L19 - Innate and adaptive immunity Flashcards
What is meant by humoral components of the immune system?
Antibodies circulating in body fluids
Why does the body need to be able to identify molecules that are non-self?
Because both humans and pathogens are composed of carbohydrates, proteins and lipids - therefore the body’s immune system needs to be able to distinguish the two!
What roles of protein are the same between hosts and pathogens?
Nutrient acquisition reproduction locomotion respiration etc...
What is the difference between humans and pathogens that the immune system can detect?
They have different proteins with different amino acid sequences
Why would a pathogen evolve to damage the host if this alerts the immune system?
Damage is an inevitable consequence of breaking through barriers to gain access to more prosperous regions and alert is an inevitable consequence of the damaging these barriers
What are the first barriers to infection in the body?
Epithelia
Define mesothelium
The mesothelium is a membrane composed of simple squamous cells that forms the lining of several body cavities: the pleura (thoracic cavity), peritoneum (abdominal cavity including the mesentery), mediastinum and pericardium (heart sac)
What type of epithelia is lining the blood vessels?
Simple squamous epithelium
What type of epithelia is the mesothelium?
Simple squamous epithelium
What type of epithelia is lining the trachea?
Pseudostratified ciliated columnar epithelium
What type of epithelia is lining the renal collecting tubule?
simple cuboidal epithelium
What type of epithelia is lining the oviduct?
ciliated simple columnar epithelium
What type of epithelia is the skin/dermis?
Keratinised stratified squamous epithelium
What type of epithelia is lining the vagina?
Non-keratinised stratified squamous epithelia
What type of epithelia is lining the bladder?
Transitional epithelium
What type of epithelia is lining the gallbladder?
Simple columnar
How do we clear pathogens from the epithelial surface of the eye (outer cornea)?
Rapid epithelial regeneration
blinking
flow of tears
How do we clear pathogens from the epithelial surface of the ear?
Rapid epithelial regeneration
Ear wax
How do we clear pathogens from the epithelial surface of the nose?
Rapid epithelial regeneration
Nasal hairs
Sneezing
How do we clear pathogens from the epithelial surface of the respiratory tract?
Rapid epithelial regeneration
sneezing
mucociliary escalator
coughing
How do we clear pathogens from the epithelial surface of the GI tract?
Rapid epithelial regeneration
vomiting
digestive enzymes
peristaltic gut movement
How do we clear pathogens from the epithelial surface of the urinary tract?
regular urine flow
What is the primary role of epithelial cells?
Block entry of microorganisms: selectively permeable barrier between the ‘outside’ and ‘inside’
What chemicals does epithelial cells produce that act as a first line of defence?
- Natural antibiotics
- Cytokines - proteins that alter the behaviour of other cells (often other IS cells)
- Chemokines - proteins that attract other cells
- May produce mucins
What mechanical properties does epithelia have that act as a first line of defence?
- Selectively permeable membrane
- Motile cilia (some)
- Rapidly renewable
- Transport antibodies from ‘inside’ to ‘outside’
Put the following steps from the general scheme of an immune response in the right order:
- Activated epithelial cells
- Cell and fluid migration
- Epithelial cytokines and chemokines released
- Epithelial cell damaged by pathogens
- Permeabilised endothelium
- Epithelial cell damaged by pathogens
- Activated epithelial
- Epithelial cytokines and chemokines released
- Permeabilised endothelium
- Cell and fluid migration
What is endothelium?
the tissue which forms a single layer of cells lining various organs and cavities of the body, especially the blood vessels, heart, and lymphatic vessels. It is formed from the embryonic mesoderm
Define opsonisation
The coating of a microorganism by antibodies or complement to render it recognisable as foreign by phagocytes, thus enhancing phagocytosis (cells have receptor for complement and antibodies)
Which factors promote vascular permeability (leakiness)?
inflammatory mediatiors
What is the function of vascular permeability?
- Leakage of antibodies and compliment at site of infection.
- Migration of macrophages, neutrophils and lymphocytes into tissues is increased (microbicidal activity of macrophages and neutrophils is also increased)
What are the signs and symptoms of inflammation?
Heat - increased blood flow
Swelling - fluid leaking out of capillaries
Redness - increased blood flow
Pain - therefore more careful of it
Loss of function - therefore won’t use it too much
Describe 2 humoral components of the immune system
complement
antibodies
Define the innate immune response
Natural, inbuilt immunity to resist infection that is NON-SPECIFIC
What are the characteristics of the innate immune response?
