Immune cell markers, passive and active immunity, vaccines

The immune system protects the body by detecting threats and coordinating responses that limit infection or other harm. Innate defences act broadly, while adaptive immunity depends on lymphocytes that recognise particular features of a threat. These features, called antigens, may be molecules from a microbe, a toxin or an abnormal cell. Recognition is not the same as destruction: immune cells must also receive appropriate signals, meet their targets and avoid damaging healthy tissue.

Adaptive immunity has two closely connected arms. In antibody-mediated, or humoral, immunity, B cells produce antibodies that bind antigens outside cells. In cell-mediated immunity, T cells recognise antigen displayed by other cells and help organise responses or kill infected or abnormal cells. Communication between immune cells matters: adhesion molecules help cells move into tissues, make contact and form signalling interfaces. LFA-1, an adhesion molecule, can help T cells activate and proliferate after their antigen receptor is engaged. More broadly, adhesion molecules support immune-cell movement and interactions with target cells.

Active immunity develops when a person’s own immune system responds to an antigen. Infection can produce active immunity, as can vaccination. The response takes time to develop because antigen-specific lymphocytes must become activated and expand. Some of their descendants become memory cells, which can respond more readily if they encounter the antigen again. The strength and duration of protection vary; a vaccine does not guarantee that infection will never occur, but it can prepare immune responses to act more effectively.

Passive immunity comes from antibodies made by another person or an antibody-producing source. It provides ready-made protection, so it can act without waiting for the recipient to build an antibody response. However, the recipient’s immune system has not necessarily generated the same memory as it would after active immunisation. Antibodies transferred from a parent to an infant are a natural example; administered antibody preparations are an artificial example. The protection is temporary as the transferred antibodies are broken down.

Vaccines expose the immune system to an antigen, or instructions for making it, in a way intended to prompt protective adaptive responses. Vaccine designs include weakened live organisms, inactivated organisms, purified components, toxoids, conjugated antigens, viral vectors and messenger RNA. These approaches differ in what the immune system encounters, but the teaching principle is shared: antigen recognition can stimulate antibody production, T-cell responses, immune memory, or a combination. Adjuvants can strengthen the response to an antigen. Vaccines are preventive tools, not treatments that instantly supply antibodies.

A cell-surface marker is a molecule on the outside of a cell that can help identify its lineage, developmental state or activity. “CD” means cluster of differentiation: the labels are standard names for molecules identified and grouped through immunological research. A marker is useful because it gives information about the cell, but it is not a complete description of what that cell is doing. Laboratory interpretation relies on combinations of markers, the tissue sample, and the clinical question.

T cells are lymphocytes whose antigen receptors recognise fragments of antigen displayed by other cells. Their functions depend on the signals received and the kind of antigen presentation they encounter. Broadly, helper T cells coordinate other immune cells by releasing signalling molecules; cytotoxic T cells can kill infected or abnormal target cells; regulatory T cells restrain responses; and memory T cells persist after an encounter. These functional groups overlap in complex ways, so a marker panel can suggest a role without proving the cell’s complete functional state.

CD8 is a surface marker associated with cytotoxic T cells. CD8+ T cells are important in protecting the host from malignant tumour growth. In general, cytotoxic T cells use their antigen receptor to recognise a target and then deliver signals or cytotoxic granules that can damage it. Effective killing requires contact with the target, not merely recognition from a distance. LFA-1 can support the contact interface between a cytotoxic T cell and its target, and can contribute to cytotoxic granule release and target-cell killing. Immune-cell adhesion also assists movement into tissues and the formation of contact-dependent signalling interfaces. ^[2]

A marker’s meaning depends on context. A T cell in blood may have a different activation state from a T cell inside an inflamed tissue or tumour. Some markers are associated with lineage, while others change with activation, migration or differentiation. A result showing a marker therefore needs to be interpreted alongside other cellular features; it does not by itself establish whether the cell is protective, exhausted, suppressive or actively killing a target.

B cells are adaptive lymphocytes that recognise antigen through a membrane-bound antibody called the B-cell receptor. When the receptor binds a suitable antigen, the B cell can take that material inside, process it and present fragments to helper T cells. Signals from these interactions can promote B-cell activation and expansion. This coordination links antigen recognition to a more complete immune response rather than making antibody production an isolated event.

