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72 Cards in this Set
- Front
- Back
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What are some examples of pathogens/viruses that are able to subvert immune responses?
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HIV
Malaria TB |
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Why must there be a balance between elimination of the pathogen and harm to the host?
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Can get increased pathogenesis caused by the host immune response
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How is immunity to extracellular bacterial infections achieved?
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Ab (mostly)
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How is immunity to intracellular bacterial infections achieved?
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Cellmediated immunity
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How do bacteria enter the body?
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Natural routes: respiratory, GI or genourinary tracts
Unnatural routes: opened up by breaks in mucous mb/skin |
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What is the severity of the bact. infection related to?
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1) # of organisms entering --innate/adaptive
2) their virulence 3)lvls of host defense(genetics) |
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Which cells secrete Ab?
Where? |
Plasma cells
In regional (draining) LN and the submucosa of the respiratory, genitourinary and GI tracts |
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Process:Attachment to host cells
What is host defense to this process? |
Blockage of attachment by secretory IgA ABs
(secreted in mucous mbs) |
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What is he bacterial evasion mechanism to this process?
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Secretion of protease that cleaves secretory IgA dimers ( N. meningitidis, N. gonorrhoeae, Haemophilus influenza)
Antigenic variation in attachement structures (pili of N. gonorrheae) |
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What does antigenic variation ensure?
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Ab that are Ag specific won't recognize the bacteria anymore cuz the Ag has changed
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Infection process: Proliferation
What is the host defense to this? |
1) Phagocytosis (Ab- and C3b- mediated opsonization)
2) Complement mediated lysis and localized inflammatory response |
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What is the bacterial evasion mechanism to this process (prolif)?
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1)-Production of surface structures (polysac capsule, M ptn, fibrin coat) that inhibit phagocytic cells
-Mechanisms to survive inside phagocytic cells (induction of apoptosis in macrophages (Shigella flexneri) 2) -Generalized resistance of G+ bacteria to complement-mediated lysis -Insertion of mb-attack complex prevented by a long side chain in cell-wall LPS (some G-) |
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Process: invasion of host tissue
What is the host defense? |
Ab-mediated agglutination
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What is the bacterial evasion mechanism to this?
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Secretion of elastase that inactivates C3a ad C5a (pseudomonas)
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Process: Toxin induced damage to host cells
What is the host defense? |
Neutralization of toxin by Ab
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What is the bacterial invasion mechanism to this process?
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Secretion of hyalouronidase, which enhances bacterial invasiveness
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How do bacteria cause disease?
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Tissue destruction (=> leads to an inflammatory response)
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What kind of toxins are produced?
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Endotoxins
Exotoxins |
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What are endotoxins?
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components of the cell wall
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What are exotoxins?
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Secretory products
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What types of Ag are there?
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1) Thymus independent Ag
2) Thymus dependent Ag |
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What are some thymus independent Ag?
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Capsules and cell wall components are polysac
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What is a TI-Ag? (thymus independent)
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Ag that can prime B cell response without the help of T-cell
--> Staphylococus enterotoxins are considered SuperAg because of this |
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How do tI-Ag stimulate B cells?
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IgM Ab and other Ab isotypses stimulated due to release of cytokines by macrophages
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What is required for Thymus dependent (TD) Ag ctivation?
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B cell activation needs direct contact with CD4 Th cells + Th cytokines
-> Ag specific help |
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What are the 2 types of TI-Ag?
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TI-1: bacterial LPS
TI-2: polymeric (repetitive) ptns (flagellin), bacterial cell wall polysac (polymeric) |
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How are the B cells activated in TI Ag?
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Direct recognition
Massive cross linking |
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What do Ab response to ptn Ag need?
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Ag specific help from CD4+ Th cells
(need interaction of BCR and CD40 on B cel with MHC and CD40L on T-cell) |
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Can TD Ag induce a B cell response in animals that lack T cells?
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No
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Describe TD Ag.
Chemical nature? Humoral response: Isotype switching (IS)? Affinity maturation (AM)? Immunological memory (IM)? Polyclonal activation (PA)? |
Chem: Soluble ptn
IS: yes AM: yes IM: yes PA: no |
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Describe TI-1
Chemical nature? Humoral response: Isotype switching (IS)? Affinity maturation (AM)? Immunological memory (IM)? Polyclonal activation (PA)? |
Chem: bacterial cell wall components
IS: no AM:no IM:no PA: yes (high doses) ->Interactions with BCR and TLR4 |
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Describe TI-2
Chemical nature? Humoral response: Isotype switching (IS)? Affinity maturation (AM)? Immunological memory (IM)? Polyclonal activation (PA)? |
Chem: Polymerric ptn Ag, capsular polysac
IS: Limited AM: No IM: No PA: No Crosslink the mlg receptor |
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What is required for B cell activation abd progression in the cell cycle?
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Signal 1: BCR
Signal 2: Costimulation |
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What's dif btw TI's and TD Ag?
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TI's dont have any development of memory
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What are Ab?
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Humoral arm of the immne response
Plays an important role vs extracellular bacteria |
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Which Abs neutralize toxins?
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IgG and IgM
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What do IgG Ab do?
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-Opsonize bacteria
-Enhance phagocytosis: by binding to the Fcy receptor present on macrophages and PMNs |
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Which Ab activate complement?
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IgM
IgG -> this leads to lysis of cells |
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What do Th cells do?
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Secrete cytokines that help B cells differentiate into Ab-secreting plasma cells
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What form does IgM have?
