Introduction to the immune system Flashcards
2 reasons we have an immune system?
1) tissue homeostasis
2) tissue defense
why do we need tissue homeostasis?
1) to remove damaged cells
2) promoting wound healing (from normal wear & tear)
what does tissue defense consist of?
1) prevent pathogen entry
2) remove/clear invading pathogens
3) Remove/clear pathogen toxins
4) Limit spread of pathogens in body
- do all w/o killing beneficial commensal organisms*
What does the immune system protect us from?
1) extracellular bacteria, parasites, fungi
2) intracellular bacteria, parasites
3) viruses
4) parasitic worms
what are the two types of immune response?
1) innate: early & preformed
2) adaptive: later & “adapts” response to the specific pathogen infecting an individual
which form of immunity generates memory of infections?
- ADAPTIVE
- innate has no memory of infection that have occurred to an individual
How does the immune system work?
- is a controlled set of responses w/ multiple choices at each step
- choice at first step influences next choice
- 2 types of responses
- “innate drives adaptive which drives innate”
process of innate immunity response?
- immediate, 0-4 hrs
1) infection
2) recognition by preformed nonspecific effectors
3) removal of infectious agent - STOP*
- we do this all the time for minor bugs
early induced immune response
- 4-96hrs
1) infection
2) recognition of microbial-associated molecular patterns
3) inflammation & activation of effector cells
4) removal of infectious agent
adaptive immune response
> 96 hours
1) infection
2) transport of antigens to lymph nodes
3) recognition by naive B & T cells
4) clonal expansion/ differentiation to effector cells
5) removal of infectious agent
innate immune response?
- early & preformed
- involves tissue cells AND professional immune cells
adaptive immune response?
- only professional immune cells
- clonal expansion of specific lymphocyte population
- recruiting and directing subsequent amplification of innate response
Kinetics of a successful inflammatory response to infection? (5 steps)
1) entry of microorganism, causes innate response
2) organisms reaches threshold and adaptive response induced
3) as adaptive induction occurs amount of microorganisms increasing
4) adaptive activated, start decreasing microorganisms amount until cleared
5) create immunological memory
specific cell types involved with innate response?
1) granulocytes
2) macrophages
specific cell types involved with adaptive response?
-lymphocytes (T and B cells)
what is the initiation of the adaptive response dependent on?
- dependent on the innate immune response
- adaptive response is initiated if innate response fails to eliminate pathogenic insult
two ways the innate response drives/ effect the adaptive response?
1) w/o an innate immune response, an effective lymphocyte (Adaptive) response can’t be generated
2) type of innate immune response helps determine & form the type of lymphocyte (adaptive) immune response
5 steps of successful inflammatory response to infection?
1) local infection, penetration of epithelium
2) macrophages/dendrites eat them, activated, go to lymph node w/ antigen presented on surface
3) activate only T cells that recognize the presented antigen
4) T cell activated, clonally expand & attack the pathogen
5) come back and tell innate immune system how to respond
what happens if you lack innate immunity?
- if lack innate will not activate adaptive immunity/lymphocytes
- you die quickly
what happens if you lack adaptive immunity?
- innate immunity can keep you alive for a while, but pathogen replication & evolution will eventually overpower innate w/o an adaptive response
- you die later on but still dead
what happens if have leaked innate & adaptive but still present?
- can give supplements/ help control it and can survive
- but still dangerous/deadly for major infections if don’t have medical help
innate immune cell production process?
1) pluripotent RBC stem cell
2) common myeloid progenitor
3) granulocyte /macrophage progenitor
4) innate immune cells
what are the 5 innate immune cells?
1) neutrophil
2) eosinophil
3) basophil
4) monocytes
5) mast cell
what are the two “middle ground” cells? (cells on border between innate & adaptive)
1) dendritic cells
2) macrophages
adaptive immune cell production process?
1) pluripotent RBC stem cell
2) common lymphoid progenitor
3) B cell, T cell, NK cell (in lymph nodes)
4) B cell= plasma; T cell= activated T cell
what are the adaptive immune cells? what do they produce?
1) B cells= plasma cells that make antibodies
2) T cells= activated. T cells
Where do B & T cells get made? Where do B cells mature? Where do T cells mature?
1) made in the bone marrow from stem cells
2) B cells mature in bone marrow
3) T cells mature in thymus
after maturation what do B & T cells do?
- migrate out via the blood stream & enter peripheral lymphoid organs
- is where naïve lymphocytes are activated by antigen.
peripheral lymphoid organs?
-lymph nodes, spleen,
tonsils and other mucosal sites
what happens once T&B cells are activated?
-T & B cells leave lymph & re-circulate between blood & tissue organs in search for their target antigen
lymphatic route of antigens?
Lymphatics drain lymph fluid from tissues to the peripheral lymphoid organs & to the sub-thoracic duct
- this empties into the left subclavian vein
importance of the lymphatic route of antigens?
1) moves antigens from tissues to lymph nodes
2) re-circulates lymphocytes back to the blood
Monocytes differentiation? what determines it?
