Lecture 12 (6B) - Immunological Memory Flashcards
Immunological memory
the ability of the immune system to respond quicker and better to pathogens that have been encountered previously
Damage and infection stimulates
inflammation
Inflammation
damaged tissues make proinflammatory cytokines
• macrophages in
• TNFα, IL-1, IL-6, IL-8
• the wound bleeds to wash out foreign bodies
• resident macrophages and the injured tissues initiate an inflammatory response
Inflammation first drives
the innate immune response • clot forms to seal the wound • macrophages • NK cells • neutrophils • fluid enters the site • IgM
keep under control until adaptive
Dendritic cells initiate
adaptive immunity
• DC gets pieces of pathogens and
• have TLR/pathogen recognition receptors on surface so can respond /recognize pathogens
• acts as danger signal
• upregulates B7 and CD40 on DC -> signal T cells to proliferate
Immature DC –> Mature DC
- in the tissues is scanning, finds danger signals
- maturation on meeting a microbial challenge (danger signals)
- becomes a mature dendritic cell that goes to the lymphatics and lymph nodes
- upregulates B7 and CD40 - the signal for the T cells to proliferate
- when mature starts chopping up bits of proteins , upregulates MHC on surface, puts protein in MHC, turns on B7 and CD40, goes to lymph nodes (primed DC)
Dendritic cells go to the lymph nodes
activates naive T cells - passes protein to other DC, they interact with naive T cells - find one that recognizes the MHC+peptide
• in through afferent lymphatics
• activate/prime T cells that proliferate
• TH1 helper T cells and cytotoxic T cells leave through efferent to the site of infection =
Cell-mediated immunity
clones of T cells leave lymph node back to site of problem
- CD4 or CD8
- CD8 kill directly - with perforin and granzymes
- Th1 cells support cytotoxic T cells and macrophages = cell mediated response, good for getting rid of pathogens that infect cells
- Th2 cells
Humoral immunity
Th2 cells help B cells make antibodies which are good at catching big pathogens
B cells become plasma cells
which produce huge amounts of diverse antibodies • IgM - makes this first, low affinitiy • IgG - blood • IgE - mast cells, allergies • IgA - mucosal
make a lot of IgG to send to site of infection
A fraction of the activated T and B cells become
memory cells and provide long-lasting immunity to that infection
A fraction of the activated T and B cells become memory cells and
provide long-lasting immunity to that infection
• cytotoxic T cells
• helper T cells
• B cells
- in an active immune response, there’s lots
- lots are left after an immune response, but not enough storage, so just want to keep the useful ones
After an active immune response
effector cells are stored for rapid deployment if infection re-occurs
• memory cytotoxic T cells
• memory helper T cells
• memory B cells
- still have more than the original, faster
- pathogens would also have to proliferate to keep up, but can’t –> can’t beat memory
Immunological memory can be maintained WITHOUT
continued exposure to the pathogen
• it is maintained by long-lived antigen-specific lymphocyte that persist for many years
Immunological memory is maintained by
long-lived antigen-specific lymphocytes that persist for many years
• can be maintained without continued exposure to the pathogen
Demonstrating immunological memory
- infect animal with virus
- animal survives
- 1 month later take the white blood cells
- transfer lymphocytes - T and B cells - to a mouse that has never seen the virus
- it is protected so when challenged with the virus, it doesn’t develop disease
Spanish flu (1918-1919)
• more recorded deaths than any other infectious disease ever
• 25 million people (estimates up to 100 million)
• most people who died were
- very young (immune system not fully developed)
- very old (immune system deteriorates)
• people who survived the russian flu had active memory for the spanish flu
B cell memory
• 100-fold more antigen-specific memory B cells than naive B cells
• antibody produced with higher affinity for antigen
(high affinity of antibody, high somatic hypermutation)
• higher MHC-II and increased B7.1 and B7.2
Higher affinity antibodies in
secondary immune response
• primary infection - made different antibodies, some with low, medium, or high affinity
• secondary infection - antibodies made from primary still there, but low affinity antibodies are outcompeted (B cell that makes it won’t make much)
• tertiary infection - almost no antibodies with low affinity, make less of medium affinity, those with high affinity are boosted (B cell selected for)
–B cells will mutate to make higher affinity
– B cells improve affinity of antibody
Somatic hypermutation in the germinal centers of lymph nodes
the process of directed mutation to the variable region of the antibody molecule, followed by selection for high affinity antibody/antigen interactions results in the progressive improvement of antibody affinities
Memory T cells
• increased frequency of cells (100-1000 fold higher)
• increased survival characteristics eg increase in Bcl-2
• can be re-stimulated much more easily - the requirement for costimulation is much reduced
(originally hard to activate because only want proinflammatory when super necessary)
• rapidly proliferated and rapidly produce effector cytokines (eg IFN-γ)
Memory t cells can be identified by their
surface molecules • CD44 • CD45RO • DD45RA • CD26L - some • CCR7 - some • CD69 - none • Bcl-2 • interferon-γ
2 types of memory T cells
for both CD4 and CD8
- effector memory T cells
* central memory T cells
Effector memory T cells
- rapidly mature to secrete IFN-γ, IL-4 and IL-5
- lack the LN-homing receptor CCR7
- have tissue-homing receptors (CCR5) and inflammatory cytokine receptors
TISSUE MEMORY CELLS
RAPID-RESPONSE UNIT
- need CCR7 to go to lymph node
- no CCR7 = goes to tissue so there when an infection comes to tissue
• CCR5 = gut homing receptor
- when activated don’t proliferate but send out cytokines
- rapid response unit
have inflammatory cytokine receptors, TCR, CCR5
Central memory T cells
• express CCR7 and reside in secondary lymphoid tissue
- CCR7 = go to lymph nodes
• expand into effector cells rapidly and in large numbers
PROVIDE REINFORCEMENTS IN LARGE NUMBERS
• help effector memory T cells
have CCR7, TCR, L-selectin
