Innate and Adaptive Immunity Flashcards
Immunoflow of Innate Immunity
2 major first steps
2 subsequent activated flows
Macrophages activated: PAMP - Toll-like Receptors;
Releases chemokines, chemotaxis
IL1, IL6 TNF alpha - pro inflammatory cytokines
Prostaglandins, Leukotrienes
- activate NKC, activate Dendritic Cells
Damaged Tissue, Microbes activate Complement
1 - form MAC - lysis, CDCC
2 - Inflammation, Mast Cell activation
3 - Opsonization, Phagocytosis
Mast Cells (activated by Compliment)
- Releases PG, LK, Histamines
- NKC activation
NKC - releases granules, cytotoxic;
- complement, cytokine IL12 activations
- AB activations by Fc receptor
Immunoflow of Adaptive Immunity
- from PAPC to T Cell differentiations and functions and locations
- what happens in order for clonal expansion
Dendritic Cells
- Maturation from phagocytic to ‘antigen-presenting’
- moves from periphery to lymph nodes
- increases Co-stimulation stuff and MHC
Dendritic Cells, Macrophages and B cells
- all are PAPC;
T Cells migrate to lymph nodes by
- secretin, CCR7
CD4 to Th1 and Th2 and Treg
- Th1: IL12, INF gamma
- Th2: IL 4
- Treg: TGF-beta
Th1 secretes IFN gamma
- M1 macrophage activation, highly bactericidal
Th2 secretes IL4, IL5, IL 13;
- IL4, IL13 for B cell class switching, gives IgE
- IL5 for eosinophil activation - helminth
- M2 macrophage activation for fibrosis, repair
note Th1 and Th2 cytokines have inter-inhibition functions
T helper cells
- releases IL2
- self binds IL2R - clonal expansion
Gimme 4 classes of T helper cells
- activating cytokines
- releasing cytokines
- functions
Th1
- activated by IL12, IFN gamma
- releases IFN gamma for M1 activation;
- FUNCTION: Intracellular bacteria, viruses
- – Cell-mediated immunity
Th2
- activated by IL4
- releases IL4, IL 13 for B cell class switching
- releases IL5 for eosinophils for helminths
- FUNCTION: extracellular parasites
Th17 and Treg
- Both activated by TGF beta
Th17: EXTRACELLULAR; fungi
- also activated by IL6
- releases IL17, IL22
Treg: Peripheral Tolerance (inhibits Th1, Th2)
- releases TGF beta
How does T Cell get activated from PAPC
- give cytokines again
3 signals
- TCR - MHCII + peptide
- CD4 to MHCII
- Co-stimulatory
- CD28 to B7; CD40 to CD40L (note blocker is CTLA4)
- wo this, anergy
- hence B7 on dendritic cell is important
- Cytokines for differentiation
- IFN gamma, IL12 for Th1
- IL4 for Th2
- IL6 for Th17
- TGF Beta for Th17, Treg
2 receptors involved in immunosuppressant
- immune checkpoints
CTLA4
- compete w CD28 for B7; stronger signal
- inhibitory
– hence anti-CTLA blocks Treg and T cell inhibition
PD1 (receptor) on activated T cells/ B cells to PDL1 (ligand 1)
- expressed on chronically expressed T cell
- blocks TCR, CD28 signals
CD8 functions [2]
Releases
- perforin, granzymes - apoptosis
- Fas Ligand on Fas receptor - apoptosis
4 classes of Antibodies and their valency and functions
IgM: complement; 10!; pentamer
IgG: neutralization, agglutination, complement, NKC; dimer
IgA: mucosal; dimer (x2)
IgE; Mast Cell, ANTI-PARASITE; basophils; dimer
5 functions of ABs
Complement activation CDCC - IgM, IgG
Opsonization - IgG
NKC activation ADCC (coat it then recruit NKC) - IgG
Ab-AG complex, Agglutination, Neutralization - IgG
Mast Cell! IgE
What activates NKC
- AB
- Complement
- Cytokines, IL12
What activates complement
Microbes, Damaged tissue
AB
What are complement functions
MAC
NKC activation
Opsonization
What activates Mast Cells
Complement
AB - IgE
How is T cell matured
From bone marrow to thymus
In Thymus
- Positive Selection: TCR weakly bind self MHC - ensure restriction
- Negative Selection: TCR bind too strongly to self MHC
- – uses self-antigens, peptides
How is B Cell matured w DNA stuff
How is B Cell selected for in Lymph Nodes
DNA
- somatic recombination
- light chain VJC recomb
- heavy chain V DJC recomb
Positive Selection: Functional heavy chain
Negative Selection: Autoreactivity
– NOTE THIS OCCURS IN THE BONE MARROW ALREADY FOR MATURATION - central tolerance acquired
- then travel to spleen // germinal centres
Class Switching
Somatic Hypermutation // Affinity maturation
Within Germinal Centres:
- Dark zones - B cell proliferation (after receiving antigens already from FDC and Helper signal)
- Iccosomes on follicular dendritic cells presented to it at light zones
- T cells activate B cells at Mantle zone
- as B cell proliferates, point mutations in V region occur - somatic hypermutation by Activation Induced Deaminase
- selection w fewer antigen, stronger affinity
- hence vaccine fewer antigens better
