Hi this is Tom from Zero2Finals.com. This video was designed to give an overview of immunology so that you understand all the basic features of the immune system. It will also help you to return to this video once you've already learned the details so that you can again fit those details back into the bigger picture about how the immune system works.
The immune system can be categorized into the innate immune system and the specific immune system. The innate immune system consists of the components that are already at the location of the infection and respond immediately with a generalized response. The specific immune system involves specialized T and B cells that are waiting in places away from the site of infection and then when they're activated they launch a specialized system that fights the specific invading pathogen.
The specific immune system takes a little while longer to recognize the infection, particularly when a pathogen is invading the body for the first time. So in this video we're gonna cover both of these systems and also talk about a system called the complement system that works alongside the innate and specific immune systems. Let's look at what happens when a pathogen invades the body.
Initially, there are physical barriers that need to be broken before an infection can take place. The skin is an example of one of these barriers. Most invaders will get stuck at this barrier. However, occasionally, an invading pathogen will get through, such as when there's a cut in the skin. As well as the skin, there's other physical barriers, such as the mucosa of the respiratory system, the gastrointestinal tract, and the urinary tract.
There are also chemical barriers that help destroy harmful pathogens before they can cause any infection, such as the hydrochloric acid in the stomach, lysozyme in sweat and tears, and lactic acid in the vagina. Let's look at the initial responses of the immune system once an invading pathogen has broken through the physical and chemical barriers to infection. Three things happen.
Number one, macrophages recognise the pathogen and activate the innate immune system. Number two, dendritic cells pick up antigens from the pathogen and then head off in the blood and lymphatic systems to track down the relevant T and B cells of the specific immune system and activate them. And number three, the invading pathogen activates the complement system directly via the lectin pathway and the alternative pathway and we'll talk a bit more on those later.
First, let's look at how the innate immune system provides an immediate response to infection. The first to respond are the macrophages. They recognise pathogens by specific characteristics that occur on pathogens but don't occur on cells of the body. These characteristics are called Pathogen Associated Molecular Patterns, or PAMPs.
They recognise PAMPs using various receptor types, including Toll-like receptors. At this point I need to talk briefly about a process called phagocytosis. Now phagocytosis is the process that macrophages and other phagocytes like neutrophils use in order to destroy pathogens. So what happens is once they've recognized the pathogen, they start to wrap their cell membrane around that pathogen and absorb them to within their cell. The pathogen is then left inside something called a phagosome, and this phagosome fuses with surrounding lysosomes that provide digestive enzymes that then break down that pathogen, destroying it and also processing all of the components into harmless waste products.
If the invading pathogens are harmless enough that the macrophages can deal with them alone, then they're cleared and it goes no further. If the attacking army is too great, the macrophages need help, so they release cytokines, which are signaling proteins, sort of like local hormones, that sound the alarm of an infection in the local area. This leads to a process called inflammation.
One of the most important actions of these cytokines is to recruit and activate more cells of the immune system such as macrophages, monocytes and neutrophils. Monocytes are precursors to macrophages that float around in the blood. Once they enter tissues they differentiate into macrophages and can then carry out all the processes that macrophages normally carry out. Neutrophils are another type of phagocyte that circulate in the blood and can enter the tissues and help by destroying invading pathogens.
The inflammatory response also involves a number of other processes that help to contain and fight the infection. These are vasodilation, increased vascular permeability, mast cell activation and degranulation, releasing more cytokines that further stimulate the inflammatory response. activation of the clotting system, and activation of the kinin system.
Inflammation itself actually stimulates macrophages and neutrophils to secrete more cytokines, notably chemicals called interleukins. This is known as the acute phase response, and it leads to a more systemic inflammatory response. This involves sending cytokines specifically interleukin-1 to the brain to tell it to produce a fever that leads to high temperatures that are poorly tolerated by many pathogens and cause reduced appetite and lethargy so that the person conserves more energy that can be used to fight the infection.
It also involves sending interleukin-6 to the liver to produce acute phase protein that act as something called opsonins. and remember this word because we'll talk about opsonins in a minute. Additionally, interleukin-8 is released that recruits and activates more neutrophils.
Interleukin-2 and 12 activate natural killer cells, and tumor necrosis factor alpha is released that does all of these effects by itself. As I just mentioned, I want to take a quick look at opsonins, as these are very important in the immune system. Opsonins are complex molecules that attach themselves to pathogens and make it easier for macrophages and neutrophils to recognize and phagocytose that pathogen. I think of them a bit like a fork that spears the pathogen so that macrophage can attach to the other end of the fork and then use it to eat the pathogen.
An example of an opsonin that you may have heard of is C-reactive protein or CRP. CRP is produced by the liver in response to interleukin-6, and we actually measure the level of CRP in our patients to assess how much inflammation there is in the body. And it can be a really good indicator of the severity of the infection that our patient is suffering with.
