Immune system Flashcards
Immune system
A versatile defence system that protects us from pathogenic microbes
Pathogens
An infectious agent that can cause disease in a host.
The body comes into contact with numerous and various potential pathogens every day, where they interact with the host immune system.
Antigens - function and types (inc antibodies)
A substance that can be recognised by leukocytes.
It is a marker for a cell (identity)
Usually proteins (3D shape
There are two types of antigens:
1. Foreign antigens (e.g. microbes (bacteria, viruses), food, drugs)
2. Self-antigens (present on cell membranes – healthy and not mutated)
Antibodies are proteins that are produced in response to a specific antigen and combine with them (create an immune response).
Leukocyte overview; Granulocytes
Leukocytes are either granular or agranular.
Granulocytes include;
* Basophils (and mast cells)
* Eosinophils
* Neutrophils:
Leukocyte overview: Granulocytes; Basophils and mast cells
Basophils and mast cells;
* In blood = basophils. In tissue = mast cells
* Release histamine (vasodilates / increases vessel permeability) and heparin (anti-coagulant) → involved in inflammation
* Express receptors for IgE and hence involved in allergy / hypersensitivity
Leukocyte overview: Granulocytes; Eosinophils
Esoinophils;
* Destroy parasitic worms via phagocytosis (less efficient phagocyte)
* Play role in inflammation (central role in asthma)
Leukocyte overview: Granulocytes; Neutrophils
Neutrophils;
* Account for 60% of leukocytes. A phagocytic cell.
* Granules release lysozymes that digest debris
Leukocyte overview: Agranulocytes
Leukocytes are either granular or agranular.
Agranulocytes include;
* Monocytes and macrophages
* Natural Killer (NK) cells
* B- and T- lymphocytes
Leukocyte overview: Agranulocytes; Monocytes and macrophages
Monocytes and Macrophages;
* In blood = monocytes. In tissue = macrophages (wandering / fixed)
* Phagocytic and secrete cytokines; e.g. interleukin-1 (fever) and TNF
Leukocyte overview: Agranulocytes; Natural Killer cells
Natural Killer (NK) cells;
* Target foreign cells and secrete perforin to induce cytolysis
Leukocyte overview: Agranulocytes; B- and T- lymphocytes
B- and T- Lymphocytes;
* Involved in adaptive (specific) immunity and immunological memory
Major Histocompatibility Complex (MHC)
MHC’s are a group of cell-surface proteins that are required for the immune system to recognise cells that are healthy body cells versus those that are ‘non-self’.
* MCH’s are each formed of four polypeptide chains and display a protein produced by the cell on its ‘bindng groove’ (this is a ‘self-antigen’ as it is produced by that healthy cell)
* MHC molecules function to present foreign antigens to T-cells
There are two types of MHC:
1. Class I Major Histocompatibility Complex (MCH-I)
2. Class II Major Histocompatibility Complex (MCH-II)
Poly = many, peptide = protein
Major Histocompatibility Complex (MHC); Class I MHC
MHC-I is located on all body cells, except erythrocytes
* When the body cell is cancerous or invaded by a pathogen (i.e. viruses or bacteria replicating in cytosol), the cell starts to produce abnormal proteins
* These proteins are combined with MHC-I and displayed on the cell membrane (indicating a ‘non-self ‘ cell) – this flags up to leukocytes (mostly to cytotoxic T-cells / CD8 cells)
MHC-I allows our leukocytes to determine healthy body cells from abnormal / infected cells
Major Histocompatibility Complex (MHC);
Class II MHC
MCH-II are located only on the cell membrane of ‘antigen presenting cells’ (Macrophages and B- Lymphocytes).
* The MCH-II displays the ‘foreign antigen’ on its binding groove, having ingested the foreign cell
* These are used specifically for communication between themselves and T-Helper cells
* MHC-II is used to display the foreign antigen and ‘present’ it to T-helper cells. They are, therefore, vital in the process of ‘antigen presentation’.
