Innate Immune System Flashcards
The immune system has two branches
Innate (natural) -born with
Adaptive (acquired) -acquire antibodies when exposed or vaccinated
Major elements of the immune system
Soluble factors
cells
difference between innate and adaptive immune system for soluble factors
Innate:
lysozyme, compliment, acute phase proteins, e.g. C-reactive proteins
Adaptive: antibodies
differences for cells with innate and adaptive immune system
innate: phagocytes and Natural Killer Cells
Adaptive: T lymphocytes
difference between innate and adaptive for first contact
Innate: same response each time
Non-specific, no memory, resistance not improved by repeated contact
Adaptive: second contact has a stronger response then the first contact
Specific, memory and resistance is improved by repeated contact
list of innate defenses (8)
1-4 are biochemical
5-8 are chemical and physical
1) lysozyme in most tears, nasal secretions and saliva
2) sebaceous gland secretions
3) commensal organisms in gut and vagina
4) spermine in semen
5) mucous
6) cilia lining trachea
7) acid in stomach
8) skin
innate immunity is always ______
present (not induced)
two main mechanisms for innate immunity
limiting entry and limiting growth
how does the skin limit entry into the host
what can a loss of skin lead to?
normally impermeable to majority of infectious agents
it is a hostile environment for many bacteria
lactic acid and fatty acid in sweat and sebaceous secretions aid to lower the pH
loss of skin for example do to a burn can lead to serious infections
how do membranes limit entry into the host?
line the inner surface of the body and secrete mucus
inhibits bacterial adherence to inhibit entry
ciliary action -sweeping motion
remove microbes and other foreign particles
flushing action -tears/saliva/urine protect epithelial surfaces -presence of antimicrobial compounds
what antimicrobial compounds can be present in flushing action of membranes?
Acids (gastric juices) -stomach
spermine and zinc in semen
lactoperoxidase (milk)
lysozyme in (tears, nasal secretions and saliva)
how can the normal flora inhibit entry into the host?
-will compete or outcompete
Bacteria and fungi which are permanent residents on the body surfaces (skin and mucosal membranes)
suppress growth of pathogenic microbes:
protective layer
compete for nutrients
produce inhibitory compounds ->acids and collicins
how does the body limit growth of pathogens that have entered the host
phagocytosis
soluble chemical factors (bactericidal enzymes)
phagocytes include
macrophages
polymorphonuclear granulocytes
neutrophils=polymorphs
how do Macrophages mature
where are they concentrated
promonocytes (in bone marrow) ->circulating blood monocytes -> mature macrophages (tissues)
concentrated in the lung, liver and lining of lymph nodes -well placed to filter off foreign material
polymorphs
are the dominant... share... no... \_\_\_dividing,\_\_\_\_lived, \_\_\_\_\_\_ nucleus \_\_\_\_\_ cytoplasm
are the dominant white blood cell in the bloodstream
share common haemopoletic precursor ->myoblast
no mitochondria ->use glycogen for energy (anaerobic conditions due to inflammation, glycolysis is used when fighting infection
non-dividing, short lived, segmented nucleus
Granular cytoplasm
The first step in Phagocytosis uses attachment by…
pattern recognition receptors
PAMPs: “pathogen associated molecular patterns” on microbe (e.g. LPS, proteins)
PRRs “pathogen recognition receptors” on phagocyte
what happens when the PRR recognizes the PAMP
NFkB: Nuclear Factor Kapa beta cells and IRF: Interferon Receptors (different types) are activated to induce transcription products in phagocyte to kill pathogen
the second step in phagocytosis is forming a phagosome after recognition of the PRR to the PAMP. how does this work?
the actin and myosin contractile system of the pseudopodia forms the phagosome
what are the last two steps once the phagosome is formed?
Granule fusion/killing and then release of the microbial products
granule fusion and killing uses oxygen independent and dependent factors
Phagocytosis and Complement system includes
contact-dependent
Formyl methionyl peptides attract leukocytes -chemotaxis -weak signal
compliment proteins
the compliment system is
how are complement components designated?
cascade in which product of one reaction is enzymatic catalyst of the next
compliment (C’) components are designated “C” followed by a number e.g. C3, the most abundant an central component
Soluble Chemical Factors of the complement system (Normal Plasma)
describe the feedback loop for the first step in the compliment system
C3 activation -> two breakdown products, C3b and C3a
C3b can complex with factor B (another C’ component)
C3bB is acted upon by an enzyme factor D to produce C3bBb
C3bBb aka C3 convertase which can split more C3 to C3a and C3b
what decides if the compliment system moves on to the alternative complement pathway?
soluble C3 convertase is unstable and degrades
in presence of CHO/ other bacterial surface molecules, C3 convertase is no longer susceptible to breakdown
alternative complement pathway begins
describe the steps in the alternative compliment pathway
C3b binds to microbial surface and acts as “opsonin”
C3b +C3 convertase act on next component C5
C5 is split into C5a and C5b
C5b becomes membrane bound and is joined by C6, C7, C8 and C9
together become inserted into the lipid layer of membrane and form membrane attack complex (MAC) ->cell lysis
in the alternative complement pathway C5a and C3a cause mast cell degranulation -release of chemicals that mediate:
1) increased vascular /capillary permeability allows flow of fluid and plasma components to site of infection, part of “acute inflammatory response”
2) chemotactic attraction of polymorphs through blood vessel walls to C3b-coated bacteria because polymorphs have a receptor for C3b on the surface of bacteria so it will tightly bind and phagocytosis occurs
Acute phase proteins
increased concentration in plasma response to injury and inflammation e.g. C-reactive protein mannose binding protein (MBL) -bind to PAMPs -fix complement and opsonize bacteria
Antimicrobial Factors
Act within phagocytic cells but also in bodily fluids
tears in saliva (lysozyme)
lactoferrin (blood) -doesnt allow iron to be available for bacteria
interferons (IFNs)
Discovered as a means of viral interference
cell infected with one virus resistant to superinfection with 2nd unrelated virus
infected cells secrete IFNs -bind to specific receptors on nearby uninfected cells
IFN causes cells to produce two types of enzymes that interfere with virus replication to limit spread
Extracellular killing via NK cells
Bind to receptors on virus-infected cells causing NK activation and release of granules
e.g. perforin that insert into host membrane forming pore (like MAC)
allow entry of 2nd molecule, granzyme B that leads to apoptosis
Extracellular killing via Eosinophils
combat large parasites -helminths (too large to be engulfed by phagosome)
bind to C3b (via C3b surface receptors) which cause activation
several toxic compounds released that damage membrane via hole formation
