Module 7 - Immunology Flashcards
What is immunity?
the ability to resist infectious disease
Immune system is comprised of:
- Cells – white blood cells (leukocytes), and other cells resident in the tissues e.g. macrophages
- Organs – e.g. spleen and lymph nodes
- Secreted factors – e.g. antibodies
Immune system functions:
- control pathogens that enter the body (viruses, bacteria, and parasites) and cancers.
- maintaining a healthy relationship with the normal microbiome at the body surface.
The study of immunology
relates to the functioning of immune cells and systems. This includes roles in homeostasis and non-infectious pathologies.
Pros of the immune system
Control of infections
Control of cancer cells
Vaccination
Tolerance of fetus
Cons of the immune system
Autoimmunity – immune system attacking
the body
Chronic inflammation – atherosclerosis,
type II diabetes, Alzheimer’s Disease,
asbestosis etc…..
Immunodeficiency – genetic deficiencies
and AIDS
Allergies
Different pathogens and their challenges
Viruses: have few molecules, replicate within cells, and have rapid evolution
Bacteria: can live in extracellular space, or within
phagosomes or cytoplasm of cells
Large worm parasites: Live within body fluids or gut
Unicellular eukaryotic: parasites frequently live
inside cells
Mechanisms mediating resistance to infection
Physical and chemical barriers:
can be breached by injury, insect bites,
invasive pathogens.
Innate immune system:
* Acts within minutes to days of infection.
* Important for control until acquired response
develops.
* If innate immunity rapidly clears the infection, an
acquired immune response will not develop.
* Responds similarly each time a specific
organism is encountered – no “memory
Adaptive or acquired immune system:
* Effective from about 4-5 days after an initial
infection.
* Has specificity for recognising particular
pathogen molecules, and memory of previous
infections – hence is essential for long-lived
immunity and vaccines.
Barriers to entry for pathogens
Physical barriers
* Skin and other epithelial surfaces have tight junctions between cells preventing entry of organisms.
* Mucus in the gut is a thick layer that prevents association between bugs and the epithelium. Mucus
in the lung entraps organisms.
* Physical removal of bacteria – flow of urine, shedding of mucus in gut, ciliated epithelium moving
mucus up and out of the lung.
Chemical barriers
* Acid pH - acid in stomach kills many bacteria (pH 2), surface of the skin is also acidic (pH 5).
* Antimicrobial peptides secreted onto epithelial surfaces – can disrupt bacterial membranes.
* Enzymes e.g. Lysozyme in tears, mucus and saliva degrades some bacterial cell walls.
Biological competition
* Commensals in gut and skin compete with pathogens – if the niche is already occupied, pathogens
cannot easily move in.
Innate Immunity
Rapidly acting – first activated within minutes to hours of infection
* Response is similar each time the same pathogen is encountered
* Initiates inflammation = redness, heat, swelling, pain – influx and activation of immune cells
* Complement system – several dozen secreted proteins that can directly attack bacteria by making
pores in the bacterial membrane leading to lysis, or alternatively by “marking” bacteria for
phagocytosis.
Phagocytosis and destruction of pathogens by neutrophils, macrophages, dendritic cells (DC)
* Other innate immune cell types - basophils, eosinophils, natural killer cells in the blood, and mast
cells in the tissues adjacent to blood vessels. Mast cells are involved in allergy
Cells of the Innate Immune system
Phagocytes
Neutrophils
Monocytes, Macrophages and DC
Phagocytosis
Recognition of organism by phagocyte
receptors
* Extension of membrane around organism,
fusion of membrane to form phagosome
* Fusion of phagosome with a lysosome, an
organelle containing degradative enzymes.
Then, acidification of the phago-lysosome.
* Bacteria are killed and degraded by the
generation of reactive free radicals –
molecules with an upaired electron (e.g.
superoxide O2) and enzymes activated by low
pH.
* Bacteria may evade phagocytosis e.g. through
having a capsule, and evade killing, e.g. by
preventing acidification
Phagocytes
play a major role in the early response to pathogens. Phagocytes include macrophages, neutrophils and dendritic cells (DC).
Neutrophils
- 60-70% of all white blood cells in humans
- Multi-lobed nucleus and cytoplasmic “granules”. Granules are membrane-bound vesicles containing
antimicrobial peptides, lysozyme enzyme that attacks bacterial cell wall, degradative enzymes. - The first cell type to migrate to sites of infection or tissue damage
- Phagocytose and kill invaders.
- Short-lived, and many die at the site of infection, contributing to the formation of pus. In the process of dying
they can release DNA and anti-bacterial proteins which together trap and kill organisms.
