Lecture 4.2 MJ slides Flashcards
PRR + PAMP Phagocytosis:
1) What do phagocytes have on their surface?
2) How many of these are in our body’s cells? What do they allow for?
1) Phagocytes have pattern recognition receptor on their surface (PRR)
2) 100 of these in our body’s cells; recognize 1000 pieces of pathogens
Allow innate immune system to latch on to foreign invaders
PRR + PAMP Phagocytosis:
1) What do phagocytes PRRs connect to? What are they?
2) What is this the same type of system as?
1) PAMPs (Pathogen associated molecular pattern): Pieces of pathogens that are recognizable and essential to pathogen’s life cycle and infectivity
2) This is the same type of system that connects to DAMPs when a cell is damaged
(Remember they are triggered by Urea, alterations in ATP, DNA (in the cytosol), etc(
PRR + PAMP:
1) What are PRR and PAMP acting as?
2) What does it initiate?
3) What does that initiation lead to?
1) PRR is the receptor, PAMP is a ligand that exists on “bad” organisms
2) Initiates phagocytosis and cytokine release
3) Leukocyte backup and vaso dilation/permeability, inflammation (you’re getting familiar with the story. . .)
Phagocytosis: there are 3 ways to grab a pathogen; list and describe them
1) PRR + PAMP, “attachment”
2) C3b receptor + C3b complement, “opsonization”
3) Antibody + FC receptor, “opsonization”
-The presence of antibody is dependent upon B cells
-Which starts the involvement of adaptive response
What is the only way to grab a pathogen for phagocytosis that doesn’t involve optimization?
PRR + PAMP; “attachment”
Major histocompatibility complex (type I):
1) What do all cells translate?
2) What go with MHC I?
3) CD8 T cells patrol the body’s tissues looking for the self antigen to be expressed in MHC I receptor
checking for “ID”. What can happen once they encounter a cell?
4) What are the main reasons for this to occur?
1) MHC I and “self antigen” > Golgi > cell surface
2) CD8 T-Cells
3) If cell encounters a CD8 T cell, it will need to present the “self antigen”
a) The body cell will survive its encounter with a CD8 T cell, as long as the self antigen is present
b) If the self antigen is missing, the cell will be destroyed by the CD8T cell – thus, CD8 is called a “cytotoxic T cell”
-The CD8 releases its cytokines that lead to apoptosis or it destroys the cell
4) Cancer and viral infection, or a cell that is not our own, as in the case of transplant
Major histocompatibility complex Type II:
1) Where is this protein?
2) What happens here?
3) What sits in the MHC II protein? Why?
1) Only exists on phagocytic APCs
2) Where APCs present the bit of ingested pathogen on their surface
3) The foreign antigen “sits” in the MHC II protein
-Here it can be recognized by a CD4 T cell
MHC type II:
1) What happens when it’s recognized by a T-cell?
2) What happens after that?
3) This is our primary way of dealing with what 2 things?
1) This CD4 “helper T cell” will go on to activate B cells, causing them to proliferate
2) B cell antibodies will further induce phagocytosis of the invading microbes
3) Bacteria and fungi
List and describe the antibody isotypes of B-cells
IgM: always first, released as pentamer and it’s “weak”
IgD: “this cell doesn’t work”
IgG: comes second, released as a monomer and it’s “strong”
IgA: mucosa
IgE: mast cells
What are the 3 ways in which B-cell antibodies (Igs) help you?
1) Neutralization: antibodies coat the virus so it can’t get into the cell
2) Opsonization: paint a target on the bacteria so it’s eaten
3) Activation of complement: Opsonization, chemotaxis, MAC attack complex
Activation of complement (by B-antibodies) is involved in what 3 things?
Opsonization, chemotaxis, MAC attack complex
B cell maturation and activation:
1) Where are B-cells created? What is happening here?
2) How dies variation happen? How is this achieved? Explain.
1) Bone marrow; it’s a numbers game: (10^12) number of cells trying to make a receptor for every “possible” antigen
2) Via DNA changes over the VDJ region (the variable end region) of the Ig; achieved through “somatic recombination”
-The DNA is “scrambling itself,” making as many combinations as possible, and some will match to foreign pathogens
Describe how B cells specialize in 4 steps
1) A mature naïve B cell receives an antigen
2) It asks T cell for permission to react
-If no > silenced
-If yes > It releases begins to divide and releases IgM pentamer into plasma
(IgM response is fast and short-lived, and not that specific)
3) Then the cell’s antibodies undergo clonal expansion > affinity maturation through > somatic mutation > leads to hyper specific binding
4) IgG is developed which is hyper specific, and it then gets stored in “memory cells
Mature naive B-cells release IgM, then IgG, what happens next?
