2.2 Flashcards
innate immunity definition ?
antigen-independent immune response
In Innate immune response :
1. antigen presenting cells present antigens to what ?
2. providing link between …?
- antigens to CD4+ T cells
- innate and adaptive immune system
what’s difference in definitions of innate and adaptive immunity ?
innate = antigen-INDEPENDENT immune response
adaptive = antigen-DEPENDENT immune response
antigen= substance that can ….
induce an immune response
a substance that can induce an immune response defines what ?
antigen
Innate immune response has 3 ways to deal with pathogens , Name these 3 ways and briefly explain them?
CAP
complement
* opsonisation of pathogens
* formation of membrane attack complex
antigen presenting cell
* Presents antigens to CD4+ T cells
* link between innate and adaptive immune system
phagocytes
* produce pro-inflammatory cytokines
* leads to inflammatory pathway
In Innate immune response
1. what does complement system do to pathogens?
2. formation of…?
- opsonisation
- membrane attack complex
3 functions of innate immune response ?
- recognition of pathogens and damaged cells
- activation
- elimination of unwanted substances
In Innate immune response :
1. what do phagocytes produce ?
2. leading to what ?
- pro-inflammatory cytokines
- inflammatory pathway
- what disorders are primary immunodeficiencies ?
- resulting from ?
- usually present at ?
- diagnosed when ?
- (PID) – inherited immune disorders
- genetic mutations,
- birth
- in childhood.
Examples of encapsulated bacteria that are possible consequences of the secondary immunodeficiency acquired aplasia
- S. pneumoniae
- H. influenzae
- N. meningitidis
5 major manifestations of acute rheumatic fever
SEA between 2C’s
1.carditis (chest pain, palpitations, dyspnea)
2. subcutaneous nodules (collagen collections)
3. erythema marginatum (non-itch rash)
4. arthritis (joint pain)
5. chorea (involuntary jerking muscle movements)
What are the antibodies that form against group A Streptococcus for Acute rheumatic fever cross reactive to?
cardiac myosin
what is acute rheumatic fever ?
- autoimmune disease
- mostly occurs following group A Streptococcal throat infction
- What is acute rheumatic fever ?
- mostly occurs following what ?
- Antibodies form against…?
- what are these antibodies cross reactive to ?
- typically presents ….following tonsilitis
- an autoimmune disease that
- group A Streptococcal throat infection
- Group A Streptococcus
- cardiac myosin
- 2-4 weeks
- Autoimmune disease can be ….. cell mediated - loss of ‘self tolerance’
- Interaction with … remains a direct trigger of autoimmune disease - molecular mimicry
- antibodies induced during …. can also bind self-antigens - often detect ….
- …. cells are usually ‘deleted’ or kept inactive, but in autoimmune disease there is a failure of these ….mechanisms
- T or B
- micro-organisms
- infection, autoantibodies
- autoreactive T, regulatory
If there is a reaction to exogenous (non-self) antigens what is it ?
allergy
If there is a reaction to endogenous (self) antigens it’s …?
autoimmune
Type I hypersensitivty reactions are mediated by ?
IgE
Type II hypersensitivty reactions are mediated by ?
IgG or IgM
Type III hypersensitivty reactions are mediated by ?
antigen-antibody
Type IV hypersensitivty reactions are mediated by ?
T cell
If protozoa and helminths/ parasitic worms are :
extracellular then what is very important in killing helminths ?
Th2 & humoral immunity very important, eosinophils and IgE are also very important in killing helminths
If protozoa and helminths/ parasitic worms are :
intracellular e.g () then what ?
plasmodium in malaria, Th1
List 2 examples of intracellular fungi
- cryptococcus
- pneumoycstis
Fungi is normally …I… and therefore ..II..
some intracellular fungi (Th1) such as ..III.. , ..IV.. and well known to cause infections when there is defective ..V.. (e.g. HIV)
I = extracellular
II = Th2
III = cryptococcus
IV = pneumocystis
V = cell mediated immunity
Viruses are intracellular and therefore are always =….I…. response
..II… cells are important for a viral response
…III… antigens expressed on the surface of infected cells and therefore ..IV… develop against the …V.. antigens - important for …VI… testing
IFN-y = …VII… response
I = cell mediated immune
II = NK
III = viral
IV = antibodies
V = viral
VI = serology
VII = cytokine
What cascade is important for bacterial infection ?
complement
List 4 examples of intracellular bacteria
- Neisseria
- salmonella
- chlamydia
- Mycobacteria
4 examples of intracellular bacteria
- neisseria
- salmonella
- chlamydia
- mycobacteria
What happens to bacteria that are intracellular ?
