Lec 2: Arms of the Immune System Flashcards
Innate Immunity
Recognition of molecular motifs with invariant non-rearranging receptors
similar or same response each time
fast (within minutes or hours)
all cells mount innate responses to varying degrees, epigenetic changes to increase the robustness of the initial respose can act as a “memory” sort of
Adaptive immunity
recognition of antigens with receptors that rearrange for enhanced specificity
improved response to repeat exposure
SLow (5-6 days)
has memory and is mediated by B and T cells
Adaptive immunity may be divided into what two catagories
Humoral immunity = B cells, and the production of antibodies
Cellular Immunity = T cells, these kill cells and direct the adaptive immune response
Why does the magnitude and speed of the immune respose increase with repeated exposure
Adoption and increase of specificity of an antibody to a specific antigen
Tolerance
The B and T cells which are selected for are non-responsive// weakly respoinsive to the cells// antigens of the host
Plasma proteins are also known as
reactive proteins
serum is
the non clotting and a cellular component of the blood
Intrinsic immunity
Sub-catagory of the innate immune system
innate immunity can be activated, but intrinsic immunity is always present
consituitvely passive immunity in most cells of the body, but expression is enhanced by innate immunit signalling
basal expression is independent of IRF3, STAT1 and IFN signalling
restriction factors
cellular proteiins that directy restrict pathogen replication and assembly
clotting factors and bacteria for example
intrinsic immunity
Antimicrobial peptides
part of intrinsic immunity
these are built into mast cells and exhibit antimicrobial activity towards bacteria, viruses and fungi
What does it mean when you say that the innate immunity is non-specific
It means that innate immunity only recognizes components of a given pathogen
ex// the cell wall of S. aureus, not the microbe it’self
What PRRs are the innate immune system mediated by
Toll like receptors (TLRs) RIG like receptors (RLRs) Nod like recep[tors (NLRs) C-type lectin receptors (CLRs) Orphan receptors
Which cell is the important link between the innate immune system and the adaptive immune system
Dendridic cell
Which transcription factors activate the innate immune system
Interferon response factors (IRFs)
Nuclear factor kappa B (NF-kB)
PAMPs
Pathogen associated molecular patterns
Bacterial or viral proteins Bacterial or viral DNA Viral RNA Foreign glycans Toxins
DAMPs
Damage associated molecular patterns
Location is super important, not just the signal
Damaged cells
Intracellualr host proteins
Host RNA, DNA and purine metabolites in the wrong compartment
Which TLR does peptidoglycan bind to
TLR2
Gram positives
Which TLR does Lipoteichoic acid bind to
TLR2
TLR6
Gram Postives
Which TLR does Lipopolysaccharide bind to
TLR4
Gram negatives
Why might TLRs be on cell surfaces
TLRs might be on a cell surface because it allows recognition before a cell is infected, or allows for the identification of microorganisms that only infect or colonize surfaces of cells
How do TLRs detect cololonization on the outside of the cell
leusine rich repeats
TIR Domain
Dimer formed by TLR and PAMP on the initial protein adapter on the cytoplasmic domain
WHy might TLRs be in endosomes
For engulfment of bacteria or when infected with a virus
What is triggered by PRR activation
IFNs
ISGs
Proinflammatory cytokines
IFNs
Interferons
(IFNa, IFNb, IFNg)
antiviral cytokines that elicit the activation of hundred of downstream genes for cellular protection against pathogens
ISGs
Interferon-stimulated genes
Hundreds of host genes for cellular protection against pathogens
THis includes restriction factors
Pro-inflammatory cytokines
promotes an inflammatory response and recruits immune cells
NFkB
What is convergent signalling
the combination of both a DAMP and a PAMP, this leades to a stronger response
What is the “clean up crew”
neutrophils and macrophages
What is the “army”`
T and B cells
Primary lymphiod organs
where immune cells develop (such as T and B cells)
Bone marrow and the Thymus
Secondary lymphoid organs
where the adaptive immune responses are initiated
What type of immunity do T cells play a role in, and where do they mature
They play a role in cell-mediated immunity and they mature in the thymus
Helper T cells
CD4+
secrete immunoregulatory protiens called cytokines
Help to activate other effector cell types
Cytotoxic T cells
CD8+
Kill virus-infected cells
Kill tumour cells
What type of immunity do B cells play a role in, and where do they mature
B cells are involved in humoral immunity and they mature in the bone marrow
Can T and B cells become long-lived memory cells?
