Infection and innate immunity Flashcards
What are the defences against pathogen used by the body?
Anatomical and physiological barriers, innate immunity and adaptive immunity
What are some anatomical and physiological barriers against pathogens?
Skin, ciliary clearance, acidic stomach lysozyme (enzyme that catalyses destruction of cell wall of bacteria FYI) in tears and saliva
What are the cells involved in innate immunity?
Neutrophils, Macrophages, Mast cells, Eosinophils
What are the cells involved in adaptive immunity?
T lymphocyte and B lymphocyte cells
How can innate and adaptive immunity both be separated into sub groups?
They have a cellular and a humoral (in the blood) component
What is the major difference between innate and adaptive immunity?
Innate is what you are born with and does not develop over time, adaptive develop
What kind of organisms have adaptive immunity?
Only higher order vertebrates
What does our innate immunity do against pathogens?
Provides the immediate response
Which is more the more primordial immune response, innate or adaptive? How is this shown?
Innate is more primordial as all organisms show some form of innate immunity, adaptive only in higher order vertebrate
In mammals, what are the innate immunity processes?
Complement system, myeloid cells and phagocytosis and pattern recognition receptors
How does innate response change as your body deals with infections repeatedly?
It doesn’t change
What are the three major types of pathogens that affect the immune system?
Viruses, bacteria and protozoa and parasites
What kind of pathogen are viruses? Why this type?
They are intracellular pathogens
They go INTO body cells and infect them with their DNA
Once a viruses infects a cell, how much of the cells synthetic machinery is used to produce viral DNA?
90%
What are some examples of viruses?
Influenze, polio, smallpox, chicken pox/varicella, HIV
What does effective defence against viruses rely on in the body? Does this response do?
Cellular immunity
Distinguishes normal cells from infected cells
What kind of pathogen are bacteria? Why this type?
They are extracellular pathogens
They exist OUTSIDE the cell
What are some examples of bacteria?
Staph aureus, tuberculosis, Strep progenies, Black Plague (Yersisia pestis), Vibrio cholera
What does effective defences against bacteria rely on in the body?
Mainly by innate mechanisms and phagocytosis
What does effective defences against protozoa and parasites rely on in the body?
Direct killing by chemical mediator released by granulocytes and mast cells
What kind of cells are involved in the protozoa and parasitic immune response?
Basophil, Eosinophil and mast cells
What do the granulocytes involved in protozoa and parasitic immune response release?
Cytotoxic chemicals (e.g. inflammatory chemicals such as histamine)
What are the two types of bacteria?
Gram positive and gram negative
What are the physical differences between gram positive and negative?
Positive: Bacteria have a thick peptidoglycan cell wall
Negative: have a thin peptidoglycan layer surrounded by an outer membrane
What is peptidoglycan?
A polymer that is composed of polysaccharide and peptide chains
How does the immune response differ between gram positive and negative? Why is it different
Positive require phagocytosis as they are almost impervious to complement membrane attack complex due to thick peptidoglycan wall
Negative can often be lysed by complement membrane attack complex as they have a thin peptidoglycan wall which is easily penetrated
Where do neutrophils reside in the body? Where are most infections?
In the blood stream
Outside of the blood stream
How do neutrophils locate and then leave the blood vessel to the infection? What is this called?
- Activation. Chemokines from tissue injury or inflammation activate the local endothelial cells lining an adjacent capillary wall to up regulate selections.
- Tethering - Neutrophil, mediated by selectins and sialyl Lewis X (sLex) (a carbohydrate antigen on neutrophils) create weak transient bonds tethering the neutrophil to the inside capillary wall slowing it down.
- Adhesion – strong binding between neutrophil integrins and ICAM-1 on the endothelium causes neutrophil to stop moving. Neutrophil is then able to flattens.
- Diapadesis– neutrophil, now flattened, squeezes between endothelial cells.
- Chemotaxis– Neutrophil migrates along a chemical gradient to the site of infection.
—This is called Neutrophil extravasation
How are chemokine released?
By the inflammation of cells surrounding infected tissue
What are the two edges of the neutrophil?
A leading and trailing edge
What is on the leading edge of neutrophil to detect bacteria? What is on the bacteria and being produced that allows them to be detected by the neutrophil?
Anaphylatoxin receptor called C5a
Convertase are covalently bonded onto bacteria and are being cleaved to produce a chemical trail of Anaphylatoxins
How do neutrophil move?
The leading edge polymerises actin and this runs underneath the neutrophil to the trailing edge where it then depolymerises
What are complement receptors?
Receptors that bind directly to activated form of complement that are on the surface of the bacteria
What happens when complement receptors cross-link?
