immunology test 1

What is immunity?

A state of protection against danger. The system protects against pathogens, self dangers such as cancer, and other damage.

What are the major categories of human pathogens?

Viruses, bacteria, fungi, and parasites. Examples include influenza virus, Mycobacterium tuberculosis, Candida albicans, and Plasmodium species.

Besides protection against pathogens, what else does the immune system do?

It constructs, repairs, clears debris, and maintains tissue homeostasis.

What are the major areas of health and disease connected to the immune system?

Infectious diseases, cancers, autoimmune diseases and allergy, primary and secondary immunodeficiency, organ transplantation, neurodegenerative diseases, atherosclerosis, ageing, development, repair, and tissue homeostasis.

What can happen when the immune system reacts too little?

Under-reaction can result in disease, including infections and cancer.

What can happen when the immune system reacts too much?

Over-reaction can result in disease, including autoimmune diseases.

What are the core components of both arms of the immune response?

Recognition of danger, signal transduction, response through effector molecules and cells, and regulation.

What are the two interconnected systems used by vertebrates in response to pathogens?

Innate immunity and adaptive immunity.

What are the major characteristics of innate immunity?

It is the first line of defense, acts quickly, is not antigen-specific, uses germline-encoded recognition, and has limited or no memory.

What are the major characteristics of adaptive immunity?

It is antigen-specific, uses somatic recombination in T and B cells, is learned, takes about 5 to 6 days or more to develop, and has potent memory.

How quickly does innate immunity respond compared with adaptive immunity?

Innate immunity responds within minutes to hours. Adaptive immunity takes days.

How does specificity differ between innate and adaptive immunity?

Innate immunity has limited and fixed specificity. Adaptive immunity is highly diverse and can adapt to improve during the immune response.

How does the response to repeat infection differ between innate and adaptive immunity?

Innate immunity responds the same each time. Adaptive immunity responds more rapidly and effectively with each subsequent exposure.

What are the major components of innate immunity?

Barriers such as skin, phagocytes, and pattern-recognition molecules.

What are the major components of adaptive immunity?

T and B lymphocytes, antigen-specific receptors, and antibodies.

What are PAMPs?

Pathogen-associated molecular patterns. They are specific molecular structures on pathogens that are recognized by pattern-recognition receptors.

What are DAMPs?

Damage-associated molecular patterns. They are specific molecular structures associated with apoptotic host cells and damaged or senescent cells.

What is important about PAMPs and DAMPs?

They are generic molecules found on many different types of pathogens or damaged host cells.

What are PRRs?

Pattern-recognition receptors. They are germline-encoded receptors that recognize PAMPs and DAMPs.

What happens when PAMPs or DAMPs bind PRRs?

They lead to anti-infection, antitumor, and other immunoprotective responses.

What are the major innate effector responses?

Cytokines and chemokines, complement activation, cytotoxicity, inflammation, and phagocytosis.

What is humoral immunity?

Adaptive immunity that combats infectious agents using antibodies that bind antigens. It primarily targets extracellular soluble agents.

What produces antibodies?

B lymphocytes, or B cells. Antibodies are also called immunoglobulins, or Ig.

What is cell-mediated immunity?

Adaptive immunity produced by T lymphocytes. T cells can eradicate cellular infectious agents, clear infected self-cells, or help other cells induce immunity.

What does the TCR recognize?

T-cell receptors bind peptide and major histocompatibility complex, or MHC, complexes called pMHC.

Where are pMHC complexes presented to T cells?

On the surface of cells, mostly dendritic cells.

What is clonal selection?

B and T cells each have an individual specificity for an antigen. When the appropriate antigen is encountered, the matching cell is selected and can expand into a clone.

Why is random receptor generation important?

It produces a large repertoire of receptors so that the population of B and T cells can theoretically recognize any antigen.

What is clonal deletion?

Removal of detrimental receptor rearrangements, including those recognizing self antigens or common antigens.

Where does B-cell development occur?

Bone marrow.

Where does T-cell development occur?

Thymus.

