Lecture 4.2: Immunity Flashcards
List some components of innate immunity
Epithelial barriers, phagocytes, dendritic cells, NK cells, complement
True or false: both neutrophils and macrophages are innate
True
B & T cells are a part of what immunity?
Adaptive
How do the following defend the body?:
1) Neutrophils
2) Macrophages
3) Dendritic cells
4) NK cells
1) Neutrophils: Phagocytes + granules (enzymes that kill pathogens) (Elastase, lactoferrin)
2) Macrophages: Phagocytes, APCs
3) Dendritic Cells: Phagocytes, APCs
4) NK cells: Phagocytes
Complement (pt of innate immunity): what are the 3 aspects? What allows for this?
1) Chemotaxis: Recruitment of leukocytes
2) Opsonization: Painting a target on microbe
3) MAC; Attack complex, creates a giant pore
-C3
Sum up what cytokines (pt of innate immunity) do
1) Induce inflammation
2) Induce Vasodilation
3) TNF, IL-1 (systemic response to infxn, including fever)
4) Damage microbes
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
Innate: What accounts for how the adaptive immune system is introduced to the foreign invader?
Antigen presentation
Describe how antigen presentation works (5 steps)
1) After phagocytosis, the vacuole becomes a phagosome
2) The pathogen gets digested inside of the phagosome
3) Bits of the pathogen are placed on the APC cell surface
4) These components of the digested microbe encounter B and T cells
5) These cells induce further phagocytosis of the invader, as well as a more targeted response
-B and T cells will amplify the immune response
-This involvement of B and T cells is what creates the bridge from innate to adaptive immune response
List 5 traits of the adaptive immune system
1) Generates specific chemical and cellular responses to destroy invading pathogens.
2) Is more effective than nonspecific defenses.
3) Has a memory component that allows for a rapid and specific response to subsequent exposures to specific pathogens.
4) Is mediated by lymphocytes.
5) Deficiencies in immune defenses and inappropriate activation both cause disease.
B-cells:
1) Where do they mature?
2) What do they produce?
3) What do they control?
1) In the bone marrow
2) Produces antibodies
3) Controls antibody-mediated (humoral) immunity
T-cells
1) Where do they mature?
2) How do they become no longer naive?
3) What do they control?
1) Matures in the thymus
2) Develop from naive → effector cells with the help of antigen presenting cell
3) They can also fight on their own and be cytotoxic. Controls cell-mediated (cellular) immunity
List the 3 ways cytotoxic cells “attack”
1) Perforins: poke holes in membranes
2) Fas ligand: activates apoptosis
3) Cytokines: activate apoptosis
HLA (MHC = HLA):
1) What is it? Where is it?
2) Are they polymorphic?
3) Inheritance of particular alleles can form what?
1) Gene complex responsible for coding MHC in human cells Located on chromosome 6
2) Yes, HLA genes are polymorphic + there are alternative forms or alleles.
3) Harmful immunologic responses (HLA B27 causing JRA or ankylosing spondylitis just to name a few).
-Presence of HLA mutation can cause your body to attack healthy cells.
Describe immunoglobulin
1) Y shaped proteins that can either be an antibody or a receptor
2) Has an Fc portion (the stem)
Fab portion of immunoglobulin (antigen binding tips of the Y)
1) Has a variable portion
2) Has a hyper variable region as well
VDJ
1) What is the top portion of a B-cell?
2) What is the bottom portion?
1) Top portion of the Y is the “idiotype”
2) Bottom portion of the Y, the stem, is called the “isotype”
IgM, IgD, IgG, IgA, IgE
T & B cell recap:
1) What do helper cells (CD4) do?
2) What do cytotoxic “Killer” T cells (CD8+) do?
3) What do memory T cells do?
1) Stimulate proliferation of B cells; can also stimulate phagocytes.
2) Secrete enzymes to destroy infected body cells; directly attack viruses, bacteria, cancer cells, and transplanted organs.
3) Activate the immune response if the same antigen is reintroduced.
B cells are genetically programmed to produce large quantities of unique antibodies called what?
“Plasma cells”
Antibodies recap: what does each do?
1) IgG
2) Both IgM and IgG
3) IgA
4) IgE
1) Antibodies coat (opsonization) microbes for phagocytosis
2) Actively transported across placenta to provide passive immunity until newborns immunity is mature
3) Secreted in mucosal tissue to bind microbes in GI and respiratory tracts
4) Asthma and allergies: They also coat helminthic parasites and functions with mast cells and eosinophils to kill them
Blood type:
1) What are two blood groups of major significance?
2) What is it important to remember? Explain
1) Two blood groups are of major significance: the ABO system and the Rh blood group
2) Surface antigens that are absent lead to antibodies in the blood (b/c self-tolerance was never developed for them)
In some cases, mother-fetus incompatibility in the Rh system can cause maternal antibodies to destroy red blood cells of the fetus, resulting in what?
