I&I adaptive immunity 1 Flashcards
What are the steps involved in the development of immunity?
– Initial infection stimulating an
immune response
Innate & Adaptive (Acquired)
– Recovery due to immune activity
– Lasting acquired immunity
Specific
Often for life
How is the innate response to new infection and what does it act on?
The Innate Response to new infections is FAST
acts on PRE-DETERMINED NON-SELF SIGNALS
What are examples of cell mediate(innate) responses?
-Phagocytes
-Natural killer (NK) cells
What are examples of humoural(extracellular innate) responses?
-Complement & Pentraxins (CRP)
-Pattern receptors (soluble TLR)
-Enzymes (Lysozyme)
-Cytokines releasing antimicrobials
-Binding proteins (Lactoferrin)
What is the speed like in adaptive response and what does it select and generate?
The Adaptive Response to new infections is
SLOW and SELECTS for SPECIFIC SIGNALS
and generates MEMORY
Where are T or B cells made and what are they randomly assigned?
Each T or B cell is made
in the bone marrow with
a randomly assigned
antigen-binding
specificity.
How do T lymphocytes get processed?
- Naive(double negative) T lymphocyte will migrate to the thymus gland, where its processed
- This leads to the T lymphocytes maturing into
-CD8+ cytotoxic T lymphocyte(CTL)
-CD4+ Helper T lymphocyte
-Or destroyed if it strongly recognises self antigens(central tolerance)
How do b lymphocytes get processed?
Developed and matured in Bone Marrow to express a single epitope
antibody used as a receptor for a single antigen
What are the steps involved in the endogenous antigen pathway leading to cytotoxic T cell priming?
- Cells are infected by the virus
- Viral proteins in the cytoplasm are detected and processed
- Viral antigens are presented with MHC class I molecule on cell surface
- CD8+ T cell (CTL) recognize antigen and becomes cytotoxic and begins to make cytokines
5.The CTL proliferates making memory cells and CTL cells looking for cells with presented antigen - Infected cell is destroyed by cytotoxic cell
What are the steps involved in the exogenous antigen pathway leading to T helper cell priming?
- Dendritic cell or macrophage engulfs pathogen into vesicle
- Antigen is processed into small peptides
- Antigen is presented with MHC class II molecule on cell surface
- T helper cell(Th) recognises the presented antigen
- CD4 T cell becomes primed and can either help activate B cell (TH2) or macrophages(TH1)
What are the steps involved in B cell priming(T cell independent)?
- Pathogen containing multiple identical antigen epitopes like lipopolysaccharides(LPS) are able to strongly activate B cell
- Activation initiates proliferation with some cells being memory cells and some being committed to antibody production
- Activated B-cells convert to plasma cells and begin making antibody
- This pathway is restricted to specific antigens and is not checked for tolerance
-This can lead to problems such as toxic shock syndrome
What are the steps involved in B cell priming(T cell dependant)?
- B cell recognises antigen presented by a professional APC
- Chemokines then attract T helper cell because antibody production requires co-stimulation that’s already been screened in the thymus against self.
- Activation initiates B cell proliferation with some cells become memory cells
- B cell committed to antibody production
- Cytokines can direct AB isotype-switching
What is the basic structure of an antibody?
-2 identical antigen-binding sites
-A hinge region flexible spacer between binding sites
What generates antibody fragments?
Protease cleavage generates
large fragments
What are the 2 antibody fragments called?
Fab (antigen binding)
Fc (crystallisable)
What is the Fab region?
Fab variable region binds antigen
What is the Fc region?
Fc constant region binds to
receptors on phagocytes,
activates complement
How many polypeptide chains are there in an antibody and what interactions is it held by?
4 polypeptide chains held together by non-covalent interactions and by disulphide crosslinks between cysteine a.a. residues into a
Y shaped molecule
What are the 2 types of light chains in antibodies ?
There are 2 identical light chains.
-They are either Kappa or lambda, never both
What is the structure of IgM?
-Pentamer of basic sub-unit in plasma (secreted & highly antigenic)
-Contains a J chain - a polypeptide involved in pentamer polymerisation
What is the major class of antibody classes and what’s it made by?
