Lecture 9 Innate Immunity and Antigen Presentation Flashcards
What is innate immunity?
The innate immune system is made of defenses against infection that can be activated immediately once a pathogen attacks. The innate immune system is essentially made up of barriers that aim to keep viruses, bacteria, parasites, and other foreign particles out of your body or limit their ability to spread and move throughout the body.
The innate immune system includes:
Physical Barriers - such as skin, the gastrointestinal tract, the respiratory tract, the nasopharynx, cilia, eyelashes and other body hair.
Defense Mechanisms - such as secretions, mucous, bile, gastric acid, saliva, tears, and sweat.
General Immune Responses - such as inflammation, complement, and non-specific cellular responses.
- The inflammatory response actively brings immune cells to the site of an infection by increasing blood flow to the area.
- Complement is an immune response that marks pathogens for destruction and makes holes in the cell membrane of the pathogen.
The innate immune system is always general, or nonspecific, meaning anything that is identified as foreign or non-self is a target for the innate immune response.
The innate immune system is activated by the presence of antigens and their chemical properties.
What is adaptive immunity?
The adaptive immune system, also called acquired immunity, uses specific antigens to strategically mount an immune response.
Unlike the innate immune system, which attacks only based on the identification of general threats, the adaptive immunity is activated by exposure to pathogens, and uses an immunological memory to learn about the threat and enhance the immune response accordingly.
The adaptive immune response is much slower to respond to threats and infections than the innate immune response, which is primed and ready to fight at all times.
What are the 3 things phagocytosis is promoted by?
Phagocytosis promoted by:
- Receptors for common bacterial cell wall components (pathogen-associated molecular patterns PAMPs) (weak interaction)
- Receptors for C3b complement component (complement-mediated opsonisation)
- Receptors for Fc region of antibodies (immune complex-mediated opsonisation)
What are 3 types of PAMPs?
Pathogen-associated molecular patterns (PAMPs) lead to immune danger signals (tells our immune system that something potentially harmful is happening)
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Common cell wall structures:
- Lipopolysaccharides (LPS)
- Peptidoglycans (e.g. mannans and mannoproteins)
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Bacterial metabolic products:
- N-formylmethionine peptides (e.g. f-Met-Leu-Phe)
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Heat-shock proteins:
- Conserved molecules released by prokaryotes and eukaryotes (stressed cells- not-ideal environment)
- Activate inflammatory response
- Conserved molecules released by prokaryotes and eukaryotes (stressed cells- not-ideal environment)
What are PAMPs recognised by?
PAMPs- pathogen associated molecular patterns (e.g. common cell wall structures, bacteria metabolic products, health-schock proteins)
Dendritic Cells ( in skin = l_argerhan cells_) they are distributed around a lot of places where we might meet infections. They have large processes and pattern recognition receptors.
When they recognise the presence of PAMPs, they release hormones that are danger signals that inhance inflammatory and immune responses
What are Acute phase proteins?
What are they activated by?
What do they do?
(badly named)
A set of molecules that are involved in inflammatory responses, complement cascade and activating the adaptive immune response.
Plasma proteins activated by tissue injury alarm systems (i.e. danger signlas) due to trauma or infection
Mostly produced by liver.
They act to:
- E_nhance host resistanc_e
- Limit tissue injury
- Promote resolution and r_epair of inflammatory lesions_
What are the functions of the complement system?
Several proteins work toegther to form an enzyme (First complemetn components) and these activate other enzymes
1) _Increase vascular permeabilit_y (account for swelling in local site)
2) Chemotaxis (attract neutrophil)
3) Opsonisation (C3b- bind to surface and enhance phagocytosis)
- These inhance our innate immune response
Where are the lymphocytes produced and How do they Circulate?
Lymphocytes are made in the bone marrow and in the thymus
- B lymphocytes are derived in the BM
- The early precursor of lymphocyte leave the BM and go into the Thymus where it generates the T lymphocytes.
Lymphocytes can migrate out of the blood system into tissues through specialized area of capillaries called high endothelial venules (HEV).
Recirculating lymphocytes pass from blood through lymphoid system and back to blood, percolating through lymphoid organs where they may contact processed antigens.
- Not all classes of lymphocyte recirculate to same extent, and various cell-surface and intercellular signals influence flow of lymphoid cellular traffic.
- Long-lived lymphocytes (mostly T cells and memory cells) are the most mobile.
Note that only 10% of lymphocytes are circulating at any time. Most are sitting in the lymphoid organs (in l_ymph nodes_, spleen and in the gut-associated lymphoids e.g. tonsils)
What are the subpopulations of lymphocytes?