Hemolytic disease of the newborn (HDN)
Type I hypersensitivity normally happens when?
Under normal circumstances this happens 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?
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)
Autoimmune rxns cause what?
The body to attack itself
True or false: autoimmune conditions can be systemic or limited to one organ
True
Rheumatoid arthritis:
1) What is it?
2) What is going on inside the body?
3) Prevalence & demographics?
4) What is a proposed etiology? What is the sensitivity type?
1) Chronic, systemic, inflammatory, autoimmune disease that affects mainly the joints
2) Proliferation of synovial membranes with destruction of articular cartilage and bone causes disabling arthritis
3) Prevalence of 1% (3-5X more common in women)
-Any age, usually in second to fourth decades; genetic predisposition
4) Proposed environmental trigger is activation of helper T cells by self-antigen or microbial antigen
Type IV hypersensitivity
Systemic Lupus Erythematosus:
1) What is it?
2) Sx?
3) Demographics?
4) Etiology?
5) Sensitivity type?
1) Systemic autoimmune disease caused by autoantibodies against self-antigens (mainly nuclear antigens) and formation of immune complexes
2) Fatigue, fever, malaise, nephritis, skin lesions, arthritis, but highly variable
3) More common in female and black populations
Can occur at any age, usually young adults over 30
4) Inherited susceptibility in Class II MHC and complement genes
5) Type III Hypersensitivity
Acquired Immunodeficiency Syndrome (AIDS):
1) What is it?
2) Etiology?
3) Transmission?
1) A collection of disorders that develop as a result of infection by human immunodeficiency virus (HIV)
2) HIV is a retrovirus that selectively infects and kills the helper T cells
3) Transmission of blood or body fluids that contain HIV:
-Sexual contact (75%)
-Parenteral inoculation: IV drug users, blood transfusions
-Vertical transmission: Infected mothers to newborns
Acute phase of HIV:
1) What is being infected?
2) Sx?
3) What is seroconversion and when does it happen?
4) What then happens towards the end of this phase?
1) Infection of memory T cells in mucosal lymphoid tissues
2) High levels of virus production, viremia; signs of systemic infection
3) Immune system responds and antibodies against HIV appear (1-6 months)
4) Viremia abates and helper T cell numbers return to nearly normal
Virus continues to replicate in CD4+ T cells and macrophages
Chronic phase (clinical latency) of HIV:
1) What is happening inside the body? Is the pt symptomatic?
2) Describe the CD4+ cells right now
3) How long does this last?
1) Virus is continuing to replicate; Immune system still largely intact
-Minor opportunistic infections
2) Number of CD4+ cells begin to decline
3) Greater numbers of surviving CD4+ cells are infected; immune defenses diminish
May last 7-10 years
Rejection of solid organ transplants is initiated by what?
Mainly by host T cells that recognize the foreign HLA antigens of the graft, either directly (on APCs in the graft) or indirectly (after uptake and presentation by host APCs).
List and describe 4 types/ mechanisms of solid organ transplant rejection
1) Hyperacute rejection:Preformed anti-donor antibodies bind to graft endothelium immediately after transplantation, leading to thrombosis, ischemic damage, and rapid graft failure.
2) Acute cellular rejection:T cells destroy graft parenchyma (and vessels) by cytotoxicity and inflammatory reactions.
3) Acute antibody-mediated (humoral) rejection:Antibodies damage graft vasculature.
4) Chronic rejection:Dominated by arteriosclerosis, this type is caused by T cell activation and antibodies. The T cells may secrete cytokines that induce proliferation of vascular smooth muscle cells, and the antibodies cause endothelial injury. The vascular lesions and T cell reactions cause parenchymal fibrosis.
1) Treatment of graft rejection relies on what?
2) What does transplantation of hematopoietic stem cells (HSCs) require?
1) Immunosuppressive drugs, which inhibit immune responses against the graft.
2) Transplantation of hematopoietic stem cells (HSCs) requires careful matching of donor and recipient and is often complicated by graft-vs-host disease (GVHD) and immune deficiency.
What is a group of conditions in which extracellular deposits of fibrillar proteins are responsible for tissue damage and functional compromise?
Amyloidosis
Amyloid is defined based on the physical properties of the of the fibers; list 3
1) Abnormal folding of proteins
2) Arranged in beta-pleated sheets
3) Aggregate and deposit as fibrils in extracellular tissues
Definitive diagnosis of amyloidosis is made only by demonstrating amyloid in tissue, which requires what?
Biopsy
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
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? Explain how this works
3) Explain the rxn
1) Antibodies develop against the self
2) Dependent upon 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 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
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
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
