Session 9: Adaptive Immunity

List the properties of the adaptive immune response

- Specificity

- Diversity

- Memory

- Clonal selection and expansion

- Specialisation

- Homeostasis

- Non-reactivity to self

Difference between humoral adaptive and cell-mediated adaptive immune responses

HUMORAL

- Antibody-mediated

- B-cell (bone marrow)

- Recognizes proteins, carbohydrates and nucleic acid

- Targets extracellular pathogens

- Antibodies in serum

- Primary defense against bacteria

CELL-MEDIATED IMMUNITY

- Cell-mediated

- T-lymphocytes (thymus)

- Recognizes proteins

- Targets intracellular pathogens

- Direct cell-to-cell contact

- Defense against viral, fungal, tumor antigens, graft rejection, intracellular organisms

Natural Killer T cells (NKT)

- Kill tumor cells

- Kill virally-infected cells

- NKT cells determine the type of adaptive response

What do NKT cells recognize

IgG

Lipids

MHC class I

What cytokines do NKT cells release?

IFN

TNF

IL12

How do NKT cells induce apoptosis?

Induce apoptosis by pumping proteases through target cell membrane

Where do B lymphocytes originate

Bone marrow

Where do T lymphocytes originate

Thymus

B-cells recognize ___ pathogens

extracellular

T-cells recognize ___ pathogens

intracellular

What percentage of lymphocytes are circulating?

2% of lymphocytes are circulating

The rest of the lymphocytes are in lymphoid tissues

Which division of the immune system...

Targeting of pathogens by secreted immunoglobulin molecules

Adaptive: humoral

Which division of the immune system...

Killing of infected cells in an MHC-dependent fashion

Adaptive: cell-mediated

Which division of the immune system...

A non-specific and rapid response to a challenge that does not create a memory of the pathogen

Innate immune system

Order the following circulating immune cells in order of abundance with 1 being the most abundant...

Basophils

Eosinophils

Monocytes

Neutrophils

Lymphocytes

1) Neutrophils = most abundant

2) Lymphocytes

3) Monocytes

4) Eosinophils

5) Basophils = least abundant

Naive lymphocytes

Express antigen receptors but have not responded to antigen

Effector lymphocytes

Differentiated progeny of naive cells after antigen exposure - cells produce molecules which actively eliminate the antigen

Diagram remember labels for exam

T and B cells are morphologically indistinguishable. They are identified by cell surface markers known as ___ of ___

Cluster of Differentiation (CD)

Deletion of potentially self-reactive thymocytes, thereby generating a repertoire of peripheral T cells that is largely self-tolerant

Negative selection

Clonal selection

The process by which an antigen selectively binds to and activates only those lymphocytes bearing receptors specific for the antigen.

The selected lymphocytes proliferate and differentiate into a clone of effector cells and a clone of memory cells specific for the stimulating antigen.

Clonal expansion

The rapid multiplication of B or T cell clones after activation by an antigen

Where are lymphocytes activated?

Spleen and lymph nodes

After activation, memory lymphocytes are dispersed to ___ and ___ mucosa

GI and respiratory mucosa

These are close to sites of potential reinfection - allows for rapidity of response if exposed to the same antigen again

Strategic location of antigen presenting cells

- Skin (SALT)

- Mucous membranes (GALT, NALT, BALT)

- Lymphoid organs (lymph nodes, spleen)

- Blood circulation (plasmacytoid and myeloid DC cels)

Pathogen capture occurs in two main ways - what are these?

1) Phagocytosis (whole microbe)

2) Macropinocytosis (soluble particles e.g., toxins released by bacterium)

Humoral adaptive response MHC class

MHC class II

Cell-mediated adaptive response MHC class

MHC class I

Antibody structure diagram labelled

Fab = arm

Fc = stem

MHC class I (cell-mediated adaptive)

Present in all nucleated cells and displays endogenous antigens to cytotoxic T-cells CD8+

MHC class II (humoral adaptive)

Found on macrophages, dendritic cells, and B cells, it binds to CD4+ T-helper cells

How many signals are required for T cell activation?

