Immune System Part 2 Flashcards
Major Histocompatibility Complex (MHC)
=
- MHC often used to refer to self-antigen or ____ antigen
- MHC is actually the?
Most important set of proteins that are self-antigens
- HLA
- set of genes that codes for HLA antigen
MHC 1
- Found on which cells?
- Recognized by which cells?
- Function =
- All cells except for RBCs
- Cytotoxic T and NK cells
- Indicates virus infected, non-self, or abnormal self cells
MHC II
- Found on which cells?
- Recognized by which cells?
- Function =
- Antigen presenting Cells (Macrophages, Dendritic Cells, B cells)
- Helper T cells
- Involved in antigen presentation and activation of adaptive immune response
MHC 1 (Notes)
Self antigen found on all cells EXCEPT ____
- The most _____ from one person to the next
- Start as ______ proteins -> before it travels to _____ it binds to other proteins produced by the cell -> then displays that protein on membrane _____ (Self _____ + Abnormal _____)
- Signals to you that?
- Signals read by (2) - cells that are responsible for identifying abnormal cells (ie virus or cancer cells)
- Ex) If a host cell is virus infected, MHC 1 will bind to the ____ protein before it gets to the membrane and ____ the viral protein in the air and signals “this is a host cell that belongs to my body and it is making viral protein”
RBC’s
- varied
- intracellular -> membrane, surface (self recognition + abnormal protein)
- “I belong to your body and I am making this type of protein right now”
-
NK and CD8 T cells
- viral protein, wave
MHC II (Notes)
Self antigens found only on (3) cells -> bc they carry out specific job of? which is the key first step in?
- Recognized by?
- ex) macrophage digests a pathogen and binds it to MHC II -> MHC II presents antigen to CD4 T cell -> CD4 T cell recognizes MHC II as self and antigen as virus then initiates adaptive immune response
Macrophages, Dendritic Cells, B cells -> Antigen Presentation -> Adaptive immune responses
- CD4 Helper Cell T cells
MHC II: secondary MHC protein found on these 3 cells and is key in communicating with CD4 T cell to trigger adaptive immune response
Overview of Adaptive Immune Response
APC =
- Presents _____ (red triangle) attached to MHC __ to ____ cell (red receptor)
- Triggers either __ or __ cell response
- B Cell Response:
- T Cell Response:
- Each response creates a
- Banked set:
- Effector set:
Antigen Presenting Cell (Macrophage, Dendritic Cell, B lymphocytes)
- Antigen, MHC II, CD4 Helper T cell
- B or T
- CD4 T cell has to find the complementary B lymphocyte and once triggered B cell to make copies of itself
- CD4T will find the complementary CD8 T cell and once triggered will make copies of itself
- 1 set is banked as memory cells to sit in lymphatic system for next time we encounter this pathogen
- B cells that will undergo terminal differentiation into plasma cells that will secrete the antibodies to fight the infection vs. T cell set that goes off and attacks the pathogen in the plasma (adaptive immune response)
Steps in Development of the Adaptive Immune Response
2 major steps
-
Generation of Clonal Diversity:
- Key aspect:
- Clonal Selection:
Initial process of developing our huge library of B and T cells that can respond to any antigen we encounter, happens mostly in early development
We produce all these B and T cells before we EVER encounter the pathogen
Selection, proliferation, and differentiation of individual B or T cell that specifically complements the antigen, and eventually fights the pathogen
Production of T and B cell Library
T cells
- Produced in ___ ____ as ___-T lymphocytes and migrate to the ____ gland
- Acquire ___ and ___ surface _____ that will determine their ____
- Also requires a T cell ____ that indicates the cell’s ____ (what antigen this T cell can fight)
- Bone marrow, pre, Thymus
- CD4 or CD8, surface markers, function
- receptor, specificity
Why can we produce T cell receptors against antigens we’ve never encountered?
(3) Basic Sets of Genes that code for T cell receptors
Random Rearranging of genes that code for a variety of T cell Receptors
V gene
J gene
C gene
Risk of Randomization
Risk:
Clonal Deletion:
Central tolerance:
Randomization can produce Autoreactive T cell receptor that binds to self-antigen and kills our own cells
Process that Kills autoreactive cells done by self-antigen epithelial cells throughout the thymus gland -> this produces
Central Tolerance (bc happens within central lymphoid structures)- our first level of protection against autoimmune disorders (which happens when autoreactive cells avoid clonal deletion)
B Cells
Process is almost identical
B cell development happens in the?
Bone Marrow (Central tolerance)
Genetics of the B cell Receptor
Coded by a set of genes (3) that are randomaly rearranged to produce a wide variety of B cell receptors
- And in the bone marrow we have epithelial cells that display self-antigen -> so if any newly formed B cells bind to self antigens, they are ______ = _____ _____
V, D, J genes
deleted = Central Tolerance
Conclusion: The mature B and T cells leave the bone marrow and thymus gland, carry B and T cell receptors that are naive but capable of fighting pathogens they have not yet encountered and are hopefully not auto-reative.
