For the exam
What is the immune system?
Complex network of cells, tissues, organs and substances that helps the body fight diseases.
Main functions of the immune system?
Defend against foreign particles
destroy
maintain homeostasis
Benefits of the immune system?
Protection against invaders
elimination of altered self
Detrimental effects of the immune system?
Discomfort due to inflammation
Damage to self when autoimmunity occur.
Components of the immune system?
Mucous membrane
Tonsils
Thymus
Lymph nodes
Spleen
Bowel
Bone marrow
Skin
Primary lymphoid organs
Where immune cells are generated and matured:
Thymus, bone marrow
What happens to primary lymphoid organs?
Atrophy with age and has no contact with antigen.
Secondary lymphoid organs
Organs which maintain mature naive lymphocytes and initiate adaptive immune response.
Have contact with antigens
Increase in size with age.
Haematopoiesis
Place where all immune cells are born. Cascade of immune response starts once needed.
Haematopoietic stem cells
Lymphoid progenitor cells
T-cells
B-cells
Myeloid progenitor cells
Platelets
Granulocytes
Monocytes
Erytrocytes
What is important regarding the immune system?
Balance. Activated when needed and suppressed when not needed.
How do we classify immune system?
Innate immunity (non-specific)
Adaptive immunity (specific)
Further classification of immune system?
Innate;
Humoral: complement, interferon, TNF
Cellular: Cells which phagocytise
Adaptive;
Humoral: antibodies
Cellular: T-cells, B-cells and other effector cells.
What is innate immune system?
The immune system we are born with which is antigen independent and has no time lag.
Phagocytes
Dendritic cells
Complement
Natural killer cells
What is adaptive immune system?
The immune system which develops over time.
Antigen dependent and can recognise what response is best suited for a specific antigen —> develops memory.
Takes 14 years until activated and developed.
B-cells
Plasma cells
Antibodies
T-cells
Effector T-cells
Components of innate immunity?
Physical barriers: skin, gut villi, lung cilia
Soluble factors: Protein and non-protein secretion
Cells: Phagocytes, NK cells, eosinophils
Components of adaptive immunity?
Physical immunity: none
Soluble factors: immunoglobulins
Cells: T- and B-cells
Why is innate immunity needed?
Detects overwhelming reactions quickly.
Protects us until adaptive immune system activates.
Sends stimulus to adaptive system.
Physical components of innate immunity?
Barrier between microbes in environment and host:
Skin + mucosal surface
Levels of physical protection
Secretion from epithelial cells
Intraepithelial T-cells
What are the levels of physical protection in innate immunity?
Tight junctions
Keratin
Mucus assisted by cilia
What do epithelial cells produce as defence?
Antimicrobial chemicals:
Defensins
Further impede entry of microbes
How do cilia and mucus protect us?
Bacteria get stuck in the mucus of the respiratory tract and cilia sweep this mucus into throat for coughing or swallowing.
How does saliva protect us?
Chemicals break down bacteria.
What happens if bacteria survive saliva?
Broken down by stomach acid
What does macrophages do in innate immunity?
Remove damaged tissue, cells and bacteria through phagocytosis.
Antigen presentation to T-cells.
What does neutrophils do in innate immunity?
Contain granules with bactericidal enzymes and are 80% of leucocytes in humans.
What does dendritic cells do in innate immunity?
Present antigen to T cells to initiate adaptive immune system.
What do Natural killer cells do in innate immunity?
Kill virus and tumor cells without specificity. '
Release perforin
Release granzymes which induce apoptosis
What do mast cells do in innate immunity?
Release inflammatory mediators when damaged and under influence of IgE.
Release histamine, heparin and cytokines
What is phagocytosis?
Attachment to microorganisms using cell surface receptors or adapter molecules.
Pseudopods hugs microbe and fuse to form phagosome
Lysosome fusion which braks down microorganism through enzymatic reaction.
Release of undigested products.
What are soluble components of innate immunity?
Molecules that respond to microbes and promote innate response in blood and ECF.
Act as opsonins to enhance phagocytosis
Promote inflammation
Complement,
Cytokines
chemokines
defensins
What is the complement system?
A series of heat-labile serum proteins which when activated acts as enzyme which cleaves several molecules of the next component in the sequence.
What are the parts of the complement system?
Major fragment: With one site that binds to cell membrane and other site which enzymatically cleaves next complement compound.
Minor fragment: Generated when component is cleaved and increase vascular permeability (C3a) in inflammation. Other attract neutrophils and macrophages for subsequent opsonisation and phagocytosis (C5a).
Enzyme site which destroys pathogen
Cleavage site which cleaves other complement fragments
How is complement system activated?
Antigen-antibody complex
MBL: bound to surface carbohydrates on pathogens
Alternative pathway
How is the complementary system regulated?
Some activated compounds are unstable and will decay.
Inhibitors: C1 esterase inhibitor, Factor I and H.
Proteins in cell membrane block complement action.
What are the major actions of innate immunity?
Inflammation
Phagocytosis
What makes lymphocytes special?
