Professional Documents
Culture Documents
Immunology
Immune Response
If you'd like to support us and get something great in return, check out our awesome
products:
PSA Questions
Table of Contents
Improve Article
Immunology seems to be one of those things that people either love or hate; I think it’s
fascinating, but I know there will be a lot of people out there who approach the subject
with a mixture of terror, frustration and loathing. To make the normal immune response
less of a horrendous nightmare to learn, I made a summary diagram showing friendly,
loveable cartoon immune cells doing what they do best – pwning pathogens. I know it
looks pretty complicated, but don’t panic! I’m also going to explain everything step by
step, so by the end of this article it will all make sense and you’ll feel super clever.
You can click on the diagram to enlarge it, and please feel free to download and print it
too.
P.S. This article is a bit of a whopper, so while things are printing I would nip and get a
cup of tea/coffee/your unhealthy revision fuel of choice to ensure you’re sufficiently
energised before you start!
the spleen is basically a massive lymph node and is, therefore, another site of
antigen presentation to mature lymphocytes. It is part of the reticulo-endothelial
system which filters blood and removes old cells, tissue debris, pathogens and immune
complexes. It also stores red blood cells and immature monocytes.
finally, the liver is also a site of antigen presentation and contains its own cohort
of phagocytes and lymphocytes. This is a vital role, as the liver filters large volumes of
potentially contaminated venous blood from the gastrointestinal (GI) tract. It also
synthesises acute phase proteins such as CRP in response to infection.
the movement of mucus by cilia in the lungs also helps prevent the stagnation
of secretions and the adherence of inhaled droplets and particles. Mucus is moved
upwards towards the pharynx, where it is then swallowed or coughed up.
natural acids persist in many parts of the body, for example, fatty acids on the
skin, lysozymes in saliva and hydrochloric acid in the stomach
there are also many natural antibacterial peptides on the skin and the surface
linings of the lungs and gut. These include cathelicidins, defensins, proteinase inhibitors
and chemokines.
normal bacterial flora colonising various parts of the body compete with infective
microorganisms, and some also produce antimicrobial substances. For example, vaginal
lactobacilli produce lactate, which creates an acidic environment and destroys many
potentially infectious organisms.
GRANULOCYTES
A family of white blood cells containing granules in their cytoplasm
NEUTROPHILS
normally make up 40-75% of all white blood cells (2-7.5 x 109/L on a full blood
count)
the first line of defence against all infections
act by phagocytosing invading organisms and presenting antigens to the
immune system
Neutrophil
EOSINOPHILS
normally make up 1-6% of white blood cells (0.04-0.44 x 109/L on a full blood
count)
they specifically act against multicellular parasites (e.g. worms) by dissolving
their cell surfaces
Eosinophil
BASOPHILS
normally make up 0-1% of white blood cells (≤0.01 x 109/L on a full blood count)
they are the circulating counterparts of tissue mast cells and are rather
mysterious
BLOOD MONOCYTES
normally make up 2-10% of white blood cells (0.2-0.8 x 109/L on a full blood
count)
they are produced in the bone marrow and travel in the bloodstream to their target
tissues, where they become macrophages
Monocyte
TISSUE MACROPHAGES
these are tissue cells and therefore aren’t found on a full blood count
they are derived from blood monocytes, which differentiate once they reach
their target tissues and express CD14 receptors
they “tidy up” any pathogens, foreign debris and old or dead cells from their
tissues using phagocytosis
Macrophages
DENDRITIC CELLS
this complex family of cell types are the main “professional” antigen-presenting
cells of the immune system
they play a vital role in activating T helper cells and memory cells
they are formed in the bone marrow and circulate in the bloodstream until they
reach their target tissues, where they are activated by pathogens and differentiate
into their mature forms
Dendritic cells
LYMPHOCYTES
Small, specialised white blood cells with large nuclei and no granules
normally make up 20-45% of all white blood cells (1.3-3.5 x 109/L on a full blood
count)
there are three main subtypes of lymphocytes: B cells, T cells and natural killer
(NK) cells
Lymphocyte
B CELLS
B cells represent about 25% of the total lymphocyte population – this varies
depending on the activity of the immune response and can be up to 50%
important B cell surface markers include CD19, CD20 and CD21, as well
as MHC II
B cells
T CELLS
T cells represent about 70% of the total lymphocyte population – this varies
depending on the activity of the immune response and can be up to 90%
all T cells express CD3 on their surfaces, along with T cell receptors (TCRs)
which recognise specific antigens presented in an MHC I or MHC II molecule
there are numerous different T cell subtypes with different roles, which each
have their own identifiable surface markers – there are absolutely loads of these, so I’ve
only discussed the most important ones below
helper T cells (CD4) facilitate the activation of the immune response and
stimulate division and differentiation of various effector cells
T cells
Let’s start at the very beginning. An evil pathogen has penetrated the body’s barrier
mechanisms and is plotting to start a nasty infection…
Part 1 – Innate immune system
This is the first line of defence against any infection. It is very fast – it is established
within about 4 hours – but is non-specific and has no memory, so it is not strong
enough to effectively tackle an infection on its own. It consists of a cellular response by
the innate immune system, a chemical response by cytokines and complement, and the
subsequent initiation of an acute inflammatory response.