- Th1
- cellular immune response
- activation of APCs e.g. macrophages
- cytotoxic T cells
Bacterial infections are usually …. (therefore Th2 ->….response with B cells and….)
- extracellular
- humoral
- antibodies
… Presentation takes place with the activation of ….
- antigen
- specific T helper cells (Th1, Th2)
What does the innate immune system trigger in order to contain an infection ?
an acute inflammatory response
What is IFN-y ?
interferons- gamma
What are Treg cells ?
regulatory T cells (Tregs) are T cells
Treg = T regulator cells
What role do Treg cells have ?
regulating or suppressing other cells in the immune system
What do Tregs control ?
immune response to self and foreign antigens & help prevent autoimmune disease
What do Treg cells suppress activation of ?
CD4+ and CD8+ T cells
- What do some bacteria have ?
- what does being encapsulated enhance for a bacteria ?
- what does being encapsulated inhibit for a bacteria ?
Therefore the body relies on other opsonins such as antibodies
- a capsule
- ability to evade phagocytosis
- binding of complement, and complement interactions with phagocytes (opsonisation)
Which 4 areas of the body are B cells found ?
spleen, peyer’s patches (ileum), tonsils, appendix
- B cells internalise …. that bind to their ….
- can also present ….
- when activated by a …cell, they undergo …., maturation and formation of …. cells
- Activated B cells mature into … and start to make…
- found in 4 areas of the body…
- antigens, B cell receptor
- antigens
- T, isotype switching, memory
- plasma cells, antibodies
- spleen, Peyer’s patches, tonsils, appendix
Hummoral immunity (Th2) is used to kill …1…. as :
antibodies …2… on ….3… surface
…4…pathogens
activates …5……pathway
- extracellular pathogens
- bind to antigens
- pathogen
- opsonise
- classical complement
Humoral immunity is the term for a specific adaptive immune response activated by …1..
leading to the production of …2…
- Th2 cells
- B cells and antibodies
- What are CD8+ cytotoxic T cells also referred to as ?
- they recognise …?
- release ..?
- induces ..?
- release what interleukin ?
- T killer cells or Tc cells
- antigen on presented by APC on MHC I
- perforin - makes hole in cell wall
- apoptosis of infected cells
- IFN-y
Cell mediated immunity (Th1) is used to kills what ? give examples
intracellular infections e.g.
* viruses
* intracellular bacteria
* fungi
* some protozoa (plasmodium, toxoplasma)
What is cell-mediated immunity a term for ?
a specific adaptive immune response activated by Th1 cells
What does cell mediated immunity lead to ?
activation of antigen-presenting cells and a cytotoxic T cell response
- What 2 cells can T helper (CD4+) cells be divided into ?
- What’s the difference between these 2 cells ?
- Th1 or Th2 cells
- differences:
* Th1 cells - stimulate cellular immune response, secrete inflammatory cytokines, activate macrophages
* Th2 cells - stimulate humoral immune response
What are the functions of CD4+ Th cells ?
- regulate immune response
- release cytokines
- allow B cells to mature
What are CD8+ cytotoxic T cells primarily involved in ?
- destruction of cells infected by foreign agents e.g. virsuses
- killing of tumour cells expressing appropriate antigens
What are CD8+ cells & CD4+ cells ?
CD8+ cells = cytotoxic T cells
CD4+ cells = T-helper cells
What does antigen presentation process stimulate ?
T cells to differentiate primarily into either cytotoxic T cells or Th cells (CD8+, CD4+)
What action of the MHC-antigen complex and TCR further control the immune response ?
- MHC-antigen complex activates the TCR
- T cell secretes cytokines
What are the opportunities for the right T cells to be in contact with an APC carrying the appropriate peptide MHC complex increased by ?
- circulation of T cells throughout the body (via lymphatic system & blood stream)
- their accumulation (together with APCs) in lymph nodes
When are T cells activated ?
when they encounter an APC that has digested an antigen and is displaying the correct antigen fragments (peptides) bound to its MHC molecules
CD4 or CD8 molecule are T cell molecules known as co-receptor, which are required for antigen recognition alongised TCR.