Express highly diverse membrane receptors and recognise wide variety of foreign substances.
Takes a week to develop but provides long-term memory which ensure faster and better response under second infection.
Categories of adaptive immunity?
Natural:
Active: through contact with diseases
Passive: through mothers milk
Artificial:
Active: Vaccine with suppressed antigen
Passive: immune serum with immunoglobulins.
What are the types of adaptive immunity?
Humoral immunity:
Mediated by secreted antibodies
Defend agains extracellular microbes
Cell-mediated immunity
Mediated by T-cells and their products
Defence against intracellular microbes
List all the phases of adaptive immune response.
Antigen presented to naive T-cells or sometimes B-cells.
Activation and multiplication of lymphocytes.
Differentiation
Antigen elimination
Apoptosis of cells and production of memory cells.
How does lymphopoiesis work?
Lymphoid progenitor cells differentiate into B or T cells.
Immature B-cells mature in spleen and lymph nodes into plasma cells.
Immature T-cells mature in thymus.
How are T-cells activated?
Antigen must be presented on the surface of host cells by antigen presenting cells and need a costimulatory signal.
What are the main antigen presenting cells?
Dendritic cells: activate naive T-cells
Macrophages: Activate effector T-cells
B-cells: B-cells activate into plasma cells and antibodies are produced.
What are helper T-cells?
T-cells with receptors recognising antigens and release cytokines to stimulate B-cell division.
What does B-cells do?
Produce antibodies
Differentiate into plasma cells or memory cells.
Plasma cells produce antibodies
Memory cells retain memory of invader for future reference.
How are B-cells activated?
Recognise antigen without APC or MHC molecule.
antibody on cell surface act as B-cell receptor.
Secondary signals promote increased activation and signalling.
What can antibodies do?
Neutralize microbes
Opsonisation and phagocytosis of microbes.
Lysis of microbes
Activation of complement system.
What occurs when the immune system is to active?
Autoimmune diseases and allergy
What happens too weak system?
Immunodeficiency
What is homeostasis?
Self-regulating process by which biological systems maintain stability.
What defines as mucosa?
A mucous membrane that lines cavities in the body and covers surface of internal organs which contains components of the innate and adaptive immune system.
Located strategically.
Structure of the mucosa?
Epithelium
Loose connective tissue (lamina propria)
Smooth muscle (muscular mucosa)
With certain cells which secrete mucus, digestive enzymes and hormones.
Characteristics of the mucosal immunity?
Largest organ of immune system (300m²)
Selectively permeable and can distinguish between nutrients and foreign particles.
Immune reactions are concentrated on the surface of the mucosa.
80% immunoactive cells are located here.
What does mucosal immunity do?
A system that occurs at mucosal membranes of intestine, urogenital tract and respiratory system
Protects and maintains tolerance.
What is the innate defence of the mucosal immunity?
Physical barriers:
epithelium,
goblet cell mucus production,
cilia.
Mucosal antibacterial molecules:
a-defensins in intestine,
b-defensins in oral cavity,
lactoferrin in mammary and salivary glands.
Cellular:
mucosal NK,
dendritic cells.
What does the mucosal immune system consist of?
Cellular
Humoral
Defence mechanisms
Physical barriers
Chemical factors as antimicrobial peptides and pH.
What are the physical barriers in mucosal immunity?
Tight junctions
Rapid turnover of epithelium from stem cells.
Presence of mucus
Ciliated surface
Optimal pH
Presence of microflora.
What are defensins?
Antibacterial beta-sheet proteins with antimicrobial effects similar to antibiotics.
Cellular part of mucosal immunity
NK cells are found in lamina propria and intraepithelial compartment.
Secondary lymphoid tissue
In upper respiratory tract and gastrointestinal tract
effector tissues.
Inductive site
What is effector tissue?
The vast areas of the mucosal immune system charcterized by diffuse collections of lymphoid cells and termed the effector tissues. These include the interstitial tissues of the mammary, lacrimal, salivary, sweat glands, lamina propria of the GI tract.
What is the inductive site?
Organized lymphoid tissue (MALT)- discrete collections of lymphoid tissues that share distinctive features, including a unique type of epithelium, unique set of cells- antigen presenting cells, B cells (with predominant production of IgA).
What is the aim of MALT?
To protect permeable surface from microbes by initiating immune mechanisms in organised follicles.
Is highly specialised
MALT describes all organised systems of the lymphoid tissue.
Why is sIgA a big molecule
Easier to survive gut environment and it survives by being bound to a receptor.
Main functions of microbiota?
Metabolism
Tolerance
Regulate immune response
Protects
How does the mechanism of MALT work?
M-cells take up microbes and present it to;
Antigen presenting cells (phagocytes) which further presents the antigen to:
T-helper cells which presents it to
B-cells which produce antibodies.
What are the functions of the mucosal immune system?
First line defence from harmful substances and microbes;
Prevents systemic immune responses to commensal bacteria and food antigens;
Regulates appropriate immune responses to pathogens.
What is and how does GALT work? (peyer´s patch)
It is an organised lymphoid follicle in the gut.
