Overview of the adaptive immune system Flashcards
Principles of adaptive immune system
Why do we need the adaptive immune system when we have the innate immune system?
- Allows for enhanced specifity as a consquence of previous events (exposure or vaccination)
- Allows for memory and a anamnestic response (not forgetting)
Describe the purpose of adaptive immune system and why we have it?
- Protection and defence against pathogens: Also role in malignancy surveillance. Also linked to damage healing and repair
- The same pathogens often come back and attack again: Opportunity to have effectors ready which are specific and potent
- Some pathogens stick around (in the body even after infection is resolved e.g. HSV): Need controlling by effectors
- These effectors are primarily lymphocytes
How pathogens are recognised
How are pathogens spotted from the adaptive immune system?
- Generic recognisable features e.g. PAMPS
- Presence is associated with damage -> danger hypothesis
2a. Damage requires co-stimulation with CD28+ cells
2b. Recognition of Damage-associated molecular pattern molecules (DAMP)
2c. Danger hypothesis = It is based on the idea that the immune system
does not distinguish between self and non-self, but rather between things that might cause damage and things that will not - Re-exposure to previous infections
- Autoimmunity -> distinguishing self vs non-self
- PRRs
Drivers of adaptive response
How does the immune system set up a system to recognise things not yet seen and describe the potential problems from this?
- Undergoes a “massive array of possibilities” approach
- Problems:
1. Over- or under- assidious (great detail) recognition
2. Time and energy consuming
3. Self recognition -> can target self
Lymphocytes
State 3 types of B cell lymphocyte deficiency/ defect syndrome?
- Congenital agammaglobulinaemia
- Common variable immunodeficiency (CVID)
- Novel biologics - Rituximab
- Often leads to major life-threatening clinical problems
Lymphocytes
State 3 types of T cell lymphocyte deficiency/ defect syndrome?
- Severe Combined Immunodeficiency (SCID)
- DiGeorge syndrome -thymic failure
- Acquired - HIV / Chemotherapy / Novel biologics
- Often leads to major life-threatening clinical problems
State the cells found within the innate/adaptive spectrum?
- Innate: Neutrophils, Monocytes, Eosinophils, basophils Macrophages, NK cells, DC cells. Tissue cells, platelets
- Adaptive: B cells, T cells, Plasma cells
State the bridging cells found in the innate/adaptive spectrum?
- Memory NK cells
- iNK T cells
- V52+ Y5 T cells
- MAI T
State the 5 factors used to define lymphocytes?
- Morphology: White cell; small, large nucleus
- Lineage: T and B cells
- Location: Tissue-resident memory cells (TRM) - Marginal zone B cells
- Differentiation: Naïve / memory (central, effector, stem cell memory) - b. Immature / mature or differentiated / senescent
- Function: What they do: eg Helper / Cytotoxic / Regulatory / Antibody-producing
State the 4 characteristics used to show what a lymphocyte is?
- Phenotype: What surface markers they express
-Eg CD4, CD8, CD28 … Usually functional receptors-not just there for our convenience! - Specificity: What target - What Ab produced or epitope recognised (TCR)
- Type of receptor: Ig class for B cells / a vs y for T cells
- By what they produce: TH1 (IL-2, IFN-V). TH2 (IL-4, IL-5, IL-6, IL-10)
- Key point: Dimensions (I have 9) co-exist and co-define cells
Mechanism of adaptive immunity
State the key features involved in adaptive immunity? (3)
- Specificity
- Memory
- The pivotal role of clonal selection: One clone - one specificity. Progeny can be expanded and retained
Describe clonal selection in adaptive immunity? (PART 1)
- Occurs via two key lineages of adaptive immunity -> B and T cells
- Basic tenet - one cell one specificity •
Describe clonal selection in adaptive immunity? (PART 2)
- For B cells - one cell, one Ig/B-cell receptor
- Defined by their antibody
- May class switch / undergo affinity maturation
- But always the same basic Ig
Describe clonal selection in adaptive immunity? (PART 3)
- For T cells - one cell, one T cell receptor - TCR
- Selection and expansion of that clone + differentiation
- Retention in “memory” of clonal progeny
Describe clonal selection in adaptive immunity? (PART 4)
- Continued protection:
- Continued production of antibody (B cells / Plasma cells)
- More rapid specific secondary responses (Band T cells)
Describe the structure of an Ig, T-cell receptor and antibody?
VD
Describe how TCR detects peptides presented?
- TCR does not just “go fishing” in the extracellular milieu
- Detects a peptide sequence in association with MHC
- Pathogen peptides need to be processed and presented
- All cells process their intracellular contents and present on MHC-1: Recognised by CD8 T cells through their TCR. Crucial to defence against viruses
- Specialised antigen-presenting cells (APC) process and present peptides in MHC-II: Binds to TCR on CD4 T cells
State positive and negative thymic selection of T cell?
- Positive selection must bind MHC
- Negative selection must not bind self peptides
What occurs once thymus selection has occured for T cells?
- Naive/memory cells recirculate
- Primarily from blood to lymph nodes
Describe the turnover rate for Naive/memory T cells?
They have slow turnover rates -> considered the ‘sleeping beauties’ of the immune system
State the T-cell differentations stages and how their features change as u go along?
VD
Describe differences between Central memory T cells (TCM) and effector memory (TEM)? (PART 1)
- TEM:
- Effector Memory cells
- Short-lived population continually replenished doubling time about 15 days
- CCR7+ CD62L+
- Enter lymph node and recirculate
Describe differences between Central memory T cells (TCM) and effector memory (TEM)? (PART 2)
- ТСМ
- Central memory cells
- Turnover at a significant rate - Doubling time about 48 days
- CCR7 - CD62L
- Migrate into tissues
- Rapid effector activity: Cytolytic, Cytokines (IFg/IL4/IL-5)
- Turnover rate: TEM > TCM
Describe regulatory T cells (Treg)?
- Also very dynamic
- Control the responses of other T cells
Describe the key concepts behind immunological memory?
- Accrued cumulatively over time
- “Stored” for future use
- Readily available when required
- Dynamic process
Describe features of B cell repertoire selection?
- Positive + negative selection
- Receptor editing
- Transition to IgM+ IgD+ mature B cell
- Antigen recognition leads to proliferation/differentiation
- Activated B cells transform into Plasma cells: “Antibody factories”. also produce CD27+ memory B cell
Lymphocyte anatomy
Describe the structure of lymph nodes? VD
- Lymphocytes are mainly organised into LN
- Structure this way to facilitate cellular interaction
- Valves stop lymph from flowing in the wrong direction
- Lymph flows out of the node through wide vessels
- Lymph flows into node through narrow vessels
- Has densely packed B and T cells, macrophages and plasma cells
Which organ has a key role in antibody generation and describe what can increase the risk of infection if affected?
- Key role of Spleen in antibody generation
- Splenectomy increases the risk of infection
- Especially pneumococcal infection - recommend vaccination
Describe the role of tissue resident T cells and state its key marker?
- CD69+ key marker
- TM cells which resides long term in epithelial barrier tissues