- differentiate into many different types of macrophages within tissues
- the type is dependent on local environmental cues
Mast cell differentiation? what determines it?
-involved w/ histamine responses
`- differentiate within tissue sites
-the type is dependent on local environmental cues
Neutrophil activate function?
-phagocytosis & activation of bactericidal mechanisms
eosinophil activated function?
-killing of antibody coated parasites (coated w/ IgE)
basophil activated function?
- may help w/ antibody production & communication w/ B cells
- but still being identified
mast cell activated function?
-release granules containing histamine & other active agents
macrophages cell activated function?
- phagocytosis & activation of bactericidal mechanisms
- antigen presentation
dendritic cell activated function?
- antigen uptake in peripheral sites
- antigen presentation in lymph nodes
when and how does innate immunity get started?
-infection by pathogens and/or tissue damage (injury) are detected by PAMP and DAMP receptors on tissue & immune cells
PAMPs
- Pathogen Associated Molecular Patterns (PAMPs)
- recognized by pattern recognition receptors
- conserved pathogen molecules (not found in mammals) so are easily detectable as bacteria
pattern recognition receptors
-expressed by innate immune cells (and sometimes by tissue cells) and recognize PAMPs & DAMPs
What are conserved pathogen molecules?
- PAMPs
- molecules that generally are not found in mammalian systems
ex: peptidoglycans- if receptor senses peptidoglycan can assume bacteria infections
DAMPs?
Danger Associated Molecular Patterns
- molecules that are released/expressed only when cells are damaged/infected
- ex: high levels of ATP indicate lysis of cell
First step in innate immunity? (after pathogen/ injury is detected)
1) bacteria trigger macrophages to release cytokines/chemokines
2) vasodilation & increased vascular permeability cause redness, heat & swelling
3) inflammatory cells migrate into tissue, release inflammatory mediators that cause pain
4) blood clotting occurs in the micro vessels
how determine which cytokine/chemokine you make?
- macrophages have PAMP/DAMP receptors, depending on which receptor is activated determines which cytokines/chemokines are released
are vasodilation and increased vascular permeability the same thing?
- no
1) vasodilation due to smooth muscle alterations
2) permeability is acting on endothelial cells
why do you need blood clots in innate immunity?
- want to halt systematic blood flow through the body so don’t spread bacteria
- allows you to localize the infected blood
what happens after innate immune response?
innate response raises alarm causing:
1) tissue dendritic cells to capture antigen & go to lymph node
2) dendrite presents antigen to naive & memory T cells
3) only T cells able to recognize the antigen proliferate & become active
4) leave lymph nodes & search for pathogenic target
how tell difference between immature B & T cells?
- you can’t
- are identical under EM until after differentiation into plasma cells & effector T cells
whats an antigen?
- molecule that binds T cell receptor or B cell receptor & initiates T/ B cell responses
- can be molecule captured from pathogen
How do lymphocytes “see” antigens?
- with T & B cell Receptors
- these are antigen receptor/binding sites
T cell receptors
T cell have T cell receptors
-these are antigen receptors that bind to specific antigens when antigens are in presence of MHC
B cell receptors
- on B cells
- also called the surface immunoglobulin
- these are antigen receipts that bind to specific antigens
How does BCR differ from antibody made by each B cell?
- BCR lacks a membrane domain
- so antibodies are the secreted form of the BCR
what is the specificity of the immune response due to?
-expression of unique antigen receptors on each T and B cell called the TCR and BCR
What do B cells mature into?
-mature to be plasma cells that make antibodies
How to B cells make antibodies?
- B cells capture specific antigens w/ BCR
- present captured antigen to a CD4 T cell to get “cytokine” help in growing up to be full-fledged antibody producers
plasma cells
- are terminally differentiated, efficient antibody production factories derived from B cells
3 immune defense functions of antibodies? How do this?
1) neutralization
2) opsonization
3) complement activation
- antibodies can coat pathogen & neutralize it
two types of T cells? How determine which kind to make?
1) CD4 T cells
2) CD8 T cells
- determined by how the innate immune system was activated (PAMP/DAMP receptors)
CD4 T cells
- act as generals recruiting and activating other types of immune cells to destroy the pathogen
- recognize peptide antigens only in pocket of MHC class II
CD8 T cells
- cytolytic killer cells (CTL)
- recognize peptide antigens only in pocket of MHC class I
- CD8 kill cells infected by pathogens
- kills the antigen presenting cells (dendrites/ macrophages
What does T cell require to detect and respond to target antigen?
- T cell alone can’t detect/ respond to target free antigens
- require help of antigen presenting cells (APC)
APC? What does it need to be an APC?
- antigen presenting cell
- can be macrophages, dendritic cells, B cells
- to be APC cell must be express MHC & capture (phagocytose) antigen
When does T cell receptor recognize antigens? What happens after?
-when in complex of APC w/MHC + antigen
-triggers antigen-dependent
T cell proliferation & activation