Antigen enters through M-cells
Present it to antigen presenting cells which introduce the antigen to CD4+ (T-helper cells)
They activate B-cells to form plasma cells which secrete secretory IgA
What happens with antigens that enters by mistake, (not entering (Payer´s patch).
CD8+ suppressor cytotoxic cells catch the antigen and activate cytotoxic T-cells to destroy the pathogen.
What is sIgA?
Immunoglobulins secreted in the mucosa by B-cells bound by J-chain in a dimer.
What is the action of sIgA?
Destroy pathogen through cytotoxic activity
Connect to antigen in lamina propria and remove through transcytosis.
Bind to proteins inside epithelial cells and take them out through transcytosis
What is transcytosis?
sIgA enters epithelial cell through endocytosis and transports the antigen to the surface where it is expelled from the endoscope into the lumen again.
Roles of immunoglobulin A?
Protects by inhibiting microbial adherence, neutralising virus and toxins.
Anti-inflammatory
The structure prevents IgA from getting broken down.
Opsonisation
What is opsonisation?
Opsonization is an immune process which uses opsonins to tag/mark a foreign pathogen for elimination by phagocytes.
Functions of the microbiota?
Metabolise
Fill niches to prevent pathogen colonisation.
Develop immune system
Maintain tolerance
E-coli is part of our microbiota. Still we can get sick with e-coli, why?
Because tolerance is disrupted and E-coli most likely starts to overpopulate and could even fill niches which they normally do not do. For instance travel to blood stream.
Why does microbiota differ in different places of the body?
Because different sites have different environments with different needs.
Influencing factors of the microbiota?
Age
Birth
Drugs
Disease
Exercise
Diet
Antibiotics
How does antibiotic affect our natural microbiota?
It not only kills of the bad bacteria but also kills our good and non-harmful bacteria which leads to dysbiosis which can develop into other diseases.
How can we modulate our microbiota?
Probiotics
Prebiotics
Postbiotics
Microbiota transplantation
What cells are involved in the innate immune response?
Macrophages
Granulocytes
Mast cells
Dendritic cells
Complement protein
NK
How effective is the innate immunity?
Does not require prior activation to be effective and activates immediately when meeting antigen.
Lysosome
Secreted by macrophages which catalytically cleaves gram-negative bacteria.
Lactoferrin
A multifunctional protein found in secretory fluids (milk, saliva, tears) that interacts with DNA and RNA acting bactericidal and fungicidally.
Interferrons
Proteins produced by many cells (macrophages and DC) in response to viral infection, inhibiting viral replication.
Antimicrobial peptides
Secreted by neutrophils, intestinal wall, pancreas and kidney epithelial cells which damages microbial membranes. Causes intracellular processes by suppressing synthesis of DNA or proteins.
Tumor necrosis factor (TNF)
Secreted by macrophages and dendritic cells.
Activate endothelial cells triggering inflammation and coagulation. Increased blood flow and immune cell recruitment.
Activate neutrophils to migrate.
In the liver triggers acute phase protein synthesis.
Triggers fever from the hypothalamus and catabolises fat (cachexia).
Triggers apoptosis of cells.
Cytokines
Low molecular weight proteins or glycolipids important in cell signalling that are secreted by cells after stimulation.
Type I interferons (IFN-a, IFN-B)
Produced from macrophages and fibroblasts
Activate NK cells
Induce expression of MHC-I
Interleukin 1 (IL-1)
Produced by macrophages and endothelial cells
Activates endothelial cells and neutrophils
Induce fever and synthesis of acute proteins
IL-6
Produced by macrophages, endothelial and T-cells
Induces synthesis of acute phase proteins
Induce proliferation of B-cells and antibodies
IL-10
Produced by macrophages and T helper2 cells
Induce proliferation of B-cells
Inhibits pro inflammatory cytokine products
IL-12
Macrophages and dendritic cells produce them
Activates NK and T-cells
Induces synthesis of IFN-gamma
Increases cytolytic activity
Induces differentiation of T-cells toward Th1 cells
Why are receptors important?
They recognise surface compounds common to many bacteria and can phagocytise them. When phagocytized in macrophages, synthesis of biologically active substances causes inflammation.
Neutrophils
First to appear during inflammation
Protects against bacterial invasion
Secrete biologically active substances
Eosinophils
Have same enzymes as neutrophils except antibacterial.
Detox of poisons
Phagocytizes immune complex
Basophils
Allergic reactions: degranulates and produces heparin and histamine.
How does macrophages activate?
Monocytes circulate in the blood and migrate into the tissue where they become macrophages.
Activated by T-cells cytokines —>
size increases,
lysosomal enzymes increase,
metabolism activates.
How can tissue repair be bad?
It can lead to fibrosis where an overproduction of collagen decreases elasticity and function of the tissue. For instance, in lungs during cystic fibrosis.
What does NK cell do?
Lyse virus infected cells and produce interferons.
Mast cells
Degranulates due to trauma, heat, UV and releases histamine and heparin.
Dendritic cells
Antigen presenting cells and stimulating signals.