Innate Immune Response Flashcards
What are the 3 main components in first line innate immune response?
- Skin
- Mucous membranes and Secretion
- Normal Flora
What are the 4 main components in second line innate immune response?
- innate immune cells
- inflammation
- complement
- antimicrobial substances
What are mucous membranes
thin and permeable barriers that line the respiratory, GI and genitourinary tracts
What is technical removal
- the two components involved are the ciliated cells and mucous secretions
- produces a ciliary escalator –> dust particles sitting on the mucous membrane will be pushed either down the digestive tract or up through the airways and out of the lungs by movement of cilia underneath
4 types of secretions
- Tears, Saliva (contains lysozyme that breaks down peptidoglycan - can eat away gram + and - layer)
- Crevicular Fluid (fluid that flows into gingival crevice - has similar composition to blood serum)
- Gastric juices (have low pH)
- Urine/Vaginal Secretions (have flushing action, and maintain a certain level of pH)
What is the normal flora in the mouth
Alpha streptococci
what is the normal flora on the skin
staphylococcus epidermidis
what is the normal flora in the lower GI
bacteroids spp. (aerobic gram neg)
What composes an inflammatory response
SHARP
Swelling Heat Altered function Redness Pain
what is pus?
mixture of dead cells, neutrophils and body fluid
what is an abscess?
accumulation of pus (pustules and boils are examples)
what are pyogenic bacteria? what are two examples?
pyogenic bacteria are pus causing bacteria (causes pus production)
- streptococcus pyogenes
- staphylococcus aureus
5 types of white blood cells?
- Granulocytes (PMNL - polymorphonuclear leukocytes) –> four types: neutrophils, basophils, eosinophils, and mast cells
- Monocytes –> White blood cells in the blood stream that are travelling to the infectious tissue
- Macrophages
- Dendritic Cells –> stay in skin
- Natural Killer Cells (destroy infected host cell, intracellular bacteria, virus or cancer cells) but does not kill bacteria directly, it just kills the host cell; it looks like a lymphocyte and attacks any organism without prior knowledge or exposure
What are polymorphonuclear leukocytes? what do they have?
PMNL are granulocytes (type of WBC) that differentiates into:
- Neutrophils
- Basophils
- Eosinophils
- Mast cells
What is hematopoiesis
the process of blood cells differentiating from stem cells in the bone marrow
What are neutrophils?
- 60 to 70% of total WBC (most amount)
- able to phagocytose
- short life span, no mitochondria (less than a day)
- first to arrive and initiate phagocytosis at infected site
- forms NETs when they die (sticky DNA that traps bacteria and makes it easy for other neutrophils to eat it in large amounts)
- have vacuoles with granules that have anti-microbial proteins and inflammatory mediators
What do the granules of neutrophils have?
myeloperoxidase (turns pus green) and superoxide radicals (oxygen radicals that kill organisms)
What are macrophages?
- 3 to 8% of total WBC
- very efficient phagocytes
- eats damaged cells like dead neutrophils
- is an antigen presenting cell
what are macrophages called in blood circulation?
monocytes
what are macrophages called in tissue?
macrophage
Antigen Presenting Cell
cells that can break down infectious pathogens and present its parts on the cell surface
what are dendritic cells
- efficient antigen presenting cell
- phagocyte
- activates adaptive immunity (specific response)
- carries the antigen from infected tissue to lymph glands where the T and B lymphocytes live and presents it to them to help them remember what it is
What are eosinophils
- provides defence against PARASITIC infection
- secretes cytolytic enzymes upon contact with pathogens (causes cells to burst)
- cells circulate in the blood until recruited to inflamed tissue
- they secrete enzymes to break down the cuticle of parasites
- increased eosinophils in the blood indicate a parasitic infection (the start of one)
What are mast cells?
- mostly in submucosal tissues
- cell surface receptor for igE (immunoglobulin E)
- important in allergic reactions
- releases histamine once the igE is activated
What are basophils?
- found in blood
- similar function to mast cells
- release histamine from their granules
What are two types of leukocyte granules?
- Lytic granules (contain digestive enzymes like lysozyme to breakdown endocytose pathogens
- Secretory granules
- kills pathogens that are too big to eat like parasites, - contain chemical messenger substances that attract other immune cells to the site like chemokines
- have inflammatory mediators like histamine
What are Natural Killer Cells (NK)
- lymphocytes without memory but live in our lymph gland
- first line of defence against intracellular pathogens (viral infections, intracellular bacteria/protozoa, and cancer cells)
- secrete cytolytic granules that cause targeted cell destruction
which 3 cell types do NK cells destroy?
- infected cells –> when there’s a microbial antigen present on MHC 1
- Virally infected cells which have lost the expression of MHC 1 on the surface
- Cancer cells that have LOST MHC 1 in general (dont even have it)
What is MHC Class 1?
- receptor thats on the surface of normal nucleated cells (NOT ON RBC BECAUSE THEY DONT HAVE NUCLEUS)
- Healthy cells present a self protein that is bound in the MHC 1
- sick cells (virus or cancer) may have a foreign peptide in the MHC 1
what is the role of MHC 1?
provides a way for cytotoxic T cells to scan and detect intracellular infection (third line - adaptive immunity)
and NK cells detect the cells that are not showing self-peptides and kill them
- presents endogenous peptides (peptides made by the own cell either by a virus or the healthy cell itself
- activates CD8+ cytotoxic cells
what are MHC 1 receptors called in humans?
