Mar21 M2-Adaptive Immunity 1 Flashcards
concept of biological medications and how they work in general (for Crohn’s, asthma, etc.)
slow or block the immune system
main actions of T lymphocytes
- coordinators of immunity and make cytokines
- anticancer**
- antiviral action
- antiTB action
- cytotoxic action
main actions of B cells
- produce abs
- produce cytokines
- present antigens**
how B and T cell change once exposed to an antigen
their progeny will change its Rs so that it has better affinity to the antigen (but the cell itself doesn’t do that tho)
how innate vs adaptive recognition of antigen differs
innate: patterns (lipopolysaccharides (LPS), viral DNA or RNA, etc.).
adaptive: specific peptides + can change recognition to make it better (the clone of B and T cells)
mucosal immune responses mechanism
- cold or allergy or invader destroys mucosa
- invader picked by surveillance cells (often dendritic cells) and presented to B and T cells in lymph nodes
(IMPORTANT) what T cells receptors recognize
peptides (broken down, native form of the protein. not the invader itself)
MHC class 1 found on what cells and interacts with what
all NUCLEATED cells of the body. MHC class 1 recognized by CD8+ T cells. ALWAYS on cell surface.
MHC class 2 found on what cells and interacts with what
found on APCs. present antigen to CD4+ T cells.
7 APCs in the body
monocytes, macrophages, B cells, dendritic cells, Langerhans cells (skin), Kupffer cells (liver), astrocytes (brain)
dendritic cells: how they recognize foreign substances and recognize what else
- with TLRs 1 to 11
- also recognize antibody coated antigens and complement coated antigens
dendritic cell goal
engulf and digest antigens to make them peptides and show them to T cells
what dendritic cell does at same time as it digests antigenic peptide to present it on MHC class 2
- becomes activated
- produces cytokines to help activate T cells like IL-12 and IFN-gamma
MHC class 1 vs class 2 when they’re on cell surface
- class 1 only on surface where there’s an invader
- class 2 always there. will present an antigen if there is one.
how MHC class 1 works to present an antigen
- viral invaders and other pathogens degraded in PROTEASOME
- MHC 1 + peptide complex together (assembled) in ER
- exported together to plasma membrane in a vesicle
how MHC class 2 works to present an antigen
- MHC 2 complex assembled in ER
- exported in acidic environment in endosomic vesicle
- pathogens degraded in same vesicle by acid + enzymes. peptide bind
reaction to allergen: what cell does the dendritic cell present antigen to
to CD4+ effector T cells in lymph nodes
WBCs distribution in the blood (%) and lymphocytes distribution
neutrophils 55% lymphocytes 33% (80% is T cells. 20% is B cells) monocytes-macrophages 5% band neutrophils 5% eosinophils 3% basophils 1%
biggest lymph node in the body + biggest collection of lymphocytes in the body
spleen
GIT biggest collection of lymphocytes
T lymphocytes recognition ability
- we’re born with limited repertoire of antigens that T cells can recognize
- exposure helps mature and refine the responses
lymphocytes mostly where in body
neck, tonsils, groin, spleen
lymph node vs peripheral B:T cells ratio
lymph node: 50-50
peripheral blood: more T cells (80%)
3 things T cells must have to recognize antigens + the one that’s a T cell marker
- CD3 (signaling complex) ***T cell marker
- CD4 OR CD8 (immature T cells have both)
- receptor for a peptide (TCR = T cell R)
one therapy knocking out T cells used in transplants to avoid rejection
anti-CD3 therapy. spleen recognizes T cells and removes them. get temporary immune deficiency that grows back
elements needed in T cell - APC interaction
- CD4 interaction with MHC class 2 to recognize it as self
- CD3 - TCR interaction with the MHC class 2 - peptide complex
* IT’S THE TCR THAT IS SPECIFIC TO AN ANTIGEN OR PEPTIDE*
step after T cell - APC full interaction
T cells picks molecule on APC and transduces intracellular signal
costimulation molecules in the T cell - APC (dendritic cell) interaction + WHY needed
- CD28 on T cells.