- the major class overall (75% of all Ig)
- the major class made by secondary responses
What is IgG only able to cross and protect?
only class able to cross the placenta and protect
developing fetus
What is the function of antibody classes?
- very good at activating complement via classical
pathway (removing the pathogen) - acts as an “opsonin” inducing phagocytosis
– Fc region recognised by “Fc-receptors” on surface of
immune cells. eg, neutrophils and macrophages
What may IgG indicate and why is that so?
It can be present for long periods
in the serum thus IgG antibodies
may indicate past exposure and
not current infection !!!
What does the presence of IgM antibody to an antigen indicate?
Presence of specific IgM antibodies to an
antigen indicates a recent primary response to
that antigen
What does IgM imply?
Implies a current primary infection
What is IgM excellent at activating and why?
excellent at activating complement via classical
pathway (ie, because of its pentameric structure)
What increases overall affinity of IgM?
higher valency of pentamer increases overall
affinity (ie, by binding higher number of epitopes)
What does IgM bind immune cells via?
binds immune cells via Fc receptor (ie, inducing
phagocytosis)
What does the primary response involve?
- Latent period
- Exponential phase
- Steady phase
- Isotype switching
- Decline phase
What is involved in preferred isotype switching?
1.Ig heavy chain genes are in a specific order
2. IgM comes first in the queue
3. Different cytokines signal specific gene rearrangement/excision
4. The new heavy chain alters the C region(class of immunoglobulin) but not the V region holding antigen specificity
How is the adaptive response to re-infection and what does it ensure?
The adaptive response to re-infection is
FAST and SPECIFIC and ensures long lasting MEMORY
What are the interactions between an antibody-antigen?
Electrostatic, hydrophobic, van der Waals forces, hydrogen bonds
Depends on the antibody binding site being exactly complementary,
sterically and chemically, with a site on the surface of the antigen
What are epitopes?
A single antigen can have many possible binding sites (epitopes)
What does it mean by polyclonal?
Natural immune responses are
polyclonal
Meaning:
-More than one clone of B-cells is generated
-More than one Ig is synthesised
Why is the immune response polyclonal?
– Multiple antigens on organism
– Multiple epitopes on each antigen
– More than one Ig may recognise the same epitope
How does the antibody fight infection?
- By coating and neutralising a pathogen
- By activating complement
- By opsonisation
What happens in coating and neutralising a pathogen?
if a virus is coated with Ab it cannot bind to its receptors on the cell surface
What happens by activating complement?
Which can then form holes in a bacterial cell membrane
How does opsonization work?
– Phagocytes have Fc receptors to Fc fragments on Abs on their cell membrane
– They thus bind to pathogens coated with Ab, and phagocytose them
What is the most abundant class of antibodies in external secretions?
secretory IgA - most abundant class in external
secretions (milk, sweat, tears, saliva, gut fluids etc)
What does secretory IgA initiate?
initiates localised mucosal response different from
more general circulating immune response
What does the secretory component of IgA protect?
secretory component protects IgA from degradation,
hence it can work in harsh environments (eg, GI tract)
What is the second most abundant class of antibodies in circulation?
second most abundant class in circulation is IgG
What can circulatory IgA not activate?
circulatory IgA cannot activate complement
What does circulatory IgA bund on immune cells and what does this initiate?
circulatory IgA binds Fc receptor on immune cells
–initiates inflammatory reactions
What is the harmful function of IgE and how does it do so?
harmful function in allergies
- binds to specific Fc-receptor on mast cells and basophils
releasing histamine
What is the useful function of IgE and how does it do so?
useful function in response to parasitic worms
-releases chemicals from mast cells
activates eosinophils (via Fc receptor binding)
What can an over response with IgE cause?
Over response can cause anaphylactic shock
What is the concentration of IgE like normally?
normally low concentration in circulation
What is the concentration of IgD like normally?
extremely low concentration in circulation
What is the role of IgD?
Unclear
Where is IgD mainly found?
mainly found on surface of B cells as antigen-
binding B cell receptor