Antigen Presenting Cells
(3)
- How do B lymphocytes act as antigen presenting cells?
- Primary role of dendritic cell is?
- Which two are phagocytic?
B Lymphocytes
Dendritic Cells
Macrophages
- only in a narrow circumstance -> once mature, in the course of that migration from bone marrow to secondary lymphoid tissue - can encounter the specific pathogen its designed to fight (very few bacteria can immediately activate the B cell), most of time that B cell still has to carry the antigen and present it to the T cell in order to activate itself (“meeting your soulmate in preschool”)
- Antigen presentation (highly specialized for it)
- Dendritic and Macrophage
Immune System protects against 4 classes of pathogen
Main diff in pathogens, again is if it infects the extracellular (mainly ____ ) or intracellular (mainly ____) space
- However there is a small group of bacteria that infects cells intracellularly (1)
- Predominantly infects ____ cells esp the macrophage
- Example: Bacteria that causes TB, Leprosy, Malaria
- Crafty bacteria bc have evolved to avoid _____ - so macrophages come across this bacteria and try to phagocytize it but once inside this bacteria will stop the process of phagocytosis and proliferate in vesicles inside the macrophage (we kill that macrophage and go kill more)
bacteria, viruses
-
Parasites
- immune
- avoids phagocytosis
Intracellular Bacteria (Parasites)
TH1 =
Subtype of CD4 T cell that engages in killing of these bacteria by binding to this antigen and trigger fusion of lysosomes with those vesicles
Antigen Presentation
When triggering an adaptive immune response, till now we have thought it to be activating a T or B cell but in reality ____ are activated and respond to antigens
- If the antigen presenting cell is _____ cell (expert antigen presenter) - can present and activate CD8 T cell directly, if it encounters it first and then activates CD4 T cell later
- _____ have to go through the CD4 T cell
both
- Dendritic can activate CD8 directly
- Macrophage needs to use CD4
How do CD4 T cells activate CD8 cells?
Release of (1) onto CD8 to trigger its proliferation
- (1) process of antigen presentation involves this bc the APC finds and selects its particular clone of the T receptor that binds to this antigen
- (1): proliferation of the specific CD8 T cells that are activated (one set banked, one set effector cells)
IL2
Clonal Selection
Clonal Expansion
CD8 Mediated Extracellular Killing
Once CD8 binds to antigen with its specific T cell receptor -> will release protein call ______ that eats away at the plasma membrane through ______ and the cell ______ (so pretty much the CD8 T cell is going to find the very particular infected cell and go kill it)
perforin, eats away at plasma membrane through lesions, lyses
Antibody Mediated Immunity by B cells
Preschooler on its way to the LN happened upon the particular antigen, so even though this B cell is programmed to find this antigen - needs ____ cell to activate it
CD4 cell releases (3) to trigger expansion of the B cell group, one set banked, one set effector cells
Plasma Cells =
CD4 T cell
IL4, IL5, IL6
Terminally differentiated B cells that are the ones that produce antibodies to fight the infection
Also known as humoral immunity (hormonal immunity) bc the antibodies are released directly into the bloodstream like hormones and go off to fight infection
How Antibodies Fight Infection
(3)
+ Definitions
Opsonization
tagging an organism for phagocytosis by another cell
Neutralization
antibody binds to the organism and makes it impossible for the organism to cause harm (neutralizes it)
One type of organism it can do this to is VIRUSES (bc if virus is bound to antibody it can’t infect the cell) - but in order for antibody to bind to virus the virus has to be in the ECF (where they spend a brief amount of time before entering cell)
Activation of the Complement System
triggers production of cytokines that make you feel sick (fever, malaise, increase wbc)
Classes of Immunoglobulins (Antibodies)
Antibody structure looks like a capital Y
Red branches =
Blue stem =
(5)
Antigen binding site determines Specifity of the antibody
determines the class of the antibody which indicates its function
IgG, IgM, IgD, IgA, IgE
Affinity and Avidity
Affinity =
Avidity =
- Which antibody is a pentamer?
- Which antibody is a dimer?
- Which antibodies are monomers?