Activated B cells can become plasma cells, which secrete antibodies, or memory B cells, which persist and can respond to later encounters. Antibodies bind specific antigens. Depending on their properties and location, they can block a pathogen from attaching to cells, mark targets for other immune components, or help neutralise toxins. Different antibody classes have distinct roles and distributions. The key distinction is that the B-cell receptor is attached to the B cell, while secreted antibody circulates or enters tissues to bind antigen beyond the cell.

This biology explains the difference between vaccine-induced and passive antibody protection. A vaccine can stimulate B cells to produce antibodies and generate memory, while transferred antibodies provide immediate, temporary binding capacity without requiring the recipient to make them. Vaccines can also stimulate T-cell responses, so protection is not always limited to circulating antibodies. The balance depends on the antigen and vaccine design. An antibody measurement may show that antibodies are present, but it does not automatically show how well they bind, whether they reach the relevant tissue, or whether other immune functions are adequate.

B-cell identification also uses surface markers, interpreted as a pattern rather than as a complete functional diagnosis. Surface immunoglobulin is informative because it forms the B-cell receptor. Other surface proteins may contribute to antigen presentation, signalling or cell adhesion. Adhesion is relevant to B cells because they must move through tissues and interact with other cells; it is distinct from antigen recognition by the B-cell receptor.

Disease can alter these patterns. In chronic lymphocytic leukaemia, the expression of adhesion molecules including β2- and β1-integrins, CD54, CD62L and CD44 is very low on peripheral-blood and bone-marrow CLL cells compared with cells from healthy donors. This finding illustrates why a marker associated with cell contact or movement should not be treated as a universal B-cell label: expression can differ between healthy and malignant cells. Integrin signalling can also be abnormal in CLL cells, and LFA-1 may be active without the chemokine-induced clustering seen in healthy B cells. Such changes affect how cells interact with their surroundings; they do not redefine the basic role of B cells in antibody-mediated immunity. ^[2]

Natural killer (NK) cells are lymphocytes of the innate immune system. They respond to signs that a cell is stressed or abnormal, rather than relying on the highly specific antigen receptors used by B and T cells. Their response depends on the balance between activating and inhibitory signals from the target. If activating signals prevail, an NK cell can release cytotoxic granules that damage the target and can produce cytokines, including interferon gamma, that influence other immune cells. These abilities make NK cells relevant to defence against infection and to surveillance of transformed cells.

Markers help distinguish NK cells from other lymphocytes, but their meaning depends on the combination being measured. In the mouse tumour experiments described here, cells that were NK1.1-positive and CD3-negative also stained for CD49b and granzyme B; this pattern suggested conventional NK cells rather than ILC1 cells. NK1.1 is also an activating receptor: stimulating it in vitro led NK cells to secrete the chemokines CCL5 and XCL1. These chemokines can help explain how NK cells influence the wider immune response, not merely attack targets directly. ^[1]

In mouse tumours, NK cells were found near type one conventional dendritic cells, or cDC1. The two cell types formed clusters, with NK cells located within 5–10 μm of cDC1. This close positioning may support communication between the cells. NK-cell chemokines can help draw cDC1 into the tumour environment, while chemokines from cDC1 may also attract NK cells; their clustering could therefore reinforce local interaction. The proposed consequence is a link between innate recognition and adaptive immunity: cDC1 can help initiate T-cell responses, and the NK–cDC1 interplay is associated with CD8-positive T-cell-dependent anti-tumour immunity. ^[1]

Experiments that removed NK cells show why their role is broader than direct killing. NK-cell depletion led to rapid growth of tumours in the mouse model. It was also associated with fewer intratumoral cDC1 and fewer CD8-positive, but not CD4-positive, T cells. Conversely, cDC1 deficiency did not alter NK-cell numbers in that model. Together, these findings support a pathway in which NK cells can help recruit or position cDC1, while also contributing to tumour control through their own effector functions. ^[1]