How are BCRs and TCRs generated?

Through somatic V(D)J recombination, producing randomly generated receptors.

What does V(D)J stand for?

Variable, diversity, and joining.

How specific are BCRs and TCRs compared with PRRs?

BCRs and TCRs bind very specific antigens, whereas PRRs recognize generic PAMPs or DAMPs found on many pathogens or damaged cells.

What happens during a primary adaptive immune response?

It is initiated during the first exposure to an antigen, and memory lymphocytes are left behind after pathogen eradication.

What happens during a secondary adaptive immune response?

A second exposure to the same antigen produces a faster, higher-magnitude, and more specific response.

Why is immunological memory important for vaccination?

The secondary response is faster, higher in magnitude, and more specific. This memory mechanism is the basis described for vaccination.

Does innate immunity have the same type of memory described for adaptive immunity?

No. This type of memory is not present in innate immunity.

What is active immunity?

Immunity produced by one's own immune system. Examples include vaccination, infection, and damage repair.

What is passive immunity?

Transfer of immune protection between individuals. Examples include immunity passed from mother to newborn or fetus, antiserum treatment, and prophylactic immune serum administration to immunocompromised individuals.

How does innate immunity influence adaptive immunity?

Innate immune cues inform the adaptive immune system whether a response is appropriate and what type of response should occur. At least two signals are required to activate T and B cells.

What innate immune effectors are used by adaptive immunity?

ADCC through NK cells, ADCP, and CDC.

What does ADCC stand for?

Antibody-dependent cell-mediated cytotoxicity.

What does ADCP stand for?

Antibody-dependent cellular phagocytosis.

What does CDC stand for?

Complement-dependent cytotoxicity.

What must the immune system tolerate?

Self-antigens and common harmless exposures.

What is hematopoiesis?

The process of generating differentiated cells from hematopoietic stem cells, or HSCs. It is highly regulated.

What are the two major properties of HSCs?

They are self-renewing and pluripotent.

What does pluripotent mean?

HSCs can differentiate into all types of blood cells.

How rare are HSCs in bone marrow?

There are fewer than 1 HSC per 5 × 10⁴ cells in bone marrow.

What are the primary lymphoid organs?

Bone marrow and thymus. They are where immune cells develop.

What are the secondary lymphoid organs?

Lymph nodes, spleen, and mucosa-associated lymphoid tissues, or MALT. They are where immune responses are initiated.

What are tertiary lymphoid organs and tissues?

Lymph-node-like structures that arise in peripheral tissues in response to chronic inflammation such as chronic infection, cancer, or autoimmune disease.

What is the overall organization of the immune system?

Immune cells are distributed throughout the body and most are migratory. Immune responses require coordination among many cells, organs, and microenvironments.

What are the two major progenitor types produced from HSCs?

Common myeloid progenitors, or CMPs, and common lymphoid progenitors, or CLPs.

What does differentiation do to a cell?

It reduces self-renewal potential and increases lineage commitment in a one-way process.

What transcription factors drive multipotent progenitors toward the myeloid lineage?

GATA-1 and PU.1.

What transcription factors drive multipotent progenitors toward the lymphoid lineage?

Ikaros and GATA-3.

Where does hematopoiesis occur during fetal development?

It begins in the aorta-gonad-mesonephros region near the kidney, yolk sac, and placenta, then migrates to the fetal liver. HSCs seed the bone marrow late in fetal development and ultimately populate the bone marrow after birth.

What are the major myeloid cell types that develop from CMPs?

Monocytes/macrophages, dendritic cells, granulocytes, megakaryocytes, and erythrocytes.

What do megakaryocytes supply?

Platelets.

What are the three main lymphoid cell types?

B cells, T cells, and innate lymphoid cells, or ILCs.

What do monocytes and macrophages do?

They are phagocytic cells specialized in engulfing large particles and cells. Monocytes are in blood, while macrophages are in tissues. They can also act as antigen-presenting cells for activating naïve T cells.

What do dendritic cells do?

