Immunology 5

Question 1

What is involved with the adaptive immune response?

Answer 1

Dendritic cells are the communication between innate and adaptive systems B cells + antibodies T cells

This response can take days-weeks to occur

Question 2

What are the stages of T and B cells recognising and responding?

Answer 2

Be able to recognise the pathogen

Find the pathogen

Activate

Respond

Question 3

Difference between innate and adaptive immune systems?

Answer 3

Innate - rapid, non-specific response in minutes-hours; same general response to many different pathogen species with PRRs on innate cells and PAMPs on pathogens (non-specific recognition)

Adaptive - slow, specific response (days) that is unique to each individual antigen (B and T cells do not have PRRs but do have antigen receptors for the antigens on pathogens). Responsible for generating immunological memory

Question 4

What are antigens?

Answer 4

Adaptive immune responses are induced by antigens - any substance which can cause an adaptive immune response by activating B and T cells

Question 5

Describe movement of T and B cells

Answer 5

Constantly circulate through the blood, lymph and secondary lymphoid tissues Inactive until meeting with antigen

Question 6

Functions of B and T cells?

Answer 6

Some are very long-lived (memory cells)

B cells - key role in defense against intracellular pathogens via ANTIBODY PRODUCTION

T cells - key role in defense against intracellular pathogens, (VIRUSES, mycobacteria):

Helper T cells - key regulators of entire immune system

Cytotoxic T cells - kill virally infected body cells

Question 7

PAMPs vs antigens?

Answer 7

PAMPs:

Non specific recognition - limited no. of PAMPs which are common to many different pathogens

Only a small no. of different PRRs are required to stimulate innate immune cells

Antigens:

Specific recognition - millions of different antigens; individual T and B cells only express one specific antigen receptor, which binds to only one specific antigenic epitope

Question 8

How do T cells and B cells recognise antigens?

Answer 8

T cell antigen receptor (TCR) - membrane-bound heterodimer that has an α chain and a β chain

B cells antigen receptor (BCRs) - membrane-bound antibody (IgM or IgD); BCRs have 4 chains (2 heavy chains and 2 light)

Question 9

What are antibodies?

Answer 9

AKA immunoglobulins - proteins produced by B cells in response to an antigen and which bind SPECIFICALLY to that particular antigen:

Expressed on B cell surfaces

Secreted as soluble proteins into extracellular fluids

Question 10

Function of antibodies?

Answer 10

Provide defense against extracellular pathogens (most bacteria, viruses and toxins)

Question 11

What are the regions of an antibody?

Answer 11

Each heavy and light chain contains a VARIABLE REGION (forms antigen binding site) and a CONSTANT DOMAIN

Different types of antibodies exist with same basic structure but DIFFERENT HEAVY CHAIN CONSTANT REGIONS

Question 12

Examples of differing heavy chain constant regions?

Answer 12

IgM - µ heavy chain

IgG - γ heavy chain

IgA - α heavy chain

IgE - ε heavy chain

IgD - δ heavy chain

Question 13

Describe specificity of antibodies and what advantage does this give the adaptive immune system

Answer 13

Individual antibodies have unique, differently shaped antigen-binding sites, so they bind specifically to one particular antigenic epitope

Adaptive immune system able to recognise and respond to millions of different, highly diverse antigens

Question 14

How can the adaptive immune system recognise millions of different antigens, when there are less genes than antibodies?

Answer 14

Antibody heavy and light chain proteins are encoded for by SEGMENTED GENES in the germ-line genome of HAEMATOPOIETIC STEM CELLS

RANDOM REARRANGEMENT of these gene segments occurs in individual B cells as they mature - produces a huge no. of antigen receptors and antibodies without having a lot of genes

Similar process of rearrangement of TCR α and β chain gene segments in developing T cells

Process of gene rearrangement is entirely RANDOM - giving rise to hugely diverse B and T cell populations and also to potential for AUTO-REACTIVE cells

Question 15

Where do adaptive immune responses occur?

Answer 15

In SECONDARY LYMPHOID TISSUES:

1. Mature antigen-specific T and B cells constantly re-circulate between different secondary lymphoid tissues, blood and lymphatic vessels
2. Mature dendritic cells, pathogens, antigens, debris, etc are trapped in secondary lymphoid tissues:

Lymph - lymph nodes

Blood - spleen

Question 16

How do T and B cells enter lymph nodes?

Answer 16

Use transendothelial migration

After several days, if they do not encounter specific antigen, B and T cells return to blood system via efferent lymphatics

Question 17

How do antigens enter a lymph node?

Answer 17

1. Particle and antigens derived from pathogens are released by phagocytes
2. Inflammatory TNFα stimulates immature tissue-resident dendritic cells, leading to B7 expression (on activated antigen-presenting cells) and dendritic cells also begin to PRRs
3. Dendritic cells phagocytose pathogen-derived particles and antigens
4. Dendritic cells digest pathogen-derived proteins and display small peptides on surface in complex with MHC proteins (Major Histocompatibility Complex)
5. Pathogen-derived particles, antigens and mature dendritic cells travel to local draining lymph nodes

Question 18

Function of dendritic cells?

Answer 18

“Professional” antigen-presenting cells that are:

Present in peripheral tissues in a “immature” state PHAGOCYTOSE antigens, cell debris and particles

Mature and migrate into secondary lymphoid tissues where they play a key role in ANTIGEN PRESENTATION

Question 19

Lymph node structure?

Answer 19

Tissue fluid (lymph) enters via afferent lymphatics and exits via efferent lymphatics Inside lymph nodes:

T cell zone

B cell zone with stromal cells

High Endothelial Venules (HEV) - express selectins allowing wbcs to bind and move down vessel

Question 20

Function of stromal cells in B cell zones?

Answer 20

“Trap” opsonised antigens, e.g: C3b on opsonised antigen and C3b receptor on stromal cells

Question 21

How are B cells activated?

Answer 21

Activation requires TWO SIGNALS

Protein antigens:

Signal 1: BCR + antigen

Signal 2: T cell help

Any antigen:

Signal 1 - BCR + antigen

Signal 2: PRR + PAMP

Antigens with repetitive antigenic receptors:

Signal 1 + 2: Multiple BCRs and antigens engagedw

Question 22

Function of Major Histocompatibility Complex (MHC)?

Answer 22

Bind peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells

T cells can only recognise peptide antigens presented by MHC, AKA HLA (HUman Leucocyte Antigens) - able to present many different peptides, encoded by highly polymorphic genes; first identified in early transplantation procedures

Question 23

Two classes of MHC proteins?

Answer 23

Class I MHC - expressed on ALL nucleated cells and present peptide antigens to cytotoxic T cells

Class II MHC - expressed ONLY on professional antigen-presenting cells, like dendritic cells, also macrophages and B cells; function is to present antigen to helper T cells

Question 24

Fate of antigen activated B and T cells?

Answer 24

Resting cells can become activated by specific antigen and co-stimulation

Activated cells:

Entry into cell cycle/mitosis

Differentiation to form EFFECTOR cells and MEMORY cells

Over 7-10 days