They initiate phagocytosis
How is the rate of phagocytosis by neutrophils influenced?
Anaphylatoxin recognition of immobilised complement and the soluble small polypeptides released on activation of complement molecules
What are the two ways which neutrophils can break down bacteria?
Neutrophil phagocytosis and FcR mediated phagocytosis
What is the difference between neutrophil phagocytosis and FcR mediated phagocytosis?
Neutrophil phagocytosis involves the neutrophil going to the bacteria, FcR has the bacteria come to it
How does FcR mediated phagocytosis destroy bacteria?
1-Antibodies IgM and IgG bind to bacteria antigens
2-the end of the antibodies has a Fc region which binds to an Fc receptor on the neutrophil
3-Once the bacteria is attached onto the surface of the neutrophil, the membrane invaginate (e.g. turns inside out to form a vacuole [a space enclosed inside the cell FYI] FYI) and engulfs the bacteria forming a phagosome (small enclosed space inside the cell)
4 - The phagosome then forms a cytoskeleton between the lysosome forming a phagolysosome
5 - phagolysosome acidifies and superoxides killing the bacteria
How does being exposed to certain substances (e.g. pollen) stimulate an allergic response?
The substance reacts with IgE (antibody that stimulates allergic response) which then binds to mast cells causing them to rupture and release Cytotoxic chemicals such as histamine resulting in an allergic response
What are molecular patterns?
Complex arrangement of antigens that are associated with specific pathogens
What is molecular pattern recognition?
The innate immune response to recognise the molecular patterns of pathogens
How is the adaptive immune response impacted by molecular pattern recognition?
Unless the innate immune response is stimulated by molecular pattern recognition, the adaptive immune response doesn’t work as well
What are pattern recognition receptors?
Receptors that bind the molecular patterns of microbes onto cells
What is the most well known pattern recognition receptor?
Toll - Like receptors (TLR)
What causes the innate immune response to cause chronic illness? What are some examples of chronic illnesses influenced by the innate immune response
Chronic simulation of innate response by pattern recognition response
Diabetes, arthritis etc.
What have Toll - Like receptors most likely evolved from? What indicates this relationship?
Drosophila toll molecules (fruit fly)
Toll molecules in drosophila regulate pattern development by allowing individual cells to recognise differences between each other which is an essential characteristic of TLR to identify different molecular patterns
What are pathogen associated molecular patterns?
Molecular patterns of specific pathogens which are identified by pattern recognition receptors
What are serotype’s?
A distinct variation within a species of bacteria or virus or among immune cells of different individuals
Are pathogen associated molecular patterns (PAMPS) varied, relate to serotypes? How does this affect our immune response?
They are very varied with many hundreds of serotypes existing within a single bacterial species
The immune system will only be protected against a few strains of bacteria (1 strain = 1 type of serotype on bacteria FYI) because the body will never have seen some of the many hundreds out there
What is the difference between an antigen and antibody?
An antigen is a foreign particle which stimulates the immune response
An antibody (aka immunoglobulin) are substance the body produces to target antigens for the immune response
What is lipopolysaccharide (LPS)?
It is a membrane component of all gram negative bacteria (NOT found in gram positive)
How much LPS is needed to generate an innate response?
Only a tiny amount
What kind of substance do LPS produce? How does it affect the body?
Pyrogen
Causes fever
Why is LPS an important in the pharmaceutical industry? Where can you find LPS commonly?
It contaminates things very easily and in a vaccine it can produce negative effects (e.g. fever)
Drinking water
People who are infected with uncontrollable gram negative bacteria can undergo what kind of shock? What causes this shock?
Septic shock
LPS has been so stimulated that there is a strong systemic release of molecules associated with the inflammatory response
What is the main molecule involved in the inflammatory response of septic shock? When is this molecule released? What is its relative affect on the body?
Tumor necrosis factor alpha (TNF)
end product of all pattern receptor recognition response
most toxic affect systemically (on the body FYI)
What can be done to patients who have septic shock?
Put them on life support and hope they patient’s immune response figures itself out, is normally fatal
What toll-like receptor is receptive to tutor necrosis factor alpha (TNF)? Where is this mainly found?
Toll-like receptor 4 (TLR4)
Myeloid cells
What are the two parts of a lipopolysaccharide LPS?
An inner core and Lipid A (the main immunogenic component FYI)
Does TNF vary between bacteria species? How does this affect TLR4 ability to recognise TNF? Why is this?
Yes greatly - remember only found on gram negative bacteria
It is able to recognise almost all of them
The lipid A is highly conserved and TLR4 is receptive to this component of the LPS
Why is lipid A on the lipopolysaccharide highly conserved?
Most likely due to its ability to stabilise the bacteria membrane
