RHEUMATOLOGY IMMULOGY HEMATOLOGY

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1. Pathophysiology of immune compromise secondary to spleenectomy

The spleen contains macrophages which are immune cells that phagocytose the

bacteria. Particularly, these macrophages are activated when bacteria are bound by

IgG antibodies or the complement component C3b. The antibodies and complement,

immune substances referred to as opsonizers, are molecules that bind to the surface of

bacteria to facilitate phagocytosis.

In the event of spleenectomy, IgG and C3b are still bound to bacteria, but cannot be

removed from the circulation due to loss of the splenic macrophages. Therefore the

bacteria are free to cause infection. These include common human pathogens with

bacterial capsules e.g. Streptococcus pneumoniae, Salmonella typhi, Neisseria

meningitidis, E. coli, Hemophilus influenzae, Streptococcus agalactiae, Klebsiella

pneumoniae) etc. Capsules composed of polysaccharides allow the bacteria to evade

phagocytosis by macrophages alone, since solely proteins are directly recognized by

macrophages in phagocytosis. Therefore, humoral immunity in forms of IgG and

complement proteins is immune system's response for bacterial capsules.

2. Function of macrophages located in the Medulla of the lymph node structure

Antigen presentation on the surface of infected macrophages in a lymph node

stimulates TH1 (type 1 helper T cells) to proliferate. When a B-cell in the lymph node

recognizes the very same unprocessed surface antigen on the bacteria with its

surface-bound antibody, the antigen is endocytosed and is processed. The processed

antigen is later presented in MHCII at the surface of the B-cell. T cells that express

the T cell receptor which recognizes the antigen-MHCII lead the B-cell to make

antibodies which help opsonization of the antigen so that the bacteria can be cleared

by phagocytes in a better way.

3. Which lymph node structures contain T cells?

Paracortex of the lymph node is the site for T cells.

4. What is the site of B-cell localization in a lymph node?

B cells are primarily found in the outer (superficial cortex) being clustered together as

follicular B cells in lymphoid follicles.

5. Why is the paracortex of the lymph node underdeveloped in DiGeorge

Syndrome?

Paracortex of the lymph node is underdeveloped in DiGeorge syndrome because of

having prominent medullary cystic changes in the paracortical regions of the lymph

nodes and absence of T cells.

6. Why is the thymus enlarged in myasthenia gravis?

In patients with myasthenia gravis, the thymus gland is enlarged. It is due to clusters

of immune cells in the thymus gland similar to lymphoid hyperplasia. Some people

with myasthenia gravis also develop thymomas which are mostly benign tumors of

the thymus gland.

7. What are HLA Genes and what do they code for? What is their purpose?

The human leukocyte antigen (HLA) system is a gene complex which encodes the

major histocompatibility complex (MHC) proteins in human beings. They are

cell-surface proteins responsible for regulating the immune system in humans. The

HLA gene complex resides on a 3 Mbp stretch within the chromosome 6p21. HLA

genes are very polymorphic meaning that they have many different alleles, allowing

them to fine-tune the adaptive immune system. The proteins encoded by certain genes

are known as antigens. Different classes have different functions.

When a pathogen enters the body, some specific cells termed antigen-presenting cells

(APCs) engulf the pathogen via the process of phagocytosis.

Any cell having some other HLA type is considered "non-self" and is viewed as an

invader by the host body's immune system, culminating in the rejection of the tissue

having those cells. This is especially significant in the case of transplanted tissue

because it can lead to transplant rejection. Because of the significance of HLA in

transplant, the HLA loci are among the most frequently typed by serology and PCR.

HLA types are inherited and sometimes are connected with autoimmune disorders and

some other disorders.

Some HLA-mediated diseases are also involved in the production of cancers.

8. What are MHC Proteins? What is the difference between MHC I and MHC

II proteins in terms of function, binding, and what types of cells they are

expressed on (nucleated cells vs. APCs)

The major histocompatibility complex (MHC) is defined as a set of cell surface

proteins necessary for the acquired immune system for recognition of foreign

molecules in vertebrates, in turn determining histocompatibility. The core function of

MHC molecules is to bind to antigens originating from pathogens and displaying

them on the surface of the cell for their recognition by the T-cells.

MHC class I is expressed on all nucleated cells and in platelets i.e. all cells but

except the RBCs. It presents epitopes to killer T cells, also called cytotoxic T

lymphocytes (CTLs). A CTL expresses CD8 receptors, in addition to TCRs. When a

CTL's CD8 receptor docks to an MHC class I molecule, if the CTL's TCR fits the

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1. Pathophysiology of immune compromise secondary to spleenectomy The spleen contains macrophages which are immune cells that phagocytose the bacteria. Particularly, these macrophages are activated when bacteria are bound by IgG antibodies or the complement component C3b. The antibodies and complement, immune substances referred to as opsonizers, are molecules that bind to the surface of bacteria to facilitate phagocytosis. In the event of spleenectomy, IgG and C3b are still bound to bacteria, but cannot be removed from the circulation due to loss of the splenic macrophages. Therefore the bacteria are free to cause infection. These include common human pathogens with bacterial capsules e.g. Streptococcus pneumoniae, Salmonella typhi, Neisseria meningitidis, E. coli, Hemophilus influenzae, Streptococcus agalactiae, Klebsiella pneumoniae) etc. Capsules composed of polysaccharides allow the bacteria to evade phagocytosis by macrophages alone, since solely proteins are directly recognized by macrophages in phagocytosis. Therefore, humoral immunity in forms of IgG and complement proteins is immune system's response for bacterial capsules. 2. Function of macrophages located in the Medulla of the lymph node structure Antigen presentation on the surface of infected macrophages in a lymph node stimulates TH1 (type 1 helper T cells) to proliferate. When a B-cell in the lymph node recognizes the very same unprocessed surface antigen on the bacteria with its surface-bound antibody, the ...
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