1. Where is CD4 present & only binds to what ?
2. Where is CD8 present & only binds to what ?
- T helper cells, antigen-MHC II complexes
- cytotoxic T cells, antigen-MHC I complexes
As well as the TCR, another T cell molecule is required for antigen recognition
1. what is this known as ?
2. these are either what molecules ?
- a co-receptor
- CD4, CD8
T cell receptors (TCR):
1. TCR are specific for…
2. they only recognise an antigen if…., what is this known as ?
- specific not only for a particular antigen but also for a specific MHC molecule
- only recognise an antigen if a specific antigen with a specific MHC molecule is present : phenomenon called MHC restriction
- Where does T cell maturation occur ?
- Any …. T cells with ….for self-antigens are …
- What happens to T cells that survive selection ?
- What can T cells that survive encounter ?
- thymus
- immature, receptors, removed
- mature and leave the thymus
- antigens
List 6 adaptive immune cells
- B cells
- plasma cells
- T helper cells (CD4+)
- cytotoxic T cells (CD8+)
- regulatory T cells
- memory cells (T and B cells)
Function of B cells as an adpative immune cells
humoral immunity
Function of plasma cells as an adpative immune cells
mature B cells that secrete antibodies
Function of T helper cells (CD4+) as an adpative immune cells
- activate immune system
- stimulate macrophages
- pro-inflammatory cytokines
Function of cytotoxic T cells (CD8+) as an adpative immune cells
- cell mediated immunity
- destruction of infected cells
- induce apoptosis
Function of regulatory T cells as an adpative immune cells
limit the immune system to prevent excessive damage
Function of memory cells (T and B cells) as an adpative immune cells
‘remeber’ so can have a faster, more effective response on secondary infection
What importance does the function of the adaptive immune response being able to recognise specific ‘non-self’ antigens have ?
distinguish them from ‘self’ antigens
What are the 3 primary functions of the adaptive immune response ? & why that’s important
- recognition of specific “non-self” antigens - distinguishing them from “self” antigens;
- generation of pathogen-specific immunologic effector pathways - that eliminate specific pathogens or pathogen-infected cells
- development of an immunologic memory - that can quickly eliminate a specific pathogen should subsequent infections occur
When do NK cells become inhibited ?
when NK cells detect MHC-I on the surface of ‘self’ cells
which cells are killed by NK cells ?
any cells with no MHC-I on the surface
what do NK cells initiate ?
apoptosis
If cells are infected with virus :
1. what is suppressed ?
2. what can NK cells release when the above is suppressed ?
3. to do what ?
- MHC-I
- toxic granules
- induce apoptosis
Which response are NK cells part of ?
non-specific immune response
There are different classes of MHC, which have different functions.
what are the classes and differences between them[found where, typically present what] ?
MHC class I molecules
* found on all nucleated cells (not just professional APCs)
* typically present intracellular antigens such as viruses
MHC class II molecules
* found on APCs
* typically present extracellular antigens such as bacteria
- Where are MHC class I molecules found ?
- typically present as …?
- found on all nucleated cells (not just professional APCs)
- typically present intracellular antigens such as viruses
- Where are MHC class II molecules found ?
- typically present as …?
- found on APCs
- typically present extracellular antigens such as bacteria
How are antigens delivered to the surface of APCs?
major histocompatibility complex (MHC) molecules
What are major histocompatibility complex molecules known as in humans ?
HLA = human leukocyte antigen
- What does antigen presentation link between ?
- 2 examples of antigen presenting cells
- what do APCs display ?
- innate (antigen independent) and adaptive (dependent)
- dendritic cells, macrophages
- antigens on the surface for other immune cells to recognise
- Acute inflammatory response = localise and contain the infection from …hours after onset before …occurs
- Initiated by …. cells, …. cytokines and …. system
- Initiates …., increased …. permeability
- release of ….mediators
- ….of neutrophils to the site of ….
- 4-96 , immune response
- innate immune, pro-inflammatory, complement
- vasodilation, vascular
- inflammatory
- migration, inflammation
what is neutrophil chemotaxis ?
process where neutrophils are attracted to and migrate towards sites of infection in response to chemical signals called chemoattractants
List 8 cytokines (interleukins, TNF, chemokines):
IL-1
IL-6
IL-8
IL-12
TNF-alpha
IL-4, IL-5 + IL-13
IFN-γ
IL-10
activation of complement pathway and formation of C3 convertase induces what ?
- inflammatory reactions
- opsonisation
- C5-C9 phagocytosis
- lysis of target pathogens
With inflammatory reactions what are the important mediators of inflammation ?
