Immune System 1-4 🗸 Flashcards
Innate immunity
immunity present from birth and is generally non-specific
includes physical barrier, inflammatory mediators, complement proteins, acute phase proteins, immune cells, etc.
barriers to infection
skin, mucus, commensal bacteria
skin barrier
physical barrier - tightly packed, highly keratinised cells
low ph (5.5)
low oxygen tension
sebaceous glands- hydrophobic oils, lysosomes, ammonia
Mucus
mucous membranes line all body cavities that are in contact with the external environment
mucus traps bacteria lysosomes and defensisns that directly kill invading pathogens
Secretory IgA
Commensal bacteria
compete with pathogens for resources and produce fatty acids and bactericidins that stop pathogens growing
Cytokines
interferons released by virally infected cells to signal to neighbouring uninfected cells
destroy RNA and reduce protein synthesis
undergo apoptosis
interferons also activate immune cells e.g. NK cells
Macrophages
Phagocytose bacteria
Seven steps of macrophage
- PRRs on macrophages bind to PAMPs on pathogen, which signals the formation of the phagocytic cup
- cup extends around the pathigen and pinches off - phagosome
- Phagosome fuses with lysosome - phagolysosome
- pathogen killed and contents degraded
- debris released into extracellular fluid
- pathogen-derived peptides expressed on special cell surface receptors (MHC-II)
7.Pro-inflammatory mediators released (TNF⍺)- acute inflammation
Mast cells
deal with pathogens too large for phagocytosis
associated with allergy
Two step process of mast cells
1.when PRRs on mast cell bind to PAMPs on pathogen, the mast cell is stimulated to release pre-formed pro-inflammatory substances such as histamine and tryptase - degranulation
2.as this happens, the mast cell also begins to produce pro-inflammatory substances ie histamine, TNF, chemokines, leukotrienes
Transendothelial migratiom
recruitment of neutrophils to the site of infection/damage during acute inflammation
5 steps of neutrophils
- loss of intravascular fluid in the presence of inflammation causes slower blood flow, allowing neutrophils to undergo margination (moving close to endothelial cells instead of the centre of the vessel)
- neutrophils can then encounter and bind to adhesion molecules expressed by the endothelial cells (selectins, ICAM-1)
- neutrohpils migrate across the endothelium via diapedesis
- Once in the tissues, the neutrophils travel to the exact site of injury via chemotaxis
- Neutrophils are then activated by PAMPs and pro-inflammatory mediators such as TNF⍺
Three killing mechanisms
Phagocytosis
Degranulation
NETs
Phagocytosis (killing mechanism)
phagolysosomal killing via the production of reaction oxygen species (ROS)
Degranulation
release of anti-bacterial granules
NETs
release pf a net-like structure that traps pathogens, leading to phagocytosis
Modes of ingestion
receptor mediated endocytosis
pinocytosis
phagocytosis
receptor mediated endocytosis
molecules bound to membrane receptors are internalised
(imporntant in the generation of adaptive immunity
pinocytosis
ingestion of fluid of surrounding cells
phagocytosis (ingestion mode)
bacterium engulfed by cell surface
NK cells
lymphocytes involved in the rejection of tumours and virally infected cells which respond to the reduced levels of MHC class I in cancerous and virally infected cells
kill by degranulation and release perforin
produce IFN𝛾
Dendritic cells
act as a bridge between the innate and acquired immune system
express antigens on their cell surface and present them to T cells -antigen presenting cells
basophils
granules containing histamines which act as effector cells in allergic reactions
Eosinophils
associated with allergy
What is the complement system
the activated response to inflammation which created a cascade of chemical reactions
What is the process of the complement system
C3 cleaves (splits) into C3a and C3b
C3b then cleaves C5 into C5a and C5b, it will also cause C3 to cleave more via the alternative pathway
C5b (with other things, will produce a membrane attack complex (MAC) which inserts into cell walls and destoyd the cell by allowing salt amd water in
C3a and C5a are responsible for acute inflammation (anaphylatoxins)
what are acute phase proteins?
proteins produced by the liver whose plasma concentrations increase or decrease in response to inflammation
three acute phase proteins
C3
CRP
MBL
C3
involved in complement
CRP
activates complement via classical pathway
very short half life, but numbers are very rapidly increased during inflammation
MBL
activated complement vis MBL pathway
the classical pathway can be activated by ____ and _____
IgM and IgG
what does IgG act as in the enhancement of the immune system?