yessir
What does an activated B cell transform into
a plasma cell
Plasma cells
secrete antibodies that bind to specific pathogens
antibodies can be used by other cell types to detect pathogens
antibodies can coat and neutralize pathogens
BcR
immunoglobulin
Igg
B cell receptor
recognizes macromolecules (proteins, lipids, polysaccharides and other large chemicals) in linnear or conformational motifs
TcR
T cell receptor
recognizes MHC-peptide complexes
They do NOT recognize free peptides, and weakly recognize free MHC
Antigen binding site contains hypercariable regions such that ther is one antigen recognition site/ TcR
MHC
Major histocompatibility complex
aka (HLA)
found on APCs and recognize peptides
MHC 1
present on all cells of the body
present peptides from inside the cell normally 8-10 aa in length
MHC 2
present on antigen presenting cells and is presented to T-cells
peptides can come from inside the cell but they normally recognize extracelluar peptides 13-17 aa in length
note these peptides unlike the MHC 1 class of recptors allow the peptide to stick outside of the peptide cleft
Why are dentridic cells so important
They express almsot all PRRs!
they can also travel from the skin and mucosal surfaces to the lymph nodes!
This means they are excellent for sampling tissues and activating t cells
Dendridic cells detect incoming pathogens, digest and present peptide antigens to T cells in lymph nodes (ACTIVATION)
what are the best antigen presenting cells in the body
dentridic cells
where are dendritic cells usually found
skin and mucosal surfaces
Why are dendritic cells considered a part of the innate immune system
dendritic cells express many PRRs for detection of pathogens
Why are dendritic cells considered part of the adaptive immune system
Activated dendritic cells will active T cells
How do dendritic cells activate T cells
presentation of antigens from microbes on MHC molecules
Co-stimulation of T cells
Secretion of immunomodulatory proteins called cytokines
what happens when a T cell effectors activates a T-cell
once activated, T-cells expand (clonal expansion) and divide to modulate an immune response
army recruitment
CD4+ T cells activate other types of immune effector cells
Helper CD4+ T cells direct immune responses via cytokine and chemokine production
cytokine
immune modulatory soluble protein
Chemokine
chemotaxis-inducing cytokine
B cell receptors vs antibodies
BcR= surface antibodies = soluble
the antigen binding site of BcR is hypervariable, thus is contains two antigen recognition sites
antibodies are secreted are secreted and do not contain transmembrane regions and cytoplasmic tail
How do B cells Present antigens on MHC 2 molecules?
B cells recognize intact (not processed) antigen trapped on the surface of follicular dendritic cells
this is the first stage of B cell activation via BcR stimulation
once activated, B cells become antigen presenting cells (on an MHC ) and clonally expand via T cell stimulation
Cognate B cell activation via a CD4+ Helper T cell
B cell is activated and clonally expands
This leads to the production fo antibody-producing plasma cells, germinal center B cells and memory B cells
How is exquisite specificity to an antigen achieved
Via the myriad of BcR and TcR of variable regions
each recognize a single peptide
and binding of antigen stimulated a conformational change and receptor clustering that activates downstream signalling via the cytoplasmic tails
What is the difference in the way that Tand B cells recognize antigens
T-cells recognize antigens via MHC II receptor - pepdite complex binding to TcR whereas B cells recognize free antigen via BcR ??
Genetic determinants of host susceptibility to infection
Immune systems wotk on similar processes but are different (reason = SNPs)
Gene products often alter host suseptibility
- mutations/ SNPs in cellular cell surface receptors
- Mutations/ SNPs in innate and adaptive immune pathways
- Mutations/ SNPs in tissue remodeling and repair
Can you give an example of a mutation that alters immune capacity
Mutations in signal transduction cascades involved in damage and repair