How tight it holds
of binding sites
- IgM
- IgA
- IgG, IgE, IgD
Antibody Class Functions
From narrow to wide
- IgA =
- IgD =
- IgE =
- IgM =
- IgG =
- Confers passive immunity from mom to baby in things like breasfeeding (ie mom gets infected w rhinovirus, my body makes antibodies and then breastmilk transfers antibodies to baby)
- Not produced like other antibodies -> forms a surface receptor on the B lymphocyte
- mediates classic allergies (type 1 hypersensitivity reaction) (sensitizes mast cells in first exposure, degranulates in next exposure)
- Activates complement system
- Neutralization and Opsonization (modest complement activation activity, some sensitize NK cells)
Take away: IgG better at silent ways of attacking infection, while IgM has this big messy hammer called the complement system
Primary and Secondary Antibody Responses
- 1st exposure to a pathogen
- First wave of antibodies =
- Second wave of antibodies =
- 2nd exposure to a pathogen
- First wave of antibodies =
- Second wave of antibodies =
- 1st exposure
- IgM
- IgG
- 2nd exposure
- IgG keeps going up bc you had some already
- IgM
Affinity Maturation
=
- Antibody of choice for 1st exposure of a pathogen and acute phase of an illness = ____
- IgM has low ____ but high ____ =
When affinity of T cellls and antibodies increase by learning and changing its antigen binding site shapes to match the receptor better - both IgM and IgG go through this
IgM
low affinity, high avidity = grabbing you by the strength of a two year old but with 1- arms bc remember structure of Igm is a polymer which is why its good for an acute phase reaction
Hypersensitivity Reaction
=
- Allergy =
- Autoimmune reaction =
- Alloimmune reaction =
Inappropriate reactions the immune system has to things that are nonharmful
- inappropriate immune reaction to a nonharmful environmental component
- immune reaction against a self antigen
- immune reaction to someone else’s self antigen (relevant in tissue transplantation)
Immediate (Type 1) Hypersensitivity
Mechanism of Immune Attack
Prototypic Disorders (3)
Descripton of Disorder
Production of IgE from first exposure where IgE is produced and binds to mast cells to sensitize them. Mast cells degranulate and initiate inflammatory response during second exposure
- Hay Fever
- Allergies
- Anaphylaxis
Hay fever allergies- IgE against antigens of various pollens cause varying degrees of local and systemic inflammatory responses including itching, painful and red eyes, nose, and throat or systemic effects like fever and fatigue
Anaphylaxis-an acute and severe systemic type I reaction to an allergen. Can be life threatening
Antibody-Mediated (Type II) Hypersensitivity
Mechanism of Immune Attack
Prototypic Disorder
Description of Disorder
Circulating antibodies (IgM, IgG) bind to antigen on target cell or tissue promoting either phagocytosis by leukocytes (IgG) or cell lysis by complement system (IgM)
Autoimmune Hemolytic Anemia
Immune system recognizes some antigen on RBC’s (could be the A, B, or Rh chapter) and destroys RBCs
Immune Complex-Mediated (Type III) Hypersensitivity
Mechanism of Immune Attack
Prototypic Disorder
Description of Disorder
Circulating antigen-antibodies complexes deposit in tissue and initiate an inflammatory response which causes tissue damage at site of deposition
Post streptococcal glomerulonephritis
Inflammatory damage of glomerular membranes brought on by the deposition of antigen-antibody complexes occurring after or along streptococcal infection
Cell Mediated (Type IV) Hypersensitivity
Mechanism of Immune attack
Prototypic Disorder
Description of Disorder
Antigen activation of T lymphocytes which causes tissue damange through 1) activation of inflammation and recruitment of phagocytic cells (also called delayed type hyersensitivity) and/or 2) direct cytotoxic T cell killing of antigen carrying cells
Transplant rejection
Immune attack of grafted or transplanted tissue/organs. The target for the attack (antigen) is for the most part the donor’s Major Histocompatability Complex proteins
Examples of Antibody Mediated Diseases (Type II)
Type II: looks exactly like antibody mediated immune reaction (just of a nonharmful substance)
Graves is a hypersensitivity reaction in the weirdest way: antibody binds to TSH receptor and activates it
Serum Sickness
=
- Your body has an ____ (black line), immune system attacks
- Antigen lvl goes ____
- Immune ____ rise and get ___ in joints etc -> while there causes inflammation and activation of ______ system -> damage to tissue
Example of Type III hypersensitivity caused by the reaction to the introduction of antibodies derived from non-human sources
- antigen
- down
- complexes, trapped, complement
Examples of Immune Complex Mediated Diseases
Pathogenesis of Type IV Hypersensitivity
Immune reaction involving activation of a __-cell response that tends to activate 2 subtypes of T cells
- _____ T cell response where it kills cells ( transplant rejection) or
- T cell response that just triggers widespread _____ (can look a bit like type 1, difference is that its _____) - sometimes called a?
