Immunology & Immune Responses Flashcards
is the innate immune system specific? fast or slow?
no - nonspecific responses
rapid - immediate/near immediate
what are examples of innate immune components
lymphoid and non-lymphoid tissues
- physical barriers
- pH
- mucosal antibacterial products
- complement system
what are the innate immune cells
neutrophils
macrophages
NK cells
innate lymphoid cells (ILCs)
dendritic cells - act as a messenger to activate adaptive immune response
do innate immune cells have memory
no - only act as effective pathogen killers
can easily get overwhelmed by pathogen virulence factors and abundance
what are the types of innate immune receptors
- toll like receptors
- C type lectin receptors
- NOD like receptors
toll-like receptors
recognize specific components on pathogen cell surfaces (PAMPs, DAMPs, MAMPs)
first trigger that initiates an immune response
what does TLR4 recognize
LPS on gram negative bacteria
what does TLR2 recognize
lipoteichoic acids on gram positive bacteria
what does TLR5 recognize
flagellin on flagellated bacteria (gram positive or negative)
c type lectin receptors
recognize fungal and mycobacterial components
NOD like receptors
protect from inside the cell
DAMPs
damage associated molecular patterns
released by a cell after inappropriate cell death (NOT released during regular apoptosis)
regular cell components that should only be inside the cell
innate immune system characteristics
- specificity is inherited
- triggers immediate response
- recognizes broad class of antigens
- discriminates closely related molecular structures
NOT:
- encoded in multiple gene segments
- require gene rearrangement
- undergo clonal expression
adaptive immune system characteristics
- encoded in multiple gene segments
- require gene rearrangement
- undergo clonal expression
- able to discriminate closely related molecular structures
NOT:
- specificity inherited in genome
- triggers immediate response
- recognize broad classes of pathogens
what are the three consequences of innate immune activation
- tissue macrophages destroy pathogen
- macrophages signal for help by using local cytokine and chemokine production
- dendritic cells capture antigen and go to LNs to activate adaptive system
effect of macrophage recognition
pathogen binds TLR on macrophage surface and gets phagocytoses into phagosomes
phagosomes fuse with lysosome to initiate breakdown of pathogene
effect of local cytokine/chemokine production
vasodilation and increased adhesion molecules
- attracts innate cells and stimulates extravasation to tissues
systemic effects: fever
effect of dendritic cells
immature DCs located in the tissues capture pathogens and become activated
travel to draining LNs to present antigen to T cells
changes in dendritic cells once activated
- lose phagocytic capability
- increase CCR7
- increase MHC II
- increase B7 molecules
CCR7
specific chemokine receptor that directs activated DCs to the T cell area of the lymph node
B7 molecules
CD80 and 86; costimulatory molecules required to present antigen to T cells
clonal selection theory
development of an appropriate effector lymphocyte requires:
1. thymus: single progenitor gives rise to many lymphocytes with different specificities –> self reactive lymphocytes are removed via deletion –> non self-reactive lymphocytes go to LNs
- lymph nodes: naive lymphocytes detect antigen –> lymphocyte activates –> proliferation and differentiation
how long does it take for lymphocytes to proliferate/undergo clonal expansion
7-10 days
innate immune system protects body in the meantime
lymphocyte recirculation
lymphocytes enter circulation through thoracic duct
lymphocytes exit circulation and enter lymphatics through high endothelial venules into the paracortex of the LN
where are the only sites that naive lymphocytes can be found
blood
lymphatics
lymphoid tissues
what are the three signals for T cell activation
- antigen presentation
- costimulation
- differentiation
T cell signal 1: antigen presentation
TCR + CD4/8 on T cell binds to antigen peptide + MHC II/I on dendritic cell
CD4 vs CD8 T cell activation
CD4: detects extracellular antigen peptide bound to MHC II
CD8: detects intracellular antigen peptide bound to MHC I
T cell signal 2: costimulation
CD28 on T cell binds B7 on dendritic cells
indicates presence of inflammation at the site of the foreign antigen
what happens if there is no signal 2
tolerance - no costimulation means that the antigen peptide is not eliciting a local immune response in the tissues, no responding T cells get deleted to prevent damage