opsonins (attach to target cells and make it more obvious for phagocytosis)
Acquired (adaptive) immunity
Induced by the presence of foreign material
able to discriminate between self and non-self
includes cytokines, antibodies, B and T cells
General features of innate immunity
rapid response (hours)
no memory
non-specific
basophils, eosinophils, neutrophils, mast cells, nk cells
general features of acquired immunity
slower response (days)
immunological memory (subsequent responses are quicker and more powerful)
specific
B and T cells
B cells
mature in the bone marrow
important in humoral immune response
normally circulate the primary lymphoid tissue in their inactive form (antigen presentation activates them in secondary lymphoid tissue)
B cell activation
membrane bound antibodies on the B cells bind to target antigen IgM or IgD within the B cell zone of lymph nodes
requires 2 signals to become fully active and begin proliferation ie from TH cells, PRR and PAMPs or from multiple antigens
generation of high affinity antibodies
Once active, clonally proliferate and become either plasma cell (antibodies) or a memory B cell (germinal centre response)
high affinity antibodies are generated IgM (by plasma) becomes IgG (by B cells) assisted by TH cells
transport of lymphocytes
lymph and lymphocytes leave lymph node and go to the medullary sinus then to the efferent lymphatic vessels then to the blood circulation via the lymphatic ducts at the subclavian vain
antibodies
made up of 2 light chains and 2 heavy chains
each has a unique variable region (antigen binding site) which is specific against one antigen
membrane bound antibody
located on surface of B cell
secreted antibody
secreted by plasma cells, present in serum and tissue fluids
five types of antibody
IgM
IgG
IgA
IgD
IgE
IgM
first antibody to be made in an infection
monomer when bound to B cell membrane but pentamer when released into plasma
functions of IgM
B cell activation
agglutination (immune complex formation - enhances phagocytosis)
complement system activation through classical pathway
IgG
most abundant antibody in the plasma
monomer
dominant type during secondary response
functions of IgG
foetal immunity (placenta transfer)
complement activation
NK cell activation
neutralisation
IgA
second most abundant antibody
monomer in serum, helps with neutralisation of pathogens (membrane bound form)
Dimer in secretory fluids (ie colostrum)
function of IgA
neonatal defense
protects GI tract of neonates
IgD
second least abundant antibody
monomer
function of IgD
B cell activation
IgE
least abundant antibody normally
monomer
function of IgE
produced in allergic response
T cells
mature in the thymus
four types of T cells
CD4+ Helper T cells
CD8+ Killer T cells
Regulatory T cells
Memory T cells
CD4+ Helper T cells
activate B cells and stimulate production of memory B cells
CD8+ Killer T cells
kill infected cells via perforin/granzymes/granulysin
regulatory T cells
lymphocyte suppression
Memory T cells
involved in the adaptive immune response
MHC molecules
T cells can only recognise peptide antigens that are presented to their TCR by MHC molecules
Class I or II
Class I MHC
expressed on all nucleated cells, present peptide antigens to CD8+ Killer T cells
Class II MHC
expressed only on antigen presenting cells
present peptide antigens to CD4+ Helper T Cells
T cell activation
in the presence of pro-inflammatory mediators (ie TNF⍺), dendritic cells mature and increase expression of stimulatory molecules on their surface
Dendritic cells phagocytose the pathogenic antigens, break the antigens down into short peptides and load them onto MHC II molecules
these transport to the cell surface (maturing dendrites will also move to lymph nodes via afferent lymphatic system)
Co-stimulatory molecules enable T cells to respond to antigen and fully differentiate
Two types of T cell differentiation
CD4+ T cells to make T helper cells
CD8+ T cells to make CTLs (TC cells)
CD4+ T cells to make T helper cells
antigen activated CD4+ T cells secrete IL-2 and express IL-2 receptors (T cell growth factor)
CD4+ T cells → T helper (THO) cells → effector TH cells like TH1, TH2 and TFH cells
TH1 cells
secrete pro-inflammatory cytokines (IL-2, IFN𝛾) which stimulates the production of ROS (macrophage mediated)
TH2 cells
secrete mainly IL4, IL5 and IL6 which promote B cell proliferation and induces antibody production
TFH cells
stimulated by the presented antigen peptides + MHC II molecules on B cells to proliferate and differentiate (plasma + memory) by secreting IL4 and IL21
CD8+ T cells → CTLs (TC cells)
IL-2 (provided by TH cells) promotes differentiation and proliferation of antigen activated (via MHC I) CD8+ cells into cytotoxic T lymphocytes (CTLs)
CTLs migrate out of secondary nodes and enter site of infection (via transendothelial migration) and then kill virally infected host cells by recognising pathogenic antigens attached to MHC class I
theyre also involved in killing caner cells
what kills bacteria?
phagocytes
antibody and B lymphocytes
complement system
what kills viruses
T lymphocytes
antibody and B lymphocytes
what kills fungi?
phagocytes
T lymphocytes
eosinophils
what kills protozoa
T lymphocytes
Eosinophils
what kills worms
Eosinophils
mast cells
