Immunology

What is immunity?

Host pathogen disease interaction.

List important innate mechanisms of immunity.

Barriers, phagocytes, pattern recognition molecules.

Describe the two arms of the adaptive immune response including interaction with antigen.

Mediated by B-cells and T-cells following exposure to antigen that exhibits specificity, diversity, memory, and self non-self discrimination.

What are the characteristics of innate immunity?

Minutes to hours response time, limited and fixed specificity, response to repeat infection is the same, major components are barriers, phagocytes, pattern recognition molecules.

What are the characteristics of adaptive immunity?

Days to weeks response time, highly diverse specificity that improves during the course of response.

List anatomical barriers and mechanisms of innate immunity.

Antimicrobial peptides, enzymes, acidic pH, normal flora, mechanical barriers, directional flow of fluid, cilia, coughing, sneezing.

What is phagocytosis?

Engulfment and internalization of materials such as microbes for their clearance and destruction.

How are microbes recognized during phagocytosis?

By receptors on phagocytes that may recognize pathogen-associated molecular patterns (PAMPs) using Pathogen Recognition Receptors (PRRs) or soluble opsonin proteins bound to microbes.

What cells develop from myeloid progenitors?

Red blood cells, Granulocytes (Neutrophils, Basophils/mast cells, Eosinophils), Monocytes (Macrophages, Dendritic Cells), Megakaryocytes.

What cells develop from lymphoid progenitors?

B lymphocytes, T lymphocytes (CD4+ T helper cells [Th1, Th2, Th17, Treg], CD8+ T cytotoxic cells), NKT cells, Natural killer (NK) cells.

What is the function of neutrophils?

Direct harm to pathogens by phagocytosis.

What are the key features of neutrophils?

50-75% of circulating leukocytes, circulate in blood → migrate into tissue → die, recruited to infection sites by chemokines, phagocytose microbes and secrete antimicrobial peptides in tissue, dominant cell type during acute infection (main component of pus).

What are the functions of basophils and mast cells?

Inflammation, allergy, non-phagocytic response against parasites.

What is a major granule component of basophils and mast cells?

Histamine.

Where do mast cells reside?

Skin and epithelium of gut and genitourinary tract.

What is the activated function of eosinophils?

Killing of IgE-antibody coated parasites, antiviral and anti-parasitic activity.

What is the role of monocytes?

Migrate into tissues and can differentiate into macrophages or dendritic cells.

What are the activated functions of macrophages?

Phagocytosis, activation of T-cells (act as Antigen Presenting Cells - APCs).

What are the activated functions of dendritic cells?

Antigen uptake in peripheral sites and antigen presentation (most effective activator of T-cells).

How do dendritic cells initiate an adaptive response?

DCs in blood monitor for pathogens, engulf and process encountered antigens, migrate to lymph nodes, and present processed antigen to T-cells.

What are the activated functions of Natural Killer (NK) cells?

Release granules that kill some virus-infected cells and tumour cells (attack abnormal/altered self-cells).

Do NK cells possess antigen-specific receptors?

No.

What is the complement system?

A group of serum proteins circulating in inactive form that, once activated, can lead to target cell membrane lysis, chemotaxis, and opsonization to enhance phagocytosis.

List the three activation pathways of the complement system.

Classical, Lectin, Alternative.

What types of cells are lymphocytes?

Cells of the adaptive immune system (including CD4+ and CD8+ T cells).

What is antibody-mediated (humoral) adaptive immunity?

Combats pathogens via antibodies produced by B-cells which can be found in bodily fluids.

What is cell-mediated adaptive immunity?

CD4+ and CD8+ T cells eliminate pathogens by a variety of mechanisms (including cytotoxic T cells and NK cells).

What is the hallmark of adaptive immunity?

Memory.

Describe the primary immune response.

First exposure to an antigen, during which antigen-specific memory lymphocytes are generated.

Describe the secondary immune response.

Secondary exposure to the antigen stimulates memory lymphocytes, yielding a response of greater speed and magnitude with improvement of antigen specificity.

What are the primary lymphoid organs?

Bone Marrow (for B cell development) and Thymus (for T cell development).

What happens in the bone marrow regarding B-cells?