Immune system structure
The body has a layered defence strategy which comprises of 3 parts;
1. First line (innate immunity)
2. Second line (innate immunity)
3. Third line (specific /adaptive immunity)
First line of defence
First line; innate immunity
Physical barrier against pathogens created by skin and mucous membrane
Second line of defence
Second line; innate immunity
Non-specific immune response that includes some immune cells, proteins, fever and inflammation
Third line of defence
Third line of defence; specific / adaptive immunity
Activated by the innate immune system, producing a response towards a specific pathogen
First line of defence; Skin
The skin = physical barrier with layers of tightly packed epithelial cells. The outer epidermis consist of dead epithelial cells and sheds (to remove microbes)
The dermis contains accessory structures such as sebaceous glands and sweat glands. They have an immune function;
- Sweat removes microbes from the skin and contains IgA
- Sebum contains fatty acids which inhibit microbial growth
First line of defence; Mucous Membrane
The digestive, respiratory and urogenital tracts are lined with mucous membranes. As is the conjunctiva (in the eyes)
These barriers and a number of non-specific defences attempt to prevent entry into the membrane.
- Saliva, tears and mucus secretions wash away microbes and also contain anti-microbial substances
- Mucus traps microbes and foreign particles
- In the respiratory tract, cilia propel the foreign substances towards the pharynx where they are swallowed = mucociliary escalator
- Tears and saliva contain IgA and lysozymes. Lysozymes and enzymes that break down bacterial cell walls.
- Hairs filter air in the nose
- The vagina (in menstruating women) is acidic making it unfavourable for microbes to inhabit
- Gastric acid – the acidity destroys many bacteria
- The microflora generally outcompete pathogens for attachment sites on epithelial cell surfaces (and for essential nutrients) (car park spaces analogy)
- Excretion of urine and faeces expels microbes
- Vomiting and diarrhoea are rapid means of expelling pathogens
Second line of defence; components
When pathogens penetrate the physical and chemical barriers of the skin and mucous membranes, they encounter a second line of defence.
This includes:
* Complement system
* Transferrins
* Phagocytes
* Natural killer cells
* Inflammation
* Cytokines (e.g. interferons)
* Fever
Second line of defence; Transferrins
Transferrins are iron-binding proteins in blood
* They act to inhibit the growth of certain bacteria, by reducing the amount of available iron
* Bacteria could otherwise use the iron available for their growth
Trans = across, ferr(ous) /Fe = iron
Second line of defence; Complement system
A defensive system made of over 30 proteins produced by the liver.
* Complement proteins are identified by a letter (mostly C) with a number; e.g. C3
* Proteins are inactive and only become active when split by enzymes into active fragments (a + b); e.g. C3 →C3a + C3b
* When activated these proteins act in a cascade (=amplified)
* The most common mechanism through which complement is activated is via the ‘classical pathway’, when antigen-antibody complexes are formed
* Example - glomerulonephritis
Second line of defence: Complement system; destroy microbe mechanisms
Collectively, complement proteins destroy microbes by;
1. Promoting phagocytosis: The fragment C3b ‘coats’ a microbe in a process called opsonization. This promotes the attachment of a phagocyte to a microbe (tracking device).
2. Contributing to inflammation: C3a and C5a bind to mast cells and cause them to release histamine
3. Causing cytolysis: Destroying (bursting) microbes (final 5 C = C5, 6, 7, 8, 9)
Second line of defence: Cytokines
Small protein hormones (chemical messengers) that stimulate or inhibit normal cell functions.
* A group of non-antibody proteins secreted by leukocytes
* Act on cells involved in immunity (mediate immune response)
* (Analogy = email /text to communicate between different types of cells)
Cytokines include:
* Interleukins; These act as mediators between leukocytes. Mostly produced by T-helper cells. (Different numbers do different things e.g. Interleukin 1 releases macrophages and triggers fever response)
* Interferons; Involved in anti-viral responses
* Tumour necrosis factor (TNF); Promotes the accumulation of neutrophils and macrophages and causes cell death
Second line of defence; Interferons
Interferons comprise a group of proteins produced by virus-infected cells.
* Interferons diffuse to uninfected neighbouring cells, where they induce synthesis of anti-viral proteins that interfere with viral replication
* Interferons do not stop a virus attaching to and penetrating a host cell, but they prevent it replicating
* Viruses can only cause disease if they replicate within body cells
Interferon = interferes.
