Innate and Adaptive Immunity

Question 1

Immunoflow of Innate Immunity

2 major first steps
2 subsequent activated flows

Answer 1

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

Question 2

Immunoflow of Adaptive Immunity

• from PAPC to T Cell differentiations and functions and locations
• what happens in order for clonal expansion

Answer 2

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

Question 3

Gimme 4 classes of T helper cells

• activating cytokines
• releasing cytokines
• functions

Answer 3

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

Question 4

How does T Cell get activated from PAPC

- give cytokines again

Answer 4

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

Question 5

2 receptors involved in immunosuppressant

- immune checkpoints

Answer 5

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

Question 6

CD8 functions [2]

Answer 6

Releases

• perforin, granzymes - apoptosis
• Fas Ligand on Fas receptor - apoptosis

Question 7

4 classes of Antibodies and their valency and functions

Answer 7

IgM: complement; 10!; pentamer
IgG: neutralization, agglutination, complement, NKC; dimer
IgA: mucosal; dimer (x2)
IgE; Mast Cell, ANTI-PARASITE; basophils; dimer

Question 8

5 functions of ABs

Answer 8

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

Question 9

What activates NKC

Answer 9

• AB
• Complement
• Cytokines, IL12

Question 10

What activates complement

Answer 10

Microbes, Damaged tissue

AB

Question 11

What are complement functions

Answer 11

MAC
NKC activation
Opsonization

Question 12

What activates Mast Cells

Answer 12

Complement

AB - IgE

Question 13

How is T cell matured

Answer 13

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

Question 14

How is B Cell matured w DNA stuff

How is B Cell selected for in Lymph Nodes

Answer 14

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