B-lymphocytes develop from hematopoietic stem cells. Mature antibody-secreting B-cells (plasma cells) can return to become resident cells of the bone.

What happens in the thymus regarding T-cells?

Immature T-cells develop. Immature T-cells travel to the thymus from the bone marrow via blood. The thymus helps to educate T-cells (recognize self from non-self).

What are the secondary lymphoid organs?

Lymph nodes, Spleen, Mucosal-associated lymphoid tissue (MALT).

What are the functions of lymph nodes and the spleen in immunity?

Areas of antigen recognition by lymphocytes and lymphocyte activation. Lymph brings antigens from all parts of the body to lymph nodes. The spleen plays a major role in mounting immune response to blood-borne antigens.

What are the antigen recognition molecules for B cells?

Soluble (antibody) or membrane-bound Ig (B-Cell Receptor).

What are the antigen recognition molecules for T cells?

Membrane-bound T cell receptor (TCR).

What is required for T-cell receptors to recognize antigen?

Antigen to be processed and presented in the context of self-antigen (MHC).

What is an epitope?

A single antigenic determinant that each lymphocyte recognizes.

What is the Major histocompatibility complex (MHC)?

Required for antigens to be recognized by the TCR and is also responsible for graft rejection.

What is antigen processing?

Cellular pathways that lead to antigen degradation and association with MHC.

What is antigen presentation?

Appearance of MHC-peptide complexes on the cell surface for recognition by T cells.

What are the two different forms of MHC?

MHC-I (present on all nucleated cells) and MHC-II (present only on antigen-presenting cells).

What are antigen-presenting cells (APCs)?

Cells that process antigen and present antigenic peptides on their cell surface via MHC-II (macrophages, dendritic cells, and B cells).

What happens when naive T cells are activated by APCs?

They differentiate and become effector cells (CD8+ become killer T cells, CD4+ differentiate into several subsets).

What type of antigen does MHC-I present?

Intracellular antigen peptides (self-proteins or cells infected with viruses).

To what type of T cell does MHC-I present antigen?

CD8+ T cells.

What type of antigen does MHC-II present?

Extracellular antigen peptides.

On what type of cells is MHC-II generally found?

Antigen Presenting Cells (APCs).

To what type of T cell does MHC-II present antigen?

CD4+ T cells.

What is the basic structure of an antibody?

Consists of 4 polypeptide chains (2 identical heavy chains and 2 identical light chains), both heavy and light chains have constant and variable regions, the variable region recognizes the epitope on the antigen.

What are the effector functions of antibodies?

Neutralization, Opsonization, Complement fixation, Antibody-dependent cell-mediated cytotoxicity (ADCC).

What are the cell-mediated effector functions involving Fas-FasL interaction?

Activates the Caspase 8 pathway, leading to granzyme/perforin mediated cytolysis.

What are the two broad categories of dysfunctions of immunity?

Overly active or misdirected immune responses (e.g., allergies, autoimmune disease) and Immunodeficiency (primary/genetic or secondary/acquired).

What is autoimmunity a result of?

A failure in tolerance toward self-antigen.

What is peripheral tolerance?

Eliminates, regulates, or renders self-reactive lymphocytes that have reached circulation to be non-responsive.

List factors that can influence susceptibility to autoimmune disease.

Environmental factors (diet, geographic area, etc.) and Genetic susceptibility (MHC genes linked, self-reactive T-helper cells).

What are primary (genetic) immunodeficiencies?

Genetic loss of immune function (examples include Chediak-Higashi syndrome and Mendelian susceptibility to mycobacterial diseases).

What are secondary (acquired) immunodeficiencies?

Acquired loss of immune function causing heightened susceptibility to common and opportunistic infections.

How is HIV-1 spread?

By intimate contact with infected body fluids.

How does HIV-1 infect CD4+ T cells?

Dendritic cells in virus-exposed areas may take up and harbor the virus, passing it to CD4+ T cells.

Describe the acute phase of HIV-1 infection.

Anti-HIV antibody production.

Describe the asymptomatic phase of HIV-1 infection.

Slow decrease in CD4+ T cells and an increase in viral load.

What characterizes AIDS in HIV-1 infection?

