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Chapter 3
PART I: Essential Pathology - Mechanisms of Disease
Infection and Host Response
Companion site for Molecular Pathology
Author: William B. Coleman and Gregory J. Tsongalis
FIGURE 3.1
Trypanosoma bruceiin the blood.
The African trypanosome is typically seen in peripheral blood smears from infected patients. In the
bloodstream, this extracellular parasite is exposed to complement, antibody, and white cells, but
survives to produce a persistent infection (Wright-Giemsa stain, 1000x).
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FIGURE 3.2
Mechanisms of generating antibody diversity.
C regions and sequences are in shades of purple; J regions and sequences are in shades of green, and V regions and
sequences are in shades of red. Altered or mutated sequences are in yellow. Designations of sequences (V1, etc.) are
arbitrary and not meant to represent the actual arrangement of specific elements. (A) The inherent germline diversity of
V and J regions provides some recognition diversity. (B) The combinations of V and J regions (V, D, and J in heavychains) provide additional diversity. (C) The V-J junctions undergo semirandom alterations during recombination,
generating more variants. (D) In activated B-cells, the variable regions are hypermutated. (E) V regions of both light
and heavy chains combine to form the antigen-recognition zone of the antibody. They can combine in different ways to
provide still more variety of antigen recognition.
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FIGURE 3.3A
Mechanisms for generating variant surface glycoprotein diversity in trypanosomes: VSG genome
structure.
VSG sequences are in shades of red, others are purple. Silent VSG genes are dark red; expressed
VSG genes are bright red, and VSG pseudogenes are pink. The large dots at the end of the
chromosome represent telomeres. Green arrows are VSG promoters. ESAG are Expression Site
Associated Genes, non-VSG genes, which are part of the polycistronic transcript driven by the VSG
promoter. Designations of sequences (VSG1, etc.) are arbitrary and not meant to represent the actual
arrangement of specific elements.
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FIGURE 3.4
Staphylococcus aureus and neutrophils.
A Gram-stained smear from a patient with S. aureus pneumonia. Staphylococci are located both
extracellularly and within neutrophils (Gram stain, 1000x).
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FIGURE 3.5
Chemokines secreted by macrophages in response to bacterial challenge.
Chemokines secreted by macrophages have both local and systemic effects which mobilize defenses
to infection, but may have unfortunate consequences as well.
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FIGURE 3.6
Mechanisms by which Stapylococcus aureus evades opsonophagocytosis.
The figure illustrates (a) the capsular polysaccharide, which can compromise neutrophil access to
bound complement and antibody; (b) the extracellular staphylokinase (Sak), which activates cellbound plasminogen and cleaves IgG and C3b; (c) protein A with 5 immunoglobulin G (IgG) Fc-binding
domains; (d) fibrinogen-binding protein (EfB), which binds complement factor C3 and blocks its
deposition on the bacterial cell surface. Complement activation beyond C3b attachment is prevented,
thereby inhibiting opsonization. (e) Clumping factor A (ClfA), which binds the γchain of fibrinogen.
Reprinted by permission from Nature Publishing Group, Nature Reviews Microbiology, Volume 3,
copyright 2005, page 952.
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FIGURE 3.7
Mycobacterium tuberculosis and the macrophage.
Gray arrows are host endosome processing pathways; the pink lines are mycobacterial mechanisms.
Fusion of mycobacteria into mature phagolysosomes usually leads to death of the organism, so
mycobacteria select their endocytotic pathway and interfere with mechanisms designed to result in
phagosome-lysosome fusion.
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FIGURE 3.8
A mycobacterial granuloma.
H&E stained sections of a mycobacterial granuloma. Central necrosis and an inflammatory response
consisting of macrophages, lymphocytes, and fibroblasts are apparent. A large multinucleated giant
cell, characteristic of the granulomatous reaction, is also present.
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FIGURE 3.9
How viruses damage cells.
Mechanisms by which viruses cause injury to cells. Reprinted by permission from Elsevier Saunders.
Robbins and Cotran: Pathologic Basis of Disease, 7th edition, copyright 2004, page 357.
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FIGURE 3.10
Histopathology of a herpes simplex lesion.
Herpesvirus blister in mucosa. High-power view shows host cells with glassy intranuclear herpes
simplex inclusion bodies. Reprinted by permission from Elsevier Saunders. Robbins and Cotran:
Pathologic Basis of Disease, 7th edition, copyright 2004, page 366.
Companion site for Molecular Pathology
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FIGURE 3.11
The structure of the HIV virion.
Schematic illustration of an HIV virion. The viral particle is covered by a lipid bilayer that is derived
from the host cell. Reprinted by permission from Elsevier Saunders. Robbins, and Cotran: Pathologic
Basis of Disease, 7th edition, copyright 2004, page 247.
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FIGURE 3.12
Pathogenesis of HIV-1 infection.
Pathogenesis of HIV-1 infection. Initially, HIV-1 infects T cells and macrophages directly or is carried to these cells by
Langerhans cells. Viral replication in the regional lymph nodes leads to viremia and widespread seeding of lymphoid
tissue. The viremia is controlled by the host immune response, and the patient then enters a phase of clinical latency.
During this phase, viral replication in both T cells and macrophages continues unabated, but there is some immune
containment of virus. Ultimately, CD4+ cell numbers decline due to productive infection and other mechanisms, and the
patient develops clinical symptoms of full-blown AIDS. Reprinted by permission from Elsevier Saunders. Robbins, and
Cotran: Pathologic Basis of Disease, 7th edition, copyright 2004, page 248.
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FIGURE 3.13
Opportunistic pathogen in AIDS.
Cluster of Pneumocystis jirovecii cysts in bronchoalveolar lavage of an HIV-positive patient stained
with toluidin blue (oil immersion, magnification 1000x).
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