An introduction to immunology and immunopathology

Cell

Image

% in adults

Nucleus

Functions

Lifetime

Main targets

Macrophage*

Varies

Varies

•

Phagocytosis

•

Antigen 

presentation to T 

cells

Months – years 

•

Various

Neutrophil

40-75%

Multi-lobed

•

Phagocytosis

•

Degranulation 

(discharge of 

contents of a cell)

6 hours – few 

days

•

Bacteria

•

Fungi

Eosinophil

1-6%

Bi-lobed

•

Degranulation

•

Release of 

enzymes, growth 

factors, cytokines

8-12 days 

(circulate for 4-5

hours)

•

Parasites

•

Various allergic 

tissues 

Basophil

< 1%

Bi- or tri-lobed

•

Degranulation

•

Release of 

histamine, 

enzymes, 

cytokines

Lifetime 

uncertain; likely 

a few hours – 

few days

•

Various allergic 

tissues 

Mast cell

Common in tissues

Central, single-

lobed

•

Degranulation

•

Release of 

histamine, 

enzymes, 

cytokines

Months to years

•

Parasites 

•

Various allergic 

tissues 

Lymphocytes 

(T cells)

20-40%

Deeply staining, 

eccentric

T helper (Th) cells 

(CD4+): immune 

response mediators

Cytotoxic T cells 

(CD8+): cell 

destruction

Weeks to years

•

Th cells: intracellular 

bacteria

•

Cytotoxic T cells: 

virus infected and 

tumour cells

•

Natural killer cells: 

virus-infected and 

tumour cells

Monocyte

2-6%

Kidney shaped

Differentiate into 

macrophages and 

dendritic cells to elicit

an immune response

Hours – days 

•

Various

Natural killer (NK) 

cell

15% (varies) of 

circulating 

lymphocytes and 

tissues

Single-lobed

•

Tumour rejection

•

Destruction of 

infected cells

•

Release of 

perforin and 

granzymes which 

induce apoptosis

7-10 days

•

Viruses

•

Tumour cells 

Fig. 1  Characteristics and function of cells involved in innate immunity [

1

, 

3

, 

4

]. *Dust cells (within pulmonary alveolus), histiocytes 

(connective tissue), Kupffer cells (liver), microglial cells (neural tissue), epithelioid cells (granulomas), osteoclasts (bone), mesangial cells (kidney)

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Marshall et al. Allergy Asthma Clin Immunol 2018, 14(Suppl 2):49

immune response to specific pathogens and contribute to 

immune regulation in that tissue.

The main characteristics and functions of the cells 

involved in the innate immune response are summarized 

in Fig. 

1

.

Adaptive immunity

The development of adaptive immunity is aided by the 

actions of the innate immune system, and is critical 

when innate immunity is ineffective in eliminating 

infectious agents. The primary functions of the adaptive 

immune response are: the recognition of specific “non-

self” antigens, distinguishing them from “self” antigens; 

the generation of pathogen-specific immunologic 

effector pathways that eliminate specific pathogens 

or pathogen-infected cells; and the development of 

an immunologic memory that can quickly eliminate a 

specific pathogen should subsequent infections occur [

2

]. 

Adaptive immune responses are the basis for effective 

immunization against infectious diseases. The cells of the 

adaptive immune system include: antigen-specific T cells, 

which are activated to proliferate through the action of 

APCs, and B cells which differentiate into plasma cells to 

produce antibodies.

T cells and APCs

T cells derive from hematopoietic stem cells in bone 

marrow and, following migration, mature in the thymus. 

These cells express a series of unique antigen-binding 

receptors on their membrane, known as the T-cell 

receptor (TCR). Each T cell expresses a single type of 

TCR and has the capacity to rapidly proliferate and 

differentiate if it receives the appropriate signals. As 

previously mentioned, T cells require the action of APCs 

(usually dendritic cells, but also macrophages, B cells, 

fibroblasts and epithelial cells) to recognize a specific 

antigen.

