week 2 chronic inflamm Flashcards
what are 2 types of immune responses?
innate, adaptive
General features of innate immune system?
-present in all animals
-always ready
-recognizes broad group of related microbes or other threats
-mediated by variety of cells and mediators
-does not have memory
General features of adaptive immune system?
-present in vertebrates
-highly specific
-recognizes specific molecules
-antigen specific lymphocytes effective against a particular antigen
-memory
what cells are the bridge from innate to adaptive immunity
macrophages and dendritic cells
What do dendritic cells do?
Antigen uptake and presentation in lymphoid tissue, phagocytosis, cytokine production
what do b cells do
mature into plasma cells to produce antibodies
what do helper t cells do?
help macrophages kill engulfed pathogens, help activated B cells to produce antibodies
What do cytotoxic T cells do?
directly kill cells infected with intracellular pathogens
What do Naive CD8 and CD4 T-cells do?
Present in secondary lymphoid organs awaiting activation.
Receptor diversity conveys specificity
What do macrophages do?
Antigen presentation to activate T cells , phagocytosis, cytokine secretion
What cells are involved in adaptive immunity?
T and B cells AKA Lymphocytes
Where do lymphocytes develop?
Bone marrow (B cell)
Thymus (T cell)
How do lymphocytes develop?
They first develop in primary lymphoid organs to be “educated” and then move to secondary lymphoid organs to await exposure to a specific antigen to which they are “born” to respond to
How is the diversity of cells that express different T and B cell receptors achieved?
Gene rearrangement
How is injury detected?
Signals that initiate adaptive immunity are delivered to lymph nodes via lymphatic and blood vessels
Overview of adaptive immunity- 4 steps?
- virus infects and replicates within the epithelium
- dendritic cell activation
- T and B cell priming in lymph node
- adaptive immunity
what is an example of recruitment of adaptive immunity
clonal expansion
what is clonal expansion
- activated B/T cells (those that have recognized specific antigens) are stimulated to divide and produce the number of cells needed to remove the insult
- pathogen activated lymphocytes differentiate into effector cells that eliminate the pathogen
what allows recognition in adaptive immunity
T cell and B cell receptors
Unlike innate immune response, recognition in adaptive immune response is highly ________
specific
What are T cell receptors
-one specific TCR per cell but many copies on cell surface
-specificity determined by antigen binding site
-transmembrane receptor , never secreted
-detects antigen bound on MHC (processed)
what are B cell receptors
-only one specific BCR per cell but many copies on the cell surface
-antigen specificity determined by antigen binding site
-can be membrane bound or secreted (antibodies)
-detects native (unprocessed) antigen
T cell receptors are _____ receptors and ______ secreted
transmembrane
never
B cell receptors are ________receptors and _______ secreted
membrane bound
can be
dendritic cells specifically do what in t cell recognition?
engulf offending agents/antigens and travel to lymph nodes from damaged tissues via afferent lymphatics
how does antigen presentation work?
- agents/antigens enter site of damage
- enter lymph node
- resident macrophages engulf them
- both dendritic cells and macrophages present antigens to T cells in the lymph node
What do T cells require for presentation?
Antigen presenting
Antigens must be bound to MHC
what cells are three types of “professional” antigen presenting cells
- dendritic cells
- macrophages
- B cells
how do dendritic cells activate T cell activation?
- dendritic cell takes up pathogen for degradation
- pathogen is taken apart inside the dendritic cell
- pathogen proteins are unfolded and cut into small pieces
- peptides bind to MHC molecules and the complexes go to the cell surface
- t cell receptors bind to the peptide: MHC complexes on dendritic cell surface
what are the different MHC types
MHC 1
MHC2
what is MHC 1 composed of?
one chain and beta 2 macroglobulin
what is MHC 2 composed of?
2 chains
where do MHC 1 and MHC 2 present antigens?
MHC1 : presents antigens taken up from inside cell
MHC 2: presents antigens taken up from outside the cell
where are MHC 1 and 2 present on?
MHC1 : present on all cells
MHC2: only present on professional antigen presenting cells
only ____________ express both MHC1 and MHC2
professional APCs
How does MHC binding to T cells work?
- antigen present on APC surfaces either on MHC 1 or MHC 2
- interact with naive T cells- CD8 or CD4
- MHC 1 binds to CD8
- MHC 2 binds to CD4
CD8 activates to become
cytotoxic T cell
CD4 activates to become
helper T cells
What is involved in removal?
T helper cells and Cytotoxic T cell
What do T helper cells do?
-Stay in lymph node and activate B cells to secrete antibodies
-leave lymph nodes and activate macrophages
what do cytotoxic T cells do
-leave lymph nodes
-kill pathogen infected cells
Do B cells require antigen presentation?
No because B cell receptors bind to natural forms of antigen
But, they need help from CD4 and T helper cells
how do helper t cells interact with b cells?
- b cell receptor binds antigen
- internalizes antigen via endocytosis and breaks it down
- breakdown products bind to MHC 2 present on endocytic vesicles
- MHC 2 bound product presented on the surface of B cell
- If B cell encounters a T helper cell that recognizes this complex, T helper cell activates the B cell
- activated b cells (plasma cells) secrete antibodies
what are the 2 regions of an antibody
variable , constant
most activated T and B cells become_________, some become __________
short lived effector cells
long lived memory cells
are cardinal signs present in chronic inflammation?
yes but less evident
what are causes of chronic inflammation
-persistent infection
-viruses, parasites
-hypersensitivity disease
-excessive/inappropriate activation of the immune system
-prolonged exposure to toxic agents
what is present during chronic inflammation
mononuclear cells
macrophages, lymphocytes, plasma cells
tissue destruction
attempts at healing
fibrosis and angiogenesis
what occurs at the site of infection?
-macrophages are stars of the show
-continue to secrete cytokines and growth factors
-phagocytosis
-interact with cells of adaptive immunity
-eventual signal to down regulate response and initiate resolution
what happens when macrophages can’t engulf?
-get “frustrated” and fuse
-form multinucleate giant cells
-either Langhan’s type or foreign body type
what is the morphology of Langhan’s type
nuclei on periphery
what is morphology of foreign body type
nuclei more central
what are lymphocytes and plasma cells indicative of
adaptive immune response
what immune response are eosinophils part of
innate immunity
what are some gross morphology evidence of healing?
-fibrosis
-collagen secreted by fibroblasts
-makes lesions firmer
gross morphology of chronic exudates?
-thicker, chunkier
-due to loss of fluid and mechanisms of infiltrating cells
what is fibrin
-produced by cleavage of fibrinogen
-friable, thin, easily broken down
-acute
what is fibrosis
-collagen produced by fibroblasts
-firm, hard to break down
-chronic
abscess grossly?
-attempt to wall off offending agent
-a localized collection of neutrophils
-central liquid region of necrotic inflammatory cells
-with time becomes walled off by a fibrous capsule
grossly granuloma
-attempt to wall off offending agent
-solid mass of epithelioid macrophages
-may include multinucleate cells
-may have a central area of necrosis
-with time becomes walled off by a fibrous capsule