CTLA-4
negative regulator of T cell activation
binds B7 with greater affinity than CD28
ONLY expressed as T cells start proliferating to prevent over-cloning the T cells
what is the most polymorphic part of the genome
MHC genes
high polymorphism allows a species to be able to respond to a wide variety of genes
effect of inbreeding on immune response
inbreeding causes decreased polymorphism of MHC molecules, which means inbred populations will have MHCs that are responsible for the same pathogens –> decreased ability of the immune system to respond to a variety of pathogens
MHC restriction
T cells will only respond to antigen peptide presented on MHC if they recognize both the self (MHC) and non-self (antigen peptide) components
prevents overproduction of T cells in response to the same pathogen
peptide binding groove
site where the antigen binds the MHC
MHC variability allows for recognition of diverse pathogens
superantigens
pathogen products that can activate many T cells by binding the TCR and MHC outside of the peptide binding groove
causes over-activation of T cells leading to a massive inflammatory response
T cell dependent B cell activation
two signal process of activating B cells that involves T cells
- BCR binds antigen
- CD40 on B cell binds CD40L on T helper cells
- cytokines secreted from T follicular helper cells drives class switching
B cell signal 1
- antigen enters LN through afferent lymphatics
- subcapsular macrophage bind antigen without phagocytosing
- passes antigen to follicular dendritic cells in the LN follicle
- follicular dendritic cells present antigen to naive B cells
- BCR on B cell binds the native (unprocessed) antigen
how do B cells move to the B cell area of the lymph node
express CXCL5
how do B cells move to the B/T cell border
once B cell binds antigen, it expresses CCR7 to move towards the paracortex
how do T cells move to the B/T cell border
differentiated and activated T helper cells express CXCR5 to move towards the follicle
B cell signal 2
- B cells ingest antigen and present antigen peptide on MHC II to CD4 T cells
- TCR and CD4 on T cell bind antigen peptide on BCR to activate the B cell
- CD40 on B cell binds CD40L on T helper cells to co-stimulate B cell activation
clonal expansion of B cells
- activated B cells start to proliferate inside the follicle, forming a germinal center
- cells in germinal center form a light and dark zone to undergo somatic hypermutation and class switching
- some B cells move out of the follicle and form a primary focus to release early antibodies
- remaining B cells in germinal center form plasma cells or memory B cells and exit the LN
somatic hypermutation
mutation of the antigen binding region on the BCR
class switching
functional modification of the back end of the receptor (IgG, IgM, IgA, IgE)
dark zone
“centroblast”
site of B cell proliferation, somatic hypermutation, and class switching
- creates a higher affinity receptor
B cells must express CXCR4 to remain in the dark zone
light zone
centrocyte
site of testing; follicular Th cells and follicular DCs in the light zone present antigen to test the new receptors using signal 1 and 2
higher affinity BCRs outcompete lower affinity
naive B cell characteristics
- express surface Ig
- express surface MHC
- do not secrete antibodies
- somatic hypermutation and class switching
plasmablast characteristics
- express surface Ig
- express surface MHC
- secrete EARLY antibodies
- class switch
plasma cell characteristics
- no surface Ig
- high rate of antibody secretion
- no somatic hypermutation or class switching
memory B cell characteristics
- express surface antibody
- do not secrete antibody
what are the major blood antibodies
IgM and IgG
what is the most abundant immunoglobulin
IgA
IgA
present on external mucosal surfaces (lung, gut)
does NOT fix and activate complement to avoid inflammation at mucosal surfaces
what are the 3 methods of antibody protection
- neutralization
- opsonization
- complement activation
neutralization
antibodies bind toxins to prevent them from binding to host cells
opsonization
bacteria get coated with antibody –> antibody binds Fc receptors on macrophages –> macrophage membranes fuse and create a phagosome –> lysosomes fuse to phagosome and degrade bacteria
complement activation
IgM and IgG bind to antigens on bacteria surface to initiate complement cascade
enhances opsonization and lysis of bacteria