Second line of defence; Phagocytosis process
Phagocytes perform phagocytosis (cell digestion).
* Phagocytic cells are attracted to sites of inflammation by ‘chemotaxis’
* Two major types (which migrate to an infected area) are;
- Macrophages (monocytes in blood)
- Neutrophils
* Monocytes migrate to the site of infection and enlarge to form ‘wandering macrophages’. Other macrophages are ‘fixed macrophages’ and stand guard in specific tissues
* Phagocytes are non-selective in their targets; they engulf and digest foreign materials
* Macrophages are ‘antigen presenting cells’
Chemo = chemical, taxis = order, Chemotaxis = chemical attraction
Second line of defence; Phagocytosis – fixed macrophages (type / location)
Some macrophages are ‘fixed macrophages’ and stand guard in specific tissues. These include:
* Histiocytes (connective tissue macrophages)
* Kupffer cells (liver)
* Alveolar macrophages (lungs)
* Microglia (nervous tissue)
* Langerhans cell (skin)
* Tissue macrophages (spleen, bone marrow, lymph nodes)
Second line of defence; Phagocytosis stages
Phagocytosis occurs in 5 stages:
1. Chemotaxis; release of chemicals by microbes, leukocytes, damaged tissue and by activated complement that attract phagocytes
2. Adherence; attachment of phagocyte to target (aided by complement)
3. Ingestion; the cell membrane extends projections that engulf the microbe
4. Digestion; The ingested structure merges with lysozymes to form a phagolysosome. Lysozymes and digestive enzymes ‘digest’
5. Excretion; indigestible material is excreted (some is presented on cell)
Second line of defence; Natural Killer Cells- (NK) cells
Natural Killer (NK) cells account for 5-10% of lymphocytes. They are ‘non-specific lymphocytes’.
* Present in blood, lymph nodes, spleen and bone marrow
* NK cells attack anything that they do not recognise, inc. abnormal body cells (abnormal cell membrane proteins) e.g. cancerous cells
* NK cells bind to a target cell and release granules containing the protein ‘perforin’
* Perforin inserts into the cell membrane and creates a channel for tissue to flow into the cell → cytolysis
Second line of defence; Inflammation
Inflammation is a non-specific defensive response to tissue damage.
* It can be caused by pathogens, abrasions, chemicals, cell distortion or disturbance and extreme temperatures.
* The response is non-specific, meaning the response to different insults is the same
The cardinal signs of inflammation include:
* Redness
* Heat
* Pain
* Swelling
* Loss of function
Second line of defence; Inflammation stages
Inflammation occurs in three basic stages;
1. Vasodilation and increased permeability
2. Emigration of phagocytes
3. Tissue repair
Second line of defence; Inflammation stage 1
Stage 1; Vasodilation and increased permeability:
* Vasodilation allows additional blood to the area, bringing oxygen, nutrients, immune cells and repair substances and removal of toxins and dead cells
* Increased permeability permits the movement of immune cells, defensive proteins such as antibodies and clotting factors into the tissue
* Together these create redness, swelling and heat. Pain results from injury to neurons and toxic chemicals released by microbes.