Become specialized cells; isotype switching occurs here
B cells go from IgM to IgG
Differentiate between mature naive B cells and memory B cells. What happens when each is activated?
1) Mature naïve B cells: start with IgM on cell surface > Activated plasma cell: IgM released as a pentamer
2) Memory B cells: have IgG on cell surface > Activated memory cell: IgG released as a monomer
Type I hypersensitivity normally happens when?
When CD4 cell encounters something too big for phagocytes to eat (helminth/parasites)
What happens in a type I hypersensitivity rxn? What 3 things are excreted? Define the purpose of each
1) Allergen cause B and T cells to be activated
2) CD4 cell excretes:
IL-4 > IgE (coats mast cells)
IL-5 > activates mast cells
IL-13 > allergy sx (body trying to flush out parasite)
Hypersensitivity type I: differentiate what happens during first versus second exposure
1) On first exposure mast cells become coated with IgE
2) On second exposure, the mast cells burst open (degranulate) and release lots of Histamine
-Your body also upregulates prostaglandins and leukotrienes and eosinophils
What does the amount of histamine being released in a type I hypersensitivity rxn (second exposure) cause?
THIS MUCH histamine causes vasodilation and bronchospasm (i.e. anaphylaxis)
Give epinephrine!
Type II hypersensitivity (cytotoxic):
1) What starts this?
2) What is the rxn dependent on?
3) Explain the rxn
1) Antibodies develop against the self
2) The FC portion of antibody
3) Ig = The “stick”
-Ig attaches to self cell, opsonizes cell for phagocytosis
-Compliment further opsonizes cell, initiates MAC attack, draws leukocytes
Type II (receptor) hypersensitivity
1) What lands on a receptor and what does it do?
2) Describe what can happen next in 2 different conditions
1) Ig lands on a receptor and either turns it off or turns it up
2) Ig shuts off Ach receptors in neuromuscular junction in MG
-Ig activates TSH receptors in Graves disease
1) What type of hypersensitivity is an immune deposition?
2) Why does this happen?
3) What causes good tissue to be destroyed? Give examples
1) Type III
2) Circulating antigen is bound to antibodies that get stuck in small vessels; will occur in systemic disease (like lupus)
3) FC portion initiates response: Opsonization +/- complement, which destroys good tissue
-ex: Vasculitis, arthritis, kidney dz
T cells are activated and attack the body in what type of hypersensitivity rxn?
Type IV
What 2 things can T cells use to attack the body in a type IV hypersensitivity rxn? Which T cells are involved?
1) Cytokines
2) Perforins
CD4 (use cytokines for inflammation + injury) and CD8
Give clinical examples of type IV hypersensitivity reactions
1) Type I diabetes (antigens of pancreatic beta cells)
2) MS (antigens in CS myelin)
3) RA (unknown in synovial fluid)
4) Crohn’s disease (unknown, maybe intestinal microbes)
5) Contact dermatitis (i.e. poison ivy, chemicals in evnt, etc)
T&B cell response to self antigens (incl. in joint tissues) leads to what in RA?
Pannus formation
Systemic Lupus Erythematosus: What causes it?
1) Class II MHC + complement (inherited susceptibility)
2) Environmental triggers (ex: UV)
-Both cause nuclear proteins [leads to immune complex + injury]
A chronic, inflammatory, connective tissue disease that can affect many organs describes what?
Systemic Lupus Erythematosus
AIDS (Acquired Immune Deficiency Syndrome)
1) What is it?
2) How is it defined? Explain
1) Catastrophic breakdown of immune defenses; marked increase in viremia
2) CD4+ cell count reduced below 200 cells/uL
-Even in the absence of AIDS-defining conditions, if patients have CD4+ cell counts below 200 cells/uL, they are considered to have AIDS
List 3 AIDS-defining conditions
1) Serious opportunistic infections
2) Secondary neoplasms
3) Neurologic manifestations
List some potential AIDS Sx by body system/ organ:
1) CNS
2) Lung
3) Lymphatic
4) Large intestine
5) Thigh
1) Meningitis, encephalitis, AIDS dementia
2) Pneumonia
3) Lymphoma tumors
4) Colitis + proctitis
5) Kaposi’s sarcoma