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Pentamer
Planar form while circulating in the serum ->in this form, no binding sites are exposed to C1q of complement |
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What happens when pentameric IgM is bound to a target surface?
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Called a Staple
Binding sites are exposed to C1q complement molec |
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What is teh Ab-mediated mechanism of defence?
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1) Toxin neutralization by Ab
2) Complement activation leads to lysis of bacteria 3) C3b complexes bind to bacteria serving as opsonins to increase phagocytosis 4) C3a, C4a, C5a (anaplylatoxins) induce mast cell degranulation releasing substances mediating vasodilation 5) other complement split products are chemotactic for neutrophils and macrophages |
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What is absolutely required for intracellular path?
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Definitely need T cell based response
(cuz Ab can't go inside cells) ex: Listeria is intracell path. Never really goes outside the cell. Is phagocytosed rom within one cell, to another, before it breaks out of the cellular mb |
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What is the immune response to intracellular bacteria?
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ADCC (Ab dependent cell-mediated cytotoxicity)
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How does ADCC work?
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Nonspecific cytotoxic cells are directed to specific target cells by binding to the Fc region of the Ab bound to surface Ag on the target cells
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What kind of cytokines are released in ADCC?
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Lytic enz
Perforin TNF Granzymes |
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What is another type of immune response to intracellular path?
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CD8 T cells and cytotoxicity
->Importance of IFN-y |
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What happens in CD8 T cell cytotoxicity?
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Endogenous Ag:
Degrade in the proteasome, goes into ER where it fits into MHC-1 MHC travels to outside of cell where it can interact with TCR Exogenous Ag: (Crossover path) Ag degraded in lysosome Retrotranslocated into RER -Put on MHC II -Follows exogenous path and peptide shown on MHC II on cell surface (TH-1 response) |
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What is the last immune response to intracell path?
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Delayed type hypersensitivity (DTH)
(Type IV hypersensitivity) dependence on IFN-y |
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What does DTH depend on?
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Th cells
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What is DTH?
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localized inflammatory reaction caused by secretion of Th cells when they meet certain Ag
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What characterizes DTH?
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Large influxes of inflammatory cells (especially macrophages)
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Who first described a DTH reaction?
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Robert Koch
saw that ppl infected with M tuberculosis dev'l a localized inflammatory response when injected with a filtrate of a culture of the bacteria ->tuberculin rxn |
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What is the major cellular component of the infiltrate around a DTH rxn inflammation?
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Macrophages
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Is DTH always detrimental to the body?
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no
In many cases, tissue damage is limited DTH does play a role in defense vs intracellular path and contact Ag |
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Can DTH be adoptively transferred from one experimental animal to another?
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yes
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What happens in phase 1 (Sensitization phase) of a DTH response?
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1-2 weeks after of exposure
-after 1st contact with Ag, get differentiation and prolif of CD4 Th1 cells mostly (sometimes CD8 T cells) -Secretion of Th1 cytokines APCs: macrophage langerhans cells DTH-mediated cells: Th1 usually, CD8 occasionally |
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What happens in phase II (Effector phase) of DTH response?
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2nd contact with Ag
-Secretion of Th1 cytokines (enhance inflammation) -Recruitment and activation of macrophages (further enhance response and inflam) |
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What are the Th1 secretions during the effector phase of DTH response?
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Cytokines: IFN-y, TNF-B, IL-2
Chemokines: IL-8/CXCL8, MCP-1/CCL2 |
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What are the effects of macrophage activation in the effector phase of DTH response?
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Inc MHC-II expression
Inc TNF receptors Inc O2 radicals Inc Nitric oxide |
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What happens during thepahses of DTH response?
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Th1 cytokines induce blood monocytes to adhere to vascular endothelial cells and to migrate into surrounding tissues
-Monocytes differentiate into activated macrophages -Have inc lvls of phagocytosis and ability to kill .: have synthesis of cytotoxic mediators -with inc MHC-II and adhesion molec expressions levels ->Better APCs |
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Why is DTH a double-edged sword?
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High phagocytosis rate and accumulation of lytic enz from mac's in the infected area
--> non specific tissue destruction and often elimination of the intracell path |
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What happens in a prolonged DTH response?
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It can become destructive and evolve into a granolomatous reaction
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What is a granuloma?
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Multinucleated giant cells formed by Macrophages adhere together because of their continuous activation
This displaces normal tissue cells, forms nodules and releases lytics enz |
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What happens when blood vessels are damaged?
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Can get necrosis
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Describe TB
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Leading cause of death from an infectious agent (1.5 million deaths/year)
-1/3 of teh world's pop is infected and at risk of dev'p TB -Re-emerged in the 90s, especially where HIV is high |
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Is there a vaccine vs TB?
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Yes
BCG (bacille de Calmette and Guerine) but it's losing its efficacy T-cell vaccines, .: hard to understand Not used in the US |
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What is the diagnosis of TB difficult?
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Bacteria is very slow growing
Tuberculing skin test X-ray |
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What is the treatment for TB?
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Multidrug therapy: isoniazid, rifampin, streptomycin etc
but treatments have to be taken for at least 9 months, which is hard for ppl to follow Starting to get multidrug resistant strains |
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Which cells are being infected?
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Alveolar macrophages
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How is TB surviving intracellularly?
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Inhibiting the fusion of phagosome and lysosome
->the bacteria lives and replicates within the phagosome |
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What happens in TB infection?
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Tubercle or Granuloma in pulmonary TB (in 90% of infected individ)
CD4+ T cells are rquired for resistance and control, but may be responsible for much of the tissue damage -DTH ->lok at figure on last slide |