So that summarises the innate immune system, a generalised system that recognises and responds to an invading pathogen by causing an inflammatory response and recruiting cells. that destroy the pathogens by phagocytosis. Next let's look briefly at the complement system.
The complement system works alongside the innate and the specific immune system to help them destroy pathogens. This involves a series of complement proteins labelled C1 to C9. Once a complement system is triggered, the proteins start to activate each other in something called the complement cascade.
Various products of the complement cascade have important functions such as acting as opsonins, triggering further inflammation and directly attacking and destroying the pathogens. The complement system is triggered in one of three ways. The lectin and the alternative pathway are activated directly by pathogens and the classical pathway is activated by antibody-antigen complexes that arise from the specific immune system. And that brings us nicely onto looking at the function of the specific immune system. The specific immune system involves two characters, the T and the B cells, and these are both types of lymphocyte.
They are free to float around the lymphatic system and the blood, but they spend most of their time in the lymph node and the mucosa associated lymphoid tissue. Think of these lymphoid tissues as army barracks that are full of soldiers that are all sat around waiting to get word of an enemy. that they've specifically been trained to fight. Each pathogen has molecules that are unique to them.
They're known as antigens. Each T cell has T cell receptors that are specific to a single type of antigen. B cells have antibodies on their cell membrane that, just like T cell receptors, are specific to a single type of antigen.
The result is there's millions of different T and B cells that are all specific to a single type of antigen. When a new pathogen arrives and causes an infection, the T and B cells that are specific to that pathogen need to be alerted. The trouble is they're sat in lymphatic tissue such as lymph nodes while the infection is happening somewhere completely different. This is where the dendritic cell comes in.
These cells are like messengers and they pick up the antigens at the site of the invasion, display them on their cell surface and then bring them through the blood and lymphatic system into the lymphatic tissue. When they're there, all the T and B cells have a look at the antigen and see whether they recognise it. When the T and B cells are found that are specific to that antigen, those cells become activated. So the specific immune response starts with the dendritic cell, presenting the antigens on the HLA class 2 molecules to the CD4 cells. These CD4 cells, which are a type of T cell, then proliferate and become T helper cells.
The T helper cells present antigens on their HLA class 1 molecule that can be recognized by CD8 cells, another type of T cell. They also secrete cytokines that are responsible for making the CD8 cells proliferate and differentiate into cytotoxic T cells. These T helper cells also release cytokines that stimulate B cells to proliferate and differentiate into plasma cells.
that can release large quantities of antibodies, and memory B cells that hang around as part of the immune memory to respond quickly in future inflections with that specific pathogen. The T-helper cells also travel to areas of infection and secrete cytokines that help to recruit monocytes and macrophages to the infected tissue and activate the macrophages to cause inflammation and start the process of phagocytosis. Cytotoxic T cells are responsible for killing cells that have been infected by pathogens, such as virally infected cells.
To do this, they need to attach themselves to the infected cell via the T cell receptor and the HLA class 1 molecule expressing the relevant antigen protein on the infected cell. Once they're attached to the virally infected cell, they have two killing mechanisms that they can choose from. The first is called granule exocytosis, where they basically spray the infected cell with enzymes that destroy the membrane and lead to cell lysis and cell death.
The second is they can activate the FASP molecule. The FASP molecule is like a self-destruct switch, that once it's activated it causes the cell to undergo apoptosis. Plasma cells and antibodies are an essential part of the specific immune system.
Plasma cells are B cells that have differentiated and become antibody producing cells and their job is to produce tons of antibodies that are specific to the invading pathogen. These antibodies are proteins that are shaped like a Y. One end is variable in shape to match different antigens, whereas the other end is fixed in shape and can be recognised by many cells of the immune system. These proteins float around the blood and attach themselves to antigens that match their specific variable region. And these antibodies help the immune system fight pathogens in a number of different ways.
Firstly, they can attach themselves to enemy toxins, which themselves are antigens, and neutralise their toxic effect. Secondly, antibodies can attach themselves to the receptors of viruses and bacteria and prevent them from carrying out their function. For example, it can stop viruses from being able to recognise cells that it may want to invade and therefore prevent the viral invasion of that cell. Thirdly, antibodies can attach themselves to pathogens, then clump together to slow the spread of that pathogen down.
This is called agglutination. Finally, it can be very difficult for the simplistic receptors of macrophages and neutrophils to recognise certain pathogens. Antibodies can act as opsonins that are highly specific to the invading pathogen and by attaching themselves to that pathogen, acting as opsonins, they can help the macrophages and neutrophils to recognise and destroy that pathogen. That summarises an overview of the immune system. I hope you found this video helpful.
It was created as part of a set of videos that covers everything you need to know about the immune system for medical school and practising as a doctor. So go ahead and check out the rest of those videos. If you liked this one then please like, comment and subscribe for more videos to help you achieve success in your medical career.
You can also check out the Zero to Finals website where you'll find notes, illustrations, practice questions and a blog. And I hope it's all useful for you and I'll see you in the next video.