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The flashcards below were created by user
victimsofadown
on FreezingBlue Flashcards.
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What are pattern-recognition receptors? What do they do?
- PRRs of macrophages, neutrophils, and dendritic cells recognize PAMPs (pathogen-associated molecular patterns)
- PAMPs are present on many microorganisms but NOT microorganisms
- Cells of innate immunity rely on a limited number of invariant receptors (PRRs)
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Give examples of PAMPs
- mannose-rich oligosaccharides in the bacterial cell wall
- peptidoglycans and lipopolysaccharides (LPS) in the bacterial cell wall
- unmethylated CpG DNA (rare in vertebrate genomes)
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What are the two ways that immature dendritic cells can be stimulated?
- PRR-dependent phagocytosis: recognize PAMPs with their PRRs which stimulate the cell to engulf/degrade the pathogen
- PRR-independent macropinocytosis: take up extracellular pathogens that their cell-surface receptors do not detect and degrade them
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What happens after immature dendritic cells are stimulated at a site of infection?
- Migrate through the lymphatics to regional lymph nodes
- Arrive as fully mature non-phagocytic dendritic cells that present the antigen and express the co-stimulatory molecules necessary to activate a naïve T-cell
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What are the four postulates of the clonal selection hypothesis?
- Proposed by Macfarlane Burnet
- 1. Each lymphoid progenitor gives rise to a large number of lymphocytes, each bearing a single type of antigen receptor with unique specificity
- 2. Lymphocytes bearing receptors specific for ubiquitous self antigens are deleted at an early stage in lymphoid cell development (clonal deletion)
- 3. Interaction between a foreign body and a lymphocyte receptor capable of binding that molecule with high affinity activates the lymphocyte
- 4. The differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell from which that lymphocyte was derived
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antibody vs TCR
- Antibodies are the secreted form of BCR
- TCR are the cell-surface receptor on T-lymphocytes
- STRUCTURE
- Both are composed of two regions - constant and variable
- antibody: 2 identical heavy chains, 2 identical light chains
- TWO identical antigen-binding sites
- TCR: one α and one β chain, which span the T-cell membrane
- Single site for antigen-binding sites
- FUNCTION
- Both recognize antigen
- Antibody: directly binds whole antigen
- TCR: recognizes antigen fragment on APC
- No secreted form
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What are the typical structures recognized by BCR/antibody?
Proteins, glycoproteins, and polysaccharides
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What is an epitope?
The small part of the molecular structure of an antigenic molecule which is bound by an antibody
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What is the difference beween BCR and TCR antigen recognition?
- BCR directly recognize the native antigen secreted by or on surface of pathogen
- B cells differentiate into effector plasma cells which secrete antibodies in response to this antigen
- TCR recognize antigens displayed by APCs
- Epitopes recognized by TCRs are often buried within antigens, but are presented by MHCs (major histocompatibility complexes) after degredation by the APC
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Describe the ways in which lymphocyte elimination occurs during the clonal selection process
- Too much stimulation: lymphocytes that react strongly to self antigens are removed by clonal deletion through apoptosis
- Too little stimulation: If receptor is not used within entering the periphery apoptosis occurs
- blood cell production must be balanced by loss
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Describe the process of antigens/lymphocytes encountering eachother
- Whole process takes 4-6 days from the time the antigen is recognized
- During an infection free antigens and APCs travel from the site of infection to lymph nodes
- Naïve lymphocytes recirculate constantly through the peripheral lymphoid tissue
- antigen-specific lymphocytes are activated
- Acitvated lymphocytes proliferate/differentiate and then leave cells via the efferent lymphatic vessel which returns them to the bloodstream and eventually the tissues
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Describe lymph node structure and function
- Afferent lymphatic vessels: drain fluid from tissues, carrying APCs and free antigens to lymph nodes
- Dendritic cells actively migrate, attracted by chemokines
- High-endothelial venules (HEV): allow entry by lymphocytes, attracted by chemokines
- T lymphocytes are distributed in T cell zones (more toward cortex) and B cells along the periphery of the lymph node
- This centralization aids the activation of B cells at the border
- Germinal centers are variable areas where B cell proliferation occurs
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Describe the spleen in detail
- No direct connection with the lymphatic system
- Collects antigen from the blood and lymphocytes enter/leave the spleen via blood vessels
- Collects/disposes of old RBCs
- Red pulp: site of RBC disposal
- White pulp: the site of immune response to blood-borne pathogens
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Describe the white pulp in the spleen in detail
- The periarteriolar lymphoid sheath (PALS - sheath of lymphocytes around an arteriole) contains mainly T cells
- Lymphoid follicles, occurring at intervals along PALS, contain mainly B cells
- Marginal zone has few T cells, many macrophages and immature dendritic cells, and some resident non-circulating B cells (marginal zone B cells)
- Blood-borne microbes, soluble antigens, and antigen:antibody complexes are filtered from the blood by macrophages and immature dendritic cells within the marginal zone
- Dendritic cells in the marginal zones migrate to the T-cell areas after taking up antigen and present to T-cells
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How do most pathogens enter the body?
