exam1 Flashcards
Symbiosis
intimate association of 2 or more different species
living together of unlike organisms-Heinrich Anton de Bary
doesn’t imply benefit or detriment to either partner
mutualism
both partners benefit
commensalism
one benefits, other is unaffected
ammensalism
one benefits, other is harmd: parasitism, predation, pathogenesis
where do microbes live in our bodies
skin
mucosa
-urogenital tract
-resp tract
-gastrointestinal tract
>oral
>stomach
>gut-intestineswhere are microbes not found in our bodies
internal tissues
circulatory system
nervous system
holobiont view
organisms are comunities
hologenome: host+micro genome
dominant bacteria in humans
4 phyla dominate:
- Bacteroidetes- gram-negative
- proteobacteria- gram negative
- firmicutes- gram-positive
- actinobacteria- gram positive
fungi dominant in humans
maninly yeasts
archaea in human microbiome
gut, oral tract and vaginal tracts
skin: about 5% compared to Bacteria
fungus in humans
much less abundant than bacteria
located in: skin, oral tract, vaginal tract, gut, resp tract
role of normal microbiota in health?
-nutrition
digest food esp plant polysacchrides, produce short chain fatty acids, provide vitamins, impact systemic metabolites- bloodstream
-barrier
restrict growth of other microbes. colonization resistance-prevention of pathogen growth.
reinforce barrier functions of epithelia
–immune
Educate the immune system
-Community
alter the local ecosystem via metabolic activity
interact with other microbes
the old friends hypothesis
we evolved with a community of normal microbiota
-the holobiont is the functioning unit
disruption to the normal microbiota ma have deleterious effects on health
such as diet, hygiene, medical practices disturbing diversity
population growth is increasing exposure to novel pathogens
commensal pathogens
members of normal microbiota that may cause disease in some situations
immunity
resistance to disease, specifically infectious disease
immune response
coordinated reaction of the immune system to fight and keep in check infection and against transformed cells
self vs non-self
self are normally healthy host antigens
non-self are foreign or modified self antigens
memory
the ability of adaptive response to mount more rapid, larger, and more effective responses upon repeat encounters, basis behind vaccination
tolerance
unresponsiveness to self antigens, may be broken
3 levels of immunity
INNATE IMMUNITY
1) external defenses
- skin
- mucous membrane
- secretions
2) internal defences
- phagocytic cells
- antimicrobial proteins
- inflammatory response
- natural killer cells
AQUIRED IMMUNITY
3)humoral response (antibodies) and cell mediated response (cytotoxic lymphocytes)
Innate immunity
1) external defenses
- skin
- mucous membrane
- secretions
2) internal defences
- phagocytic cells
- antimicrobial proteins
- inflammatory response
- natural killer cells
aquired immunity
3) humoral response (antibodies) and cell mediated response (cytotoxic lymphocytes)
includes: helper cells, regulatory cells, cytotoxic cells, B lymphocytes, plasma cells, antibodies
frst line of defense- anatomical chemical/nevironmental/physical
barriers: block entry of pathogens-skin
chemical: inhibit growth ex lysozymes in tears
environmental factors: non-permissive conditions ex stomach acid, anaerobic areas
physical removal: urine flow, mucociliary escalator
biological- the normal microbiota
where do cells mature and get educated
the bone marrow or thymus
what is the site of immune cell initiation
lymph nodes
spleen
lymphatic vessels
hematopoiesis
immune cell generation and development
a programmed set of steps modulated by growth factors
signaling molecules control development
occurs throughout life span
types of progenitor cells
lymphoid cell lines
myeloid cell lines
A progenitor cell is a biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its “target” cell.
