Lec #1 (Wk 1): Innate Immunity Flashcards
What are the cells of the immune system?
Monocytes (which differentiate into macrophages once in the tissue).
Mast cells
Dendritic cells
Natural Killer cells
Neutrophils
Eosinophils
Basophils
T-cells
B-cells
Let’s say a WBC is flowing & crosses through an organ, how does it distinguish between self & non-self cells?
Identifies self since there are self markers called MHCs which label the body’s cells.
MHC = Major Histocompatibility Complex.
Identifies non-self by looking for the antigens at the surface; antigen is a molecule that the immune system recognizes as a foreign.
what does it mean for something to be antigenic?
Can elicit an immune response.
Compare between innate & adaptive immunity.
INNATE IMMUNITY:
- Inherited from parents & passed on to offsprings thus, it is present at birth.
- Non-specific; will get rid of all foreign things in the same way.
- Time taken to initiate its job is rapid (Within 0-12 hours).
- No memory cells created (meaning if you were exposed to the same pathogen, body will react the same exact way).
- Composed of 1st & 2nd lines of defenses; skin, circulating effector cells (neutrophils, macrophages, & NK cells), Compliment proteins, erythrocytes, & platelets.
ADAPTIVE IMMUNITY:
- Cannot be inherited, built with immunization, vaccination, & exposure to pathogen.
- Created in response to exposure to the antigens.
- It is SPECIFIC and antigen-mediated meaning: specific antigens create the response.
- Response is slow & takes time to build up a response after encountering an antigen (1-2 weeks).
- Produces memory; if the body recognizes the same pathogen again, it will recognize it & try to kill it.
- 3rd line defense; lymphocytes & their products (e.g antibodies).
Which immunity involves, 1st, 2nd, & third line of defense?
Innate immunity = 1st + 2nd which is composed of the compliment proteins, skin, neutrophils, macrophages, NK cells, erythrocytes, & platelets.
Adaptive immunity = 3rd line of defense is
the lymphocytes + antibodies.
The innate immunity doesn’t work alone, it works with the adaptive immunity. Initial response will be carried out by the innate immunity & after that adaptive takes over. What cells are responsible for such crosstalk?
Antigen-Presenting Cells (APCs) like dendritic cells & macrophages. The APCs mediate the cellular immune response by processing & presenting antigens for recognition by the adaptive immunity. After that, adaptive immunity takes over & the T-cells & B-cells undergo clonal expansion thus the lymph nodes become swollen & tender.
What are the functions of the lymph nodes?
Lymph nodes are secondary lymphoid organ.
1- Inactivation & killing of mature T-cells.
2- Initiating & resolving immune responses.
3- Place for T cell - APC crosstalk.
In the case of endogenous antigens (antigens inside our body), it won’t be presented or produce any response but in exogenous antigens, the lymph nodes would present the antigen to the T-cells & produce a response.
Where does the crosstalk happen between T-cell & APC?
Lymph nodes
Function of dendritic cells?
Present in a small amount in the tissues. In the blood, they are in the immature state. They are Antigen Presenting Cells which capture the microbes entering the lymphatic vessels until they reach the lymph node where they present the antigen to the Naïve T cells & initiate an adaptive immune response.
What if the immune system attacks the self cells thinking they’re non-self?
Autoimmune disease.
What are the 3 lines of the immune system?
first line defense; made of physical, chemical, & biological barrier such as: skin, mucous membrane, & secretions of the skin + mucous membrane.
Second line of defense; This is the innate immunity. Involves;
- specialized cells: neutrophils, mast cells, basophils, eosinophils, NK cells, & macrophages.
- Proteins: complement system, cytokines, Mannose-Binding Lectin (MBL), & C-reactive protein (CRP).
3rd line of defense; Adaptive immunity like lymphocytes & antibodies.
What does no memory being made means?
It doesn’t remember a prior encounter with microbes & resets to baseline after each encounter. So acts against repeated exposure the same way (same potency & speed) = monotonic.
How does the innate immunity recognize that there is a pathogen trying to attack us?
Looks for:
1- Pathogen Associated Molecular Patterns (PAMPs); those are derived from the micro-organisms itself such as LPS (in gram -), nucleic acids, bacterial peptides like flagellin, peptidoglycans, lipotechoic acid, and lipoproteins.
2- Damage Associated Molecular Patterns (DAMPs); those are derived from the HOST cells, so the cell once its damaged starts releasing things like intracellular proteins, EC matrix proteins, and non-proteins such as ATP, & uric acid.
What receptors recognize the PAMPs & DAMPs?
Immune cells have Pattern Recognition Receptors (PRRs) on the surface of their cell membrane. The binding of the PRRs to the PAMPs/DAMPs recruits other immune cells like:
- Phagocytes
- NK cells
- Leukocytes
PRRs are divided into 4 families;
1- Toll-Like receptors (TLR)
2- Nucleotide-Binding Oligomerization domain like receptors (NLR).
3- C-type lectin receptors (CLR).
4- RIG-1 like receptors (RLR).
Pattern Recognition Receptors (PRRs) are divided into 4 families which are?
1- Toll-Like Receptors (TLR)
2- Nucleotide-binding Oligomerization domain like receptors (NLR).