The surfaces of APCs express a group of proteins 

known as the major histocompatibility complex (MHC). 

MHC are classified as either class I (also termed human 

leukocyte antigen [HLA] A, B and C) which are found 

on all nucleated cells, or class II (also termed HLA DP, 

DQ and DR) which are found only on certain cells of the 

immune system, including macrophages, dendritic cells 

and B cells. Class I MHC molecules present endogenous 

(intracellular) peptides, while class II molecules on APCs 

present exogenous (extracellular) peptides to T cells. The 

MHC protein displays fragments of antigens (peptides) 

when a cell is infected with an intracellular pathogen, 

such as a virus, or has phagocytosed foreign proteins or 

organisms [

2

, 

3

].

T cells have a wide range of unique TCRs which 

can bind to specific foreign peptides. During the 

development of the immune system, T cells that would 

react to antigens normally found in our body are largely 

eliminated. T cells are activated when they encounter an 

APC that has digested an antigen and is displaying the 

correct antigen fragments (peptides) bound to its MHC 

molecules. The opportunities for the right T cells to be 

in contact with an APC carrying the appropriate peptide 

MHC complex are increased by the circulation of T cells 

throughout the body (via the lymphatic system and blood 

stream) and their accumulation (together with APCs) 

in lymph nodes. The MHC-antigen complex activates 

the TCR and the T cell secretes cytokines which further 

control the immune response. This antigen presentation 

process stimulates T cells to differentiate primarily into 

either cytotoxic T cells (CD8+ cells) or T-helper (Th) 

cells (CD4+ cells) (see Fig. 

2

). CD8+ cytotoxic T cells are 

primarily involved in the destruction of cells infected by 

foreign agents, such as viruses, and the killing of tumour 

cells expressing appropriate antigens. They are activated 

by the interaction of their TCR with peptide bound to 

MHC class I molecules. Clonal expansion of cytotoxic 

T cells produces effector cells which release substances 

that induce apoptosis of target cells. Upon resolution of 

the infection, most effector cells die and are cleared by 

phagocytes. However, a few of these cells are retained as 

memory cells that can quickly differentiate into effector 

cells upon subsequent encounters with the same antigen 

[

2

, 

3

].

CD4+ Th cells play an important role in establishing 

and maximizing the immune response. These cells have 

no cytotoxic or phagocytic activity, and cannot directly 

kill infected cells or clear pathogens. However, they 

“mediate” the immune response by directing other cells 

to perform these tasks and regulate the type of immune 

response that develops. Th cells are activated through 

TCR recognition of antigen bound to class II MHC 

molecules. Once activated, Th cells release cytokines that 

influence the activity of many cell types, including the 

APCs that activate them.

Several types of Th cell responses can be induced by an 

APC, with Th1, Th2 and Th17 being the most frequent. 

The Th1 response is characterized by the production 

of IFN-γ which activates the bactericidal activities of 

macrophages and enhances anti-viral immunity as well 

as immunity to other intracellular pathogens. Th1-

derived cytokines also contribute to the differentiation of 

B cells to make opsonizing antibodies that enhance the 

efficiency of phagocytes. An inappropriate Th1 response 

is associated with certain autoimmune diseases.

The Th2 response is characterized by the release of 

cytokines (IL-4, 5 and 13) which are involved in the 

development of immunoglobulin E (IgE) antibody-

producing B cells, as well as the development and 

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Marshall et al. Allergy Asthma Clin Immunol 2018, 14(Suppl 2):49

recruitment of mast cells and eosinophils that are 

essential for effective responses against many parasites. 

In addition, they enhance the production of certain 

forms of IgG that aid in combatting bacterial infection. 

As mentioned earlier, mast cells and eosinophils are 

instrumental in the initiation of acute inflammatory 

responses, such as those seen in allergy and asthma. IgE 

antibodies are also associated with allergic reactions 

(see Table 

2

). Therefore, an imbalance of Th2 cytokine 

production is  associated with the development of 

atopic (allergic) conditions. Th17 cells have been 

more recently described. They are characterized by