1/2 - Innate & Adaptive Immune System Flashcards
Define
a system of proteins for defense against pathogens;
some proteins are enzymes, others are involved in recognition/communication
COMPLEMENT
Primary Lymphoid Organs
for development / maturation
Bone Marrow for B cells
Thymus for T Cells
Secondary Lymphoid Organs
SPLEEN
highly important for maturation of B-Cells
Lymph Nodes / Tonsils / Appendix / Peyer’s Patches
Major site of AntiBody Production
Trap & Concentrate forein materials
–> expose foreigners to cells producing AB’s
MALT
Lymphoid Tissues
Mucosa Associated Lymphoid Tissue
Present in surface mucosa of:
Resipiratory / GI / Geniitourirary Tracts
GALT
Lymphoid Tissues
Gut Associated Lymphoid Tissue
Includes:
- *Peyer’s Patches** / Appendix
- *Lymphoid Nodules in Submucosa**
BALT
Lymphoid Tissues
Bronchus Associated Lymphoid Tissue
Lymphoid Cells
T & B Cells
NK Cells
All express
AG-Specific Receptors
Myeloid Cells
1st RESPONDERS!
Neutrophils / Basophils
Eosinophils / Monocytes / Macrophages
Dedretic Cells / Mast Cells
Type of Immunity?
Antigen non-specific
RAPID response
Phagocytes / Natural Barriers
COMPLEMENT
Pattern Recognition Molecules
INNATE
Type of Immunity?
Antigen SPECIFIC
slow response / memory
Lymphocytes
B / T Cell receptors
Secreted ANTIBODIES + Cytokines
responds to new molecules
ADAPTIVE
Adaptive Response for Immunity
Specificity
discrimination of self/non-self
B / T Cells // APCs // mast cells+neutrophils
- *Humoral Immunity** = B-Cells
- *Cellular Immunity** = T-cells
Basis of Immunizations
Three types of IMMUNIZATIONS
Adaptive Response
1) EXPOSURE to antigen
2) Through TRANSFER of ANTIBODIES
3) through Transfer of IMMUNE CELLS
bone marrow xplant
Humoral Immunity
Two arms of the Adaptive Response
B-CELLS
activated by AG-Binding to cell-surface receptors
T-cells may help activate the B-cells
as can components of the complement system
Active B-cells –> Secrete ANTIBODIES (immunogloblins
–> that bind to the ANTIGEN
to clear them out of the system
Cellular Immunity
Two arms of the Adaptive Response
T-CELLS
interact with APC’s, then RELEASE CYTOKINES
which stimulate other immune system cells
- *Helper** T-cells –> release cytokines
- *Cytotoxic** (kill) T-Cells
- *Regulatory** T-cells
External / Passive
Defenses
Part of the INNATE Immunity
- *Normal Gut bacteria** + skin bacteria
- *Gut ACIDITY + Enzymes**
Skin / Mucous Membranes / tears
hair follicles
- other defenses*
- *Cough reflex / nose hairs / complement**
Intracellular Killing
INNATE IMMUNITY
done by PHAGOCYTES
Recognition of PAMP’s
(pathogen associated molecules, proteins/lipids/polysacch/lipoproteins)
Adhesion to pathogen –> PHAGOCYTOSIS
of whole cell or viral particles –> passage to endosomes / lysosomes
EXTRAcellular Killing
INNATE IMMUNITY
- *Toxic Metabolites**:
- *NO / H2O2 / Superoxide anion / hypochlorus**
PORE formation –> Cell Lysis
INduction of APOPTOSIS
Phagocytosis + Endocytosis
Can be used in BOTH INNATE / ACQUIRED immune responses
Endocytosis:
non-specific pinocytosis // specific receptor mediated uptake
fusion with endosomes –> lysosomes + degrative enzymes
Phagocytosis:
of WHOLE cells/virus particles (intracellular killing
Cell Type Involved in Innate Immunity?
Eosinophils / Basophils / NEUTROPHILS
(granulocytes)
Short lived / contain lysosomes –> produce peroxide / NO
PMN Leukocytes
polymorphonuclear Leuocytes
Cell Type Involved in Innate Immunity?
Large Phagocytic cells that process & PRESENT Antigens on the cell surface
to stimulate other immune cells
MACROPHAGES
Cell Type Involved in Innate Immunity?
Phagocytose –> Process –> present antigens on the cell surface
to stimulate immune system cells
DENDRITIC CELLS
Cell Type Involved in Innate Immunity?
secrete CYTOKINES
act like T-cells, but found mainly not the blood, but in TISSUES
ILCs
Innate Lymphoid Cells
Cell Type Involved in Innate Immunity?