Two signals required (co-stimulation)

1) TCR

2) Verification signal

Co-stimulation

Complete T cell activation requires T cell to also bind to one or more co-stimulatory signals on surface of APC

Describe the first and second stimulation (co-stimulation) of naive CD4 T-lymphocytes in the humoral adaptive response

First stimulation

- CD4+ T-helper cell binds MHC-II of APC

- TCR interacts with antigen within MHC-II

Second stimulation

- T-helper cells release IL-2 which stimulates T-helper cells to clonally expand

Activated T-helper cells proliferate and differentiate to form clone of activated and memory T-helper cells

Describe the first and second stimulation (co-stimulation) of naive CD8 T-lymphocytes in the cell-mediated adaptive response

First stimulation

- CD8+ cytotoxic T cells bind MHC-I on various cells

- TCR interacts with antigen within MHC-I

Second stimulation

- IL-2 from T-helper cells stimulates cytotoxic CD8 cells to clonally expand

Activated cytotoxic T-cells proliferate and differentiate to form clone of activated and expanded memory cytotoxic T-cells

Describe the first and second stimulation (co-stimulation) of naive B-lymphocytes

First stimulation

- Free antigen binds to BCR

- B cell engulfs, processes and presents antigen to T-helper cells

Second stimulation

- IL-4 released from activated T-helper cells which stimulates B cells

Activated B cells then proliferate and differentiate to form clone of plasma cells and memory B cells via clonal expansion. Antibodies are secreted from plasma cells.

What T-helper cells are the basis of the delayed-type hypersensitivity reaction Mantoux test in response to tuberculin?

Th1

Th17

Cytotoxic T cells (CD8) kill cells expressing recognized antigens - these cells include...

1) Normal cells containing viruses

2) Mutated/cancerous cells

What interleukins do Th2 CD4 cells respond to?

IL4, IL5, IL13 = mast cells

IL4, IL5, IL13 = eosinophils

What interleukins do Th17 CD4 cells respond to?

IL17, IL22 = neutrophils

Th2 CD4 cells produce cytokines (IL4, IL5, IL13) that activate...

- B cells = antibodies

- Mast cells = allergy

- Eosinophils = helminth

Th17 CD4 cells produce cytokines (IL17, IL22) that activate...

- Neutrophils = phagocytosis

Th1 CD4 T cells produce cytokines (CD40, IFN-gamma) that activate...

- B cells = antibodies

- Macrophages = phagocytosis

- CD8 cells = cytotoxic T cells

Which CD4 T-helper cells are involved in attack of extracellular microbes (cell-mediated)

Th2 = B cells, Eosinophils, Mast cells

Th17 = Neutrophils

Which CD4 T-helper cells are involved in the attack of intracellular microbes (humoral)

Th1 = CD8, B cells & Macrophages

The Fc region of the antibody attacks ___ cells and ___

NK cells and phagocytes

Adaptive immune response deactivation is also known as ___

Contraction (homeostasis)

The elimination of microbes lead to a loss of activation signals. T-cell regulator signalling outweights the activation signals (homeostasis).

Reduction in response leads to apoptosis of phagocytes and the surviving lymphocytes are memory cells

T-cell memory

T-memory cells no longer express effector molecules - but their genes remain in low-methylation state.

Pool of memory cells determined by future exposure.

These memory cells are converted to effector cells on second encounter with antigen that binds receptor.

Characteristics of the memory response

- Primary response is lower

- Secondary response activates memory cells to convert to effector cells. This is a faster, stronger response with a longer duration.

Removal of self-reactive immune cells

Negative selection

Process by which T- and B- cells create a vast repertoire of distinct cell surface molecules

Somatic gene rearrangement

Enrichment and proliferation of cells producing cell surface receptors with a high affinity for foreign antigens

Clonal selection

Ingestion of foreign organisms and appearance of their components on the cell surface

Antigen presentation

All healthy nucleated cells express ___

MHC-I and self-antigens

Infected nucleated cells express ___

MHC-I and non-self antigens

Macrophages (professional APCs) present ___ following ingestion of microbes and are activated by the action of ___ cells

Macrophages (professional APCs) present MHC-II and non-self antigens following ingestion of microbes and are activated by the action of T-helper cells

Label this antibody

A = Antigen binding site

B = Immunoglobulin heavy chain

C = Immunoglobulin light chain

D = Variable region Fv

E = Constant region Fc

F = Hinge region

G = Fab region

Which cytokine?

Promotes maturation of myeloid lineages

IL3

Which cytokine?

Secreted by NK cells in response to infection (or stressed cells) promoting the innate immune response

Interferon-γ

Which cytokine?

Stimulates neutrophil maturation

G-CSF

Which cytokine?

Stimulates maturation of Th2 T-helper cells

IL4

Which cytokine?

Stimulates lymphocyte proliferation

IL2

Which lymphocyte population is particularly impacted following HIV infection?

T-helper cells (CD4+)

The following diagram shows the release of IgA from mucosa-associated lymphoid tissue into the lumen of the gut to neutralize pathogens.

Identify the three cell types A, B and C

A = Dendritic cells

B = B-lymphocytes

C = Plasma cells

When an extracellular microbe is presented to an APC, which effector cell is stimulated?

CD4+

Th2/Th17