Tumours can suppress this pathway. Prostaglandin E2 (PGE2) reduced NK-cell survival and inhibited their CCL5 and XCL1 production; the reduction in chemokine secretion was dose-dependent. Interleukin-15 could rescue NK-cell survival, but not restore the impaired chemokine production. PGE2 did not induce the inhibitory receptors PD-1 and TIM-3 in the reported experiments. Thus, a change in NK-cell function should not automatically be interpreted as increased expression of those receptors: survival, chemokine output, cytotoxicity and receptor expression are distinct features to assess. ^[1]

Macrophages are tissue phagocytes: they take up microbes, damaged cells and debris, then digest the material inside the cell. They also sense signals from their surroundings and release cytokines and other mediators that shape inflammation. Depending on the tissue and the signals present, macrophages can support antimicrobial defence, remove dying cells, help regulate repair, or contribute to persistent inflammation. Their activity is not a fixed switch between two simple states; the local environment influences which functions dominate.

Macrophages can process material they have engulfed and display fragments of it to T cells. This makes them a bridge between innate sensing and adaptive responses, although dendritic cells are especially important for initiating responses from previously unactivated T cells. When interpreting macrophage markers, a single stain should not be treated as a complete description of the cell. Marker expression can vary with tissue, developmental origin and activation state, so combinations of markers are interpreted alongside cell location, morphology and function.

Haematopoietic stem cells are self-renewing cells in the blood-forming system. They generate progenitors that mature into the many blood and immune cell types. A stem cell is not itself a mature macrophage or lymphocyte: differentiation is the process by which descendants acquire the specialised features and functions of those cells. Macrophages can arise through more than one developmental route, including from circulating monocytes and from populations established in tissues. This helps explain why macrophages in different organs may behave differently even when they share broad phagocytic functions.

Active immunity develops when a person’s own immune system responds to an antigen. Infection can produce such a response, and vaccination aims to prompt it without requiring the person to undergo the disease itself. B cells can produce antibodies, while T cells can develop functions directed towards infected or abnormal cells. Some responding cells persist as memory cells, allowing a later encounter with the antigen to prompt a faster or stronger response. Macrophages and dendritic cells can contribute by taking up vaccine material and providing signals that help shape the developing response.

Passive immunity is different: protective antibodies are received from another source rather than made by the recipient’s immune system in response to that antigen. This can provide immediate antibody-mediated protection, but it does not itself create the same process of immune memory as active immunisation. The distinction is useful when tracing an immune pathway: active immunity involves recognition, activation and development of the recipient’s own response; passive immunity supplies ready-made antibodies. Neither description means that every vaccine or antibody preparation works in the same way, so the specific product and clinical context matter.

Immunity is the ability to recognise and control a threat, such as a virus or bacterium. It can arise because protective molecules are supplied from elsewhere, or because a person’s own immune system responds to an antigen and builds a response. These are called passive and active immunity. Both can reduce harm from infection, but they differ in how protection begins and whether immune memory is formed.

In passive immunity, the person receives antibodies made by another person or produced for treatment. The antibodies can bind a pathogen or its toxin, block entry into cells, or mark targets for removal. Protection can begin promptly because the antibodies are already present. However, the recipient’s immune system has not necessarily been activated to make those antibodies, so this transfer does not itself establish immune memory. As the supplied antibodies are broken down, their protective effect wanes.

Passive protection occurs naturally when maternal antibodies reach a baby, including across the placenta and through breast milk. It can also be provided as a treatment, for example with immunoglobulin preparations, a targeted monoclonal antibody, or antivenom. Each supplies a particular set of antibodies; the breadth of protection depends on what those antibodies recognise. Passive antibody can be useful when protection is needed without waiting for the recipient to mount a response, but it cannot be assumed to prevent every infection or create lasting immunity.

Active immunity develops when a person’s immune system encounters an antigen and responds. The encounter may occur through infection or vaccination. Antigen-presenting cells take up material and display antigen to lymphocytes. B cells that recognise it can develop into antibody-secreting cells, while T cells help coordinate responses or act against infected cells. Some activated cells persist as memory cells. If the same antigen is encountered again, these cells can support a quicker or stronger response.