3- C-type Lectin receptors (CLR)
4- RIG-1 like receptors (RLR)
What are toll-like receptors responsible for?
Recognizing the PAMPs. Those receptors are found on the innate immune cells like the macrophages, granulocytes, dendritic cells, & lymphocytes.
Where are toll-like receptors (TLR) found?
Found in the innate immune cells in 2 different locations;
1- Cell membranes
TLRs expressed on the cell membrane of the innate immune cells recognize the products of the extracellular microbes.
TLRs found on cell membrane: TLR 1, 2, 4, 5, & 6.
TLR4 (four) respond to the lipopolysaccharide thus recognize gram-negative bacteria.
TLR5 (Five) respond to Flagella so they recognize motile bacteria.
2- Endosomes
TLRs expressed on the endosomes recognize nucleic acids (since microbes are digested within the endosomes & their nucleic acids are released).
TLRs expressed on the endosomes: TLR 3, 7, 8, & 9.
So they can recognize viruses too.
**we have 10 TLRs but we don’t know the location of TLR10.
Which toll-like receptors are expressed on the cell membrane of the innate immune cells?
TLR1, TLR2, TLR4, TLR5, & TLR6.
**remember TLRs respond to PAMPs and since they are expressed on the cell membrane, they recognize the products of extra cellular microbes.
Which toll-like receptors are expressed on the endosomes of the innate immune cells?
TLR3, TLR7, TLR8, & TLR9.
**remember TLRs respond to PAMPs and since they are expressed on the endosome, this means that they recognize nucleic acids of the pathogen and can consequently recognize viruses too.
Explain the stages of phagocytosis.
1- Phagocytes (like neutrophils or macrophages) move to the site where the pathogen is via chemotaxis & adheres to the microbe by forming pseudopods.
2- Phagosome is formed which fuses with the lysosome to form a phagolysosome.
3- Those lysosomal enzymes start digesting the pathogens and breaking them down into smaller pieces then finally discharges them to go to the T-cells.
What are the cells of the innate immune system?
Phagocytic cells:
- Neutrophils
- Macrophages
- Dendritic cells.
Non-phagocytic cells:
- basophils
- eosinophils
- NK cells
Where are macrophages originated? What is their name in the blood? tissue?
Originate from the bone marrow.
In blood we call them monocytes, but once in tissue macrophages.
**BIG NOTICE:: Some monocytes differentiate to dendritic cells, so not necessarily always macrophages.
What can monocytes differentiate into?
- Macrophages
- Dendritic cells (that have different names in different organs).
Both are antigen presenting cells that present the antigen to the T-cells at the lymph node.
What do we call the dendritic cells (phagocytic cell belonging to the innate immunity) in the:
Liver?
Connective tissues?
Bone marrow, spleen, & lymph nodes?
Skin?
Bone?
Kidney?
Brain?
Blood?
Liver; Kupffer cells.
Connective tissues; histiocytes.
Bone marrow, spleen, & lymph nodes; macrophages.
Skin; Langerhans cell.
Bone; osteoclast.
Kidney; Mesangial cells.
Brain; Microglial cells.
Blood; monocytes.
Dendritic cells are antigen presenting cells which will present the antigen to the T cell at the lymph nodes.
Talk about how neutrophils look like, where we find them, and their functions?
Neutrophils are found in the bloodstream. They are circular containing granules with nucleus which is multi lobed (usually 3 lobes).
Functions:
1- On the surface of the neutrophils we have Fc receptors to the IgG & igA.
**Fc receptor will bind with the Fc region of the antibodies that are attached to infected cells or invading pathogens.
2- Intracellular killing by lysosomal granules.
3- Cytokine production which recruit other inflammatory cells.
What do we call basophils in the bloodstream, tissues, and mucosa?
Bloodstream: Basophils.
Tissue & mucosa: Mast cells.
What are the 2 types of mast cells?
1- Connective tissue mast cell
2- Mucosal mast cell (plays a role in allergy).
Degranulation of the mast cells release mediators which contribute to the allergy reaction.
Which cell plays a role in allergy?
Mucosal mast cells.
Which cell is responsible for capturing & killing cells with down-regulated MHC’s?
Natural Killer cells.
Cells with down-regulated MHCs are the cancer cells, cells infected by a virus.
Natural killer cells use perforins to create a hole in the cell then use granzymes to induce apoptosis.
NK cells perform their actions by expressing 2 receptors, what are they?
1- Killer Activation Receptors (KAR) –> recognize stress-related molecules.
2- Killer Inhibition Receptors (KIR) –> detects the presence of MHC protein on the host cells. If a cell has MHCs and when it binds to the KIR, it will inhibit it thus cannot perform its action. But, when a host cell without MHC binds, it will activate it thus killing the cell.
How do NK cells kill cells?
They do NOT attack the pathogen directly, they firstly detect when the cells are infected and release substances like Perforin & Granzymes.
Perforin –> perforate the cell wall (i.e make a hole).
Granzymes –> after the perforation was formed, this enables the granzymes to enter and trigger apoptosis.
What cell produces perforins and granzymes? Functions?
Natural killer cells.
Perforins –> perforate the cell membrane.
Granzymes –> enter the cells through the hole and trigger apoptosis.
