The immune response

The immune response

The immune response is a complex cascade of events that involves many interactions and communications between

different cells. A helpful way of visualising and remembering it might be to imagine it as a play with many different

characters. Some of the important characters are:





The ‘Baddies’

Antigens

 foreign proteins that the immune system recognises as ‘nonself’, whiuch may be:

- on the surfaces of pathogens

- toxins produced by pathogens

- fragments of pathogen cells

- cancer cells

- foreign cells (eg an organ or tissue transplant)





Pathogens

 ‘agents’ causing infection, including:

- prions

- viruses

- bacteria

- fungi

- macroscopic parasites

 have antigens on their surfaces that the body recognises as ‘non-self’

 have ways of invading the host’s 1st and 2nd lines of defence, infecting cells and evading or resisting the immune

system



The ‘Goodies’

MHC (major histocompatibility complex) - proteins that allow the body to recognise its own cells

 group of glycoproteins (proteins + attached carbohydrate) that the immune system uses to recognise ‘self’

 MHC molecules are found on cell membranes

 every individual has unique MHC molecules

(it is extremely unlikely that any two people - except identical twins - will have identical MHC molecules, as they

originate from 20 genes, each with more than 50 alleles)

 the immune system recognises the body’s normal MHCs on cell membranes as ‘self’

 when a body cell is invaded by a pathogen it displays a combination of self and non-self markers

 cancer cells are also recognisably non-self

 note: anything with ‘non-self’ markers is an antigen

If you are interested:

Antibodies (also called immunoglobulins or Ig’s)  There are 5 different classes of antibodies or

 Y- shaped soluble proteins immunoglobulins (IgA, IgD, IgE, IgG and IgM)

 act as specialised antigen-receptors  Each class:

 found on the cell membranes of B cells - is a different variation of a Y-shaped protein

 each different antibody is specific to its own particular - is associated with a particular activity:

antigen eg IgG is by far the most numerous (76%) and is

(if you like, a different ‘army’ of antibodies is made to the only immunoglobulin able to cross the

fight each different antigen) placental barrier to the foetus (providing it with

 antibodies bind to antigens and have several ways of immunity); IgE - the least numerous - is

inactivating them: responsible for autoimmune diseases such as

- complement fixation (proteins attach to antigen allergies, arthritis, multiple sclerosis etc

surface and cause holes to form - ie cause cell lysis)  immunoglobulins (or antibodies)consist of

- neutralisation (bind to specific sites, preventing them constant regions and variable regions - the

from attaching to cells - similar to taking their parking variable regions give them their specificity to

spaces) particular antigens

- agglutination (cause them to clump together, making

them targets for macrophages)

- precipitation (make them insoluble, causing them to precipitate out of solution)



Lymphocytes - white blood cells that carry out the immune response, which:

 originate in the bone marrow (like all blood cells)

 concentrate in the lymphatic tissues (ie lymph nodes, the thymus gland and the spleen) - hence their name

Types of lymphocytes:

B cells

 originate and mature in the bone marrow (hence ‘B’ cells)

 can detect antigens with special antigen receptor molecules (called antibodies) on their membranes

 when B cells encounter antigens that bind specifically to their antibodies, they proliferate (rapidly multiply),

producing two types of daughter cells





Plasma cells Memory B cells

- B cells that release their specific - long-lived B cells that do not release their antigens in

antibodies into the lymph response to the current infection

- these antibodies also get into the - instead they circulate in the body, ready to respond

bloodstream and circulate quickly to any invasion by the same pathogen

through the body, binding to occurring in the future

antigens









T cells

 also originate in bone marrow but mature in the thymus gland (hence ‘T’ cells)

 also have antigen receptor molecules on their membranes - these are not antibodies, but sites that

recognise molecules displayed as ‘non-self’ on the membranes of

- pathogens

- cells invaded by pathogens

- cancer cells

- tissue transplant cells

 when T cells encounter anything displaying non-self markers, they divide to produce two kinds of daughter

cells:





Helper T cells

Cytotoxic T cells (or ‘Killer T

cells’) T cells that release lymphokines, or

T cells that recognise and destroy chemicals that:

nonself cells by puncturing them, - stimulate the proliferation of B cells

causing them to lyse and cytotixic T cells

(ie cell contents to leak out) - attract neutrophils

- enhance the ability of macrophages to

engulf and destroy microbes

The action:

When the body is invaded by a pathogen, the immune system’s responses are categorised into two kinds of

responses:



The antibody-mediated response

 involves most cells

 responds to antigens or pathogens circulating in the ‘humor’ or body fluid - ie blood or lymph



A B cell’s membrane receptor molecules bind to antigens triggering the following chain of events:

 B cells rapidly divide to produce either plasma cells or memory B cells

 plasma cells release antibodies that bind with antigen or antigen-bearing pathogen

 macrophages and helper T cells stimulate B cell production

- in most cases, the antigen itself will not directly stimulate production of B cells - instead it must be

engulfed by a macrophage, T cells must bind to the macrophage and interleukins secreted by helper

T cells stimulate production of B cells





The cell-mediated response

 involves mostly T- cells

 is directed against any non-self cell including cells invaded by pathogens



Antigens on a non-self cell bind to receptor molecules on surface of a T cell - this initiates the following chain

of events:

 the T cell rapidly multiplies, producing either either cytoxic T cells that destroy non-self cells marked

with the specific antigen that they recognise or helper T cells

 Helper T cells bind to macrophages

(macrophages that have engulfed pathogens will be displaying non-self markers on their surfaces - helper

T cells recognise these and bind to these cells)

 Helper T cells produce interleukins to stimulate proliferation of T cells and B cells

(binding of helper T cells to macrophages causes them to release interleukins (communication chemicals

that allow leucocytes to communicate). The interleukins trigger a chain of positive feedback events that

result in the proliferation of interleukins, macrophages, helper T cells, cytotixic T cells and B cells)