Vaccines aim to create useful immune recognition without requiring the person to undergo the disease itself. The antigen may be delivered in different forms, so vaccine types differ in how they stimulate antibody and cellular responses. Active immunity usually takes time to develop, because the immune system must respond; once established, memory can persist, though its strength and duration vary. A person’s response can depend on factors such as health, age, immune function, and the vaccine used.

Immune markers help describe what cells are present or what a response has produced. Surface markers can help distinguish broad cell populations, while antigen-specific antibodies can indicate recognition of a particular target. A marker is evidence to interpret, not immunity itself: the presence of a cell type or antibody does not by itself establish how well a person is protected. Antibody tests after passive transfer need particular care, since detected antibody may have come from the donor or treatment rather than being made by the recipient. Tests of cellular function can add information when antibody measurement alone does not answer the question. ^[1]

A live attenuated vaccine contains a living pathogen that has been weakened so it is less able to cause disease in a person with a functioning immune response. It remains capable of limited replication. That limited activity exposes the immune system to a range of pathogen antigens in a way that can resemble parts of natural infection, while aiming to avoid the full illness. Attenuation is therefore different from simply killing or chemically inactivating a pathogen: an inactivated vaccine cannot replicate, whereas a live attenuated vaccine can.

After vaccination, innate immune sensors detect the vaccine organism and help initiate inflammation and antigen presentation. Antigen-presenting cells activate lymphocytes, and the resulting response can include antibodies, helper T-cell activity, and cytotoxic T-cell activity. Because the organism can replicate locally, the immune system may encounter antigen over a period rather than in a single exposure. Some live vaccines are given by routes that expose mucosal surfaces, which can support local as well as systemic immune responses. The response varies by vaccine and person; no one vaccine format guarantees the same degree of protection for everyone.

Examples of live attenuated vaccines include measles, mumps and rubella vaccine, varicella vaccine, yellow fever vaccine, rotavirus vaccine, and some influenza vaccines given into the nose. These examples illustrate a vaccine class, not an interchangeable set of products. Each vaccine targets a different pathogen, uses a particular weakened strain or formulation, and has its own approved route and schedule. A name alone does not establish which product is suitable for a particular person.

The ability to replicate explains both a potential advantage and an important safety consideration. Limited replication can provide substantial antigen exposure, but a live organism may pose a risk when immune defences cannot contain it. The balance depends on the person’s clinical circumstances and the product. Product-specific guidance is therefore relevant when considering vaccination for someone with severe immune suppression, or in circumstances such as pregnancy. This is not the same as saying that every live vaccine has identical restrictions.

Live attenuated vaccines can also have practical limitations. They may require careful storage to preserve the organism’s viability, and an immune response to one vaccine can sometimes affect the response to another given close in time. The details depend on the products and their use, so timing and handling should be taken from current product guidance rather than inferred from the vaccine class. After vaccination, mild symptoms may reflect a response to the vaccine, but symptoms alone cannot confirm that protective immunity has developed.

For teaching purposes, compare the vaccine’s biological behaviour with the immune outcome it is intended to produce: a weakened organism can replicate; antigen is presented; B and T lymphocytes respond; and memory may form. The pathway is not a guarantee of an individual outcome. When interpreting immune markers afterwards, distinguish evidence of exposure or antibody production from evidence that the person is clinically protected. That distinction matters for live attenuated vaccines just as it does for other vaccine types.

Vaccination introduces an immune system to a target associated with a pathogen, without relying on the person experiencing the disease itself. The target, or antigen, is recognised by immune cells. B cells can make antibodies that bind it; other immune cells can help direct the response or kill infected cells. Some activated cells persist as memory cells, allowing a later response to the same target to begin from a more prepared state. The details depend on the vaccine design: different designs present different forms of antigen and can favour different parts of the immune response.

An inactivated vaccine contains a pathogen that has been made unable to reproduce. Its components can still be recognised, but the pathogen cannot multiply and cause infection. Because it does not reproduce in the body, the immune system encounters the antigens supplied in the vaccine rather than a growing infection. An inactivated vaccine may contain the whole pathogen, so it can expose the immune system to more than one of its components.