lymphoid cell lines
NK cell T cell B cell Dendritic cells bone marrow->hematopoietic stem cells-> common lymphoid progenitro
myeloid cell lines
Bone marrow-> Hematopoietic stem cells-> common granulocyte/macrophage progenitor: eosinophil macrophage basophil mast cell neutrophil dendritic cell (also in lymphoid line)
t lymphocytes activation/generation
are activated in the thymus
b lymphocytes activation/generation
are activated in the bone marrow
cytokines
small secreted proteins involved in communication
lymphokines- made by lymphocytes
interleukins-made by one leucocyte and communicate with another
chemokines-low molecular weight, involved in chemoattraction (any of a class of cytokines with functions that include attracting white blood cells to sites of infection.)
cells involved in innate immunity
phagocytes: neutrophils and monocytes which divide into macrophages and dendritic cells NK cells eosinophils basophils mast cells
-dendritic cells (bridge gap between innate and adaptive immunity)
mediators are the complement system and cytokines
mononuclear leukocytes are monocytes, macrophages and dendritic cells (myeloid DCs and Lymphoid DCs)
mononuclear leukocytes
mononuclear leukocytes are monocytes, macrophages and dendritic cells (myeloid DCs and Lymphoid DCs)
segs and bands
segas- segmented, are mature neutrophils
bands- are immunture
normal neutrophil levels in blood are about 5000, mostly sges
during infections these rise
and during sepsis (presence of toxins/bacteria) the bands are high and segs low because they don’t have time to mature
MAMPs and PAMPs
microbe associate molecular patterns
immune system cells produce pattern recognition receptors
MAMPs and PAMPs are produced by benign and pathogenic microbes
relatively non-specific except host doesn’t have them
ex: lipopolysaccharide, lipoteichoic acids, peptidoglycan fragments
PRR
pattern recognition receptors
many different kinds
-TLR are tolllike receptors that are in the surface of or inside cells
NLR are nod like receptors that are intracellular proteins
different cell tpes have diffeent PRR, allowing them to detect and respond to different microbes
recognition leads to phagocytosis
phagocytosis
neutrophils- segs- mature into having greater than a 3 lobed nucleus, when die form pus
monocytes- are in the blood-> differentiate into macrophages
macrophages- in tissue
all function to ingest and destroy microbes
steps: leukocytes are called to site by mediators-?adhesion-> traverse blood endothelial layer-> squeeze into extra-capillary space- dispedesis
migrate to site of bacterial infection
Superorganism
is a group of synergetically interacting organisms of the same species. a social unit of eusocial animals, where division of labour is highly specialised and where individuals are not able to survive by themselves for extended periods.
Metagenome
All the genetic material present in an environmental sample, consisting of the genomes of many individual organisms
Virome
collection of viruses in and on the human body
- What else makes up our microbiome? How have we learned about the human microbiome, what is the project name and what techniques are used?
Archaea, viruses, fungi (mainly yeasts), protists, animals (mites, worms)
Culturing, molecular analysis
Project: the human microbiome project phase 1 and NIH integrative human microbiome project
Learned things through longitudinal sampling- people in the same longitude has same micrbiota
- What is the Old Friends Hypothesis? How does it relate to the concept of dysbiosis?
