Immunology

Differentiation of B cells into plasma cells

(B-cell clonal selection aka humoral immune response) - When immunocompetent B cells are stimulated by TH2 cells they proliferate and differentiate into a plasma cell (multiple copies of it). - It can be found in the blood, secondary lymphoid organs ( mostly spleen and lymph nodes), and some inflammatory sites. - Each plasma cell can produce an antibody and is dedicated to secreting that type of antibody with one variable region. (specificity against one antigenic determinant).

Describe clonal diversity and compare it to clonal selection.

Colonel diversity "occurs in the primary lymphoid organs in a fetus" a large portion of T cells and B cells are produced before birth. Clonal selection (second phase of the immune response) is the "the selection and proliferation of mature B and T cells in response to exposure to a specific antigen." Antigens initiate this second phase. 1. processing and presentation of APC cells to immature lymphocytes 2. immunocompetent B and T cells with the specific receptor are stimulated by IL-2 ( secreted from TH1 and TH2) to mature and proliferate (clonal expansion). - B cells to plasma cells - T cells to cytotoxic T cells 3. These selected cells mount a defense response against antigen - B cells (activated by T-helper cells) produce antibodies and put into surrounding tissue or circulation. (pg. 820 says depending on the combination of cytokines produced B cells can class-switch from making IgM antibodies to making and secreting IgA or IgE or IgG. 4. Produce B and T memory cells.

Describe the difference between cellular immunity (T cell) versus humoral immunity (B cell) - list 5 different cell types created in clonal selection

Difference: B response is to create antibodies which bind and then are able to neutralize bacteria and viruses (by flagging other cells to phagocytize) and activate complement cascade. The T cell response creates Cytotoxic T cells and they bind and kill the foreign antigen by releasing a toxin. Same: Both create Memory cells 5 cells: Regulatory T cell Cytotoxic T cell Memory T cell Memory B Cell Plasma Cell.

The two main components of immunoglobulins are the antigen binding fragments (Fab) and major histocompatibility complex (MHC). True False

False

What is the Major Histocompatibility Complex (MCH) Class II and describe its role in antigen presentation.

Genomic region consisting of 4 loci on chromosome 6 (short arm) that directs synthesis of the HLA antigen (many different types of HLA's are coded in different individuals because of different coding/ sequencing from person to person) - molecules codes here are separated into classes MHC class II: an antigen that presents on only certain types of cells such as lymphocytes and macrophages do allow for antigen presentation to T and B cells during the adaptive immune response

Which of the following statement about human leukocyte antigen (HLA) is TRUE? -HLA is found on all cells except the circulating blood cells and bone marrow stem cells. -HLA determines what class of antibodies to release during a normal immune response -HLA allows the immune system to determine whether to mount a primary or secondary immune response -HLA allows the immune system to distinguish cells of its own body from foreign microorganisms and tissues.

HLA allows the immune system to distinguish cells of its own body from foreign microorganisms and tissues.

Where is HLA located and what is its function?

Human Leukocyte Antigen - On all cell membranes (expect RBCs) - a cell surface protein that distinguishes self for not self HLA = the antigen MHC (major histocompatibility complex) = the gene on chromosome 6 that makes HLA antigen why we can't do organ transplants without immunosuppression and matching

Secretions from the mucous membranes of the respiratory and GI tracts primarily contain which of the following antibodies? IgM IgG IgE IgA

IgA

Which antibody would have the highest titers during a secondary immune response? -IgM -IgE -IgA -IgG

IgG

How do vaccines confer acquired active immunity against disease?

Immune cells recognize the antigen associated with the vaccine and destroy the vaccine antigen and proceed through the adaptive immunity cascade to develop memory for the particular injected antigen. When the actual antigen is encountered the immune system is able to rapidly amount a response with high levels of antibodies (IgG) and cytotoxic T cells

How do immunoglobulins recognize antigens

Immunoglobulin = antigen that has specificity to a particular antigen produced from plasma (B) cells that are dumped into the tissue/ circulation - they are in a Y shape with the "arms" containing cognition/ receptor sites for antigens = ensuring specificity. The "tail" segment (Fc) once bound "wags its tail" to instigate inflammatory mediators to the site and activates the complement system to further phagocytosis

Describe the processes that occur after the CD4 helper T cell has been activated that eventually leads to the proliferation to antibodies and cytotoxic T cells

In an inflammatory response from an infection, the macrophages phagocytose and process an antigen, release IL-1 and present their antigens (via MHC I or II) to the attracted T helper cell via CD4 protein. Once bound, TH releases IL-2 to mature to TH1 and TH2. TH1 stimulates proliferation and differentiation of T lymphocytes to become Cytotoxic T cells (TC or CD8 T cells)

Describe the function of each cell in the immune response. B lymphocytes

In the bone marrow immunocompetent B cells ( or B lymphocytes) are formed then migrate to secondary organs. In an inflammatory response from an infection, the macrophages phagocytose and process an antigen, release IL-1 and present their antigens (via MHC I or II) to the attracted T helper cell via CD4 protein. Once bound, TH releases IL-2 to mature to TH1 and TH2. TH2 stimulates the B lymphocyte to differentiate and proliferate into plasma cells.