Second line of defence; Inflammation stage 2 & 3
Stage 2; Emigration of phagocytes
* Within an hour of the process beginning, phagocytes migrate to the scene (via chemotaxis)
* Neutrophils stick to the endothelium during vasodilation and squeeze through the vessel wall to reach the damaged area (leukocytosis)
* Monocytes quickly follow and transform into wandering macrophages
* Dead phagocytes accumulate as pus
Stage 3; Tissue repair
Second line of defence; Inflammation benefits vs. harmful effects
Benefits:
. Promotes phagocytosis (via chemotaxis); the increase in temperature promotes activity
. Promotes immune response; vasodilation and increased permeability mean that cells and proteins (e.g. antibodies) can leave the blood and enter the affected site
. Dilutes toxins
. Fibrin formation; isolates the affected area and helps to bind wound edges
Harmful effects:
. Swelling; dangerous if in the cranium
. Pain; which can become chronic
. Adhesions and scar tissue
. Atherosclerosis; inflammation is a key feature of this process
Second line of defence; Inflammation outcomes
Resolution; The cause is successfully overcome (complete restoration)
Chronic inflammation; If injury-causing agent persists. Can cause chronic pain. Macrophages, plasma cells and lymphocytes become prevalent
Granuloma; Cellular attempt to contain foreign body. Aggregation of macrophages surrounded by lymphocytes
Fibrosis; Scar tissue formation. Formed by the secretion of collagen by fibroblasts. Occurs often as a result of chronic inflammation
Second line of defence; Non-specific fever
A fever is an abnormally high body temperature
* Occurs because the hypothalamus thermostat is reset
* Commonly occurs in infection and inflammation
* Many bacterial toxins elevate body temperature, which trigger the release of fever-causing cytokines from macrophages, such as interleukin-1
* One of the key functions of interleukin-1 is to induce fever
Elevated body temperature:
* Makes interferon’s more effective
* Inhibits growth of some microbes
* Speeds up reactions that aid repair
Third line of defence; Lymphocytes
Lymphocytes developed in the bone marrow.
There are two types of lymphocytes;
1. T-lymphocytes
2. B-lymphocytes
Third line of defence; T- Lymphocytes
T- Lymphocytes (T-cells) (mature in Thymus):
* Cytotoxic T-cells (CD8); break down / destroy foreign cells (analogy = FBI)
* Helper T-cells (CD4); mediates immune response (analogy = coordinator)
* Memory T cell; created after exposure to active disease
* Regulatory T-cells; turn off immune reaction when immune response should be finished.
Cyto = cell, toxic = toxic
Third line of defence; B- Lymphocytes
B-lymphocytes (B-cells) (mature in red bone marrow):
* Plasma cells (produce anti-bodies); B-cells produce plasma cells, which produce anti-bodies. They are specific. (analogy another department within FBI)
* memory B-cells
Third line of defence; B- & T-Lymphocytes – specific immunity
T- and B- lymphocytes function in adaptive (specific) immunity, whereby they learn to respond to foreign antigens
* T- and B- Lymphocytes possess specificity for antigens. They (usually) recognize self from non-self antigens. Each T- and B- lymphcyte is specific for a particular antigen
* T- and B- lymphocytes produce immune memory for previously encountered antigens.
* Immune memory allows them to produce a quicker and more effective attack with the next encounter with the antigen
Third line of defence; T-Lymphocytes (cont.)
T-Lymphocytes (or T-cells) play a central role in cell-mediated immunity
* Millions of different T-lymphocytes exist, each with a unique T-cell receptor (TCR) that only recognizes a specific antigen
* Produced in bone marrow and mature in the thymus (hence name)
* Most T-cells arise before puberty but continue to mature and leave the thymus throughout life
* T-cells are divided into; T helper cells and Cytotoxic cells
* T- helper cells are also known as CD4 cells because they express CD4 protein on their surface (as are macrophages)
* Cytotoxic T-cells are CD8 cells
Third line of defence; Self tolerance and Self recognition
To function properly, T-cells must have two traits:
1. Must be able to recognize self antigens (self recognition)
2. Must lack reactivity to fragments of self-antigens (self tolerance)
- A loss of self-tolerance leads to autoimmunity
- T-cells are ‘tested’ against thymus epithelial cells. T-cells should be able to recognize self-antigens. If they do not, these cells undergo apoptosis.
- Only 1-5% of T-cells make it through the process
- B-cells undergo a similar screening process in the bone marrow.
Third line of defence; Adaptive Immune System
The innate immune system is often sufficient to destroy invading microbes. If it fails to adequately destroy the pathogen, the third line of defence is activated.
* Cytokines (messenger molecules) mediate the connection between the innate immune system and the adaptive immune system
* The effector cells of the adaptive immune system are T- and B- lymphocytes
* T- and B- lymphocytes are normally at rest, but become activated on encountering a foreign antigen (or what they perceive to be foreign)
* A key feature of the adaptive immune system is acting specifically to target certain antigens in the immune response.
