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What describes pathogenesis of disease ?
The path microbes take in the human body that enables them to cause tissue damage and disease.
What is resistance ?
It involves many steps, and the body has evolved a variety of mechanisms to stop infection progressing that all together.
What are the mechanisms of resistance a part of?
-Innate immunity
-Adaptive immunity
Animals lacking innate immunity...
cannot clear pathogens and pathogen numbers increase rapidly.
Animals lacking adaptive immunity...
do clear pathogens somewhat, the numbers continuing to increase but at a slower rate than those without innate immunity.
Animals with both immunity show...
an increase rate of microbial growth for a period of time but then a decrease and final resolution of infection.
The physical, chemical and anatomical barriers to infection in the innate immune systems are...
-Skin
-Mucosal epithelial
-Antimicrobial chemicals
The physical, chemical and anatomical barriers to infection in the adaptive immune systems are...
Lymphocytes in epithelia and antibodies secreted at epithelial surfaces.
Blood proteins for innate immunity are...
Complement, others.
Blood proteins for adaptive immunity are...
Antibodies.
Cells in the innate immune are...
Phagocytes : Macrophages.
Cells in the adaptive immune are...
Lymphocytes.
What is the skin?
is a physical barrier and produces antimicrobial fatty acids and anti-bacterial peptides. Normal flora inhibit infection.
What is the ph of stomach and what does this ph do?
The stomachs ph is 2 (acid) and it inhibits microbial growth.
What does the normal flora do?
Competes with pathogens in the gut and on the skin.
Flushing of urinary tract...
prevents infection.
Lysozyme in tears and other secretions...
dissolves cell walls.
Mucus and cilia lining trachea...
suspend and move microorganisms out of the body.
Mucus, antibacterial peptides and phagocytes ....
in lungs prevent infection.
Blood and lymph proteins...
inhibit microbial growth.
Rapid pH change ...
inhibits microbial growth.
Epithelial cells ...
throughout the body have tight junctions that inhibit pathogen invasion and infection.
Cells responsible for Innate immunity are...
part of the Myeloid family of blood cells which develop from stem cells in the bone marrow. They are "cousins" of Lymphoid cells which develop from the same set of stem cells.
What are the name of the cells responsible for the innate immunity?
Macrophages.
Granulocytes: only neutrophil.
Circulating Phagocytic Cells whose role is...
to engulf microorganisms and destroy them.
Monocytes circulate in the...
blood and are attracted to the site of infection when they change into macrophages. They are mononuclear cells because of the shape of their nuclei.
Neutrophils
(or polymorphonuclear leukocytes from the shape of their nuclei) are motile granulocytes with large numbers of lysosomes.
Monocytes change into...
macrophages when called to site of infection or tissue damage.
Macrophages have a lot of different roles...
but their importance in immunity is as
phagocytic cells, pathogen killing cells and antigen presenting cells.
Opsonization is...
a term that refers to an immune process where particles such as bacteria are targeted for destruction by an immune cell known as a phagocyte . The process of opsonization is a means of identifying the invading particle to the phagocyte.
Complement enhances ...
Phagocytosis and Destruction of Pathogens or Causes Cell Lysis.
Most phagocytes,...
including macrophages, monocytes, and B cells have complement protein receptors.
Phagocytic processes are enhanced...
100x by C3-C3R interactions.
Steps in phagocytosis..
Phagocytic cells first engulf the microbes, then once inside the cell the vacuole(inside cell) engulfs then as well. After that the vacuole(phagosome) fuses with the lysosome containing enzymes. Once fused this is called phagolysosome, finally the waste is released by the phagocytic cell.
What happens to the bacteria inside phagolysosome?
A series of chemical reactions called myeloperoxidase and nitric oxide synthase happen withing the cytoplasmic membrane of the phagocyte. These chemical reactions lead to a phagocytosed bacteria.
What is needed for the chemical reaction of nitric oxide synthase inside the phagolysosome?
NADPH
Toxic oxygen compounds are...
produced in phagocytes to destroy pathogens by oxidation.
What are the toxic oxygen compounds produced in the phagocyte to destroy pathogens?
They are destroyed by oxidation. The toxic oxygens c. are hydrogen peroxide (H2O2), superoxide anions(O2-), hydroxyl radicals (OH-), singlet oxygen (O2), hypochlorous acid (HOCl-), nitric oxide (NO).
Some pathogens have...
mechanisms to neutralize toxic products or kill or avoid phagocytes.
Staph. aureus fights back by...
having carotenoids which quench singlet oxygen and prevent killing.
M. Tuberculosis fights back when...
it grows and persist in the macrophage by preventing fusion of phagosome and lysosome and uses cell wall glycolipids to absorb hydroxyl radicals and superoxide anions.
Strep. pneumoniae fights back when...
it makes pneumolysin which inhibits productions of oxygen radicals. Other made that kill phagocyte. Accumulated dead cells are pus. If localized these bacteria form boils or abscesses.
Bacteria with capsules are...
highly resistant to phagocytosis; capsule prevents adherence (helps bacterium hide).
Strep pneumonia: capsulated are....
virulent; non-capulated are non virulent. Antibody (acquired immunity) takes over here.
The adaptive immunity are involved in which local sites?
Exposure to pathogens
Infection
toxicity
invasiveness.
