1. Innate Immunity vs. Adaptive Immunity
Immune system is the defense system of our body. Immune system protects human body from infections of bacteria, virus and parasites. The first line of defense is the skin and mucous membrane. They can of course act as a physical barrier. Secretions of sebum and lysosomes allow them to function as a chemical barrier too. After pathogens get through the skin and mucous membrane, innate immune system is there to kill the pathogens. Adaptive immunity acts slowly but has stronger force. Innate immunity and adaptive immunity collaborate to protect our body.
Innate immunity and adaptive immunity work together to kill the pathogen and protect our body. However there are several differences between these two. Three main differences are following:
Table 1. Innate immunity vs. Adaptive immunity
2. Features of Innate Immunity
1) Cells/ Complement proteins
Cells of the innate immunity are monocytes (macrophages), neutrophils, NK (natural killer) cells, eosinophils, mast cells, basophils and dendritic cells. Complement proteins are also considered a member of innate immunity.
a. Monoctyes (Macrophages)
Monocytes become macrophages when they enter the tissue from the blood stream. Three main functions of macrophages are following:
- Phagocytosis
- Antigen presentation
- Cytokine production
Phagocytosis is engulfing pathogens to kill them. Pathogens are engulfed into phagosome which merges with lysosomes to form phagolysosomes. Pathogens are digested in the phagolysosome. The digested antigens are presented at the surface of macrophage. This antigen presentation is crucial for T-cell activation. Macrophages also produce cytokines to send signals to other immune cells and to cause inflammation.
b. Neutrophils
Neutrophils are the most abundant white blood cell. Neutrophils are similar to macrophages with some exceptions. Neutrophils enter tissues by extravasation. Once they enter the tissue, neutrophils phagocytose pathogens. Granules in the neutrophil act as lysosomes of phagocytes, and neutrophils can be subdivided by the type of granules. However, neutrophils are different from macrophages in that they do not present antigens.
c. NK (natural killer) cells
Natural killer cells (NK cells) are unusual cells of the innate immunity. They are unusual because they are lymphocytes despite being a member of the innate immunity. Lymphocytes are lineages of T-cells and B-cells which are two main members of the adaptive immunity. However, as NK cells are part of the innate immunity, they do not require antigens presented by macrophages nor have memories.
Two main functions of the NK cells are following:
- Killing infected human cells
- Producing IFN-ɣ to activate macrophages
Normally, most human cells, with typical exception of red blood cells, have MHC class 1 as their surface molecule. MHC class 1 is important for activating the adaptive immunity as antigens are placed on the MHC 1 molecules to be presented to CD8 T-cells. However some viruses block normal human cells from expressing MHC class 1 molecule. NK cells kill any human cells with reduced MHC class 1 molecule at their surface.
d. Eosinophils
Eosinophils share some similarities with mast cells and basophils. All three cell types have granules with lysing enzymes, are activated by IgE antibodies to kill parasites. Since parasites are too big to be phagocytosed, these cells release enzymes to kill the parasites.
As we can tell by its name, eosinophil is stained red by the Wright stain. Eosinophils kill parasites through Antibody-dependent cellular cytotoxicity (ADCC).
e. Mast cells & Basophils
Mast cells and basophils share even more similarities that eosinophils do not have. Both are stained blue by the Wright stain, secrete histamine and similar enzymes. One of the differences is that mast cells resident in the tissue while basophils circulate through the blood.
f. Dendritic cells
Dendritic cells are professinoal antigen presenting cells that migrate into the lymph nodes to present antigens and activate T-cells. They are found at tissues throughout our body including the skin and mucosal membranes.
g. Complement proteins
Complement proteins are soluble proteins produced by the liver. Functions of complement proteins are following:
- Opsonization
- Forms Membrane attack complex (MAC)
- Chemotaxis
- Increase inflammation
Opsonization is coating pathogens with opsonins. Macrophages can recognize and engulf pathogen with opsonins better. C3b and other complement proteins group together to form a membrane attack complex. Membrane attack complex makes pores in the bacteria and kill them. Activation of complement proteins produces chemokines that attract leukocytes, i.e., chemotaxis. Proinflammatory molecules such as C3a, C4a, C5a are produced by the activation of complement proteins. Proinflammatory molecules produced by the attracted leukocytes and activation of complement proteins increase inflammation.
2) Pattern recognition
How do immune cells know which cells are pathogens? The answer is that they recognize molecules that are not self but foreign. Immune cells have pattern recognition receptors that recognize pathogen-associated molecular patterns' (PAMPs). Once PAMP binds to the receptor, cell transduction pathway is activated which in turn activates transcription factors for expression of proteins necessary for inflammation and antiviral activity. For example, lipopolysaccharide (LPS) found in the gram negative bacteria binds to LPS-binding protein. The LPS and LPS-binding protein complex than binds to the CD14 of the macrophages. Binding to the CD14 will trigger Toll-like receptor 4 (TLR4), and this will cause sequence of reactions. Mannose binds to the mannose-binding lectin (MBL) which activates the lectin pathway of complement proteins, and peptidoglycan cell wall binds to the NOD like receptors.
3) Phagocytosis
As explained earlier, phagocytosis is the process of engulfing pathogens by macrophages, neutrophils and dendritic cells. Phagosome with engulfed pathogens merges with lysosome to form the phagolysosome. Toxic material in the lysosome kill the pathogens. The toxic materials include enzymes such as proteases, nucleases and lysozymes. Reactive oxygen species and reactive nitrogen intermediates are also included. These are separately kept in the lysosome as they are toxic to our normal tissues and cells when exposed.
Some pathogens developed their way to disrupt this phagocytosis process for survival. Mycobacterium Tuberculosis (M. tb) blocks phagosome maturation which prevents phagosome containing the pathogen from merging with lysosomes. This way they can survived inside the macrophages where they are also protected from the antibodies. Chediak-Higashi syndrome is a genetic disorder with defect in the immune system. Lysosomes fail to fuse with phagosomes.
4) Cytokines
Cytokines are cell signaling proteins. There are several types:
- Interleukins: Signals between leukocytes
- Chemokines: Chemotaxis (Attracting immune cells)
- Interferons: Interferes with viral replication
- Tumor necrosis factor (TNF): Can kill tumor cells
- Transforming growth factor (TGF)
5) Cluster of Differentiation (CD)
Cluster of differentiation are molecules found on the cell surfaces. They can be used as receptor or binding proteins. Many immune cells have cluster of differentiation, and they can be used to differentiate cells.
3. Link between Innate and Adaptive Immunity
Antigen presentation of innate immune cells are crucial for activation of adaptive immune cells. Dendritic cells move directly into the lymph node and present antigens. Cytokines secretes by innate immune cells also help activate adaptive immune cells.
When adaptive immune cells are activated, innate and adaptive immunity work together to fight with the pathogens. An example of them working together is antibody dependent cellular cytotoxicity (ADCC). ADCC begins by antibodies binding to the antigens on the surface of the pathogens. NK cells and eosinophils bind to the Fc portion of the antibodies then release toxic enzymes into the pathogens. NK cells bind to the IgG antibodies to kill the target cells while eosinophils bind to the IgE antibodies to kill parasites.
This was the outline for innate immunity. Some parts of innate immunity that I think need further elaboration (e.g. macrophages, neutrophils and complement system) will be dealt again. Thanks for reading.
