Lecture 20 - Immunity to Microbes Flashcards
What are CRP, SAP, and MBP?
L20 S6
Acute phase proteins:
- C-reactive protein
- serum amyloid protein
- both activate complement
Mannose-binding lectin:
-activate lectin complement pathway
What are the most potent chemoattracants for neutrophils?
L20 S9
- C5a
- C3a
- IL-8
What effect does C3a and C5a have on mast cells?
L20 S7
Cause mast cells to degranulate releasing histamine and bradykinin which enhances blood flow and increase capillary permeability.
What is fMLP?
L20 S9
Formyl-methionyl-leucyl-phenylalanine tripeptide
Bacterial product which acts as chemoattractant for neutrophils
What is responsible for lymphocyte homing to lymph nodes?
L20 S11
Constitutively expressed L-selectin on lymphocytes and constitutively expressed PNAd (peripheral lymph node addressin) on HEVs
What is the difference in mature and immature DC responses?
L20 S10
Mature:
-migrate to LNs with engulfed bacteria
Immature:
-engulf and internalize bacterial Ags
Where are long lived memory cells and plasma cells located?
L20 S15
- bone marrow
- LNs
- spleen
What are the different types of bacterial toxins?
L20 S16
Endotoxins:
- components of bacterial cells walls
- e.g. LPS of gram-negative bacteria
Exotoxins:
- secreted by bacteria
- e.g. diptheria toxin, cholera toxin, and tetanus toxin
What mechanisms are used to kill phagocytized bacteria?
L20 S20
iNOS (inducible NO synthase):
-produces NO
Phagocyte oxidase:
-produces ROS
What mechanisms are used by bacteria to evade humoral immunity? (5)
L20 S21
- change in surface antigens
- sialylation of LPS
- formation of decoy membrane blebs
- pili with variable regions
- IgA protease
What mechanisms are used by bacteria to evade innate immunity? (3)
L20 S22
- inhibition of complement
- resistance to phagocytosis
- scavenging of ROS
What are the mechanisms are used by the adaptive humoral immune system against extracellular bacteria?
L20 S23
Direct Ab response:
- neutralization (prevention of function by Ab binding
- opsonization (Fc receptor mediated phagocytosis)
Indirect Ab response (compliment activation via classical pathway):
- phagocytosis of C3b-coated bacteria
- inflammation (anaphylatoxins)
- lysis (MAC)
What mechanisms are used by bacteria to evade adaptive immunity?
L20
Variation of surface Ags
What are septic shock and septic shock syndrome?
What causes them?
L20 S26
Septic Shock:
-severe pathological response to disseminated bacterial infection
Septic Shock Syndrome:
- circulatory collapse
- intravascular coagulation
Caused by cytokines produced by Mφ and neutrophils that result in the production of acute phase proteins in addition to ROS/release lysosomal enzymes
What Mφ products play a role in its activity and tissue damage?
L20 S27
TNF-α:
-upregulates TF and iNOS
IL-18:
-induces IFN-γ roduction which increase Mφ activation
What is the function of superantigens (SAgs) and what are examples of disease caused by SAgs?
L20 S30-31
Binds class II MHC to variable region of TCR β chains causing activation.
Food poisoning:
-staphylococcal (mostly) SAgs
Toxic shock syndrome (TSS):
- S. aureus causes capillary leak
- S. pyogenes causes severe reaction
Kawasaki disease:
-active multi-system vasculitis of unknown etiology
Some autoimmune diseases
- via bystander effect cause by SAgs activating T cells
- e.g. rheumatic fever
What occurs in response to a primary viral infection?
L20 S35
Production of type I interferons (e.g. IFN-α and IFN-β) which can be made by none immune cells
Type I interferons stimulate class I MHC presentation of viral Ag and inhibit viral gene replication. Also activates NK and Mφ viral response.
How are viral Ags transported to the LNs?
L20 S37
Virus infected cells die and release viral components.
Viral components (such as ssRNA) activate DCs which I turn activate APCs.
APCs, such as skin Langerhans cells, transport Ag to LN via lymphatics.
Differentiate between endogenous and exogenous Ag presentation.
L20 S52
Endogenous:
- intracellular pathogens (primarily viruses)
- can display processed exogenous Ags (cross-presentation)
- Ag enters ER via TAP where it is loaded to class I MHC
Exogenous:
- extracellular pathogens
- degraded in phagolysozome where it is also loaded onto class II MHC
By what mechanisms do bacteria evade intracellular immune responses?
L20 S53
Inhibition of phagolysosome formation:
- Mycobacterium tuberculosis
- Legionella pneumophila
Inactivation of ROS and nitrogen species:
-Mycobacterium leprae (phenolic glycolipids)
Disruption of phagolysozome membrane:
-Listeria monocytogenes (hemolysis protein)
How are fungal infections recognized and cleared?
L20 S55-56
Recognition:
- PRRs binding PAMPs
- dectin-1 binding β-glucan
Th1 response:
- phagocyte activation (IFN-γ)
- most potent
Th2: response:
- Ab production
- inhibits Th1 which leads to increased susceptibility
Th17 response:
-neutrophil activation (IL-17 and IL-22)