Develop in the THYMUS, same precursor as T-cells
early responders to virus-infected or cancer cells
express KIR –> MHC (on normal cells)
(killer inhibitory receptor)
This cell will KILL cell if Not enough MHC present
pore forming –> lysis // apoptosis signaling
NATURAL KILLER CELLS
MHC-1
- *Normal=SELF** cells express MHC-1 proteins on cell surace
- foreign / infected / tumorous cells* LACK MHC-1
- NK CELLS** will ATTACK the cell if it is *lacking MHC-1
- -> pore-forming proteins –> stimulate APOPTOSIS
NATURAL KILLER T-CELLS
(NK-T)
Develop in the THYMUS from t-cell precursors
express TCR (t-cell receptors)
NK-cells do not express TCR
TCR -bind-> Membrane associated Sphingolypids (found in bacteria)
NKT cells also SECRETE IL-4 / IFN-gamma / other cytokines
to stimulate other immune cells
Also can TRIGGER APOPTOSIS via FAS-FAS interactions
important for removing B/T cells that may be anergic / improper
PAMPs
INNATE IMMUNITY
- *Pathogen-Associated Molecular Patterns**
- Conserved** (unlikely to change)* molecules produced by pathogens
ex. sugar coat outside of bacteria, lipoproteins, yeast / flaggelin
PRRs
INNATE IMMUNITY
Pattern Recognition Receptors
different from BCR or TCR or Antibodies
HIGHLY expressed on dendritic cells & other phagocytes
FOUR main classes:
- *TLRs** = toll-like receptors
- *CLRs** = C-type lectin receptors
- *NLRs** = NOD-like receptors
- *RLRs** = RIG-I-Like receptors
TLRs
Functions of PRRs
(Innate immunity)
Toll-Like Receptor
EXTRAcellular & Membrane-bound
Several different classes:
specfic for Gram +/- Bacteria
Mycobacteria
Nucleic acidsfromvirus/bacteria
CLRs
Functions of PRRs
(Innate immunity)
C-Type Lectin Receptors
EXTRAcellular & Membrane bound
(like TLRs)
Recognize particular:
CARBs produced by FUNGI
depend on CALCIUM
NLRs
Functions of PRRs
(Innate immunity)
NOD-Like Receptors
intracellular receptors that recognize cytoplasmic PAMPs
some NLRs –form–> the inflammasome for generation of cytokines
RLRs
Functions of PRRs
(Innate immunity)
RIG-I-Like Receptors
Cytoplasmic RNA HELICASES
sense viral RNA replication and
–signal–> production of INTERFERONS
INFLAMMATION
innitiated by tissue damage
–> Pain / Redness / Heat / Swelling
INCREASE in activity of WBC:
1st - Phagocytic Cells (mainly PMN Leukocytes)
2nd - Macrophages + B&T-cells
with specific responses
Acute Phase Response
1st - response to PAMPs by innate immune system cells
- *Pro-Inflammatory Cytokines** Released:
- *IL-1 // IL-6 // TNF-alpha**
Induction of FEVER –> CRP release // Complement // Fibronogen
Leukocyte Migration
Phagocytosis
INFLAMMASOMES
Multiprotein Complexes found in the CYTOSOL
respond to cytosolic inflammation
- *cytosolic PAMPs & DAMPs**
- -> NLRs bind the pathogen –> oligomerize –> form the Inflammasome
Capsase-1 cleaves precursor peptides to generate:
IL-1Beta & IL18
(inflammatory cytokines)
LOCALIZED Inflammatory Ressponses
Kinins & Cytokines
cause local smooth muscle contraction
block NERVOUS impulses –> distal muscle relaxation
INCREASE vascular permeability
Kinins –> stimulate nerves –> pain& itching
Chemotactic cytokines
lead leukocytes –> permeate –> to damage
Chemotactic Cytokines
type of Localized Inflammatory Response
Lead LEUKOCYTES –> through bloodstream near SITE OF DMG
INCREASED vascular permeability
–> allows leukocytes to pass –> TISSUE
Destruction of PATHOGEN follows
CHEMOKINES
come from DAMAGED CELLS
- *locally INDUCE INCREASED expression of:**
- *cell-adhesion molecules** + increase vascular permeability
Leukocytes carry ligands on surface
–> cell-adhesion molecules bind –> stick to site of dmg
–> ROLL along the endothelium –> PASS THROUGH
to attack pathogen
THYMUS GLAND
stops producing thymocytes as you age
OKAY, since you will have had a LARGE & LONG LASTING
population of T-CELLS
Colonized by stem cells from BONE MARROW
Site for Maturation of:
Lymphocytes + T-CELLS
also many:
Macrophages & Dendritic Cells
for digesting apoptopic thymocytes (developing t-cells)
located in the MEDULLA –> way out
SPLEEN
Secondary Lymphoid Tissue
Main FXN:
Generate Immune response to AG’s in BLOOD
- *Centers** are rich in B-CELLS
- *Periphery** rich in T-CELLS
- also LOTS OF APCs*
AG –> Spleen –> taken up by APCs
then digested / presented to B&T Cells –> stimulate immune response
LYMPH NODES
Secondary Lymphoid Tissue
Main FXN:
Generate IMMUNE REPONSE to AGs in TISSUES
Lots of B&T-Cells + APCs
- *AG –> Node** –> taken up by APCs
- -> presented to B&T cells –> stim immune response
THREE WAYS for
LYMPHOCYTE & AG Migration/Recirculation
1) AG enters BLOODstream
- -> pass through SPLEEN, meets the APCs –> Activates B&T-cells
2) AG penetrates SKIN
passes through LYMPH NODE –> generate immune response
3) AG enters GI or RESPIRATORY TRACT
meets MALT or BALT
