Lecture 1 - Innate vs. Adaptive; Pattern Recognition (Bailey) Flashcards
What is infection?
Invasion of the body by a microbe that causes damage either directly or indirectly.
What are the 6 steps of infectious disease?
- Encounter (w/ pathogen)
- Entry (into body)
- Colonization and/or Invasion
- Multiplication and/or Spread
- Damage
- Outcome
Does encounter = infection?
NO!
Nonspecific Adherence (of a pathogen to a surface)
reversible
docking
examples: random interaction, electrostatic attractions, etc.
Specific Adherence (of a pathogen to a surface)
Irreversible
Anchoring
Involves ADHESINS
What are adhesins?
Adhesins are involved in SPECIFIC ADHERENCE. They are on the surface of microbes.
They bind to adhesin receptors, which are very specific.
Example: Strep. mutans uses GLUCOSYL TRANSFERASE as an adherin
What are the two mechanisms of “spread?”
- LATERAL PROPOGATION to continuous tissues
- multiply then spread
- DISSEMINATION to distant sites
- spread then multiply
Is DAMAGE necessary for a microbe to be considered a pathogen?
Yes
What is the principal physiological role of the immune system?
To protect the organism from infectious microbes.
What are some PHYSICAL BARRIERS of INNATE IMMUNITY?
- epithelial surfaces (skin)
- mucosal surfaces
- flushing action of tears and saliva
What is a CHEMICAL BARRIER of INNATE IMMUNITY?
ANTIMICROBIAL PEPTIDES (AMP)
- present on mucosal surfaces, skin, etc. - 45 AMPs in saliva alone - tend to be cationic (pathogens are anionic)
Name 4 AMPs and their function.
- Lysozyme - cleaves peptidoglycan; active against gram + bacteria
- Cathelicidin - disrupts bacterial membranes
- Defensins - creates pores in microbes
- Lactoferrin - sequesters iron that bacteria need to survive
What is a MICROBIAL BARRIER of INNATE IMMUNITY?
Microbiota
- outnumbers cells of the body 10:1 - outnumbers human genes 100:1
What 2 categories are leukocytes divided into?
- Innate Cells
- first responders
- non-specific
- Adaptive Immune Cells
- respond later
- specific
- MHC restricted
Where to INNATE immune cells come from?
Myeloid cells
Where to ADAPTIVE immune cells come from?
Lymphoid Cells
What are the cells of the INNATE immune system?
- Monocytes/Macrophages
- Neutrophils
- Dendritic Cells
- Other Granulocytes
- eosinophils
- basophils
- mast cells
- Natural Killer Cells
Main role of Eosinophils?
parasitic infections (recognizes IgE-coated parasites)
Do neutrophils present antigens?
No, they just kill.
Which cells of the innate immune system are great antigen-presenting cells?
Monocytes/Macrophages and Dendritic cells
How are monocytes and macrophages different?
Monocytes - in circulation
Macrophages - in tissue
What are the 3 important function of macrophages?
- Kill
- Present Antigen
- Produce cytokines
What cell of the innate immune response has a multi-lobed nucleus?
Neutrophil aka Polymorphonuclear Cell (PMN)
-granulocyte
What is the main function of a neutrophil?
Kill
What is the main function of a dendritic cell
Antigen presentation
What is the PRINCIPAL cell type that LINKS the innate immune response to the adaptive immune response?
Dendritic Cell
What are the cells of the ADAPTIVE immune response?
B cells
T cells
Natural Killer Cells
Where do B cells mature?
bone marrow
Where to T cells mature?
Thymus
Where to the cells of adaptive immunity come from?
Common LYMPHOID progenitor
What are the two components of ADAPTIVE immunity?
- Humoral Component
- B cell mediated
- Cell-Mediated Component
- T cell mediated
What are the two types of T-cells, and what do they do?
- Helper T-cells (produce cytokines that attract, activate, and inactivate leukocytes)
- Cytotoxic T-cells (kill virally infected cells and tumor cells)
Which MHC to CD4+ (helper) T-cells recognize?
MHC II
Which MHC to CD8+ (cytotoxic) T-cells recognize?
MHC I
Where are cell of the adaptive immune system activated?
within lymph nodes
How are T and B cells activated in a lymph node (LN)?
- microbe infects host
- microbe is taken up by APC @ site of infection
- APC enters lymph circulation and into LN
- Naive T and B cells enter LN from circulation
What is a Pathogen Associated Molecular Pattern (PAMP)?
PAMPs are unique structures on microbes (that often involve repeated structures) that are recognized by INNATE immune cells.
What is an example of a PAMP on Gram Negative bacteria?
Lipopolysaccharide (LPS) contains repeated sugars that can be recognized by pattern recognition receptors (PRR) on innate immune cells.
What is an example of a PAMP on Gram Positive Bacteria?
Murein and teichoic acids contain repeated sugars that can be recognized by pattern recognition receptors (PRR) on innate immune cells.
What is a Pattern Recognition Receptor (PRR)?
Receptor that cells of the INNATE immune system use to recognize Pathogen Associated Molecular Patters (PAMPs) on microbes.
Name a key PRR on innate immune cells.
Toll-like receptor (TLR)
Which type of bacteria does TLR2 recognize?
Gram +
Which type of bacteria does TLR4 recognize?
Gram -
What do extracellular surface TLRs recognize?
PAMPs
What do INTRAcellular endosomal TLRs recognize?
things that are found in endosomes after phagocytosis (such as nucleic acids)
Do TLRs only have to do with innate immune cells?
TLRs are only found on innate immune cells, but the consequences of TLR litigation affect BOTH innate and adaptive immunity.
What do cells of the adaptive immune system recognize?
antigens
What is an antigen?
any substance that can be SPECIFICALLY bound by a cell of the adaptive immune system
What is an immunogen?
an antigen that elicits an immune response
What is a Tolerogen?
an antigen that induces immunological tolerance of immune non-responsiveness.
What is an Allergen?
an antigen that causes an immediate hypersensitivity (allergic) reaction
T-cells are MHC restricted. What does this mean?
They cannot recognize antigen alone. It must be presented by MHC.
B-cells are NOT MHC restricted. What does this mean?
B cells can be directly activated by antigen.
However, T cells are often needed.
What are some important receptors for INNATE immunity antigen recognition?
- Toll-like receptors (TLR)
- N-formyl-methionyl receptor
- mannose receptor
- scavenger receptor
What are the two types of antigen-specific receptors of the ADAPTIVE immune system?
B cell receptor (Ig)
-recognizes solubue intact macromolecules and small chemicals
T cell receptor (TCR)
-ONLY recognizes processed antigen fragments presented by MHC on the surface of antigen presenting cells (APCs)