Third line of defence; Adaptive Immunity - types
Adaptive immunity is the ability of the body to defend itself against specific agents
* Characterised by specificity for particular foreign antigens and the production of immune memory
There are two types of adaptive immunity;
1. Cell mediated immunity (T-lymphocytes)
2. Antibody adapted immunity (B-lymphocytes)
Third line of defence; Adaptive Immunity; Cell-mediated immunity
Cell mediated immunity;
* By T-lymphocytes
* Cytotoxic T-cells directly attack invading antigens
* Defense mostly against intra-cellular pathogens
Third line of defence; Adaptive Immunity; Antibody-mediated immunity
Antibody mediated immunity;
* By B-lymphocytes
* B-cells transform into plasma cells, which synthesise and secrete specific antibodies (Ig’s)
* Defense mostly against extra-cellular pathogens
Third line of defence; Antigen presentation
For an immune response to occur, T-cells must recognise that a foreign antigen is present.
* T-cells only recognise protein fragments (antigens) that are processed and presented in a certain way
* A class of cells called antigen-presenting cells (macrophages and B-cells) are strategically located in places where antigens are likely to penetrate the body
* Antigen-presenting cells combine the foreign antigen with MHC-II complexes on their cell membrane
* Antigen-presenting cells migrate into lymphatic tissue, where they ‘present’ the antigen to T-helper cells. This is known as antigen presentation.
Third line of defence; Antigen presentation – triggering clonal selection
For the T-lymphocytes to get ‘sensitised’ to their antigen, the antigen must be presented to the cell, usually a macrophage
* Through the action of phagocytosis, macrophages use lysozymes (enzymes) to break down the antigen into fragments. Some fragments will be combined with MHC molecules
* When the antigen fragment binds with the T-helper cell, the T-helper cell secretes a cytokine called interleukin-2 (Il-2)
* Interleukin-2 causes the T-helper cell to undergo ‘clonal selection’
Interleukin-2 is the prime trigger for T-lymphocyte proliferation and also stimulates clonal selection of B-lymphocytes
Third line of defence; Antigen presentation – clonal selection - interleukin 2
Interleukin-2 binds to receptors on the cell membrane of the T- helper cell that secreted it.
Interleukin-2 stimulates the division and proliferation of activated T-cells.
This process, called clonal selection produces;
1. Cytotoxic T-lymphocytes: Bind to target cell and destroy it using protein digesting enzymes called granzymes, and perforin
2. Memory T-lymphcytes: Inactive. Recognise the antigen with any future contact, ready to mount an immune response
3. Helper T-lymphocytes: Release cytokines which increase the acivity of immune cells such as T-, B- and NK cells
Third line of defence; Anti-body Mediated Immunity and clonal selection
B-lymphocytes form and mature in bone marrow and are fixed in lymphoid tissue, where they do not leave.
* An antigen binds to specific B-cells receptors, where it is taken into the cell and broken down into fragments. These are then expressed on the MHC-II
* Helper T-cells recognize the antigen complex on the B-cell membrane and stimulate it by releasing interleukin-2, which triggers B-cell clonal selection.
- Clonal selection produces 2 types of cells:
1. Plasma cells (secrete antibodies)
2. Memory B-cells
Third line of defence; Anti-body Mediated Immunity; conal selection – plasma cells
Plasma cells:
* Secrete antibodies into the blood
* Only produce one type of antibody
* A few days after antigen exposure, secrete hundreds of millions of antibodies each day until cells die.
* Short lived.
Third line of defence; Anti-body Mediated Immunity; conal selection – memory B-cells
Memory B-cells
* Long lived
* Remember antigen for nect time, ready to proliferate and produce more plasma cells for a second immune reaction
Third line of defence; Antibodies
Antibodies belong to a group of glycoproteins called globulins, and are hence also known as immunoglobulin’s
* Antibodies contain 4 polypeptide chains (two heavy and two light chains). There is a variable region that is different for each kind of antibody
* Antibodies generally have two antigen-binding sites
* Antibodies bond specifically with the antigen that triggered their production (lock and key). They form antibody-antigen immune complexes.