Depletion of CD4+ T cells and a high concentration of HIV in the blood.

What is the general term for foreign material within a host?

Antigen.

Are all antigens immunogens?

No, not all antigens elicit an immune response (immunogens).

What is a pathogen?

Disease-causing organism composed of many different antigens.

What is the primary role of the innate immune system in recognizing pathogens?

Carried out by cells like professional antigen-presenting cells (APCs) which recognize 'danger signals'.

List the first line of defense mechanisms (innate immunity).

Mechanical (skin, mucous membranes, cilia), Soluble/chemical (enzymes like lysozyme, peptides like defensins), Biological (commensal flora), Cellular (phagocytes).

What are the key features of the specific (adaptive/acquired) immune response?

Response directed specifically toward the foreign material (antigen) that induced it.

What are antigens usually composed of?

Usually peptides that are recognized by cells of the adaptive immune system as self or foreign.

What are lymphocytes?

Small round cells found in blood and lymph that mediate the antigen-specific immune response.

Where do immature lymphocytes originate?

Bone marrow.

What are the two main classifications of lymphocytes based on maturation site?

B cells (mature in bone marrow) and T cells (mature in thymus).

What are the key features of B cells?

Have specific surface markers and naive B cells activated by antigen exposure give rise to antibody-producing plasma cells.

What are the key features of T cells?

Mature in the Thymus and have specific surface markers.

What is the role of CD4+ helper T cells?

Help to orchestrate the immune response through direct cell-cell interaction and cytokine production.

What is the role of CD8+ (Tc) cytotoxic T cells?

Kill pathogen-infected and transformed cells.

How is antigen transported to lymphoid tissues?

Via blood or lymphatics to lymph nodes, spleen, and lymphoid tissue.

What are specialized antigen-presenting cells (APCs) that pick up antigen in lymphoid tissues?

Macrophages, dendritic cells, and B cells.

What is the humoral immune response mediated by?

Antibody produced by plasma cells.

What is the basic structure of an antibody molecule?

Y-shaped with two heavy chains and two light chains linked by disulfide bonds.

Give examples of different isotypes of immunoglobulins (Ig).

IgA, IgD, IgE, IgG, IgM.

Where is IgA primarily found and what is its function?

In secretions and on mucous membranes, helps protect mucosal surfaces.

Where is IgE primarily found and what is its role?

In tissues, attached to mast cells; release inflammatory mediators upon cross-linking by antigen.

What is the general function of antibodies?

Combine specifically with antigens, blocking their normal function or growth.

List protective mechanisms mediated by antibodies.

Blocking of attachment to host cells, opsonisation, agglutination, complement activation.

What is the complement system and how is it activated by the classical pathway?

A series of enzymes activated by antigen-antibody interaction, resulting in chemotaxis and cell lysis.

What is humoral immunity especially important in defense against?

Extracellular pathogens.

How can the presence of antibody be detected?

By in vitro serological tests (e.g., agglutination, ELISA).

What does a rise in antibody titer between acute and convalescent serum samples often indicate?

Recent infection.

What is active immunity?

Results from exposure to antigen and proliferation of antigen-sensitive lymphocytes.

What is the anamnestic (secondary) immune response?

More rapid onset and greater magnitude than the primary response.

What is vaccination?

Intentional introduction of antigen to stimulate immunological memory.

What is passive immunity?

Transfer of antibody from an immunized animal to a naive individual; does not elicit memory.

What does cell-mediated immunity depend on?

The presence of Tc cells specifically reactive to antigen.

How do Tc cells recognize infected cells?

The TCR recognizes foreign antigens presented on the cell surface by MHC class I molecules.

What is the role of Th1 (CD4+) cells in cell-mediated immunity?

Recognition of antigen-MHC complex leading to release of cytokines that stimulate other cells to enhance killing of intracellular pathogens.

What is a delayed-type hypersensitivity (DTH) reaction (Type IV)?

Cell-mediated immune response characterized by induration and erythema due to infiltration of mononuclear cells.

What are some in vitro tests to assess cell-mediated immunity?

Culturing lymphocytes with antigen and measuring cytokine production, Fluorescence activated cell sorting (FACS) to measure T cell proportions.