C5a, C4a, C3a
3 complexes involved in opsonisation
C3b, C4b, C1q
C5-C9 phagocytosis and lysis of target pathogens via what ?
Membrane attack complex
What are the 3 different pathways of the complement system ?
- classical
- lectin
- alternative
How many pathways can activate the complement system ?
3 different pathways
In the complement system :
most of the proteins are normally …1…but in response to the recognition of …2… of microorganisms they become ..3…activated in an ….4…cascade - the activation of one protein enzymatically ….5… the next protein in the cascade
- inactive
- molecular components
- sequentially
- enzyme
- cleaves and activates
what does the complement system refer to ?
a series of >20 proteins, circulating the blood and tissue fluids
What is an opsonin ?
any molecule that enhances phagocytosis by marking an antigen for an immune response
How do opsonin molecules usually bind ?
on one end to the receptor present in the antigen & on the other end to the receptors on the phagocytes
what does the binding of opsonin molecules result in ? ultimately leading to what ?
different mechanisms , destruction or removal of the particular antigen
2 examples of opsonins
- MBL
- complement proteins C3b
what is the acute phase response ?
a rapid and nonspecific reaction of the body’s innate immune system to tissue injury, infection or inflammation
During the acute phase response the liver produces…. such as… in response to …..like IL-6.
- PRRs (pattern recognitiion receptors)
- CRP and MBL
- proinflammatory cytokines
How many PRRs are produced during the acute phase response ?
a number of PRRs
What is acute phase response is stimulated by ? e.g.
pro-inflammatory cytokines e.g. IL-6 in response to injury
Where are PRRs produced and released ?
p: in liver
r: into bloodstream
what does CRP bind to ?
C-polysaccharide (phosphocholine)
what does MBL bind to ?
mannose of pathogens
Raised CRP levels in the blood is commonly used as a marker of what ?
infection and inflammation
How can bacterial pathogens evade the immune system ?
by inhibiting TLR signalling
- What PRRs are involved in the recognition of bacterial cell wall ?
- what do these PRRs detect ?
- NOD-like receptors detect the peptidoglycan on the cell wall
- TLR4 (Toll-like receptor) detects LPS
2 examples of GN bacteria one being a spp
Enterobacteriaceae
Neisseria spp
What happens when a PRR attaches to a PAMP ?
PRR = pattern recognition receptor
PAMP = Pathogen-associated molecular pattern
triggers a signalling cascade within the immune cells, leading to release of various cytokines
List 3 cytokines that could be included in the various cytokines that are released when a PRR attaches to a PAMP
- IL-1 (interleukin-1)
- IL-6 (interleukin-6)
- tumor necrosis factor-alpha (TNF-alpha)
3 types of PRRs (pattern recognition receptors of immune cell) + an example
- membrane bound PRRs e.g. toll-like receptors
- cytoplasmic PRRs e.g. NOD-like receptors
- secreted PRRs e.g. MBL (mannose-binding lectin) [regarded as member of C-type lectin family]
Example of receptor that is membrane bound PRRs
toll-like receptor
Example of receptor that’s cytoplasmic PRR
NOD-like receptors
Example of receptor that is secreated PRRs ?
MBL (mannose-binding lectin) [regarded as member of C-type lectin family]
What are PRRs ? what are they designed for ?
(immune cell) pattern recognition receptors
to recognise and bind to only non-self antigens
What are PAMPs ?
Pathogen associated molecular pattern - found on surface of pathogens which leukocytes recognise as ‘foreign’
5 examples of PAMPs and where each is found
- LPS (lipopolysaccharides) from GN bacterial cell wall
- peptidoglycan found in bacterial cell wall
- lipoteichoic acid in GP cell wall
- mycolic acid in acid fast bacterial cell wall (e.g. - M. tuberculosis)
- nucleic acid in viruses and bacteria
…1…constantly travel around the body to see if there are any pathogens
Pathogens have …2…on the surface (e.g., peptidoglycan) that the …3.. recognise as ‘foreign’
Damaged cells have ..4…. so the …5… recognise them as injured.
The receptor on the surface of a ..6… that recognises ….7… is called a …8…
- Leukocytes
- Pathogen associated molecular pattern (PAMPs)
3.leukocytes - Damage associated molecular pattern (DAMPs)
- leukocytes
- leukocyte
- PAMPs and DAMPs
- Pattern recognition receptor (PRR)
