carbs, nucleic acids, lipids - can serve as antigens;

Question 3

Antibody

Answer 3

Antigen recognition proteins secreted by B lymphocytes;
Immunoglobulins;
Y shaped structure;
Antigen combining site at the tip of each arm - these two sites are identical on a single antibody and have the same antigen specificity;
Precise region of antigen that interests with antigen combining site - antigens determinant (epitope);

Question 4

Specificity of interaction between a combining site and epitope is determined by

Answer 4

Complementarity of shape and charge - maximise potential for attractive non-covalent interactions leading to high affinity binding

Question 5

Antigen recognition by B lymphocytes

Answer 5

Antigen recognition receptors on B cells are surface immunoglobulins (sIg) that specifically bind antigens to B cell surface;
All sIg molecules expressed by a single B cell have identical antigen combining sites - a single B cell is specific for a single antigen epitope;
When B cell binds an antigen to its sIg and becomes activated - it differentiates into a plasma cell that secretes antibodies with the same combining sites as the sIg;
Body contains different families or clones of B cells each expressing Ig with a different antigen combining site;
An antigen will interact with those clones whose sIg bind it with the highest affinity - clonal selection;
Activation of B cells - causes proliferation - increases number of B cells of the specific clones an some maintained as memory cells;

Question 6

Basis of vaccination (immunisation)

Answer 6

Non- inactive forms of microbial antigens are deliberately inoculated into the body to indie primary response - generates memory lymphocytes;
If same microbe enters again - memory cells reactivated more rapidly and in lager numbers - faster and bigger response (adaptive immunity)

Question 7

Immunoglobulin structure

Answer 7

Y shaped;
4 polypeptide chains (held together by disulphide bonds);
2 identical heavy chains and 2 identical light chains;
N-terminal regions of paired heavy and light chains form an antigen combining site;
Each chain has a sequence of globular regions - Ig domains - 4/5 domains in each heavy chain and 2 in each light chain;
Each domain - 110 amino acids folded into 2 beta-pleated sheets with tertiary structure stabilised by disulphide bond;
N terminal domains of each heavy and light chain vary in structure (variable domains - VH, VL);
Constant domains (CH, CL) have the same structure in different B cells and antibodies;
Between CH1, CH2 - flexible hinge region;
2 arms of Y above hinge - fab regions (fragment antigen binding);
Each fab - VH/CH1 and VL/CL and contains an antigen combining site;
Stalk of the Y below hinge is composed of the other CH domains and is called the Fc region - interacts with other molecules of the immune system involved in generating defensive activities;

Question 8

Only difference between secreted antibodies and sIg

Answer 8

SIg contains an additional amino acid sequence at the C-terminus of each heavy chain that anchors the molecule to the B cell surface membrane;

Question 9

2 types of light chains

Answer 9

Kappa (k) and lambda

Question 10

5 types of heavy chains

Answer 10

Differ in amino acid sequences of constant domains
Gamma - IgM
micro - IgG (1, 2, 3, 4);
alpha - IgA (1, 2);
3 (molar extinction coefficient) - IgE;
... - IgD;

The differences in CH domain amino acid sequences are greater between classses than subclasses (isotypes);

Question 11

All B cells wehn they develop from stem cells in the bone marrow initially express?
When a B cell is activated following binding of antigen, it may secrete?

Answer 11

IgM (and some also express IgD) as their sIg;
IgM antibodies or may undergo class switching to produce IgG, IgA or IgE - involves changing the CH domains expressed in newly synthesized immunoglobins without changing the VH domain or the light chains (VL and CL) - thus the class of Ig is changed without altering its antigenic specificity;

Question 12

IgG, IgA, IgD, IgM, IgE structures

Answer 12

3 CH domains in heavy chains - G, A, D;
4 CH domains - M, E

Monomers (single Y shaped units) - G, E, D;
Monomers/dimers - A;
Pentamer - M;
In dimers and pentamers, monomers are linked by a polypeptide (J-chain; joining chain);
All antigen combining sites on an A dimer or M pentamer are identical;

Question 13

Antibody isotypes differ in their tissue distribution and so can help?

Answer 13

Confer immunity in different parts of the body;

Question 14

IgM is mainly restricted to the bloodstream because?

Answer 14

It is too large to diffuse readily across blood vessel walls (except in areas of inflammation)

Question 15

IgG is found in? Special property?

Answer 15

Most plentiful in blood;
In tissue fluid;
Transferred across placenta because of