Present from birth
Not specific to any particular microbe - instead shared characteristics
Not enhanced by second exposure
No memory
Cellular and humoral components
Poorly effective without adaptive immunity
How is the innate immune response connected with the adaptive immune response?
The innate response is involved in the triggering and amplification of adaptive immune responses
Define adaptive immunity
Immunity established to adapt to infection. ‘Specific’ or ‘acquired’ immunity
What are the characteristics of the adaptive immune response?
Learnt by experience Confers pathogen-specific immunity Enhanced by second exposure Has memory Uses cellular and humoral components Poorly effective without innate immunity
Why are antibodies diagnostic for infections?
They are specific to infections the individual has been exposed to
How many classes of immunoglobulins so humans have?
5
What two things imply the importance of innate immunity?
- Rarity of inherited deficiencies in innate immune mechanisms
- Considerable impairment of protection when deficiencies in innate immunity occur
Name 6 cells involved in innate immunity
Macrophages/monocytes Neutrophil Eosinophil Basophil Mast cells Natural Killer cells
What are phagocytes?
Cells able to engulf and destroy bacteria, extracellular viruses and immune complexes (cluster of bacteria bound by antibodies)
Name two phagocytic cells
Macrophages and neutrophils
Define phagocytosis
Active engulfment of particles into a phagosome
Define a phogolysosome
A digestive complex made when a lysosome and a phagosome combine
What is distinctive histiologically about neutrophils?
They are polymorphonuclear - normally have 3-5 segments of their nucleus
Where are neutrophils found
They are normally excluded from healthy tissues and are specialised for working under anaerobic conditions which prevail in damaged tissues
The arrival of which immune cell is the first even of an inflammatory response?
Neutrophil
What is the most contaminated site of the body?
oral cavity
How do neutrophils kill micobes?
- phagocytosis - induced by microbe binding to receptors
- degranulation - release granules with antimicrobial infection
- neutrophil extracellular traps
What happens to the neutrophil when all the granules are used up?
It is unable to synthesise more granules after it has been activated. Once they’re used up it dies
What happens to individuals with neutrophil deficiencies?
Often suffer recurrent infections, often by microbes of the normal commensal flora
What do macrophages phagocytose?
Microbial cells
damaged or unwanted cells
Why are macrophages important in adaptive as well as innate immunity?
Release variety of cytokines (more than neutrophils)
Acts as professional antigen presenting cells (APCs)
What do professional antigen presenting cells (APCs) do?
Show antigens to T lymphocytes (of adaptive IS), which only recognise antigens when shown on APCs
Why does opsonisation occur?
encapsulated bacteria are more efficiently phagocytosed when they are coated with antibody and C3b
What part of the immune system are natural killer cells part of?
Innate immune system
What is the function of NK cells?
Provide innate immunity against intracellular infections
- Recognise and kill abnormal cells (e.g. tumour cells)
- Directly induce apoptosis in virus-infected cells by pumping proteases through pores they make in target cells
What cell is a NK cell like?
Similar to cytotoxic T cells but it doesn’t have a specific T cell receptor
People lacking NK cells suffer from what type of persistent infections?
Viral, particularly herpes which can’t be cleared despite a normal adaptive immune response
What induces the proliferation and activation (early response) of NK cells?
Cytokine burst from virally infected cells
What is the slower adaptive immune response to viral infection?
cytotoxic T cell response - helps clear the infection
What is the function of the innate humoral components transferrin and lactoferrin?
Deprive microorganisms of iron
What is the function of the innate humoral component interferon?
Inhibits viral replication and activates other cells which kill pathogens
What is the function of the innate humoral component lysozyme?
Is in serum and tears. Breaks down bacterial cell wall (peptidoglycan) of some gram positive bacteria. Synergism with antimicrobial peptides.
What is the function of the innate humoral component antimicrobial peptides?
Synergism with lysozyme
What is the function of the innate humoral component fibronectin?
Opsonises bacteria and promotes their rapid phagocytosis
What is the function of the innate humoral component complement?
complement components and their products cause destruction of mircoorgansims directly or with the help of phagocytic cells
What is the function of the innate humoral component TNF-alpha?
Supresses viral replication and activates phagocytes
Where does the name ‘complement system’ derive from?