1) Effectors
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B cell
- Antibody production
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CD8 T cell
- T cell-mediated (antigen-specific) cytotoxicity (CD8) (cytotoxic or killer cells)
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NK/K cell
- Natural killer cells (early defence in anti-viral and tumour immunity) (NK lymphocytes)
- Antibody-dependent cell-mediated cytotoxicity (ADCC) (CD16, CD56) (K lymphocytes)
2) Regulators
- Cytokine production (CD4 T lymphocytes)
- TH/Treg cell
- Control of effector responses via cytokine production (CD4) (helper or inducer cells)
Recruitment of non-specific mechanisms
* _TH1_ (viruses, bacteria, _intracellular agents_)
* _TH2_ (parasites, allergies, _multi-cellular_)
* _TH17_ (mucosal surfaces and inflammatory processes)
* _Treg_ (regulatory T cells (_down-regulation_))
Describe the process of Antigen Transport and Presentation
1) Dendritic cells/langerhan cells uptake bacteria and release the danger signals to stimualte the acute phase proteins and the inflammatory process
2) They also collect antigenic material (phagocytose/process them) then move from that site and transport the antigens away from that location, and/or take it to the lymph node (via the lymphatic system).
3) In the lymph node, they display some of the antigenic surface to allow the lymphocytes that are sitting there to test- so see if they should be responding to this.
There are different antigen-presenting cells (depending on where they are in the body).
- Skin = langerhan cells
- Lung = Alveolar marcrophages
- Liver = Kupffer cells
- Blood = Monocytes
- Gut = Epithelial M cells
Response of adaptive immune system depends on the nature of the foreign substance and the route of entry.
- Lymph nodes (tissue antigens)
- Spleen (blood-borne antigens)
- Gut-associated lymphoid tissue (GALT) (tonsils, adenoids, peyer’s patches, appendix) (mucosal antigens)
Non-infectious material will almost certainly be treated differently from infectious agents. Infectious organisms such as viruses, that replicate inside host cells, will be treated differently from organisms such as extracellular bacteria and parasites.
Specialised or professional antigen-presenting cells (APC) transport antigens to secondary lymphoid organs and present antigenic fragments to lymphocytes there.
There are different antigen-presenting cells (depending on where they are in the body).
- Skin = _________
- Lung = _________________
- Liver = ____________
- Blood = ____________
- Gut = ___________
There are different antigen-presenting cells (depending on where they are in the body).
- Skin = langerhan cells
- Lung = Alveolar marcrophages
- Liver = Kupffer cells
- Blood = Monocytes
- Gut = Epithelial M cells
What ar ethe APC functions? (6)
- Antigen collection and transport
- Antigen concentration
- So the lymphocytes can optimally interact with them
- Process Antigens
- So the lymphocytes can see the informative parts
- Present processed antigens to lymphocytes
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Co stimulation
- Surface molecules
- Tell other lymphocytes stuff
- Pro-inflammatory cytokines
- Surface molecules
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Tolerance induction
- Tell others that “it’s me”
Describe how the antigens are presented- Exogenous Pathway
Antigens are processed by cells and peptide fragments of them are expressed on the cell surface by specialized molecules called major histocompatibility complex (MHC) molecules (called HLA in humans).
Antigens processing differs according to (1) whether antigens are i_ngested by cell;_ or (2) whether they o_riginate from within cell._
Not all peptide fragments resulting from antigen processing will be immunogenic epitopes. Only those with affinity for peptide-binding groove will be capable of being presented to l_ymphocytes._
Because of differences HLA molecules among people, not everyone will necessarily present the same epitopes to the immune system. Thus, the nature of a person’s response to an antigen is dependent on the HLA genes that he or she has.
Exogenous Pathway
Peptides that associate with class II MHC molecules usually result from processing of antigens which have been taken up and degraded by professional antigen-presenting cells using phagocytic or pinocytic mechanisms.
Because Class II HLA products are expressed only on B cells and professional APCs, only these cell types can present peptide fragments of ingested material.
Describe the Endogenous Pathway (APC)
Endogenous Pathway
Antigenic peptides that associate with class I MHC molecules are usually derived from (1) an infectious process (such as virus infection and replication); or (2) a_s a result of normal breakdown of normal cell metabolic products within cell._ (from within the cell)
Because Class I HLA products are expressed on virtually all nucleated cells in the body, most cells are able to present peptide fragments derived from metabolic breakdown or from intracellular infectious processes.
What is the difference between exogenous and endogenous pathway- of antigen presentation?
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Exogenous
- Peptides that associate with class II MHC molecules
- usually result from processing of antigens which have been taken up and degraded by professional antigen-presenting cells using phagocytic or pinocytic mechanisms. (ingested material)
- Because Class II HLA products are expressed only on B cells and professional APCs, only these cell types can present peptide fragments of ingested material.
- Dendritic cells
- B cells
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Endogenous
- Antigenic peptides that associate with class I MHC molecules
- Usually derived from (1) an i_nfectious process_ (such as virus infection and replication); or (2) as a result of normal breakdown of normal cell metabolic products within cell. (from within the cell- peptides derived crom cytoplasmic proteins)
- Because Class I HLA products are expressed on virtually all nucleated cells in the body, most cells are able to present peptide fragments derived from metabolic breakdown or from intracellular infectious processes. - Normal metabolism
- Viral peptides
- Modified self peptides