They capture antigens in peripheral tissues, mature, migrate to secondary lymphoid tissues, and present antigens to naïve T cells. They are the most potent APCs for activating naïve T cells and bridge innate and adaptive immunity.

What are granulocytes?

A group of myeloid cells whose subtypes differ in granule staining, protein content, and function. It includes neutrophils, eosinophils, basophils, and mast cells.

What percentage of circulating leukocytes are neutrophils?

Approximately 50% to 70%.

What do neutrophils do?

They are phagocytes that swarm to sites of tissue damage or infection, phagocytose bacteria, and secrete proteins with antimicrobial and tissue-remodeling effects.

What do eosinophils do?

They are important for fighting parasites, are involved in allergic reactions, are abundant in the small intestine, and stimulate inflammation.

What is associated with basophils and mast cells?

They contribute to responses involving parasitic worms and allergies. Their granules contain cytokines, lipid mediators, and histamine.

What does histamine from basophils and mast cells do?

It contributes to vasodilation and smooth muscle activation.

What are the major lymphocyte types?

T cells, B cells, and ILCs.

What are the two major types of T cells described?

T helper cells expressing CD4 and cytotoxic T cells expressing CD8. Both express TCRs.

What do CD4 T cells become?

T helper cells that assist in B-cell differentiation, as well as regulatory T cells in the lymph-node context.

What do CD8 T cells become?

Effector killer or cytotoxic T cells that destroy infected cells.

What are NKT cells?

They express a semi-invariant TCR that reacts with glycolipid antigens presented by the MHC I-related protein CD1d on APCs.

Where does B-cell development occur?

Bone marrow only.

What happens to B cells after they encounter cognate antigen and a co-stimulatory signal?

They differentiate into memory B cells and plasma cells.

What is the function of plasma cells?

They are antibody production factories.

What are ILCs?

Lymphocytes that do not express the diversified antigen receptors found on T cells and B cells. They are largely tissue-resident and include NK cells.

What is the function of bone marrow stromal cells?

They facilitate HSC proliferation, direct migration, and stimulate differentiation.

What types of cells are included among bone marrow stromal cells?

Endothelial cells, perivascular cells, sympathetic nerves, macrophages, and osteoblasts.

What is the major function of the thymus?

It helps generate a broad, self-tolerant T-cell repertoire capable of fighting infection while avoiding autoimmune disease.

What determines life-or-death decisions for thymocytes?

The strength of TCR signaling resulting from interaction with pMHC in the thymus.

Where does positive selection occur in the thymus?

The cortex.

Where does negative selection occur?

The medulla.

What are double-negative thymocytes?

Thymocytes expressing neither CD4 nor CD8.

What are double-positive thymocytes?

Thymocytes expressing both CD4 and CD8.

What are single-positive thymocytes?

Thymocytes expressing either CD4 or CD8.

What happens to thymocytes that do not react or react weakly during positive selection?

They die by apoptosis.

What happens to thymocytes that react too strongly with self-pMHC?

They undergo negative selection, or T-cell clonal deletion.

What is the purpose of secondary lymphoid organs?

They are sites where naïve lymphocytes encounter non-self or altered-self antigens, become activated, undergo clonal expansion, and differentiate into effector cells.

Why are secondary lymphoid organs important?

They increase the chances that an appropriate B or T cell encounters an antigen.

What does the lymphatic system transport?

Fluid and leaked proteins from tissues and blood, along with immune cells and foreign antigens from infection sites to lymph nodes.

What are the three major regions of a lymph node?

Cortex, paracortex, and medulla.

What is found in the lymph-node cortex?

B-cell follicles, making it the B-cell zone.

What is the paracortex?

The T-cell zone of the lymph node.

What cells are associated with the lymph-node medulla?

Macrophages and dendritic cells.

How does lymph enter a lymph node?

Through the afferent lymphatic vessel.

How do naïve T and B cells enter lymph nodes?

Through the arterial blood via high endothelial venules, or HEVs.

How do lymphocytes leave lymph nodes?

Through the efferent vessel in the medulla.