Third line of defence; antibody antigen inactivation
Antibodies inactivate antigens in different ways:
1. Neutralising; Neutralise bacterial toxins or prevent viral attachment to cells.
2. Immobilising; bind to antigens on bacterial cilia or flagellae
3. Agglutinating and precipitating; antibodies use both their binding sites to cause clumping of cells
4. Activating complement; antigen-antibody complexes activate the complement cascade
5. Enhancing phagocytosis; the antibody acts as a flag to attract phagocytes and aids phagocytosis via agglutination and complement.
Third line of defence; Antibody types
There are 4 different types of antibody (IMMUNOGLOBLINS)
1. IgG
2. IgA
3. IgM
4. IgE
Third line of defence: Antibody types; IgG
Immunogloblin G (IgG):
Location: Blood, lymph and intestines
How common? Most abundant (80% of blood antibodies)
Function: Protects against bacteria and viruses, only class of antibody that crosses the placenta
Third line of defence: Antibody types; IgA
Immunogloblin A (IgA):
Location: Sweat, tears, saliva, breast milk
How common? 10% antibodies in blood, mainly found in mucus membranes
Function: Localised protection of mucus membranes, decreases with stress
Third line of defence: Antibody types; IgM
Immunogloblin M (IgM):
Location: Blood and lymph
How common? 10% blood antibodies
Function: Main class of antibody in early immune response
Third line of defence: Antibody types; IgE
Immunogloblin E (IgE):
Location: Blood
How common? 0.1% antibodies in blood
Function: Involved in akkergic reactions. Binds to mast cells
N/B; Food intolerance creates IgG response rather than IgE (true allergy reposnse)
Third line of defence; Regulatory T-cells
Regulatory T-cells were formally ‘suppressor T-cells’.
* A specialised sub-population of T-cells which deactivate immune cells (T-helper, B-cells and macrophages) when an immune response is no longer required.
* Thereby maintain immune system homeostasis and tolerance to self-antigens
* Without the regulatory T-cells, the body would continue trying to fight of a disease that no longer exists (and would eventually end up fighting its own cells)
* Regulatory T-cells prevent excessive reactions
Immunological Memory
Based on the presence of long-lasting antibodies and very long lasting memory B- and memory T-cells.
There are 2 types of response;
1. Primary (first exposure)
2. Secondary (subsequent exposure)
Immunological Memory; Primary response
Primary response (first exposure);
* A slow response. Antibodies do not appear for several days, then a slow rise in IgM, followed by IgG
Immunological Memory; Secondary response
Secondary response (subsequent exposure);
* Memory cells can last for decades
* Much faster response because a full immune response has been developed with thousands of memory cells
* Often the secondary response is so effective, it kills off the microbes before you exhibit any signs or symptoms
Vaccination
Immunological memory is the basis for vaccination against certain diseases.
* Vaccines contained weakened (attenuated) whole or partially-killed portions of microbes – microbes are immunogenic but are not supposed to be pathogenic
* B- and T- cells are activated – primary response. Not many cells have the correct specificity to respond to the antigen, so a response can take several days.
* Subsequent exposure to the living pathogen initiates a far more effective secondary response
Acquired Immunity
Ways to acquire immunity:
1. Naturally-acquired active immunity; Natural exposure to a disease
2. Naturally-acquired passive immunity; Transfer of IgG antibodies across the placenta from mother to child, transfer of IgA form mother to child via the breast milk
3. Artificially-acquired active immunity; vaccination
4. Artificially-acquired passive immunity; injection with immunoglobulin’s, e.g. snake anti-venom
Digestion system defences:
70% of body’s immune system is found in the GIT
* GALT (gut associated lymphoid tissue) contains immune cells (e.g. macrophages, B- and T- lymphocytes)
* GALT is in the tonsils, oesophagus, small intestine and large intestine
* The health of the digestive system plays a critical role in a healthy immune system. Leukocytes learn from the microflora
* Poor function affects immunity, nutritional status and toxic load
Pathogens - entry to body
Pathogens can enter the body and cause disease through openings such as:
* Breaks in the skin
* The respiratory system
* The digestive system
* Male / female reproductive systems
* Eyes
