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Pathogens are organisms which cause disease. Most bacteria in our body are commensals
which benefit at no expense to the other organism.

An antigen is a molecule capable of inducing an immune response.

Mechanisms preventing infection:

1) Mucosal barriers (physical) e.g. skin, respiratory tract, intestines
2) Innate immune system
- Immediate, acts within minutes
- Recognises foreign pathogens via germ-line encoded receptors (slightly specific)
- No memory
3) Adaptive immune system
- Takes days to develop
- Highly specific due to sophisticated rearrangement of receptor genes
- Generates memory

If a pathogen/microbe/highly abnormal cell is detected, the immune response will attempt

clearance. A cytopathic (cell-destroying) pathogen, if unsuccessfully cleared can lead to acute
(severe) disease. A prolonged attack of self by the immune system can lead to chronic disease.

Major immunological tissues:

Primary lymphoid organs (Thymus & Bone Marrow) where immune cells develop.
Secondary lymphoid tissues (Spleen, Lymph Nodes, Peyers Patches etc.) where immune
responses occur.
The spleen is a blood filtration organ that removes damaged red blood cells, but is also involved in
immune function.

The innate immune system contains mostly phagocytic cells. They have a limited number of
receptors that recognise broad molecular patterns not present in eukaryotes.

Macrophages: Induce inflammation through the release of soluble factors (cytokines and
chemokines). They are the best cell at phagocytosis of antigens and bacteria. They reside in the
peripheral tissues as the first line of defence.

Neutrophils: Most abundant white blood cell which migrate rapidly to site of inflammation. They
are are short lived and highly motile. They can also ingest and kill bacteria (phagocytosis) and
release granules containing toxic components or NETs.
The adaptive immune system is composed of B-cells, T helper cells and cytotoxic T-cells. B and
T cells express antigen-specific receptors (antibodies in the case of B-cells). They are highly
variable so can recognise many different antigens but are each confined to a single clone.
Antibodies (B-cell) recognise the 3D shape of the antigen, but TCR (T-cell receptors) only
recognise protein in broken down form as a peptide.
Following activation of the antigen receptor the T and B cells expand, mature and differentiate into
specialised populations.

Dendritic cells are at the interphase of innate and adaptive immunity.

They are phagocytic cells but their main role is in the activation of the adaptive immune system
(are you ok? cells) as they actively survey peripheral tissues. Once activated they will migrate to
the lymph nodes via the lymphatic system transporting the antigen of the pathogen and interact
with T helper cells. The lymphatic vessels are also involved in drainage of interstitial fluid from
peripheral tissues which is deposited back into the bloodstream.

Innate response starts when a cell or organism encounters a microbe. Its very fast but not highly
specific. It aims to clear the pathogen or infected cells AND alert the adaptive arm of the immune
response. Many animal species (e.g. insects) rely solely on innate immunity.

Upon encountering a microbe a cell will try to:

1. Clear the microbe (phagocytosis) or inhibit its replication (interferon system)
2. Process the microbe and present its antigens to the adaptive immune system
3. Alert and attract other cells to help clear the infection (secrete cytokines/chemokines, up-
regulation of surface receptors)
4. Kill itself by apoptosis
All cells can perform these processes, but innate immune cells are specialised to perform them.

All immune cells so far are derived from haematopoietic stem cells. Macrophages, neutrophils,
and some dendritic cells derive from the CMP, whereas B, T, and NK cells derive from the CLP.
Inflammation. A process occurring as a result of an infection (or physical damage) of a tissue
which aims to clear infection and/or repair damage. Characterised by heat, swelling, redness and
pain. It is a prerequisite for a successful immune response.
Its roles are:
1. Delivery of effector cells and molecules to the site of infection for clearance of pathogens.
2. Initiate blood clotting to form a physical barrier and prevent infection of the bloodstream.
3. Enhancement of tissue repair process.
During inflammation, the blood vessels surrounding the inflammation change:
1. Increased vessel diameter and reduced speed of flow for cells/molecules exiting
bloodstream.
2. Increased adhesion molecules that bind leukocytes for extravasation.
3. Increased vascular permeability allowing exit of fluid/proteins.

Neutrophils. Form the polymorphonuclear family with basophils and eosinophils. They are the
most abundant type of white blood cell, which are recruited to the site of infection within minutes
(predominant cells in pus). There are very motile, quick acting and short lived.
They kill in three ways: phagocytosis, degranulation or NETs.

Phagocytosis occurs in phagocytes such as neutrophils and macrophages (best). Targets are
usually covered in opsonins - protein tags that label the pathogen that enhance phagocytosis, such
as the antibody FcR. Phagocytosis occurs over 5 steps:
1. Adhesion and engulfment
2. Formation of phagosome
3. Recruitment of lysosome
4. Fusion to form phagolysosome
5. Microbe death due to oxidative species, defensins, hydrolytic enzymes and low pH

Degranulation is the release of azurophilic (primary) or specific (secondary) granules containing

proteases, defensins and reactive oxygen species.

Neutrophil extracellular traps are networks of extracellular fibres composed of DNA and
antimicrobial proteins that trap bacteria and kill them.

Macrophages are the mature form of monocytes. They reside in tissues (monocytes are in
circulation) and upon infection they phagocytose microbes. Circulating monocytes are recruited
and mature into macrophages. Macrophages become activated through either direct interaction
with pathogens or through factors secreted by T helper lymphocytes (cytokines like IFN, IL4).
They are best at phagocytosis; they can present antigens to T-lymphocytes but not the best at it.
Importantly, they secrete cytokines that orchestrates the inflammatory response. They can also
contribute to tissue repair and formation of new blood vessels (growth factors).

Dendritic cells are the best are presenting. They are phagocytic but not as much as
macrophages. Immature dendritic cells migrate from bloodstream or are tissue resident; upon
encountering antigens they mature and become activated. During maturation:
1. Become less phagocytic and endocytic
2. Proliferate
3. Process microbial proteins to small peptides that can be recognised by T-cells.
4. Up-regulate expression of surface proteins and cytokines that are required for optimal antigen
presentation.
5. Secrete type I interferons (IFN and IFN) that inhibit pathogen replication, induce apoptosis of
nearby infected cells and enhance antigen presentation
6. Migrate to the nearest lymph node through the lymphatic system to find T-cells.

Natural Killer cells are terminally differentiated cells of the lymphoid lineage. They are bigger than
B and T cells. They are characterised by cytoplasmic granules containing cytotoxic proteins that
can be secreted to kill infected cells. They secrete IFN and kill infected cells before cytotoxic T-
cells. Activation is in response to type I interferons (IFN and IFN) secreted by myeloid cells like
macrophages or dendritic cells. Their cytotoxic activity is controlled through inhibitory and
activating receptors on their membrane.

1. Clearance of missing self (MHC) cells:

Almost every cell expresses MHC-I on its surface and is how our cells are recognised as self and if
they are infected. Many pathogens down regulate MHC-I to hide from immune system; also
common in cancer cells. NK cells programmed to kill any cell with no/low MHC-I expression.

2. Antibody-Dependent Cellular Cytotoxicity:

Infected or
cancer cell

NK cells also have receptors for the Fc region of antibodies. Cells coated with antibodies can be
bound by NK cells causing release of their cytotoxic granules (perforin and granzymes).