How does the immune system recognise pathogens?

Question 1

define antigen

Answer 1

antigen= anything that binds to a specific receptor on an immune cell (generates antibody)

• Can be bits of bacteria, viruses (foreign antigen) - pathogens contain many antigens
• Can be bits of our own bodies - self antigen

Question 2

define immunogen

Answer 2

Immunogen= anything that elicits an immune response
Most (not all) antigens are immunogens

Question 3

define epitope

Answer 3

Epitope = antigen portion that is recognised and bound by receptor on immune cell {fits into paratope}
Antigens can contain multiple epitopes

Question 4

what are the antigen recognition molecules used by B cells

Answer 4

Recognition of antigen by B cells - membrane-bound antibodies :

• The antigen recognition molecules use by B cells are **immunoglobulins (Ig) **
• Immunoglobulins aka antibodies
• Membrane bound Ig function as B-cell receptors (BCR)
• Antigens are recognised directly without involvement of other cells
• Antigen epitopes recognised often 3D conformation - folded peptide antigens

Question 5

Activated B cells differentiate into _____ ______ which secrete

Answer 5

Activated B cells differentiate into plasma cells- secrete immunoglobulins with specificity identical to BCRs

Question 6

what type of bond holds the heavy chains on a typical antibody together

Answer 6

The two heavy chains are linked to each other by disulfide bonds and each heavy chain is linked to a light chain by a disulfide bond. In any given immunoglobulin molecule, the two heavy chains and the two light chains are identical, giving an antibody molecule two identical antigen-binding sites

Question 7

B cells can make different classes (aka isotype) of antibodies like IgM/IgG/IgE/IgA

each antibody class listed can mediate different functions; what are they

Answer 7

Immunoglobulin A (IgA): It’s found in the linings of the respiratory tract and digestive system, as well as in saliva (spit), tears, and breast milk.

Immunoglobulin G (IgG): This is the most common antibody. It’s in blood and other body fluids, and protects against bacterial and viral infections.

Immunoglobulin M (IgM):this antibody is made first by B cells in primary immune response; it has a pentomeric structure. Found mainly in blood and lymph fluid, this is the first antibody the body makes when it fights a new infection.

Immunoglobulin E (IgE): Normally found in small amounts in the blood. There may be higher amounts when the body overreacts to allergens or is fighting an infection from a parasite.

Immunoglobulin D (IgD): This is the least understood antibody, with only small amounts in the blood.

Question 8

what is affinity maturation of B cells

Answer 8

Affinity maturation is the process by which B cells increase their affinity for a particular antigen. This “fine tuning” of B-cell specificity occurs through a repeated process of somatic hypermutation of B-cell receptors and subsequent clonal selection.

B cells are undergoing a type of ‘class switching’
* Antibody specificity remains constant whilst biological effector functions are varied - affinity maturation - antibodies gain increased affinity, avidity, and anti-pathogen activity
* Affinity - strength of interaction between antigen epitope and antibody paratope at singular binding site
* Avidity - total binding strength of an antibody at every binding site - aka functional affinity, determined by:
* Binding affinity - strength of relationship at singular binding site
* Valency - total no binding sites involved
* Structural arrangement - structure of antigen/antibody involved

Question 9

we have measured a patient IgM and IgG levels in blood. The IgM levels are very high, what does this suggest to us in terms of how recent the infection is?

Answer 9

the infection is recent as IgM levels are high

n.b. if IgG levels high infection likely to have been a long time ago

Question 10

How is antibody receptor diversity generated?

Answer 10

Somatic hypermutation and class switch recombination generates antibody diversity in activated B cells after antigen stimulation. B cells are preferentially selected based on their affinity for the target antigen, thereby promoting affinity maturation

they generate this diversity by “mixing and matching” gene segments within heavy/light chain loci (variable, diversity and joining segments)

Question 11

what is the mechanism of somatic DNA recombination?

Answer 11

• Making an immunoglobulin heavy chain :
• Germline - DNA inherited, present in all cells - as B cells develop this locus is rearranged
• Lots of V/D/J segments - randomly choose VDJ segments - DJ-joining then V-DJ joining happens - splicing out DNA
• Then transcription happens and splicing brings together constant regions
• Similar process happens in light chains - then heavy/light chains bind together

Question 12

How do T cells recognise antigen?