T cell
- Classic
- inflammation, delayed -> Delayed hypersensitivity reaction
Examples of T Cell Mediated (Type IV) Hypersensitivity
Autoimmunity
Immunological Tolerance =
Self Tolerance =
Which goes through both
Central Tolerance = (1)
Peripheral Tolerance = (2)
Immune unresponsiveness to an antien as a result of exposure to lymphocytes to that antigen
breakdown of self confidence, ability to NOT react to self antigens
occurs in bone marrow and thymus gland through clonal deletion (deleting autoreactive B and T cells)
Occurs in peripheral tissues through Anergy: lack of activation of an adaptive immune response or Deletion by Apoptosis
Mechanisms of Autoimmunity
Autoimmunity arises from a combination of the _____ of ____ genes, which may contribute to the ____ of self-tolerance, and _____ triggers such as infections and tissue damage with promote the activation of self-____ lymphocytes
Most common genes associated with autoimmune disorders are found on the (1) locus
Recent epidemiologic studies suggest that the incidence of autoimmune disorders in developed countries has ______ while the rate of other infections are better controlled. While in animal models infections greatly reduce the incidence of autoimmunity.
Paradoxically, infections may protect against some autoimmune disorders by enhancing the production of regulatory ____ cells
Autoimmune diseases can be ____ specific (Graves) or _____ (Lupus) and _____ mediated (AI hemolytic anemia) vs. _____ mediated (Multiple Sclerosis)
More common in which gender?
inheritance of susceptible genes + environmental triggers -> breakdown of self-tolerance, activation of self reactive lymphocytes
MHC/HLA locus
in humans, autoimmune infx increased even though infections have decreased (opposite seen in animals)
CD4
organ vs. systemic, antibody vs. T cell mediated
Women
Graft/Transplant Rejection
Alloimmunity =
- Usually (1) mediated (Type 4 Hypersensitivity reaction)
- Direct pathway =
- Indirect pathway =
- We also see (1) mediated (humoral rejection)
-
Hyperacute rejection =
- always _____ mediated, and more w what type of pts, why?
-
Hyperacute rejection =
immune reaction to another person’s self-antigens (usually grafted or donated tissue)
-
T cell
- involves donor APC and recipient T cells
- involves recipients APCs and recipient T cells
-
Antibody
-
happens immediately (like in the transplant surgery) - the person already has antibodies that will attack the new organ
- always antibody mediated, and more with renal transplant pts - bc ppl on chronic dialysis where u get a lot of transfusion with self antigens from diff ppl and more likely to build antibodies to a variety of self antigens -> increased risk for hyperacute rejection
-
happens immediately (like in the transplant surgery) - the person already has antibodies that will attack the new organ
Acute Rejection
(vascular/humoral vs. cellular/Tcell)
=
Chronic Rejection
=
always expected and treatable, extremely common almost everybody goes through it in the first 3-6m, usually T-cell mediated but sometimes can be antibody mediated
starts with acute rejection + repeated bouts of low lvl rejection overtime
Transplantation of Hematopoietic Stem Cells
Harvested from (1) or (1)
Two unique problems (2)
bone marrow or peripheral blood (pretty much transplanting immune systems)
Graft vs. Host (GVH)
Immunodeficiency
Immunodeficiency
=
Graft vs. Host Disease
=
Acute GVH =
Chronic GVH =
usually when ppl are about to get bone marrow transplants they have to have their immune system wiped out (irradiated) which leaves them with a window of time where they are vulnerable to infections before they get donor cells
When donated cells attack host cells (very specific to BMT not other transplants)
usually acute, treatable, person can recover
happy medium between donor cells and recipients somatic cells are never reached
Issues of Immunity
_____ Process
Antimicrobial _____
Preventing disease through ______
____/____
Infectious Process
Antimicrobial Resistance
Vaccination
HIV/AIDS
most microorganisms in our environment are harmless
Categories of pathogenic microorganisms
Prions =
misshaped _____ that when encounters another protein also causes them to be _____ and lose ____ - interferes with the function of a cell as a whole (controversy on if its actually an infectious disease but kind of considered one rn)
- (2) disease potentially considered a prion disease dt amyloid protein plaques and fibrillary tangles and may be transmissable if person comes in contact w affected persons CNS
- Most infectious diseases that effect humans actually originate and mostly spread by ______
misshaped proteins, mishaped, function
- Mad cow disease, Alzheimers
- animals
Morphology of Bacteria
Bacteria: ____ celled organisms that contain genetic material and also contain all of the organelles and protein needed to ____ themselves (entirely ___-contained)
Cocci =
Staphylococci =
Streptococci =
Bacilli =
single, replicate, self contained
spherical shape
Cocci in clusters
Cocci in chains
oval shaped
1 victim of viruses =
Viruses
= genetic material in the form of ___ or ___ and surrounded by a protein coat (but that’s it, no organelles, ____ replicate on its own, basically parasites - must get into cell and hijack that host cell’s nucleus
RNA, DNA, can’t replicate on own, hijacks host cells nucleus
bacteria
Tend to see diff organisms infect diff parts of the body