HLA (Human Leukocyte Antigen)
What is MHC class 2?
- it is the receptor that found ONLY on ANTIGEN PRESENTING CELLS (I.E. macrophages, dendritic cells and B-lymphocytes)
- Bind and presents the antigen (peptides) to t-helper cells in order to initiate adaptive immune response
- presents exogenous peptides (peptides made outside the cell like fragments of bacteria that was phagocytosed)
- activates CD4+ t-helper cells
what is phagocytosis?
when a cell engulfs a solid particle
what is diapedesis?
the migration of cells across the endothelium through the cell junctions (how cells get from blood vessel to tissue site)
what is chemotaxis?
the directed movement of cells in a concentration gradient (substances emitted by bacteria that WBC can sniff out)
What are the 7 steps of phagocytosis by Antigen Presenting Cells?
- bacterium binds to the receptor on phagocyte
- Phagocytosis - bacterium is engulfed by cell membrane
- Bacterium inside the cell vesicle (phagosome)
- fusion of lytic granule (like lysosome) and phagosome forming a phagolysosome
- digestion of bacterium by lysosomal enzymes
- transport of bacterial fragments to cell surface (binds to the MHC 2 receptor on the phagocyte)
- release of waste material
Cytokines
small proteins that are made by cells, that function to change or communicate with other cells (cause us to have a fever)
What are two types of Cytokines?
- chemokines –> cytokines that are used for attracting other cells to the site of infection (proteins made by WBC that cause a chemical signal)
- interleukins –> cytokines that alter the function of other cells
What are Pattern Recognition Receptors and whats an example?
PRR’s are receptors on the inside or outside of a cell that recognize parts of foreign cells
and example is the toll Like Receptor (TLR) which recognizes different molecules from pathogens
i.e. the outer TLR’s recognized Lipopolysaccharide, peptidoglycan and flagellin while the inner TLRs detect RNA and DNA
What 3 things happen after a TLR is triggered by a foreign molecule?
- Chemokine release: calls in help from the circulation
- Proinflammatory cytokine release: activates neighbouring cells (cells around the endangered cell) and helps with cell signalling
- increased microbicidal activity: destroys the ingested pathogen
Antigen
a substance that is usually foreign, that is capable of producing an immune response (i.e. virus, bacteria, protozoa, pollen and transplanted tissue)
Epitope
the specific site on an antigen thats recognized by immune cells or antibodies
antibody
also called immunoglobulin (Ig)
- protein produced by B-lymphocytes that recognizes a specific epitope on an antigen –> this leads to removal of that antigen
What is the complement system and how is it activated?
the complement system is a group of serum proteins (liquid part of blood) produced by the liver in the circulation to defend against pathogens
the complement immune reaction occurs on the surface of the cell and punches a hole in bacterial cell wall and it explodes
what are the three complement pathways?
- classical
- alternative
- Lectin
What is the classical complement pathway?
- triggered by antibody-antigen complex (antibody binds to epitope on antigen)
- Then, C1 breaks into C2 and C4
C2 and C4 break into C2a and C2b as well as C4a and C4b
C2a and C4a make C3 which splits into C3a and C3b,
c3b makes c5 which splits into c5a and c5b
then c5b joins with c6 + c7 + c8 + c9 to form the membrane attack complex (MAC)
what is the alternative pathway?
- triggered y lipid-carbohydrates (LPS) which is just C3 splitting into c3a and c3b and then c3b going to make c5 which splits into c5a and c5b and c5b goes to join with C6-9 to form MAC
what is the lectin pathway?
triggered by mannose and results in formation of MAC complex as well
What is the role of c3b in the complement pathways?
c3b is an opsonin and is involved in opsonization –> attracting phagocytes to the pathogen; this coats the bacteria and phagocytes have a c3b receptor to find it
what is the role of c3a and c5a?
ANAPHYLATOXINS –> mast cell degranulation (i.e. releasing histamine from mast cells) which mediates inflammation
what is the role of c5a alone?
chemoattractant to leukocytes (WBC) [recruits phagocytes, this is chemical not cytokines]
what is the role of c5b, c6, c7, c8, and c9?
they form the MAC (membrane attack complex) which bores a hole in the outer membrane of the pathogen
what are interferons (IFN)?
type of cytokine (cell signalling)
- produced by virally activated cells [released by host cells in response to certain viruses]
- defence molecule against viruses
(causes nearby cells to heighten antiviral defence)
antimicrobial peptides (AMPs)? [2 types]
- production is triggered by activation of toll-like receptors (binding to foreign pathogen parts)
- broad spectrum antibiotic that destabilizes membranes of gram + and - bacteria as well as fungi and enveloped viruses
- two types:
- dermcidin: produced by sweat glands
- defensives: produced by neutrophils and macrophages
C-reactive protein (CRP)
C-reactive protein CRP is an acute phase protein (protein that increases or decreases in plasma content) that marks BACTERIA for enhanced phagocytosis (opsonization)
it is produced in the liver during infection
increased levels of CRP indicate a bacterial infection/inflammation
this is important in paediatrics as babies cant tell you the symptoms of a bacterial infection but increase CRP in their blood stream tells you they are dealing with it and they have an infection
Why is innate immunity important?
- its the first response to invasion by pathogens and it doesnt need to be primed
- it holds the fort until the adaptive system is ready to help out
- continues to help with defencing even when the adaptive system is initiated (OVERLAPPING)
- has a large degree of redundancy in case one branch is defective