- Through mucosal surface which are exposed to air, food, and natural flora
- ~50% of immune cells are under the mucosa for this reason
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What are the types of mucosa-associated tissues?
- Gut-associated lymphoid tissues (GALT)
- Nasal-associated lymphoid tissues (NALT)
- Bronchus-associated lymphoid tissues (BALT)
- Urogenital-associated lymphoid tissues (UALT)
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Describe the GALT in detail
- Includes tonsils, adenoids, appendix, and Peyer's patches in the small intestine
- Peyer's patches: function to collect antigen from the epithelial surfaces of the GI tract
- the antigen enters directly from the guy across specialized epithelial cells called M cells (microfold cells)
- Lymphocytes enter from the blood and leave through efferent lymphatics
- The sub-epithelial dome is rich in dendritic cells, T cells, and B cells
- B cells are housed within follicles with germination centers
- Activated dendritic cells present the antigen to T cells, and effectory lymphocytes travel through the lymphatic system, into the blood stream, and then into mucosal tissue
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Describe co-stimulatory molecules
- Antigen alone is not sufficient to initiate an adaptive immune response
- Lymphocytes require additional signals delivered by cell-surface molecules (co-stimulatory molecules)
- Activated dendritic cells usually deliver this signal to naïve T cells
- Activated helper T cells deliver this signal to naïve B cells
- Contact with antigen WITHOUT costimulatory molecules inavtivates naïve lymphocytes rather than activating them
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Describe the three types of APCs
- Dendritic cells: most important
- initiate adaptive immune response
- Macrophages and B cells: act as APCs at later stages after T cells have acquired particular effector activities
- All present using MHC II (MHC I is on all nucleated cells)
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Describe lymphocyte proliferation in detail
- There are typically a few lymphocytes that can bind to a given foreign antigen, but not enough to mount a response
- On recognizing its specific antigen a naïve lymphocyte becomes a lymphoblast (enlarged with increased rate of RNA & protein synthesis)
- Lymphoblasts duplicate to produce a clone of around 1000 identical daughter cells (3-5 days) which differentiate into effector cells
- Effector lymphocytes do not recirculate like naïve lymphocytes
- Cytotoxic t cells: detect and migrate into sites of infection from blood
- Helper t cells: some stay in lymphoid tissues to activate B cells
- Plamsa cells: some remain in the peripheral lymphoid organs, but most return to bone marrow and "pour" antibodies into the blood stream
- Effector cells from mucosal immune system typically stay there
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Why is immunological memory so effective?
- Some activated B and T cells persist after infection as memory cells
- The secondary antibody response has a shorter lag time, response level, and the antibodies have an increased affinity for the antigen (affinity maturation)
- T cells DO NOT undergo affinity maturation
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Where are antibodies found?
- Fluid component of blood (plasma) and extracellular fluid
- This lends to the name humoral (fluid) immunity
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What are the 5 types of constant region seen for antibodies?
IgM, IgD, IgG, IgA, and IgE
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What are the 3 ways antibodies participate in host defense?
- Neutralization: binding to pathogen or products block access to host cell
- block virus from entering/replicating
- block bacterial toxins
- Opsonization: coat pathogens which facilitate phagocytosis (neutrophil or macrophage)
- This is important for the bacteria that can evade innate immunity by having a coat without PAMPs
- Complement activation: protein cascade which...
- can kill the bacterial directly (via pore)
- make pathogen easier to phagocytize
- Induces inflammatory responses which fight infection
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