Phagocytes
Phagocytes are a very important part of the innate immune system, as they act to fight
the new infection and present antigens. Examples of “professional” phagocytes
include dendritic cells, blood monocytes, tissue macrophages and, most
importantly, neutrophils. Neutrophils are an absolutely key component of this initial
process which only appear in response to infection or injury, and are therefore not found
in healthy tissue.
phagocytes then present the digested protein antigens to the cells of the adaptive
immune system via major histocompatibility complexes (MHCs) on their surfaces.
The MHC complex acts as a safety mechanism. It prevents the immune system from
being activated too easily, as it ensures that T cells can only react to an antigen if it is
presented within an MHC complex. This phenomenon is known as MHC restriction.
unlike T cells, they do not require activation by specific antigens, which means
they are able to respond immediately when exposed to a pathogen
“self” cells are protected from the destructive action of NK cells by the inhibitory
effects of MHC I, which is expressed on the surface of all nucleated body cells
normally, NK cells cannot attack healthy “self” cells. However, MHC I expression
is often suppressed if cells are infected with viruses, or have become cancerous. NK
cells can, therefore, perform additional vital roles in viral immunity and tumour
rejection.
INNATE CHEMICAL IMMUNE RESPONSE
Complement system
Complement is a cascade of chemicals similar to the clotting cascade.
There are three separate pathways that activate the complement system:
dendritic cells laden with digested antigens travel via the circulation to lymph
nodes
once they arrive there, they start to present their antigens to naive T helper
cells (TH0) within MHC II complexes on their cell surfaces
The combination of the right antigen, an MHC II and a B7 second signal gives the
green light for naive T helper cells to get going. The next step is for them to differentiate
into either TH1 cells, which promote cytotoxic T cells and cell-mediated immunity,
or TH2 cells, which promote B cells and humoral immunity.
ANTIBODIES
Antibody molecules are essentially secreted B cell receptors which provide an antigen-
specific action. They are Y-shaped molecules with a complex structure comprising:
Antibody
There are five antibody classes or “isotypes”. These are dictated by the structure of
the heavy chain constant region.
when mature B cells are activated by their specific antigen, they start to produce
IgM antibodies, and also undergo isotype class switching to produce different types of
antibody adapted for various locations within the body
Once the infection has been cleared, some plasma cells will remain as dormant
“memory” B cells:
Part 4b – Cell-mediated
immunity
Cell-mediated immunity is the term for a specific adaptive immune response activated
by TH1 cells, which leads to activation of antigen-presenting cells and a cytotoxic T
cell response.
T CELL RECEPTORS
T cell receptor diversity is just as important as antibody diversity, as both
systems need to be able to cover any possible infectious antigen. T cells generate this
genetic diversity in essentially the same way as B cells do during their development in
the bone marrow, using VDJ recombination by RAG proteins, junctional diversity and
the addition of N regions, but they do not undergo class switching or somatic
hypermutation during their maturation.
Once activated, the cytotoxic T cells are very keen to get out and start hunting and killing
things. They identify infected cells by recognising the antigen displayed within MHC
I on their surfaces. They then destroy these cells using one of several mechanisms:
they classically form an immunological synapse with their target cell – this just
means the cell membranes touch – and release a substance called perforin to make a
hole in the cell wall. They then use this hole to release granzymes and granulysin into
the cell, which induce apoptosis and DNA fragmentation.
Fas ligand interactions between the cell surfaces can also
produce apoptosis of the infected cells via the aptly named death-inducing signalling
complex (DISC)
Some types of pathogens can only exist as either extracellular or intracellular organisms,
whilst other types can vary depending on the individual species. There are also unique
variations in aspects of the immune response for some organisms.
BACTERIA
bacterial infections trigger the classic immune response as described in the main
article above
bacterial infections are usually extracellular
VIRUSES
viral infections are intracellular and therefore handled by cell-mediated
immunity
interferons are a family of cytokines which act as the equivalent of
complement in viral immunity, and also have additional unique functions. For example,
cytotoxic T cells release interferon-gamma, which inhibits viral replication within
infected cells without damaging the cells themselves.
natural killer cells also play a vital role in viral immunity, as they recognise and
destroy infected cells which have either expressed antigen on their surfaces or lost their
inhibitory MHC I
FUNGI
the normal immune response is able to deal with fungal infections very swiftly and
effectively
fungal infections are usually extracellular and therefore dealt with by humoral
immunity
PROTOZOANS
our immune response to protozoa isn’t that great. This is probably because many
species have evolved hundreds of clever protective mechanisms which turn the
immune system to their advantage. Examples of protective mechanisms include
resistance to phagocytosis and complement lysis, antigen variation, antigen shedding
and even direct modifications of host immune mechanisms.
examples of extracellular protozoa include Giardia, which infects the intestines
and may have caused many of you the joys of traveller’s diarrhoea; Entamoeba, which
causes dysentery and nasty amoebic liver abscesses; and Trypanosoma, which causes
sleeping sickness and featured in an excellent episode of House.
The end
I hope you found this guide helpful and fun. I certainly enjoyed creating the little immune
cells and telling their story (perhaps a bit too much actually). It was a mammoth
undertaking to write this thing, and while I have tried to be as thorough and accurate as
possible if any of you clever folks out there have noticed any
mistakes/miscommunications/other cock-ups please do let me know so I can correct
them for the benefit of everyone else. In return, you shall receive the reward of your
name immortalised below and a Geeky Medics gold star…
References
1. Immune System Anatomy. By OpenStax College [CC BY 3.0], via Wikimedia
Commons. Available from: [LINK]
2. Andy Gennery’s totally excellent immunology lectures given at Newcastle Medical
School in 2009 and 2011 (I hope I did them justice)