Basics of Immunity

What are the reaction times of the innate and adaptive immune system?

innate respones: 1-12 hours ; adaptive response 1-7 days (memory of cells)

What are the 3 immunological components in the blood, lymph and tissue?

• White blood cells (leukocytes): lymphocytes+ granulocytes

• Plasma proteins: complement, antibodies

• Lymphatic system: circulates immune cells and connects lymphoid organs

Distinguish between the primary and secondary lymphoid organs.

• primary: development of the adaptive immmune cells (b-cells → bone marrow, t-cells → thymus)

• secondary: activation of the adaptive immune cells (spleen and lymph nodes)

What are the different progenitors of the immune cells?

• myeloid progenitors: granulocytes, macrophages, dendritic cells

• lymphoid progenitors: b-cells, t-cells, adaptive NK cells

→ note some lymphocytes cells can also be innate

What are the 3 lines of defense in immune system?

• physical barrier - skin (first line of defense)

• innate immunity - quick response by production of inflammation by cytokine and chemokine signalling for actiavtion and migration.

• adaptive immunity - dendritic cells activate CD4 and CD8 T-cells and also B-cells in the secondary lymphoid organs during inflammation.

What are 4 characteristics of innate immunity?

• rapid within a few hours

• fixed response

• limited number of specificities

• constant during course of response

Adaptive immune system is …

slow and adaptable

How does an immune response go from being innate to being adaptive?

• pathogen uptake → innate immune respone → chemokines, cytokines, macrophages → inflammation → activation of dendritic cells → migration of DCs to secondary lymphoid organs → activation of B/T-cells for adaptive immunity

Show the interactions between immune cells during adaptive immunity?

Distinguish between B/T-cells?

• T-cell: cellular response, interaction with other cells, effect will be on interacting cell

• B-cell: differentiation into plasma cells that produce antibodies with effector functions.

What are some antibody effector functions?

• neutralisation

• opsonisation

• complement activation

Innate Immune Receptors

• pattern recognition receptors → can recognise major pathogenic species

• binding of associated molecular patterns → pathogens or danger signals

Adaptive Immune Receptors

• T/B-cell receptors

• Specificty is different per cell - can differentiate within major pathogen species

• Can recognise antigens (peptides recognised by receptors)

How do B/T-cells express receptors with the correct specificity?

• T/B-cells express mant TCR and BCR but only have one specificity per cell

• When an ongoing infection happens the antigens are recognised and the T-cells are activated in the secondary lymphoid organs

• Those cells will proliferate and become clones with all the same specificity (for one epitope)

• → clonal expansion (takes a week) - creates memory

What are macrophages?

• Big eaters (phagocytosis) is the innate immune system and alert the system upon infection

• Present in the tissue

• Receptors distinguish between self and non-self

What are the two modes of interaction with macrophages?

• C-Type lectin receptors: belong to the family of scavenger receptors

  • non-self pathogens have carbohydrate residues so the entire pathogen binds extracellularly to the CTL of the macrophage

  • results in phagocytosis and degradation

• Toll-like receptors

  • recognise pathogen specific structures (peptides, RNA, DNA)

  • ligands are highly preserved and essentiatl to pathogen survival

  • intracellular/extracellular

  • results in activation and cytokine secretion

What are neutrophils and when are they activated?

• during a bacterial infection macrophages can recruit neutrophils from the bone marrow to collaborate and clear the bacterial infection through phagocytosis

• Recruited to infection site from bone marrow

• Signature multi-lobular nucleus

• Express scavenger receptors

• efficient killers with short life span

What is the accute phase response?

• macrophages induce the acute phase response upon bacterial infection for systemic responses

• the acute phase response induces production of proteins that enhance inflammatory etector functions

What do macrophages do upon a viral infection?

• Macrophages activate NK cells to kill virally infected cells.

• Virally infected cells secrete cytokines such as IFN alpha and beta which ensure the activation of the recruited NK cells

• These NK cells have receptors which can distinguish between self and non-self

Explain the ligand receptor interaction for NK cells.

• target cells express inhibiting (always expressed) and activating (only in stress) ligands

• NK cells have ligands which can distinguish between healthy and un-healthy and we have a combination of activating and inhibiting receptors being expressed.

• Interferons alpha/beta activate NK cells

• When a target cell gets infected → expresses activating ligands → ligands bind to receptors on NK cells and cells can enhance the killing of those infected cells

So what are the main functions of interferons?

• reduce viral replication and activate NK cells

What is the complement pathway?

• complements inflammation

• C3 is key component which is cleaved for tag and recriutment

• C3 → C3a anaphylatoxin (inflammation and immune cell recruitment) & C3b opsonin (complement fixation)

What does C3a do?

• enhance inflammation within minutes by activation of endothelium and immune cell recruitment

What does C3b do?

• complement fixation

  • recruited immune cells like macrophages express CR receptor which C3b, bound to pathogen, can bind to

  • CR-C3b binding causes phagocytosis of the pathogen and degradation by acidic lysosomes.

• formation of the memrane attack complex for lysis of pathogen

What are the 3 pathways that can form C3 convertase and start complement fixation?

• alternative pathway, lectin pathway, classical pathway

Alternative Pathway

Lectin Pathway

in liver

Classical Pathway

in liver