It was discovered to complement/enhance the opsonising effects of antibody
What has the antibody response evolved to do?
Enhance the mechanisms of complement activation and phagocytosis
What does the complement system do?
It marks pathogens for destruction by covalently binding to their surface
Where are complement proteins found?
Ubiquitous in blood and lymph
When does complement activation occur?
Immediately after an infection begins (long before any pathogen-specific antibody is made)
What three main functions does complement have?
- recruitment of inflammatory cells
- Opsonisation of pathogens
- Direct killing
What are the most important functions of complement for host defence against infection?
recruitment of inflammatory cells
opsonisation of pathogens
How does complement directly kill pathogens?
Different complement proteins form a complex called the ‘membrane attach complex’ (MAC) which makes a pore in the membrane of pathogens, leading to cell lysis and death
Give an example of an inherited complement deficiency
SLE aka lupus (systemic lupus erythematosus)
Name two cells of the adaptive immune system
T and B lymphocytes
What are antigens?
molecules that elicit a specific immune response when introduced into the tissues of an animal
What is the name of the precursor of T and B lymphocytes?
common lymphoid precursor (CLP)
Where do T lymphocytes develop?
Their precursor develops in the bone marrow, but those destined to become T cells then migrate to the thymus (hence thymus-dependent (T) lymphocytes)
Where do B lymphocytes develop?
Bone marrow
What two cell types can T lymphocytes develop into?
T helper cells and cytotoxic T lymphocytes
What do B lymphocytes develop into?
Plasma cells
What is the function of T helper cells?
Activate B cells and macrophages
What is the function of cytotoxic T lymphocytes?
Kill virus-infected cells
What is the function of plasma cells?
Produce antibodies
What happens to B lymphocytes when they become plasma cells?
They increase in size and increase their ER
Why did the role of lymphocytes remain unknown until the 1960s?
They are essentially inactive until they encounter an antigen
What happens to the antibodies of B lymphocytes?
Some remain bound as antigen receptors - SURFACE IMMUNOGLOBULIN
Some released
What do both B and T cells express?
Antigen receptors
What is the name of the B cell antigen receptor
surface immunoglobulin
What is the name of the T cell antigen receptor
T cell antigen receptor
Why is each B cell and T cell specific?
Each antigen receptor binds to a different antigen and each cell only has one antigen specificity. Only a few cells of each antigen in the body, which clonally expand to deal with infection
What are the three main ways in which antibodies protect the host from infection?
Neutralisation
Opsonisation
Complement activation
What is the antibody protective effect, neutralisation?
Antibody bound to bacteria prevents it adhering to cells and therefore its ingress into the body
What is the antibody protective effect, opsonisation?
Antibody promotes phagocytosis
What is the antibody protective effect, complement activation?
Antibody activates complement, which enhances opsonisation and lyses some bacteria
What is the problem with the clonal distribution of antigen receptors?
It means that lymphocytes of a particular specificity will be too infrequent to mount an effective response
What is clonal selection of lymphocytes?
A process similar to natural selection which raises the clonal frequency of cells with a particular specificity after they have become activated by antigen interaction.
Clonal selection induces proliferation and increases effector cell frequency.
Which type of lymphocyte requires an antigen presenting cell to become activated?
T lymphocyte
Why does an adaptive immune response take a few days to kick in?
Because it takes time for an antigen interaction to take place, activating the specific lymphocytes. It then takes times for these lymphocytes to clonally expand and produce enough daughter cells to cross the threshold of protective effector function
What are the 5 phases of adaptive immune response?
- Recognition phase (clonal selection)
- Activation phase (clonal expansion)
- Effector phase (differentiation to effector cells)
- Decline homeostasis (T& B cell apoptosis)
- Memory
What occurs in the adaptive immune response ‘effector phase’?
Differentiation of effector cells:
B lymphocytes -> antibody producing cells (plasma cells)
T lymphocytes -> T helper cells and cytotoxic T lymphocytes
Why is the secondary adaptive immune response to the same antigen quicker?
After the first response the specific lymphocytes does not return back to its original number but remains slightly higher. Therefore after the second exposure to the antigen it requires less time for clonal expansion before it exceeds the threshold of protective effector function.
B cells cannot become plasma cells unless what occurs?
Unless they are activated by T helper cells
What is the role of antigen presenting cells?
They have non-specific antigen uptake by endocytosis and present these peptide fragments on their cell membranes. These activate T helper cells