From a clinical perspective, compare and contrast the inflammatory response and the immune response.

Inflammatory Response (a.k.a. Innate Immunity) · Rapid · Nonspecific · No memory - will respond the same way every time · Involves many cells (neutrophils, monocytes/macrophages eosinophils, endothelial cells, platelets, etc.) and plasma systems · Fevers Immune Response (a.k.a. Adaptive Immunity) · Slower - few weeks (-5 days for a response - weeks for peak) · Specific · Memory - knows the difference between good and bad pathogens (Repeat exposures are quicker) · Involves lymphocytes and antibodies (B and T cells) · Can be induced by vaccination · Has to be primed or activated to respond · Clonal expansion - stronger, faster response each time it see the same pathogen · Memory cells

What role do antigen presenting cells (APCs) and helper T cells play in mounting an immune response? Be sure to describe the role of CD proteins and cytokines.

Once the APC has phagocytized the antigen, the APC presents the antigen to its surface receptors aka the MHC Class 11 receptor. At the same time are presents the antigen to the receptor it also signals Th cells (via IL-1 production) to come for that specific bound antigen. Once the Th cells arrive, they bind to the antigen on the APC using CD4 protein. Th cells secrete IL-2 which stimulates that Th cell to mature into functional Th1 cells (cytotoxic T cells) and Th2 cells (B cells)

Primary versus secondary organs

Primary lymphoid organs (thymus and bone marrow) are where lymphocytes differentiate into immunocompetent cells. T cells in the Thymus and B cells in the bone marrow in a fetus. - immunocompetent means they have the collective ability to recognize any antigen but each clone has receptor specificity for only one antigen. -differentiation of B cells and T cells in primary lymphoid organs results in expression of several characteristics surface markers such as, CD4 on helper T cells, CD8 on cytotoxic T cells, and CD21 and CD40 on B cells (pg. 818 point 3 under clonal diversity). -After the differentiation they enter circulation and travel to secondary lymphoid organs/tissues Second lymphoid organ and tissue: (Spleen, lymph nodes, adenoids, tonsils, peyer patches (Intestines), appendix, and mucosal and cutaneous lymphoid tissues). Most aspects of clonal selection begin here. The cells get here through blood vessels and enter in high endothelial venules (HEVs) where they bind to endothelium and enter the lymphoid tissues which are rich with B and T cells.

Compare the primary and secondary immune responses.

Primary: initial immune response to antigen. IgM is primary immunoglobulin (antibody) produced in this response after about 5 days Secondary: more rapid than primary (responds immediately when antigen that is recognized is encountered by memory cells?), and produces more IgG immunoglobulins (antibodies) IgG is what you will check for when you draw a titer level to test someone's immunity.

During antigen processing, after an antigen is phagocytosed by a antigen presenting cell (APC), what happens to it? -The antigen stimulates B cells to produce antibodies. -The antigen is presented to a helper T cell. -The antigen is metabolized and the metabolites initiate the complement cascade. -The antigen becomes a specific antibody.

The antigen is presented to a helper T cell.

All of the following statements about antibodies are TRUE EXCEPT: -Antibodies neutralize both bacteria and viruses -Antibodies are immunoglobulins -The clotting cascade is activated by antibodies -Antibodies opsonize bacteria and other foreign organisms

The clotting cascade is activated by antibodies

Describe the differences between the different types of vaccinations. mRNA

teaches cell how to make antigenic material via protein production/ pieces of proteins to display to the cell surface which the immune system then recognizes as antigen and amounts an immune response. These are not live and they don't enter the cell nucleus so it is not integrated into the DNA, and once the protein is produced the mRNA is broken down

The generation of clonal diversity is: -the development of a population of immunocompentent B and T lymphocytes that have the ability to recognize all foreign antigens. -the process by which lymphocytes migrate through the spleen as they mature. -the mechanisms through which humans gain natural immunity. -the reaction of a T or B lymphocyte to a specific antigen.

the development of a population of immunocompentent B and T lymphocytes that have the ability to recognize all foreign antigens.

Describe the differences between the different types of vaccinations. Synthetic

antigens formed in lab environment from recombinant proteins and other molecules

Blocking the Th (Th1 and Th2) response would: -decrease macrophage activity. -decrease the T and B lymphocyte response to infection. -increase T cell and B cell activity during infections and allergic reactions. -increase Treg cell activity.

decrease the T and B lymphocyte response to infection.