Adaptive immunity is always...
specific.
Adaptive immunity to extracellular bacteria have...
Antibodies that can block infection and enhance phagocytosis and also neutralize toxins.
Adaptive immunity to intracellular bacteria have...
phagocytes activated by specific CD4 T cells that can kill bacteria. They also have CD8 T cells that are activated by phagocytosed bacteria that can kill infected cells.
Adaptive immunity to viruses have...
Antibodies that block viral binding and enhance viral phagocytosis during extracellular stage of infection. They also have cytotoxic lymphocytes that kill infected cells.
Cells responsible for adaptive immunity are cells of the...
lymphoid lineage that develop from stem cells in the bone marrow.
Lymphoid precursors develop into a ...
T cell line and a B cell line.
What is the cell in the adaptive immune system that comes from thymus maturation?
Cell mediated immunity.
What is the cell in the adaptive immune system that comes from the bone marrow maturation?
Antibody production.
T cells mediate two different types of adaptive immunity to pathogenic microorganism...
Phagocytes activated by specific CD4 T cells will kill intracellular bacteria. CD8 T cells activated by phagocytosed bacteria will kill cells infected by intracellular bacteria or cells.
Adaptive (specific) immunity can kill extracellular bacteria by..
producing antibody that can block infection and enhance phagocytosis. Producing antibody that can neutralize toxins.
Adaptive (specific) immunity can kill viruses by...
creating antibodies that block viral binding and enhance viral phagocytosis during extracellular stage of infection.
How do antibodies work?
When a toxic molecule is bound to a cell the antibody attaches to it and neutralizes it.
Bacterial cells are more likely to be phagocytized and destroyed when...
antibody binds to antigen on its surface and complement also binds.
Phagocytic process enhanced...
10x by antibody FcR interactions and 10x more by C3-C3R interaction.
Innate (specificity)
For structures shared by groups.
Adaptive (specificity)
For antigens of microbes and for non-microbial.
Innate (diversity)
Limited; germline encoded.
Adaptive (diversity)
Very large; receptors are produced by somatic.
Innate (memory)
None
Adaptive (memory)
Yes
Innate (non-reactivity to self)
Yes
Adaptive (non-reactivity to self)
Yes
Innate immunity...
very little specificity; one cell type can bind to many groups of pathogens, and groups share structures.
Each antibody interacts with...
Only with one epitope
The antibody response is...
very specific
Each cell produces antibodies that...
can react with only one epitope
Each antibody interacts with...
with a very small portion of the larger molecule (antigen) or microbe - That portion is called an epitope.
Antibodies are so specific they can tell the difference between ....
two sequences of amino acids that are different by only one amino acid.
A large protein antigen may have many different...
epitopes and different antibodies are made that recognize and react with each of the different epitopes.
Immunogen
substance capable of eliciting an immune response. An antigen may or may not be an immunogen.
Antigens are...
substances that react with antibodies or TCRs (T cell receptors); may not have actually induced/activated them by themselves.
Hapten
Low molecular weight substance which cannot act as an immunogen by itself.
When hapten is attached to high molecular weight materials...
an antibody response is made to the carrier (the high molecular weight material), as well as to the hapten which acts as an epitope. Complex is immunogenic, i.e not hapten alone.
What happens when hapten appears again (attached to a high molecular weight material)?
it can react immediately with those antibodies previously made to it.
Even though all antibodies have different specificities, they have...
physical characteristics that make them similar to each other, but not identical.
Compare how antibodies separate in an electric field: All albumin molecules migrate in a...
narrow band - this is a homogeneous molecule
Compare how antibodies separate in an electric field: If slightly different in charge...
get smear - ie gamma globulin
Compare how antibodies separate in an electric field: Small differences due to this fraction being composed of antibodies of different specificities whose...
basis is slightly different structure.
Compare how antibodies separate in an electric field: Different structures localized to...
small part of molecule.
In an electric field what has the highest jump homogenous or hetergenous?
Homogenous
The enzyme Papain cleaves the...
mmunoglobulin molecule into three pieces, two Fab fragments and one Fc fragment (upper panels).
The Fab fragment contains the...
V regions and binds antigen.
The Fc fragment is...
crystallizable and contains C regions.
The enzyme Pepsin cleaves...
immunoglobulin to yield one F(ab′)2 fragment and many small pieces of the Fc fragment, the largest of which is called the pFc′ fragment (lower panels).
F(ab′)2 is written with a...
prime because it contains a the cysteines that form the disulfide bonds and joins two Fab subujnits..
Fc fragment and hinge regions differ in...
antibodies of different isotypes.
IgG composed of
4 peptide chains - 2H and 2L
In IgG each chain has a..
variable region and a constant region, V and C
In IgG 4 chains held together by
disulfide bonds
IgG has 2...
binding sites for antigen with same structure, and domains are a result of configuration of VH (variable heavy) and VL (variable light) domains.
In IgG structural differences in different antibodies based on different specificities located in ...
antigen binding domains.
IgG, IgA and IgD have similar...
structures
IgE is found in serum ...
in very small amounts (unless individual is allergic).
IgE is the only antibody that....
that binds to eosinophils, arming these granulocytes to target eukaryotic parasites.
IgE mediates...
Immediate-type hypersensitivities (allergies): hay fever; asthma .