- CD80,CD86 (binding partner of CD28) on dendritic cells
- needed to make interaction closer and allow T and APC to activate each other better
Substance released upon T - APC interaction (2 important) (TH1 type here)
- dendritic cell makes IL-12. IL-12 causes T cell to produce cytokines like IFN-gamma
- T cell makes IL-2
functions of IFN gamma released by CD4+ cells in response to IL-12 from dendritic cells
- IFN gamma activates dendritic cell back
- if virus or TB, IFN gamma recruits macrophages and monocytes
function of IL-2 produced by T cells
IL-2 binds IL-2 R on T cells***
**T cells upregulate IL-2 Rs 6 hrs after interaction. Otherwise can’t proliferate.
important ligand for T cells and B cells to communicate better
CD40
why MHCs is what is used to recognize cells as self
because differs genetically from person to person. everyone has a different MHC
3 roles for T cells (depending on T cell type)
- fight IC infections (CD8. viruses, TB, IC pathogens)
- assist other cells (CD4+ to activate them and make them multiply and differentiate)
- signals to inhibit or slow down immunity (T reg. CD4+ Foxp3+)
4 CD4+ effector T cells categories
th1, th2, th9, th17
characteristic of cytokines released by leukocytes in general
ability to turn off after they turn on
th1 cells function + KEY cytokine
supply cytokines to MONOCYTES to help them fight IC organisms (viruses, IC pathogens)
**IFN-gamma (there’s also IL-12)
th2 cells fct + key cytokines
- supply cytokines for B cells to make Abs responses. (to fight parasites + slow pathogens by mucous prod for ex)
- *IL4 and IL13
th17 cells fct + key cytokine
- supply cytokines for phagocytes and cells of innate immunity to destroy bacteria (especially staph) and fungi
- IL-17 (part of a group of th17 cytokines)
reg T cells fct + key cytokines (CD4+ Foxp3+)
-regulate all cell activities via ***IL-10, TGF-beta and also via cell-cell contact
IL-10 and TGF-beta actions
turn OFF cytokines
helper cell type and cytokine category involved in response to allergens
TH2 and TH2 cytokines (bc want to make Abs to the allergen)
what happens when naive T cell is stimulated
changes its surface architecture, meaning:
- upregulates IL-2 Rs
- upregulates chemokine Rs like CCR3, CCR4, CCR5 (to leave lymph node)
-upregulates adhesion molecules like CD28
how the response of a T cell to T cell - APC interaction is amplified
- T cells multiply
- maturing T cells that are producing cytokines are cloned
- maturing T cells change the genetic makeup of their TCR to remember peptides better
2 types of T cells in general
- effector T cells (stimulate or attack cells, magnifies the response)
- memory T cells: small clone of antigen recognizing cells
Th1 function and key cytokines + key to remember
-fight IC organisms
-IFN gamma**
(also IL-12, IL-18)
th2 function and key cytokines + key to remember
- IL-4 and IL13** (for Ab production and parasite defense)
- fct in allergies + prod of IgE
- IL-5 for stimulation of eosinophils
- IL-9 for mucous prod
th17 function and key cytokines + key to remember
- antibacterial and antifungal
- IL-17, IL-22
Treg cells function and key cytokines + key to remember
- turn off immune response (regulation)
- IL-10 and TGF-beta
th1, th2, th17 and treg cells are part of which category
EFFECTOR CD4+ (helper) T cells
where T cell-APC interaction occurs
in lymph node
CD8+ cytotoxic T cells fct and how they recognize that they have to act
- directly fight viral AND FUNGAL infections
- recognize viral peptides produced and expressed by all cells of our body on MHC class 1
how CD8 cells kill other cells
produce perforin and granzyme causing cell to apoptose (and necrose too)
other functions of CD8 cells
- produce pro-inflam cytokines like IFN-gamma (also prod by th1 CD4+)
- some CD8 regulatory cells exist and produce IL-10, TGF-beta
viral infection to MHC 1 presentation
- virus gets in epith cell
- replictes
- proteasome picks up viral protein and degrades it to peptide
- presentation on MHC class 1
how cytotoxic T cells operate once get through epithelium and reach virally infected cells
for each infected cell:
- CD8 and TCR (specific to one antigen) recognizes MHC1+peptide
- T cell activated and and produces perforin, granzyme, etc.
why cells killed by CD8 cells die by apoptosis
so they don’t release their contents and cause massive inflammation
most common congenital problem of T cells (low T cells number)
SCID of a defective cytokine receptor for IL-2. (X-linked SCID)
causes of acquired problems of T cell function (low T cells number)
- HIV
- drugs used for transplant, cancer, etc.
examples of diseases that T cells are important in initiating and maintaining
- autoimmune diseases
- allergy
- cancers (especially dermatologic)
cause of immune exhaustion in cancer (and why cancer can take over immune system)
after some time, T cells respond to T reg cells and stop acting
immune exhaustion: molecules involved
checkpoint molecules on T reg cells surface (adhesion molecules) like CD28 and PD1. They tell cells to stop acting
downside of checkpoint inhibitors
25% of people get side effects of a completely uncontrolled (overwhelming) immunity. Looks like sepsis.