Monocytes, Macrophages and DC
Macrophages are phagocytes resident in tissues – involved in immunity as well as wound healing and
tissue remodelling
* Monocytes are the blood precursors of macrophages, and are approx. 5-10% of leukocytes (white
blood cells)
* In an infection, tissue resident macrophages play a role in phagocytosing pathogens, but there is also
recruitment of monocytes from blood which differentiate into macrophages, and then phagocytose and
kill pathogens
* Release proteins to attract other cells (“chemokines”) and activate other immune cells (“cytokines”)
* Dendritic cells (DC) are phagocytic innate immune cells closely related to macrophages, but are more
specialised for activating T cells and the acquired immune response.
Inflammation
The body’s early response to infection or injury – swelling, redness, pain, heat
* Inflammation helps to attract and activate immune cells, and prevent the spread of infection
* Requires release of chemokines and cytokines by innate immune cells. Inflammatory cytokines
increase blood vessel permeability leading to swelling (edema), and cause fever. Fever boosts both
innate and acquired immunity.
* Inflammation should progress to, and promote wound healing as infection clears
* Chronic inflammation that doesn’t get switched off causes tissue damage
* Systemic (body-wide) inflammation can cause septic shock and death
Initiation of inflammation
Inflammation can be initiated by:
(i) Cell damage - release of molecules
from damaged cells – “danger signals”
(ii) Recognition of pathogen molecules –
PAMPs
How do innate immune cells recognise pathogens?
Innate immune cells recognise characteristic molecules that are conserved amongst classes of
pathogens. These are called “Pathogen Associated Molecular Patterns” or PAMPs
* PAMPs include many bacterial and yeast cell wall products, e.g. lipopolysaccharide, the major
component of Gram-negative bacterial outer membrane. Nucleic acids (DNA and RNA) are major
PAMPs for recognition of viruses.
* These bind to receptors on innate immune cell cell surface or in the cytoplasm. There are a limited
number of different receptors (maybe several dozen) recognising these characteristically foreign
PAMPs
Responses to PAMPs include:
- Secretion of cytokines and chemokines – enhanced inflammation
- Recognition of organisms for phagocytosis
- Enhanced killing by phagocytes
- Maturation of dendritic cells, so they can activate T cells
Cytotoxic T Cells
*Kill virally infected cells or tumour cells.
*Release granules which induce apoptosis.
Where do immune cells develop?
bone marrow stem cells
Why do lymph nodes swell in infections?
– active immune response and cell influx
– infection of node
Lymph contains:
*Leukocytes
*Proteins similar to plasma
*Cell debris
*Pathogens
*(Cancer cells)
Is the lymph pumped?
Lymph is not pumped, but moved via skeletal muscle contractions
Why is fluid from peripheral tissues drained?
Drainage of fluid from the peripheral tissues into lymph nodes allows surveillance for foreign molecules in the lymph node
Functions of The Lymphatic System
- Some blood plasma (and a few leukocytes but no red cells) leaves the capillaries and enters tissues.
- Fluid drains out of the tissues into the lymphatic capillaries and vessels.
- Lymph fluid returns to the blood stream via the thoracic duct.
- Lymph nodes are filled with immune cells, and act as filters which capture pathogens, antigens and particulate material.
Uses of Antibodies
- as a drug: e.g. in rheumatoid arthritis to inhibit cytokines causing inflammation, and to neutralise toxins after snakebite
- in medical diagnosis: e.g. pregnancy testing, infections, blood cell counts
- in experimental science used in many applications, including to:
- measure the levels of proteins (e.g. in serum)
*examine the location of proteins of interest using fluorescently-labelled antibodies and fluorescence microscopy
structure of an antibody
a Y-shaped structure which consists of four polypeptides — two heavy chains and two light chains
Architecture of the Immune System
Immune cells develop in the primary lymphoid organs - bone marrow and thymus. All immune cells develop from bone marrow stem cells. T cell progenitors move to the thymus in the embryo and early life, where they mature. They undergo “central tolerance” here – i.e. T cells that strongly react to self-molecules die off. All other immune cells develop in the bone marrow.
* Mature naïve T and B cells circulate through the blood and lymph and secondary lymphoid tissues in a surveillance pattern, looking for foreign
* The B and T cell response to foreign antigens* is initiated in the secondary lymphoid tissues. These are the spleen, lymph nodes and mucosal-
associated lymphoid tissues (MALT) – e.g. tonsils, adenoids, Peyer’s patches in the gut.
Where do antigens go?
- Antigen from peripheral tissues, drains to lymph nodes
- Antigen from blood infections, collects in the spleen
- Antigen from mucosal surfaces accumulates in MALT