Lecture 33 - linking innate to adaptive immunity

Question 1

What is special about vertebrates?

Answer 1

Only vertebrates have the specialised adaptive immune system

Question 2

What are the main cells that are involved in adaptive immunity?

Answer 2

Leukocytes ( white blood cells - despite being a minor constituent of blood they are the main cells involved in immunity)

Question 3

Adaptive immune system

Answer 3

The body’s built in specific defense system that stalks and eliminates with nearly equal precision of almost any typeof pathogen that intrudes the body.

When it operates effectively, the adaptive immune system protects us from a wide range of infectious agents as well ass from abnormal body cells. When it fails, or is disabled, devastating diseases such as cancer and AIDS result. The activity of the adaptive immune system tremendously amplifies the inflammatory response and is responsible for most complement activation.

Question 4

Antigen sampling and presentation

Answer 4

Dendritic cells are present in major organs. They phagocytose antigen and process it down to peptides. Dendritic cells migrate from organs (e.g. the skin) to draining lymph node. They present peptides on MHC to other white blood cells called T cells.

Peptides are broken down fragments form a microbe and they have enough amino acid variety despite being relatively short they contain enough variety to show its a foreign microbe

Question 5

Antigen

Answer 5

an antigen is a molecule or molecular structure, such as may be present at the outside of a pathogen, that can be bound to by an antigen-specific antibody or B cell antigen receptor

Question 6

MHC

Answer 6

Major histocompatibility complex proteins

Major histocompatibility complex (MHC), group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances. MHC proteins are found in all higher vertebrates.

Question 7

APC

Answer 7

Antigen presenting cells … These cells engulf antigens and then present fragments of them on their own surfaces where T cells can recognise them. Naive T cells can only be activated by antigens that are presented to them on MHC proteins by APCs i.e. APCs present antigens to the cells that will deal with the antigens. The major types of cells acting as APCs are dendritic cells, macrophages, and B lymphocytes/B cells

Question 8

Most potent APC?

Answer 8

Dendritic cells are the most potent APC

Question 9

Dendritic cells

Answer 9

With their long, wispy extensions, dendritic cells are very efficient antigen catchers. Once they have internalised antigens by phagocytosis, they enter nearby lymphatics to get to a lymph node where they will present the antigens to T cells. Migration of dendritic cells to secondary lymphoid organs is now recognised as the most important way of ensuring that lymphocytes encounter invading antigens.

Antigen present cell type - Dendritic cells present peptides on MHC to T cells

Question 10

CD4+/CD4 T cells

Answer 10

CD4 T cells help B cells make antibody

Question 11

CD8+/CD8 T cells

Answer 11

CD8 T cells become cytotoxic and kill virus infected cells and cancer cells

Question 12

What is an antigen?

Answer 12

Anything that has the potential to be recognised by the immune system

Foreign antigen (transplants, pathogens, some chemicals). Anything from ‘outside’

Auto (self)-antigen = immune system normally tolerant of self antigen. Self-antigen may be recognised in autoimmune disorders such as rheumatoid arthritis or Type I diabetes

Question 13

Foreign antigen

Answer 13

Foreign antigens originate from outside the body. Examples include parts of or substances produced by viruses or microorganisms (such as bacteria and protozoa), as well as substances in snake venom, certain proteins in foods, and components of serum and red blood cells from other individuals.

Question 14

Auto(self)-antigen

Answer 14

Auto (self)-antigen = immune system normally tolerant of self antigen. Self-antigen may be recognised in autoimmune disorders such as rheumatoid arthritis or Type I diabetes

any molecule or chemical group of an organism which acts as an antigen in inducing antibody formation in another organism but to which the healthy immune system of the parent organism is tolerant

Assuming that your immune system has been programmed properly, your self-antigens are not foreign to you, but they are strongly antigenic to other individuals.

Question 15

Purpose of antigen uptake

Answer 15

Clearance of pathogens (innate response)
For presentation to T cells (adaptive response) (Antigen presentation allows for specificity of adaptive immunity and can contribute to immune responses against both intracellular and extracellular pathogens.)

Question 16

Invertebrate vs vertebrates (evolution of immunity)

Answer 16

Vertebrates (anything with a spine) has both innate and adaptive immune systems therefore can vaccinate them and have an adaptive immune response.

Invertebrates have the innate immune system but do not have an adaptive immune response - one way that they are though to overcome this is by producing a lot of offspring

Jawless fish are vertebrates but their adaptive immune system is based on different structures compared to other vertebrates

Question 17

MHC expression

Answer 17

MHC-I presents endogenous (intracellular) antigen. Expressed on all nucleated cells

MHC-II presents exogenous (extracellular) antigen. Expressed only on APCs.

Question 18

Endogenous antigens

Answer 18

Endogenous antigens are signals produced within your body’s own cells that start an immune response. They alert cytotoxic T cells that a body cell is either infected with a virus, such as influenza, or has become cancerous.