Describe the differences between the different types of vaccinations. Subunit

initiates immune response from injected microbial proteins and/or polysaccharides

Describe the differences between the different types of vaccinations. Live Attenuated

live microbes injected but treated to reduce their pathogenicity - not used for immunocompromised people, boosters required less often

Describe the differences between the different types of vaccinations. Inactivated

viral microbes killed so they are no longer effect in producing a pathogenicity but retain their ability to amount an immune response - requires multiple doses

Provide examples of foreign antigens

· Viruses · Bacteria · Pollens and other environmental allergens · Food or drugs

List 4 different classes of antibodies (immunoglobulins) and describe their functional differences.

- IgM: Produced more in a primary immune response, general antibody with 5 segments/ arms, used to determine if active infection is occurring clinically - IgG: Produced more in a secondary immune response, general antibody with Y shape, continues to circulate following a primary response, used to determine past infection clinically - IgA: antibody mostly in mucosal lining that is the first line defense to inhaled/ injected antigens, and it the antibody that is the highest in number found in the body - IgE: antibody produced in allergic responses - leads to type 1 hypersensitivity reactions (also have an IgD antibody but we don't understand its role or fx as clearly.)

Describe the function of each cell in the immune response. Memory cells (T and B)

- Memory B cells on second exposure will release cytokines that signal other B lymphocytes that are specific to this exact antigen to start differentiating and proliferating. This happens immediately. It does not wait for the inflammatory response or for antigen processing. - Memory T cells are similar to memory B cells. They signal immunocompetent T cells to differentiate into Cytotoxic T cells upon repeated exposure to a given antigen.

Antigen processing and presentation to immature lymphocytes

- This is the duty of APCs; most cells have the: capacity to present antigen to some degree (pg. 780), but dendritic cells (most effective for TH cells), macrophages, and B lymphocytes are the most efficient at antigen presentation (they are the 'professionals'). - Antigen processing: the process the antigens are linked to the appropriate MHC molecule and then presented on the receptor surface of the cell. MHC II for exogenous antigens MHC 1 for endogenous antigens (pg 783-4). - IL-1 signals T- helper cell. The specific T-helper cell then binds to antigen being presented (T-helper cells glycoprotein site that binds is called a CD4- usually). - T-helper secretes IL-2 which makes them mature to a TH1 or TH2. TH1 stimulates the T cell response and differentiation/proliferation into Cytotoxic T cells . TH2 stimulates the B cell response and differentiation/proliferation into plasma cells.

Differentiation of T cells into cytotoxic T cells

- When immunocompetent T cells are stimulated by TH1 cells they proliferate and differentiate into Cytotoxic T (Tc or CD8 T cells). - They are responsible for cell-mediated destruction. Very effective killers

Production of both B and T memory cells

- some B and T cells are stimulated to differentiate to memory cells - They retain memory of foreign antibodies and live for a long time. Some last longer than others. Why sometimes need boosters for vaccines. - This will help us have a more immediate response to exposure the second time. Helps bypass the antigen presentation.

Describe the function of each cell in the immune response. Cytotoxic T cells (Tc)

1. Bind to the T cell receptor on the antigen via CD8 protein on the cytotoxic T cell surface. 2. Release toxins to destroy the target cell

List 3 functions of antibodies.

1. neutralize bacteria and viruses with binding (some also neutralize toxins produced from bacteria) 2. Promotes phagocytosis via opsonization: FC portion (tail) of the antibody waves to attract phagocytes, some organisms can evade this process 3. Activates the complement cascade - brings more complement proteins to opsonize and phagocytize antigen and results in membrane attack processes to the targeted antigen

What is an antigen?

A molecule that is recognized by lymphocytes and reacts with antibodies foreign (virus, bacteria, pollen, food) or self-antigen (HLA)

Describe the differences between the different types of vaccinations. Conjugated

microbial polysaccharides coupled with proteins to stimulate T helper cells

Receptor specificity

one lymphocyte can recognize one antigen

Describe the differences between the different types of vaccinations. Toxoid

produced from inactivated bacterial toxins (tetanus, diphtheria)

Which of the following descriptions is TRUE about attenuated vaccines? The vaccine is made from microbial antigens that are formed from recombinant proteins in a lab The microbe used in the vaccine is killed using heat or chemicals Attenuated vaccines may not be safe for immunocompromised individuals Gene sequencing is used to create an artificial microbe that is then used for vaccination

Attenuated vaccines may not be safe for immunocompromised individuals

Which statement about B cell activation into either plasma cells or memory B cells is TRUE. -B cells are activated by IgM -B cells are activated and become plasma cells when they recognize a particular antigen -only bursal bound (immunocompetent) B cells can react with antigen -B cells become active when they recognize the antigen presented by the MHC class I

B cells are activated and become plasma cells when they recognize a particular antigen