A subunit vaccine contains selected parts of a pathogen rather than the whole organism. These might be a protein or another component that the immune system can recognise. This focused design avoids introducing the complete pathogen, but the selected antigen must still prompt a useful immune response. A conjugate vaccine is a particular strategy for presenting an antigen: a polysaccharide is linked to a carrier protein. The protein helps recruit T-cell help, which supports a stronger, more organised antibody response to the linked target.

A toxoid vaccine uses a toxin that has been changed so that it no longer causes its toxic effect but remains recognisable to the immune system. The response can then produce antibodies that bind the toxin if it is encountered later. This is different from targeting the organism that made the toxin: the vaccine is designed around the harmful product.

An mRNA vaccine provides instructions for making a selected pathogen protein. The body’s cells use those instructions to make the protein temporarily; the immune system then recognises it as an antigen. The vaccine does not supply a whole replicating pathogen. The instructions are not the immune target in the same way as the protein they encode: the aim is for the protein to be made and recognised.

Do not treat active and passive immunity as two names for vaccination. In active immunity, the person’s own immune system responds to an antigen and may form memory cells. Vaccination is intended to produce active immunity without requiring the person to acquire the disease. Passive immunity instead supplies ready-made antibodies. Those antibodies can act without waiting for the recipient to make them, but they do not train the recipient’s immune system to make its own lasting memory in the same way.

A related error is to assume that every vaccine uses the same antigen or produces the same kind of response. An inactivated vaccine presents a pathogen that cannot reproduce; a subunit vaccine presents selected components; and an mRNA vaccine supplies instructions so that cells make a protein. A toxoid targets a toxin, while a conjugate links a polysaccharide to a carrier protein. These distinctions explain why it is important to identify what the vaccine is designed to make the immune system recognise.

αDβ2 (CD11d/CD18) is expressed on neutrophils, monocytes and NK cells. ^[2]

Cell interaction also matters. During contact between a dendritic cell and a T cell, LFA-1 binding to ICAM-1 helps stabilise the immunological synapse. The organised contact site has regions with different molecules: LFA-1 and ICAM-1 are associated with its peripheral region, while the central region is enriched in T-cell receptors and associated molecules. Large molecules such as CD45 and CD43 are in the distal area of the synapse. This organisation helps explain why cell markers and cell behaviour are related, but not interchangeable. ICAM-1 can increase during inflammation, and its binding to leukocyte integrins helps cells move across the endothelium towards inflamed tissue. ^[2]

A useful way to think through a vaccine is to ask what the intended immune target is, how that target is presented, and what sort of protection is sought. A pathogen may cause harm through its own invasion or through a toxin it produces. A vaccine directed against a toxin therefore asks the immune system to recognise a different target from a vaccine directed against a pathogen component. Similarly, linking a polysaccharide to a carrier protein is not simply adding another antigen: it is a way to bring T-cell help into the response to the linked target.

Passive immunity has a different practical role from vaccination. Ready-made antibodies can provide antibody activity without waiting for the recipient to generate an active response. In contrast, a vaccine aims to prompt the recipient’s immune system to respond and form its own memory. The distinction helps explain why passive antibody and vaccination are not interchangeable descriptions of the same intervention. The choice depends on the purpose and clinical context; no particular product, schedule or dose can be inferred from the vaccine categories alone.

When reading an immunology result, begin with the cell population and then consider the marker pattern. For example, dendritic cells can present antigen and interact with T cells. Their contact is not just a collision: adhesion molecules help keep the cells together while the T cell receives signals. LFA-1 is present across leukocytes and is especially prominent among lymphocytes, whereas αXβ2 is most abundant on myeloid dendritic cells. LFA-1–ICAM-1 binding also contributes to the organised dendritic-cell–T-cell synapse. This gives a practical link between marker expression, cell interaction and the development of an immune response, without making a marker alone a measure of protection. ^[1][2]

A teaching outline for classifying the vaccine design is:

In practice, classification is a starting point, not a substitute for considering the actual vaccine and the person receiving it. The category tells you how the target is presented; it does not, by itself, establish an individual’s immune status or guarantee protection. Keep the mechanism, the intended target, the person’s clinical context and any measured immune response conceptually separate.