we evolved with a community of normal microbiota
-the holobiont is the functioning unit
disruption to the normal microbiota ma have deleterious effects on health
such as diet, hygiene, medical practices disturbing diversity
population growth is increasing exposure to novel pathogens
Dysbiosis (also called dysbacteriosis) is a term for a microbial imbalance or maladaptation on or inside the body,[1][2] such as an impaired microbiota. For example, a part of the human microbiota, such as the skin flora, gut flora, or vaginal flora, can become deranged, with normally dominating species underrepresented and normally outcompeted or contained species increasing to fill the void. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract,[2] particularly during small intestinal bacterial overgrowth (SIBO) or small intestinal fungal overgrowth (SIFO).[3][4] It has been reported to be associated with illnesses, such as periodontal disease, inflammatory bowel disease,[6][7][8] chronic fatigue syndrome,[9] obesity,[10][11] cancer,[12][13] bacterial vaginosis,[14] and colitis.[15]
MAMPS and Toll-like receptors:
MAMAPS and PAMPs are produced by benging and pathogenic microbes. They are nonspecific except that the host doesn’t have them. Toll-like receptors are PRRs that are on the surface of or inside cells
b. PRRs and NLRs:
Nod-like recptors are intracellular proteins
PRR: different cell types have different PRRs allowing them to detect and respond to different microbes- recognitions leads to phagocytosis. Immune system cells produce these
c. Antigen/epitope
foreign substance that induces an immune response. Made up of epitopes (smaller antigenic determinant). Antigens are recognized by receptors on B cells and T cells. B cells can recognize antigens without help, but T cell receptors only recognize antigens when they are presented via MHC (MHC1 on all nucleated cells except red blood cells, MHC2 only on immune antigen presenting cells- macrophages, dendritic cells, B cells)
d. Antigen-Presenting Cell
Dendritic cell, macrophages, B cells
e. Lymphocytes
B cells and T cells. Small white blood cell with a single nucleus. Function is to eliminate antigen
f. Chemotaxis
movement of an organism/cell in response to a stimulus.
g. Cytokines Lymphokines- Interleukins leucocyte Chemokines
small secreted proteins involved in communication
Lymphokines- made by lymphocytes
Interleukins- made by one leucocyte and communicate with another
Chemokines-low molecular weight, involved in chemoattraction
Antibodies/Immunoglobulins
are made of 4 peptides, 2 heaby 2 light. They have a variable region that determines antigen binding. They have a constant region that determines the class of antibody-biological activity. The constant regions bind phagocytes and activates processed involved in removal of the pathogen
i. Complement
activation-group of proteins that circulate in the blood, they eventually go through a cascade and the net effect is anti-microbial. Most are enzymes, different subunits have different functions. Form MAC- microbial attack complex- effective against Gram neg bacteria (gram pos have peptooglycan cell wall so are not affected)
There are 3 pathways to activate the complement: alternate, lectin (for fungi) and classical (with antibodies). Alternate and lectin are part of the innate immune respone. Classical pathways required adaptive response.
Steps:
1) lyse bacteria by forming a MAC.
2) Tag pathogens to enhance recognition and destruction by phagocytes (opsonization)
3) activate inflammatory response by triggering release of histamine from mast cells
4) enhance clearance of antigen-antibody complexes
j. Antibody-Mediated Immunity
: leads to the production of antibodies, critical in protection from extracellular pathogens and soluble toxins.
B cells play main role in this, although T-helper cells (CD4) are also needed
B cells are made in bone marrow, after stimulation B cells are activated and become plasma cells (antibody factories)
B cells also have immunoglobulins on their surface and are also antigen processing cells
Major functions:
-neutralize microbes and toxins, prevent binding (antibodies block binding of virus or exotoxin)
-opsonization (pathogen is marked for phagocytosis) and phagocytosis of microbes
-complement fixation with goals to lyse microbes, opsonize and phagocytize, and mediate inflammation
-facilitated aggulutination of bacterial cells- make a big glob of cells that can’t affect host as well.
k. Hematopoeisis
production of blood cells and platelets in the bone marrow
A hematopoietic stem cell is a stem cell that can differentiate into other cells
A programmed set of steps, modulated by growth factors. Signaling molecules control development. Occurs throughout lifespan
l. Cell Mediated Immunity:
T cells are the stars, T cells are made in the bone marrow but educated in the thymus, play a major role in combating intracellular pathogens, although important in AMI also
can only recognize antigens in context of MHC
different types of t cells: T helper CD4+ and T cytotoxic CDB+
CMI’s role in immunity is the death of the pathogen.
m. Diapedesis
cells squeezing into extra-capillary space (during phagocytosis/inflammation esp)
n. MHC-which cells express each:
MHC1
MHC2
i. MHC 1 : present on all nucleated cells (except RBCs)
ii. MHCII: only present on immune antigen presenting cells- macrophages, dendritic cells, B cells.