Endogenous antigens are antigens found within the cytosol of human cells such as viral proteins, proteins from intracellular bacteria, and tumor antigens.

Question 19

Exogenous antigens

Answer 19

Exogenous antigens are antigens that have entered the body from the outside, for example, by inhalation, ingestion or injection Examples include bacteria, free viruses, yeasts, protozoa, and toxins. These exogenous antigens enter antigen-presenting cells or APCs (macrophages, dendritic cells, and B-lymphocytes) through phagocytosis. The microbes are engulfed and placed in a phagosome.

Question 20

Difference between exogenous and endogenous antigens

Answer 20

The key difference between endogenous and exogenous antigens is that the endogenous antigens generate within the cells while the exogenous antigens come from the outside of the body.

Exogenous antigens are those from outside cells of the body. Examples include bacteria, free viruses, yeasts, protozoa, and toxins.

Endogenous antigens are antigens found within the cytosol of human cells such as viral proteins, proteins from intracellular bacteria, and tumor antigens.

Question 21

MHC-I antigen processing

Answer 21

Antigenic proteins (a protein that can stimulate the production of antibodies) are degraded to peptides in the cytoplasm

Peptides are imported into the endoplasmic reticulum (ER)

Peptide loading of MHC-I takes place in the ER

There is NO phagolysosome so protein from the virus for example are present in the cytoplasm

Cytoplasmic antigen could be a virus growing inside the cell for example

Question 22

MHC-II antigen processing

Answer 22

Phagocytosis of exogenous antigen

Antigenic proteins are degraded in acidic phagolysosome

Peptide loading of MHC-II takes place in the phaglysosome

There is then destruction of the remaining exogenous antigen

Question 23

Peptides

Answer 23

Fragments of protein antigen that are displayed by MHC-I and MHC-II on cells

Question 24

Basic antigen definition

Answer 24

Anything that can be recognised by an immune system

Question 25

MHC-I molecules present antigens from which source?

Answer 25

Endogenous (antigens expressed in cytoplasm)

Question 26

What type of antigen is presented in exogenous antigen processing?

Answer 26

Antigen from extracellular bacteria/viruses is presented by this pathway

Question 27

How long ago did the adaptive immune system evolve?

Answer 27

Evolved 500 million years ago

Question 28

MHC-I is present on ______ while MHC-I and MHC-II are both present on ___________

Answer 28

All nucleated cells

Antigen presenting cells (have both MHC-I and MHC-II)

Question 29

Cell-mediated immunity mainly involves …

Answer 29

Activated white blood cells (leukocytes) killing infected cells

Question 30

What is fever caused by?

Answer 30

Interleukin-1 (IL-1) acting at a distance on the hypothalamus

Question 31

Secondary lymphoid organ

Answer 31

Lymph node

Spleen

Question 32

Primary lymphoid organ

Answer 32

Bone marrow

Thymus

Question 33

What happens at the lymph nodes?

Answer 33

Adaptive immune response

It is at the lymph node that antigen, APCs e.g. dendritic cells, together with T and B cells interact to begin producing antibody against antigens bought via the lymph

When antigenic material in the lymph enters the lymph node, APCs phagocytose and breakdown the antigenic material, presenting it as peptides along with MHC-II on the surface of the macrophage. CD4 (helper) cells with receptors corresponding to these particular MHC-II/peptide combinations are then activated. These activated CD4 T cells begin to release cytokines. These cytokines are one of the two triggers required to activate B cells to differentiate into plasma cells (antibody secreting B cells). The other signal is the native antigen (unprocessed antigen) which triggers antigen-specific B cells. Only when both signals are present the B cell will become activated. The secretion of antibody by plasma cells causes an increase in antibodies in the blood. These antibodies can then participate in opsonisation, neutralisation and activation of complement.

Question 34

Steps leading to antibody production

Answer 34

Antigens from bacteria are broken down in the APC are presented in association with MHC molecules on the cell surface.

A CD4 T cell recognises the peptide/MHC-II complex and begins to proliferate and secrete cytokines

The cytokines stimulate the B cell to divide. B cells must also bind native antigen to become activated

B cells develop into antibody secreting plasma cells

The antibody enhances bacterial destruction by opsonising bacteria, initiating bacterial lysis (with complement) or by neutralising bacterial or viral toxins

Question 35

Antibodies are divalent…

Answer 35

Means that antibodies have two antigen binding ‘arms’

Question 36

Is antibody bound to its corresponding antigen invisible to the naked eye?

Answer 36

Yes, however antibodies are divalent, when the antigen is a part of a large structure (RBCs or bacteria for example) the reaction may be visible because the large structures clump together.

Question 37

Opsonin

Answer 37

Any molecule that enhances phagocytosis by marking an antigen for an immune response or marking dead cells for recycling