Answer 12

T cells recognise antigen using T cell receptor (TCR)

Antigen recognition by T cells:
* when a macrophage or dendritic cell digests a pathogen fully, it uses the linear (peptide) antigens from pathogen surface membrane to create APC’s (antigen presenting cells) which are recognised by T cells.
* these antigens are combined w a special glycoprotein in cytoplasm aka MHC (major histocompatibility complex)
* next MHC complex moves pathogen antigens to the T cell’s surface membrane: creating an APC.
*TCR (t cell receptor) interacts with both linear peptide and MHC

n.b. The digested pathogen will be removed from the phagocyte by exocytosis but they will keep some antigen molecules to present on the surface of their cells - this serves to alert other cells of the immune system to the presence of a foreign antigen. The phagocyte is now referred to as an antigen-presenting cell (APC)

Question 13

What is the function of the ‘hinge region’ on an antibody

Answer 13

the hinge region provides the antibody molecule w flexibility; allowing it to bind to 2 antigens simultaneously

Question 14

professional APCs, such as dendritic cells (DCs), epithelial Langerhans cells (LCs), macrophages, and B cells, are derived from ______ ____ ___ ____ ____ ____ ____ ____ _____. forming an integral part of the immune system.

Answer 14

professional APCs, such as dendritic cells (DCs), epithelial Langerhans cells (LCs), macrophages, and B cells, are derived from hematopoietic stem and progenitor cells in the bone marrow (BM), forming an integral part of the immune system.

Question 15

we can identify helper T cells because they express ____ on their surface

we can identify cytotoxic T cells because they express ____ on their surface

Answer 15

we can identify helper T cells because they express CD4+ on their surface

we can identify cytotoxic T cells because they express CD8+ on their surface

Question 16

what is the clinical relevance of MHC and what name does it go by in humans vs. in mice

Answer 16

MHC= major histocompatibility complex- major genetic region that determines compatibility of tissues transplanted between individuals

MHC is aka HLA, H-2

in humans: HLA genes- human leukocyte antigen genes
in mice: H-2

Question 17

There are 2 types of MHC (major histocompatibility complex):

MHC Class I is expressed on all nucleated cells

MHC Class II is expressed on _______ ______ only

both MHC class I + II have peptide-binding clefts to which the antigen binds to

Answer 17

MHC Class I (made up of alpha) is expressed on all nucleated cells

MHC Class II (made up of beta) is expressed on antigen presenting cells (APC) only

both MHC class I + II have peptide-binding clefts to which the antigen binds to

Question 18

MHC-I presents antigen to _____ T cells

MHC-II presents antigen to _____ T cells

Answer 18

MHC-I presents antigen to ‘cytotoxic’ T cells (CD8+)

MHC-II presents antigen to ‘helper’ T cells (CD4+)

Question 19

what is the peptide presentation by MHC molecules expressed in patients with coeliac disease?

Answer 19

• Relatively common ~ 1:200 Caucasians
• Chronic inflammation of small intestine - inappropriate immune response to wheat gluten

The immunology:
* Only occurs in ppl carrying particular MHC class II molecules - HLA-DQ2 or HLA-DQ8 -
* Only these MHC molecules can present gliadin peptides (in gluten) to T cells to cause disease
* Only occurs in ppl carrying HLA-DQ2/DQ8 since only these MHCs can bind to gliadin peptides
* tTG (tissue transglutaminase) deaminates gliadin into glutamic acid - increase -ve charge, makes them bind more strongly to HLA-DQ2/DQ8 MHC

Question 20

Define immunological tolerance and explain it in terms of
* central tolerance
* peripheral tolerance

Answer 20

• If generation of receptors on B/T cells is random, what is there to stop generation of cells that recognise self-antigens - nothing
• However, immune system attempts to eliminate/control such potentially self-reactive cells - **immunological tolerance **
• **Central tolerance **- as T cells develop in thymus (and B cells in bone marrow) their receptors are tested for reactivity to self-antigens - if self-reactivity too strong then lymphocytes are killed
• Peripheral tolerance - self-reactive lymphocytes that escape deletion during thymus/bone marrow development can be controlled by periphery e.g. By regulatory T cells - Treg

Question 21

MHC genes are polymorphic and polygenic, what does this mean?

Answer 21

The MHC genes have 2 properties ensuring the maximum number of peptides that can be presented
* They are polygenic and polymorphic
* Polygenic - made up of multiple genes
* Polymorphic - multiple variants of each gene (alleles) within population as a whole
* MHC genes are most polymorphic genes known